title: Efficacy and safety of oral tibolone 1.25 or 2.5 mg/day vs. placebo in postmenopausal women. Estrogen effects on the vaginal pH, flora and cytology in late postmenopause after a long period without hormone therapy. Menopausal Symptoms in Older Women and the Effects of Treatment With Hormone Therapy Effect of raloxifene on sexual function in postmenopausal women Absence of systemic hormonal effects in an oestradiol diether topically active on the vaginal mucosa. Health related quality of life after combined hormone replacement therapy: randomised controlled trial Effect of androgens combined with hormone therapy on quality of life in post-menopausal women with sexual dysfunction Oral ultra-low dose continuous combined hormone replacement therapy with 0.5 mg 17β-oestradiol and 2.5 mg dydrogesterone for the treatment of vasomotor symptoms: results from a double-blind, controlled study. The effects of postmenopausal hormone therapy on social activity, partner relationship, and sexual life – experience from the EPHT trial Efficacy of Low-Dose Estradiol Vaginal Tablets in the Treatment of Atrophic Vaginitis: A Randomized Controlled Trial Effect of continuous administration of conjugated estrogen plus medroxyprogesterone acetate (Premelle) in postmenopausal women in Taiwan. Ospemifene effectively treats vulvovaginal atrophy in postmenopausal women: results from a pivotal phase 3 study Efficacy of low-dose intravaginal estriol on urogenital aging in postmenopausal women Effects of estrogen with and without progestin on urinary incontinence. Estradiol 1 mg and drospirenone 2 mg as hormone replacement therapy in postmenopausal Chinese women Hot flushes and biochemical markers for cardiovascular disease: a randomized trial on hormone therapy Low-dose, vaginally administered estrogens may enhance local benefits of systemic therapy in the treatment of urogenital atrophy in postmenopausal women on hormone therapy. Micro-dose transdermal estradiol for relief of hot flushes in postmenopausal Asian women: a randomized controlled trial Tibolone increases bone mineral density but also relapse in breast cancer survivors: LIBERATE trial bone substudy Different effects of tibolone and continuous combined estrogen plus progestogen hormone therapy on sex hormone binding globulin and free testosterone levels – an association with mammographic density [Evaluation the efficacy and safety of estradiol and drospirenone tablets in the treatment of menopausal symptoms among postmenopausal Chinese healthy women:a randomized, multi-center, double-blind, placebo-controlled clinical study]. Hormone replacement therapy and vigilance: double-blind, placebo-controlled EEG-mapping studies with an estrogen-progestogen combination (Climodien, Lafamme) versus estrogen alone in menopausal syndrome patients. Efficacy and tolerability of a novel estradiol vaginal ring for relief of menopausal symptoms. The Women's international study of long-duration oestrogen after menopause (WISDOM): a randomised controlled trial Randomized, multicenter, double-blind, placebo-controlled trial to evaluate the efficacy and safety of synthetic conjugated estrogens B for the treatment of vulvovaginal atrophy in healthy postmenopausal women. Vaginal oestradiol for the treatment of lower urinary tract symptoms in postmenopausal women--a double-blind placebo-controlled study. Patterns and predictors of sexual activity among women in the Hormone Therapy trials of the Women's Health Initiative Suppression of vasomotor and vulvovaginal symptoms with continuous oral 17&bgr;‐estradiol Effects of bazedoxifene/conjugated estrogens on quality of life in postmenopausal women with symptoms of vulvar/vaginal atrophy Effects of hormone replacement therapy in rheumatoid arthritis: a double blind placebo-controlled study. Are randomized trials of hormone replacement therapy in symptomatic women with breast cancer feasible? Hormonal replacement therapy does not affect self-estimated pain or experimental pain responses in post-menopausal women suffering from fibromyalgia: a double-blind, randomized, placebo-controlled trial. Effects of hormone therapy with estrogen and/or progesterone on sleep pattern in postmenopausal women. Comparison of Pueraria lobata with hormone replacement therapy in treating the adverse health consequences of menopause A randomized, open, parallel-group study on the preventive effect of an estradiol-releasing vaginal ring (Estring) on recurrent urinary tract infections in postmenopausal women. Efficacy of a new, oral estradiol acetate formulation for relief of menopause symptoms Synthetic Conjugated Estrogens-B and Postmenopausal Nocturnal Vasomotor Symptoms: A Randomized Controlled Trial Low-dose (0.3 mg) synthetic conjugated estrogens A is effective for managing atrophic vaginitis. Effects of ultra-low-dose estrogen therapy on muscle and physical function in older women. Is sexual life influenced by transdermal estrogen therapy? A randomized trial of the effect of testosterone and estrogen on verbal fluency, verbal memory, and spatial ability in healthy postmenopausal women. A 20-week randomized controlled trial of estradiol replacement therapy for women aged 70 years and older: Effect on mood, cognition and quality of life Comparative effects of estrogens plus androgens and tibolone on bone, lipid pattern and sexuality in postmenopausal women. Quality of life of postmenopausal women on a regimen of transdermal estradiol therapy: a double-blind placebo-controlled study. Effects of raloxifene and hormone replacement therapy on serum Th2 and Th3 type cytokine concentrations in healthy postmenopausal women: a randomised controlled trial Testosterone aromatization and cognition in women: a randomized, placebo-controlled trial Effect of female sex hormone supplementation and withdrawal on gastrointestinal and colonic transit in postmenopausal women. Local Treatment of Urogenital Atrophy with an Estradiol-Releasing Vaginal Ring: A Comparative and a Placebo-Controlled Multicenter Study
   Pulsed estrogen therapy improves postmenopausal quality of life: a 2-year placebo-controlled study. Low-dose tibolone (1.25 mg/d) does not affect muscle strength in older women Effects of oral raloxifene on serum estradiol levels and other markers of estrogenicity. [Clinical study on combination of multiple regimens in treatment of osteoporosis in perimenopause and postmenopausal women]. The effects of 3-week estrogen hormone replacement on cognition in elderly healthy females Tibolone for the treatment of moderate to severe vasomotor symptoms and genital atrophy in postmenopausal women: a multicenter, randomized, double-blind, placebo-controlled study Local estrogen treatment in patients with urogenital symptoms. Results from the Estonian postmenopausal hormone therapy trial [ISRCTN35338757]. Complex regulation of GH autofeedback under dual-peptide drive: studies under a pharmacological GH and sex steroid clamp. Doppler flow analysis of the palmaris superficial branch of the radial artery in postmenopausal women with acroparesthesia: the role of hormone therapy. A pilot study Raloxifene and Estrogen Effects on Quality of Life in Healthy Postmenopausal Women: A Placebo‐Controlled Randomized Trial A Multicenter, Open-Label Study to Evaluate Satisfaction and Menopausal Quality of Life in Women Using Transdermal Estradiol/Norethindrone Acetate Therapy for the Management of Menopausal Signs and Symptoms Effects of conjugated equine estrogen on health-related quality of life in postmenopausal women with hysterectomy: results from the Women's Health Initiative Randomized Clinical Trial. Sustained efficacy and safety of bazedoxifene in preventing fractures in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled study Supplementation with DHEA: effect on muscle size, strength, quality of life, and lipids. Effects of hormone replacement therapy on cognitive performance in elderly women. Obesity and sarcopenia after menopause are reversed by sex hormone replacement therapy. Safety and efficacy of a continuous once-a-week 17beta-estradiol/levonorgestrel transdermal system and its effects on vasomotor symptoms and endometrial safety in postmenopausal women: the results of two multicenter, double-blind, randomized, controlled trials. Low dose estriol pessaries for the treatment of vaginal atrophy: a double-blind placebo-controlled trial investigating the efficacy of pessaries containing 0.2mg and 0.03mg estriol. Low-dose 17 beta-estradiol vaginal tablets in the treatment of atrophic vaginitis: a double-blind placebo controlled study. [Clinical effects of hormone replacement therapy with estradiol valerate and cyproterone acetate in perimenopausal women]. Low Dose of Transdermal Estradiol Gel for Treatment of Symptomatic Postmenopausal Women: A Randomized Controlled Trial Effect of Raloxifene on Sexual Function in Older Postmenopausal Women With Osteoporosis Body mass index does not influence response to treatment, nor does body weight change with lower doses of conjugated estrogens and medroxyprogesterone acetate in early postmenopausal women The effects of tibolone on vaginal blood flow, sexual desire and arousability in postmenopausal women Transdermal estradiol gel for the treatment of symptomatic postmenopausal women Clinical usefulness of a low-dose maintenance therapy with transdermal estradiol gel in Japanese women with estrogen deficiency symptoms A randomized study of low-dose conjugated estrogens on sexual function and quality of life in postmenopausal women Effective Treatment of Vaginal Atrophy With an Ultra–Low-Dose Estradiol Vaginal Tablet Effects of ospemifene (FC-1271a) on uterine endometrium, vaginal maturation index, and hormonal status in healthy postmenopausal women. Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial. Some clinical effects of oestrogen-progestogen therapy in surgically castrated women. Monophasic Estrogen-Progestogen Therapy and Sexuality in Postmenopausal Women Effects of 5 years of hormonal replacement therapy on menopausal symptoms and blood pressure-a randomised controlled study. Endometrial thickness for invasive investigations in women with postmenopausal bleeding Hormone therapy in menopausal women with cognitive complaints Effects of ultralow-dose transdermal estradiol on postmenopausal symptoms in women aged 60 to 80 years Vaginal estrogen therapy and overactive bladder symptoms in postmenopausal patients after a tension-free vaginal tape procedure: a randomized clinical trial Gender, sex-steroid, and secretagogue-selective recovery from growth hormone-induced feedback in older women and men. Low-dose esterified estrogens (0.3 mg/day): long-term and short-term effects on menopausal symptoms and quality of life in postmenopausal women Double-blind cross-over study with org OD 14 and placebo in postmenopausal patients Estrogen Improves Psychological Function in Asymptomatic Postmenopausal Women [Influence of hormone replacement therapy on the quality of life in postmenopausal women with hypertension]. Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women. The effect of ultralow-dose transdermal estradiol on sexual function in postmenopausal women. Differential effects of estrogen-androgen and estrogen-only therapy on vasomotor symptoms, gonadotropin secretion, and endogenous androgen bioavailability in postmenopausal women. Dose-response and withdrawal effects on climacteric symptoms after hormonal replacement therapy. A placebo-controlled therapeutic trial. Effects of bazedoxifene in nonflushing postmenopausal women: a randomized phase 2 trial Changes in sex behaviour after menopause: effects of tibolone. Sexually and well-being in early menopause. Effect of transdermal estradiol therapy. Tibolone in the treatment of psychosomatic symptoms in menopause. A randomized, placebo- and active-controlled trial of bazedoxifene/conjugated estrogens for treatment of moderate to severe vulvar/vaginal atrophy in postmenopausal women Short-term urogenital effects of raloxifene, tamoxifen, and estrogen. One-year long-term safety extension study of ospemifene for the treatment of vulvar and vaginal atrophy in postmenopausal women with a uterus Comparison of the effects of hormone therapy regimens, oral and vaginal estradiol, estradiol + drospirenone and tibolone, on sexual function in healthy postmenopausal women. The Effect of Short‐Term Estrogen Replacement Therapy on Cognition: A Randomized, Double‐Blind, Cross‐Over Trial in Postmenopausal Women Effect of different preparations of hormone therapy on sexual dysfunction in naturally postmenopausal women Raloxifene as an adjunctive treatment for postmenopausal women with schizophrenia: a double-blind, randomized, placebo-controlled trial. The therapeutic effect of a new ultra low concentration estriol gel formulation (0.005% estriol vaginal gel) on symptoms and signs of postmenopausal vaginal atrophy: results from a pivotal phase III study Transdermal estradiol gel 0.1% for the treatment of vasomotor symptoms in postmenopausal women Microdose transdermal estrogen therapy for relief of vulvovaginal symptoms in postmenopausal women Twice-weekly synthetic conjugated estrogens vaginal cream for the treatment of vaginal atrophy
abstract: BACKGROUND tibolone at usual doses of 2.5 mg/day in postmenopausal women has been shown to improve climacteric complaints , without affecting endometrial thickness and lipid profile or blood glucose . However , the potentially similar efficacy , but better tolerability , of a low dose of this drug ( 1.25 mg ) has never been established . METHODS 162 healthy , non-obese , post-menopausal women , aged 40 - 65 years , with an intact uterus were enrolled in a national , single centre , r and omised , double blind , placebo controlled , parallel group trial . After 1 week of runin , patients were treated for 24 weeks with placebo , tibolone 1.25 mg or 2.5 mg/day . During the study laboratory tests , endometrial ultrasound scans and mammography were performed . Occurrence of menopausal signs and symptoms , including vaginal bleeding , and quality of sexual life were also checked . RESULTS in the 120 patients terminating the study without major protocol violations , climacteric symptoms were similarly improved by tibolone 1.25 and 2.5 mg ( 78 % and 90 % reduction at week 24 for hot flushes , 36 % and 34 % for sweating episodes and 44 % and 51 % for vaginal dryness ) , but not by placebo . Benefits occurred earlier in the group treated with tibolone 2.5 mg . Quality of sexual life was almost invariably improved by tibolone as compared to placebo , but improvement occurred earlier in the tibolone 1.25 mg group . Severity of vaginal bleeding was not different between placebo and active treatment groups , except at week 12 when was higher . At the end of treatment vaginal bleeding occurred in 15 % of patients treated with placebo , 14 % treated with tibolone 1.25 mg and 12 % treated with tibolone 2.5 mg . Endometrial thickness and breast density were not changed by treatment , as well as FSH , 17-beta-estradiol , total cholesterol , HDL and LDL cholesterol , triglycerides and blood glucose . Adverse events were reported by 14.7 % , 26.7 % and 24.4 % of patients treated with placebo , tibolone 1.25 mg and tibolone 2.5 mg/day , respectively . CONCLUSIONS tibolone at doses of 1.25 or 2.5 mg/day given for 24 weeks to postmenopausal women displayed similar efficacy and safety profiles , though were more effective than placebo . Tibolone 1.25 mg induced a more gradual relief from climacteric symptoms and a more prompt improvement of sexual function In this report we evaluated the action of conjugated equine estrogens ( CEE ) on vaginal symptoms , cytology , pH , and flora in late postmenopausal women without any previous hormone therapy . The study was a r and omized , double-blind , placebo-controlled trial with 48 late postmenopausal women who received placebo or unopposed CEE ( 0.625mg/day of CEE orally ) during three months of treatment .  Vaginal and sexual complaints were evaluated through daily diary cards . We analyzed vaginal changes through cytology and pH measurements . After three months of treatment , 20 % of placebo-treated patients and 80 % of the CEE-treated patients reported improvement in vaginal dryness and irritation . In the latter group , the vaginal cells and Lactobacillus increased and the vaginal pH decreased , without other changes in sexual complaints . We concluded that estrogen ameliorated the genital tract of late postmenopausal women without any previous hormone therapy OBJECTIVE In some women , hot flashes and other symptoms attributed to menopause persist for many years after the cessation of menses . The frequency and severity of such symptoms and response to hormone therapy in older women have not been well documented . METHODS We used data from the Heart and Estrogen/Progestin Replacement Study , a blinded , clinical trial among 2763 women with documented coronary disease and a uterus who were r and omized to receive either conjugated estrogens 0.625 mg plus medroxyprogesterone acetate 2.5 mg in one tablet or placebo .  Participants were queried at baseline and annually regarding menopausal symptoms . Breast symptoms were self‐reported , and uterine bleeding was recorded on a daily diary . RESULTS Symptoms associated with menopause were relatively common among Heart and Estrogen/Progestin Replacement Study participants , whose average age was 67 years and who averaged 18 years since menopause . At baseline , 16 % of women reported frequent hot flashes , 26 % vaginal dryness , 10 % genital irritation , 55 % trouble sleeping , and 53 % early awakening . Women assigned to hormone therapy reported less frequent hot flashes , vaginal dryness , and trouble sleeping compared with women assigned to placebo , but more frequent vaginal discharge , genital irritation , uterine bleeding , and breast symptoms . The reporting of breast symptoms among women in the hormone group decreased from 40 % at 1 year to 13 % by the 4th year . Uterine bleeding was reported by 31 % and spotting by an additional 33 % of women in the hormone group during the 1st year of treatment ; by the 4th year , these proportions had fallen to 11 % and 20 % , respectively . CONCLUSION Symptoms typically attributed to menopause are common in elderly women .  Postmenopausal hormone therapy  reduces hot flashes , trouble sleeping , and vaginal dryness , but at st and ard doses in elderly women is associated with vaginal discharge , genital irritation , uterine bleeding , and breast symptoms Objective : To determine the effects of raloxifene on sexual function in postmenopausal women with pre-existing vaginal atrophy treated with vaginal estrogen cream . Methods : A total of 187 naturally postmenopausal women , 42 - 80 years of age , with signs of genitourinary atrophy were enrolled in this 6-month , multicenter , parallel-group study . Subjects were r and omized to oral raloxifene HCl 60 mg daily or matching placebo ; the same subjects were also r and omized to receive one application of either vaginal conjugated estrogen cream 0.5 g twice weekly for 6 months or non-hormonal vaginal moisturizer twice weekly for 3 months , followed by conjugated estrogen cream for 3 months . Both investigators and subjects were masked to the identity of the oral medication . The vaginal preparations were administered in an open-label fashion . The Sexual Activity Question naire ( SAQ ) was administered at baseline and at 3 and 6 months . Safety was assessed throughout the study . Results : A total of 102 women were sexually active at baseline and , of these , 82 were also sexually active at the 6-month end-point . At 6 months , raloxifene and placebo , in the presence of vaginal conjugated estrogen cream , were both associated with improvement from baseline in vaginal dryness and reduced discomfort during sexual activity . There were no significant differences between raloxifene and placebo groups in any SAQ item . Enjoyment of sexual activity significantly increased from baseline with raloxifene but not with placebo . No difference in adverse events was observed between groups . Conclusion : Raloxifene had no negative effects on sexual function in postmenopausal women with vaginal atrophy who were treated concomitantly with vaginal estrogen cream The women in this study were either post-menopausal or ovariectomised for at least 1 yr prior to the study . They had also been treated for cancer of the cervix ( 27 women ) , endometrium ( 5 ) , ovaries ( 5 ) or breast ( 1 ) . All women presented with sexual troubles , mainly genital discomfort ( dyspareunia or vaginism ) . In a double-blind fashion , gynaecological capsules containing either an oestradiol diether ( ICD : promestriene ) or only the excipient were administered for 40 consecutive days . At the end of the treatment , the FSH , LH , oestrone ( E1 ) and oestradiol ( E2 ) plasma levels were not found to be significantly different from the pre-therapeutic values . These results suggest that promestriene acts on the vaginal mucosa , therefore not being converted back into the hormone from which it was derived . Also , in its dietheroxide form , promestriene is incapable of crossing the malpighian ( vaginal or epidermal ) epithelium and of reaching the general blood circulation . This discrepancy between the local anti-atrophic effects and the inability to exert systemic oestrogen activities singles out promestriene and justifies its therapeutic use when hormonally active oestrogens are contra-indicated , as in patients who have an oestrogen-sensitive cancer in their medical history Objective To assess the effect of  combined hormone replacement therapy ( HRT )  on health related quality of life . Design R and omised placebo controlled double blind trial . Setting General practice s in United Kingdom ( 384 ) , Australia ( 94 ) , and New Zeal and ( 24 ) . Participants Postmenopausal women aged 50 - 69 at r and omisation ; 3721 women with a uterus were r and omised to combined oestrogen and progestogen  ( n=1862 ) or placebo  ( n=1859 ) . Data on health related quality of life at one year were available from 1043 and 1087 women , respectively . Interventions Conjugated equine oestrogen 0.625 mg plus medroxyprogesterone acetate 2.5/5.0 mg or matched placebo orally daily for one year . Main outcome measures Health related quality of life and psychological wellbeing as measured by the women ’s health question naire . Changes in emotional and physical menopausal symptoms as measured by a symptoms question naire and depression by the Centre for Epidemiological Studies depression scale ( CES-D ) . Overall health related quality of life and overall quality of life as measured by the European quality of life instrument ( EuroQol ) and visual analogue scale , respectively . Results After one year small but significant improvements were observed in three of nine components of the women ’s health question naire for those taking combined HRT compared with those taking placebo :  vasomotor symptoms ( P<0.001 ) , sexual functioning ( P<0.001 ) , and sleep problems ( P<0.001 ) . Significantly fewer women in the combined HRT group reported hot flushes ( P<0.001 ) , night sweats ( P<0.001 ) , aching joints and muscles ( P=0.001 ) , insomnia ( P<0.001 ) , and vaginal dryness ( P<0.001 ) than in the placebo group , but greater proportions reported breast tenderness ( P<0.001 ) or vaginal discharge ( P<0.001 ) . Hot flushes were experienced in the combined HRT and placebo groups by 30 % and 29 % at trial entry and 9 % and 25 % at one year , respectively . No significant differences in other menopausal symptoms , depression , or overall quality of life were observed at one year . Conclusions Combined HRT started many years after the menopause can improve health related quality of life . Trial registration IS RCT N 63718836 Aim . To evaluate with vali date d instruments changes in quality of life and sexuality in women receiving hormonal replacement therapy ( AHT ) .  Design . R and omised , double-blind , double-dummy study with two parallel treatment arms . Patients and methods . Forty-seven healthy post-menopausal women , aged 45–64 years , were evaluated using the Female Sexual Function Index ( FSFI ) and the menopause-specific quality of life question naire ( MENQOL ) . Of them , 40 diagnosed with sexual dysfunction were r and omised ( 1:1 ) to receive daily 0.625 mg of conjugated estrogens plus 1.25 mg of methyl-testosterone and 100 mg of micronised progesterone or placebo . After 3 months follow-up , FSFI and MENQOL question naires were administered for a second time . Results . Quality of life was unchanged in the placebo group whereas AHT significantly improved scores of vasomotor , psychological , physical and sexual symptoms . As expected , FSFI was not modified in the placebo group while in AHT group the FSFI score improved significantly . In addition , at the end of the study , 68.7 % of subjects of the AHT group did not fit did not fit the criteria for sexual dysfunction as per the FSFI ( p < 0.0001 ) . Conclusions . Adding methyl-testosterone to hormone therapy  improves quality of life and sexuality in post-menopausal women with sexual dysfunction OBJECTIVES Guidelines recommend using the lowest effective dose of oestrogen for the management of vasomotor symptoms in postmenopausal women . The primary aim of this double-blind , multi-centre , r and omised study was to assess the efficacy of oral ultra-low dose continuous combined hormone replacement therapy with 17β-oestradiol and dydrogesterone . STUDY DESIGN 313 women with ≥50 moderate to severe hot flushes during the previous week were r and omised to 0.5 mg 17β-oestradiol/2.5 mg dydrogesterone ( E 0.5 mg/D 2.5 mg ) , 1 mg 17β-oestradiol/5 mg dydrogesterone ( E 1mg/D 5 mg ) or placebo for 13 weeks . The placebo group then switched to E 0.5 mg/D 2.5 mg for a further 39 weeks , whilst the other groups continued on the same treatment . RESULTS After 13 weeks , the reduction in the number of moderate to severe hot flushes/day in the E 0.5 mg/D 2.5 mg group was greater than in the placebo group ( -6.4 vs. -4.9 , p<0.001 ) and comparable to that in the 1/5 mg group ( -6.3 ) . E 0.5 mg/D 2.5 mg and E 1mg/D 5 mg significantly improved the total Menopause Rating Scale score . The number of bleeding/spotting days was lower with E 0.5 mg/D 2.5 mg than with E 1 mg/D 5 mg . The overall amenorrhoea rate with E 0.5 mg/D 2.5 mg was 81 % ; this increased to 91 % in months 10 - 12 . CONCLUSIONS Continuous combined 0.5 mg 17β-oestradiol and 2.5 mg dydrogesterone was effective in alleviating vasomotor symptoms and improving quality of life , and was associated with a high amenorrhoea rate and a good tolerability profile Background With the exception of sexual functioning and weight , social and behavioural effects of postmenopausal hormone therapy ( HT ) have not been reported from trials . This paper reports such results from the EPHT-trial in Estonia . Methods A r and omized trial , with a blind and non-blind sub-trial in Estonia . From 1999–2001 , 1778 women were recruited . The mean follow-up was 3.6 years . Women 's experiences were asked in the first and final study year by mailed question naires ( 74 and 81 % response rates ) . Comparisons of the groups were made by cross-tabulation and logistic regression , adjusting for age . Results There were no differences between the HT and non-HT groups in regard to being employed , the extent of social involvement or marital status or opinions on aging . There was no difference in the frequency of free-time exercise , or overweight . Some of the indicators suggested less sexual inactivity , but the differences were small . Conclusion In a trial setting , postmenopausal hormone therapy did not influence work or social involvement or health behaviour . Trial registration IS RCT OBJECTIVE : To evaluate the efficacy of two vaginal doses of estradiol ( E2 ) compared with placebo in the treatment of atrophic vaginitis . METHODS : In a multi-center , r and omized , double-blind , parallel-group study , 230 postmenopausal women received treatment with 25 mcg or 10 mcg E2 or placebo for 12 weeks . Efficacy was measured through composite score of three vaginal symptoms and grading of vaginal health . Additional analyses included maturation of vaginal and urethral mucosa . Safety assessment s included endometrial biopsy , adverse events , changes in laboratory tests , and physical examinations . After 12 weeks of treatment , all patients were switched to the open-label extension and received treatment with 25 mcg E2 up to week 52 . RESULTS : Vaginal tablets with 25 mcg and 10 mcg E2 showed significant ( P<.001 ) improvement in composite score of vaginal health . Other results with 10 mcg E2 were not entirely consistent with those for 25 mcg E2 . Over 12 weeks , both active treatments result ed in greater decreases in vaginal pH than placebo . There were no significant differences between the 25 mcg and 10 mcg E2 groups in terms of improvements in maturation value or composite score of three vaginal symptoms . The efficacy was maintained to week 52 with 25 mcg E2 . CONCLUSION : Vaginal tablets with 25 mcg and 10 mcg E2 provided relief of vaginal symptoms , improved urogenital atrophy , decreased vaginal pH , and increased maturation of the vaginal and urethral epithelium . Those improvements were greater with 25 mcg than with 10 mcg E2 . Both doses were effective in the treatment of atrophic vaginitis . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00465192 and NCT00464971 LEVEL OF EVIDENCE : BACKGROUND To compare the metabolic effects on lipids and acceptability and safety of , and compliance with , a continuous administration of conjugated estrogen plus medroxyprogesterone acetate ( Premelle ) versus a placebo in non-hysterectomized postmenopausal women . METHODS Sixty-six generally healthy , female , early post-menopausal women , from 45 - 60 years of age , were r and omized for an administration of conjugated estrogen plus medroxyprogesterone acetate ( Premelle , Premarin 0.625 mg plus medroxyprogesterone acetate 2.5 mg/tablet orally ) or a placebo for 6 months . The changes in each patient 's lipid profiles from baseline , the frequency of hot flushes , bleeding occurrences , and climacteric symptoms , were evaluated . Safety was monitored by means of physical examination , Papanicolau smear , transvaginal ultrasonography , and laboratory check-up . Adverse events were also recorded . RESULTS The difference before and after treatment in serum LDL-C and total cholesterol ( TC ) was statistically significant in the Premelle group ( LDL-C , p = 0.006 , TC , p = 0.040 ) . No statistically significant difference in the change from baseline was observed in the levels of LDL-C and TC in the placebo treatment group . There was a statistically significant change from baseline in menopausal symptoms , which were evaluated by the Greene Climacteric Scales in the Premelle group . There was no clinical ly significant finding in the physical examination , vital signs , laboratory data , or endometrial thickness in either treatment group . The difference in the number of patients who reported an adverse event was not statistically significant between the 2 treatment groups . CONCLUSIONS This study demonstrated that Premelle was effective in decreasing LDL-C and total cholesterol levels , and also showed an improvement in some menopausal symptoms , such as vasomotor and sexual dysfunction symptoms . No significant bleeding was observed with Premelle , which was well tolerated in this study . The results of this study could support the use of Premelle tablets as a convenient alternative hormone therapy Objective : The aim of this study was to study the efficacy and safety of ospemifene , a new selective estrogen receptor modulator , in the treatment of vulvovaginal atrophy in postmenopausal women . Methods : A r and omized , double-blind phase 3 study in which 826 postmenopausal women were r and omized 1:1:1 to receive treatment with ospemifene 30 or 60 mg/day or placebo orally for 12 weeks was conducted . The primary inclusion criteria were having 5 % or less superficial cells on the vaginal smear ( maturation index ) , vaginal pH greater than 5.0 , and at least one moderate or severe symptom of vulvovaginal atrophy . The four co primary endpoints were the change from baseline to 12 weeks in the percentage of superficial and parabasal cells on the vaginal smear , change in vaginal pH , and change in severity of most bothersome symptom ( vaginal dryness or dyspareunia ) compared with placebo . All participants were given a nonhormonal vaginal lubricant for use as needed . Results : Ospemifene was statistically significantly superior to placebo in each of the co primary endpoints at the 60-mg dose . Statistically significant results were achieved for all co primary endpoints with the 30-mg dose except for dyspareunia .  Ospemifene was well tolerated at both doses and demonstrated a favorable safety profile . Conclusions : Ospemifene was shown to be effective and well tolerated for the treatment of the symptoms of vaginal dryness and dyspareunia associated with vulvovaginal atrophy over and above the use of provided lubricants Objective To assess the efficacy and safety of intravaginal estriol administration on  urinary incontinence , urogenital atrophy , and recurrent urinary tract infections in postmenopausal women . Design Eighty-eight postmenopausal women with urogenital aging symptoms were enrolled in this prospect i ve , r and omized , placebo-controlled study . Participants were r and omly divided into two groups , with each group consisting of 44 women . Women in the treatment group received intravaginal estriol ovules : 1 ovule ( 1 mg ) once daily for 2 weeks and then 2 ovules once weekly for a total of 6 months as maintenance therapy . Women in the control group received inert placebo vaginal suppositories in a similar regimen . We evaluated urogenital symptomatology , urine cultures , colposcopic findings , urethral cytologic findings , urethral pressure profiles , and urethrocystometry before as well as after 6 months of treatment . Results After therapy , the symptoms and signs of urogenital atrophy significantly improved in the treatment group in comparison with the control group . Thirty ( 68 % ) of the treated participants , and only seven ( 16 % ) of the control participants registered a subjective improvement of their incontinence . In the treated participants , we observed significant improvements of colposcopic findings , and there were statistically significant increases in mean maximum urethral pressure , in mean urethral closure pressure as well as in the abdominal pressure transmission ratio to the proximal urethra . Urethrocystometry showed positive but not statistically significant modifications . Conclusions Our results show that intravaginal administration of estriol may represent a satisfactory therapeutic choice for those postmenopausal women with urogenital tract disturbances who have contraindications or refuse to undergo st and ard hormone therapy CONTEXT Menopausal hormone therapy has long been credited with many benefits beyond the indications of relieving hot flashes , night sweats , and vaginal dryness , and it is often prescribed to treat urinary incontinence ( UI ) . OBJECTIVE To assess the effects of menopausal hormone therapy on the incidence and severity of symptoms of stress , urge , and mixed UI in healthy postmenopausal women . DESIGN , SETTING , AND PARTICIPANTS Women 's Health Initiative multicenter double-blind , placebo-controlled , r and omized clinical trials of menopausal hormone therapy in 27,347 postmenopausal women aged 50 to 79 years enrolled between 1993 and 1998 , for whom UI symptoms were known in 23,296 participants at baseline and 1 year . INTERVENTIONS Women were r and omized based on hysterectomy status to active treatment or placebo in either the estrogen plus progestin ( E + P ) or estrogen alone trials . The E + P hormones were 0.625 mg/d of conjugated equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate ( CEE + MPA ) ; estrogen alone consisted of 0.625 mg/d of conjugated equine estrogen ( CEE ) . There were 8506 participants who received CEE + MPA ( 8102 who received placebo ) and 5310 who received  CEE alone ( 5429 who received placebo ) . MAIN OUTCOME MEASURES Incident UI at 1 year among women without UI at baseline and severity of UI at 1 year among women who had UI at baseline . RESULTS Menopausal hormone therapy increased the incidence of all types of UI at 1 year among women who were continent at baseline . The risk was highest for stress UI ( CEE + MPA : relative risk [ RR ] , 1.87 [ 95 % confidence interval { CI } , 1.61 - 2.18 ] ; CEE alone : RR , 2.15 [ 95 % CI , 1.77 - 2.62 ] ) , followed by mixed UI ( CEE + MPA : RR , 1.49 [ 95 % CI , 1.10 - 2.01 ] ; CEE alone : RR , 1.79 [ 95 % CI , 1.26 - 2.53 ] ) . The combination of CEE + MPA had no significant effect on developing urge UI ( RR , 1.15 ; 95 % CI , 0.99 - 1.34 ) , but CEE alone increased the risk ( RR , 1.32 ; 95 % CI , 1.10 - 1.58 ) . Among women experiencing UI at baseline , frequency worsened in both trials ( CEE + MPA : RR , 1.38 [ 95 % CI , 1.28 - 1.49 ] ; CEE alone : RR , 1.47 [ 95 % CI , 1.35 - 1.61 ] ) . Amount of UI worsened at 1 year in both trials ( CEE + MPA : RR , 1.20 [ 95 % CI , 1.06 - 1.36 ] ; CEE alone : RR , 1.59 [ 95 % CI , 1.39 - 1.82 ] ) . Women receiving menopausal hormone therapy  were more likely to report that UI limited their daily activities ( CEE + MPA : RR , 1.18 [ 95 % CI , 1.06 - 1.32 ] ; CEE alone : RR , 1.29 [ 95 % CI , 1.15 - 1.45 ] ) and bothered or disturbed them ( CEE + MPA : RR , 1.22 [ 95 % CI , 1.13 - 1.32 ] ; CEE alone : RR , 1.50 [ 95 % CI , 1.37 - 1.65 ] ) at 1 year . CONCLUSIONS Conjugated equine estrogen alone and CEE + MPA increased the risk of UI  among continent women and worsened the characteristics of UI among symptomatic women after 1 year . Conjugated equine estrogen with or without progestin should not be prescribed for the prevention or relief of UI Objectives Drospirenone is a novel progestogen that , combined with 17β-estradiol , reduces the frequency and severity of menopausal vasomotor symptoms ( VMS ) in different population s. This double-blind , multicenter study compared the efficacy , safety and tolerability of 2 mg drospirenone/1 mg estradiol ( DRSP/E2 ) vs. placebo in Chinese postmenopausal women with moderate to severe VMS . Methods Women , aged 45–65 years , were r and omized to  DRSP/E2  ( n = 183 ) or placebo ( n = 61 ) once daily for four 28-day cycles . Changes in the frequency and severity of hot flushes were analyzed as primary variables , together with other climacteric and urogenital symptoms , clinical global improvement , adverse events and physical/gynecological parameters . Results Relative changes in numbers of hot flushes/week were −80.4 % for DRSP/E2 vs. −51.9 % for placebo ( treatment difference −28.5 % , p < 0.0001 ) . There were trends toward a greater reduction in severity of hot flushes with DRSP/E2 treatment . Patients treated with DRSP/E2 were more often free from sweating episodes ( p < 0.0001 ) and vaginal dryness ( p = 0.0008 ) . Other climacteric symptoms , including nervousness and pollakisuria , followed a trend of greater response with DRSP/E2 . Similar to other combination HRT regimens , DRSP/E2  increased occurrences of bleeding , but these decreased over time . Adverse events in patients treated with DRSP/E2 were mostly mild to moderate and withdrawal rates were low . Conclusions Daily treatment of postmenopausal Chinese women  with DRSP/E2 for 16 weeks significantly reduced the incidence of hot flushes and demonstrated advantages vs. placebo for other climacteric symptoms . These results indicate that DRSP/E2 is effective , safe and well tolerated in postmenopausal Chinese women Introduction Menopausal hot flushes may affect the responses of various vascular risk factors to hormone therapy ( HT ) . We compared the responses of biochemical markers for cardiovascular diseases to HT in recently postmenopausal women with tolerable or intolerable hot flushes . Methods Healthy , non-smoking freshly postmenopausal women ( n = 150 ) with no previous HT use were studied . Seventy-two women reported intolerable hot flushes ( ≥7 moderate/severe episodes/day ) and 78 women tolerable hot flushes ( ≤3 mild episodes/day ) . The participants were treated in r and omized order with either transdermal estradiol gel ( 1 mg ) , oral estradiol valerate ( 2 mg ) with or without medroxyprogesterone acetate ( 5 mg ) , or placebo for 6 months . Treatment-induced changes in lipids , lipoproteins , apolipoproteins , sex hormone binding globulin ( SHBG ) and high-sensitivity C-reactive protein were compared . The trial is registered in the US National Institutes of Health Clinical Research Registry ( no. NCT00668603 ) . Results Pretreatment hot flush status was not related to the responses of these markers to different forms of HT . However , when all active regimens were evaluated together as a post-hoc analysis , 7/10 markers showed a tendency toward greater beneficial changes in women with intolerable hot flushes . Furthermore , in women with intolerable hot flushes and with HT use , the increases in SHBG ( Spearman 's rho = − 0.570 , p < 0.001 ) were related to the reductions in hot flushes during the use of HT . Conclusions Hot flushes appear to be no significant determinant for the responses of vascular  markers to HT use BACKGROUND When genital atrophy exists , systemic hormone therapy ( HT ) has a timing until to induce vaginal proliferation and symptomatic relieve . Thus , in order to obtain a prompt improvement , the association of local therapy acting on the genital epithelium to the systemic treatment should be considered . OBJECTIVE To evaluate the effects of a combined therapy consisting of vaginal estriol with transdermal 17-beta-estradiol ( 50 microg/day ) plus medroxyprogesterone acetate ( 5 mg/day ) per os in shortening the period of uro-genital symptoms . SUBJECTS AND METHODS In a r and omized , double blind , controlled with placebo study , 27 women with climacteric symptoms and atrophic vaginitis were treated for 4 months with HT plus vaginal estriol 0.5 mg/day ( group E ) or placebo ( group P ) . Patients use the local medication daily for the first 3 weeks and twice-weekly thereafter . Before entering in the study , patients were asked about HT and selected for inclusion . In the first visit , electible patients after written informed consent were r and omized to receive HT plus local estriol or placebo . All the subjects had baseline studies , including medical history , physical examination , blood and urine analysis . In order to evaluate the effect of local treatment on urinary and genital symptoms , a score for genital , urinary and colposcopic complaints ( 0 minimum-100 maximum ) was developed . This score and Blatt-Kuperman were recorded and performed in every control . RESULTS There were no differences on climacteric symptoms relief between the two groups . Additionally , the improvement in urinary symptoms at the end of the study was similar for both groups ( from 16.5 + /- 6.1 to 8.5 + /- 2.4 for E group and from 15.8 + /- 7.8 to 8.8 + /- 2.7 for P group ; P < 0.01 versus basal ) ; however , those women in group E reached significant improvement on urinary complaints since the first month of treatment . Additionally , a significant difference between E and P was observed at months 2 and 3 , although no differences were detected at the end of the study . Papanicolaou smear showed reactive or reparative changes and karyopyknotic index exhibited a significant increase in superficial cells in both groups and at the end of the study . CONCLUSIONS Adding vaginal estriol to HRT may shorten the latency period for urinary symptoms Objectives To compare the effect of micro-dose transdermal estradiol and placebo on the incidence and severity of menopausal symptoms and well-being in postmenopausal Asian women with vasomotor symptoms . Design Multicenter , double-blind , r and omized , placebo-controlled study . Results Of 165 subjects r and omized to estradiol 0.014 mg/day or placebo for 12 weeks , 80 per group were included in the analysis . Groups were comparable at baseline , although time since menopause was slightly shorter in the estradiol group . There was a greater reduction in mean weekly hot flushes at week 12 in the estradiol group ( 55 % ) than the placebo group ( 40 % ; p < 0.01 ) , which was evident by week 4 . A similar pattern was seen for moderate and severe hot flushes ( −58 % vs. −39 % , respectively ) . Reductions were statistically significant at weeks 4 , 8 , and 12 . Vaginal pH fell significantly in the estradiol group by week 4 and then remained stable throughout the treatment period , but there were no significant changes in the placebo group . Vaginal maturation value increased more in the estradiol than the placebo group ( p < 0.001 ) . Few subjects had vaginal bleeding or spotting . Quality of life improved similarly in both groups . Urogenital symptoms improved considerably from baseline in both treatment groups , with no significant differences . Eight subjects experienced treatment-related adverse events ( seven in the estradiol group ) . Conclusions In Asian women , micro-dose estradiol was significantly superior to placebo in improving vasomotor symptoms . The bleeding profile was comparable with that of placebo . Micro-dose estradiol was safe and well tolerated in Asian women Introduction The Livial Intervention Following Breast Cancer : Efficacy , Recurrence and Tolerability Endpoints ( LIBERATE : Clinical http://Trials.gov number NCT00408863 ) , a r and omized , placebo-controlled , double-blind trial that demonstrated that tibolone ( Livial ) , a tissue-selective hormone-replacement therapy ( HRT ) , increased breast cancer ( BC ) recurrence HR 1.40 ( 95 % CI , 1.14 to 1.70 ; P = 0.001 ) . A subgroup of women was entered into a study of bone mineral density ( BMD ) . Methods Women with surgically excised primary BC ( T1 - 3 , N0 - 2 , M-0 ) within the last 5 years , complaining of vasomotor symptoms , were assigned to tibolone , 2.5 mg daily , or placebo treatment for a maximum of 5 years . The BMD sub study enrolled 763 patients , using dual-energy X-ray absorptiometry ( DXA ) scanning at baseline and at 2 years . Results In the bone sub study , 699 of 763 women were eligible ( 345 allocated to tibolone , and 354 , to placebo ) . After undergoing DXA scans , 300 ( 43 % ) women had normal BMD ; 317 ( 45 % ) , osteopenia ; and 82 ( 11.7 % ) , osteoporosis . Low body-mass index ( P < 0.001 ) , Asian race ( P < 0.001 ) , and late age at menarche ( P < 0.04 ) predicted low bone mass at baseline . Tibolone  increased BMD by 3.2 % at the lumbar spine and 2.9 % at the hip compared with placebo ( both P < 0.001 ) . The majority of fractures ( 55 % ) occurred in osteopenic patients . Women with normal BMD had increased recurrence with tibolone , 22 ( 15.6 % ) of 141 compared with placebo , 11 ( 6.9 % ) of 159 ( P = 0.016 ) , whereas no increased BC recurrence was seen in women with low BMD ; 15 ( 7.4 % ) of 204 taking tibolone versus 13 ( 6.7 % ) of 195 taking placebo . Conclusions Tibolone is contraindicated after BC treatment , as it increases BMD and BC recurrence . Risk of BC recurrence was elevated in BC women with normal BMD ( compared with low ) who took tibolone Objective To compare the effects of tibolone and continuous combined hormone therapy on circulating sex steroids and their binding proteins and their relationship to  mammographic density .  Study design A prospect i ve , double-blind placebo-controlled study . A total of 166 postmenopausal women were equally r and omized to receive tibolone 2.5 mg , estradiol 2 mg/norethisterone acetate 1 mg ( E2/NETA ) or placebo . Serum analyses of sex steroids , insulin-like growth factor ( IGF-I ) and binding proteins and assessment of mammographic breast density were performed at baseline and after 6 months of treatment . Results Estrogens were markedly increased and and rogens decreased by E2/NETA . In contrast , tibolone had only a minor influence on circulating estrogens . Sex hormone binding globulin ( SHBG ) levels were reduced by 50 % , while levels of and rogens increased . Baseline values of estrone sulfate ( E1S ) , around 1.0–1.1 nmol/l , were increased to 44.7 nmol/l by E2/NETA and to only 1.7 nmol/l by tibolone ( p < 0.001 ) . Mammographic breast density displayed a negative correlation with age and body mass index and a positive association with SHBG . After 6 months there was also a negative correlation with levels of free testosterone . Conclusion We found that tibolone and E2/NETA caused distinct differences in estrogen/ and rogen status and blood levels of possible breast mitogens . The negative association between free testosterone and mammographic density could be a possible explanation for tibolone having less influence on the breast OBJECTIVE To study the efficacy and safety of estradiol and drospirenone tablets ( Angeliq ) in treatment of menopausal symptoms among postmenopausal Chinese healthy women . METHODS Total 244 postmenopausal Chinese healthy women who had moderate to severe hot flushes were r and omly assigned into estradiol and drospirenone ( observation group , n = 183 ) or placebo group ( n = 61 ) by the ratio of 3:1 for 16 weeks in this r and omized multi-center double-blind placebo-controlled study . During the trial , the follow-up visits were conducted at week 4 , 8 , 12 , 16 of treatment and 2 weeks after treatment respectively . Height , weight , vital signs , hot flushes , other relevant menopausal symptoms and vaginal bleeding were observed in each follow-up visit , while the clinical global impression scale was assessed at 16 weeks as well . RESULTS It showed that hot flushes were reduced significantly more in observation group than that in placebo group ( P < 0.01 ) , although both treatments were effective . The absolute values of mean severity index of total hot flushes decreased by -0.6 ± 0.5 in observation group and -0.4 ± 0.4 in placebo group from baseline respectively , which reached significant difference ( P < 0.05 ) . However , the absolute values of mean severity index of moderate to severe hot flushes decreased by -0.6 ± 0.8 in observation group and -0.3 ± 0.6 in placebo group from baseline respectively , which had no significant difference ( P > 0.05 ) . After 16 weeks treatment , it also showed that estradiol and drospirenone had significant better efficacy than placebo on moderate to severe sweating , vaginal dryness and clinical global impression scale ( P < 0.01 ) . During the trial , blood pressure in observation group was stable . The rate of vaginal bleeding in observation group was higher than that in the placebo group , especially during the week 4 to week 8 when 48.9 % ( 87/178 ) in observation group and 10.7 % ( 6/56 ) in placebo group of patients bled . Although the cumulative amenorrhea rate of observation group was lower than that of placebo group in each cycle ( 28 days ) , it increased gradually along with duration of the treatment . The commonest adverse event in observation group was breast tenderness which accounted for 12.0 % ( 22/183 ) . The level of serum potassium was in the normal range in observation group mostly . Meanwhile , the other adverse events rate was low . Serious adverse events reported in this trial were assessed as not study drug related or as unlikely study drug related . CONCLUSION Estradiol and drospirenone tablets which could effectively alleviate menopausal symptoms in postmenopausal Chinese healthy women is a novel hormone replacement therapy regimen with high safety and efficacy UNLABELLED The aim of the double-blind , placebo-controlled study was to investigate the effects of a continuous combined estrogen-progestogen treatment ( Climodien , Lafamme ) as compared with estrogen alone on vigilance in insomniac postmenopausal syndrome patients , objectified by EEG mapping . METHODS In a 3-arm , 2-month parallel group design phase , patients received a combination of estradiol valerate 2 mg and the novel progestogen dienogest 3 mg ( Climodien 2/3 ) or estradiol valerate 2 mg alone or placebo . In a subsequent open-label phase , all patients received estradiol valerate 2 mg+dienogest 2 mg ( Climodien 2/2 ) . EEG mapping was carried out before and after the 2-month double-blind phase as well as after the 2-month open-label treatment . RESULTS As compared with placebo , Climodien 2/3 induced a marked and highly significant increase in absolute power in all frequency b and s , specifically in alpha-2 activity . Moreover , a significant increase in relative alpha-2 power , a decrease in relative delta and beta power as well as an acceleration of the dominant frequency and of the delta and alpha centroids suggested a marked improvement in vigilance . In contrast , under estradiol valerate 2 mg alone , only a slight augmentation of alpha and attenuation of relative delta and beta power occurred , suggesting only a slight vigilance improvement as compared with placebo . Thus , dienogest 2 mg increased the estrogen effect , which was also confirmed by a statistical evaluation of the differences between Climodien 2/3 and estradiol valerate alone ( augmentation of alpha-2 , attenuation of relative beta , acceleration of the dominant frequency ) . Moreover , Climodien 2/2 also markedly increased alpha-2 power , decreased relative beta-2 power and accelerated the alpha centroid . Finally , comparing Climodien 2/3 with Climodien 2/2 , there was even a dose-efficacy relation . CONCLUSIONS Estradiol valerate 2 mg improves vigilance slightly , thereby confirming previous findings . The additional administration of dienogest does not minimize the effect of estrogen , but on the contrary increases it , which makes the combination superior to both placebo and estradiol valerate alone . Vigilance improvement may be of great therapeutic benefit to menopausal syndrome patients at a time when increased adaptability is needed to adjust to increasing sexual , marital , occupational and social difficulties known to occur specifically in this period of life OBJECTIVE To assess the efficacy , tolerability , and acceptance of a vaginal ring delivering the equivalent of 50 or 100 microg per day of estradiol ( E2 ) , compared with placebo , for relief of moderate to severe vasomotor symptoms and urogenital symptoms in postmenopausal women . METHODS Women with moderate to severe vasomotor symptoms ( seven or more per day or 56 per week average ) received 13 weeks of treatment with a vaginal ring delivering 50 microg per day E2 ( n = 113 ) or 100 microg per day E2 ( n = 112 ) , or a placebo vaginal ring ( n = 108 ) . Severity of vasomotor symptoms was assessed by a daily diary card and the Greene Climacteric Scale . Urogenital signs and symptoms were evaluated via patient and physician assessment and vaginal cytology . Participant satisfaction with the vaginal ring was evaluated via question naire . RESULTS Vasomotor symptoms significantly improved in both treatment groups , compared with placebo ( P < .05 ) . There was a trend toward greater improvement in patient assessment of urogenital signs with active rings compared with placebo . For women with vaginal atrophy at baseline ( n = 60 ) , the maturation index improved significantly in both treatment groups compared with placebo . Total Greene Climacteric Scale scores significantly improved for both E2 vaginal ring groups ( P < .05 ) compared with placebo . The vaginal rings were well tolerated . Most adverse events were mild or moderate and consistent with estrogen therapy . CONCLUSION A novel vaginal ring delivering the equivalent of 50 or 100 microg per day of E2 significantly reduced the number and severity of vasomotor symptoms and improved urogenital symptoms , compared with placebo . The E2 vaginal ring was well tolerated Background At the time of feasibility work and final design of the trial there was no r and omised control trial evidence for the long-term risks and benefits of hormone replacement therapy . Observational studies had suggested that long term use of estrogen was likely to be associated , amongst other things , with reduced risks of osteoporosis and ischaemic heart disease and increased risks of breast and endometrial cancer . Concomitant use of progestogens had been shown to protect against endometrial cancer , but there were few data showing how progestogen might affect estrogen actions on other conditions . Disease specific risks from observational studies suggested that , overall , long-term HRT was likely to be beneficial . Several studies showed that mortality from all causes was lower in HRT users than in non-users . Some secondary cardiovascular prevention trials were ongoing but evidence was also required for a range of outcomes in healthy women . The WISDOM trial was design ed to compare combined estrogen and progestogen versus placebo , and estrogen alone versus combined estrogen and progestogen . During the development of WISDOM the Women 's Health Initiative trial was design ed , funded and started in the US . Design R and omised , placebo , controlled , trial . Methods The trial was set in general practice s in the UK ( 384 ) , Australia ( 94 ) , and New Zeal and ( 24 ) . In these practice s 284175 women aged 50–69 years were registered with 226282 potentially eligible . We sought to r and omise 22300 postmenopausal women aged 50 – 69 and treat for ten years . The interventions were : conjugated equine estrogens , 0.625 mg orally daily ; conjugated equine estrogens plus medroxyprogesterone acetate 2.5/5.0 mg orally daily ; matched placebo . Primary outcome measures were : major cardiovascular disease , osteoporotic fractures , breast cancer and dementia . Secondary outcomes were : other cancers , all cause death , venous thromboembolism and cerebro-vascular disease . Results The trial was prematurely closed during recruitment following publication of early results from the Women 's Health Initiative . At the time of closure , 56583 had been screened , 8980 entered run-in , and 5694 ( 26 % of target of 22,300 ) r and omised . Those women r and omised had received a mean of one year of therapy , mean age was 62.8 years and total follow-up time was 6491 person years . Discussion The WISDOM experience leads to some simple messages . The larger a trial is the more simple it needs to be to ensure cost effective and timely delivery . When a trial is very costly and beyond the re sources of one country , funders and investigators should make every effort to develop international collaboration with joint funding OBJECTIVE To evaluate the safety and efficacy of synthetic conjugated estrogens B ( SCE-B ; 0.3 mg/d ) for 12 weeks in the treatment of vulvovaginal atrophy in symptomatic , postmenopausal women . DESIGN Prospect i ve , r and omized , multicenter , double-blind , placebo-controlled trial . SETTING Forty-two participating sites in the United States . PATIENT(S ) Postmenopausal women with at least one moderate to severe symptom of vaginal atrophy . INTERVENTION(S ) Daily oral administration , in a r and omized , placebo-controlled setting , of SCE-B ( 0.3 mg ) or of placebo for 12 weeks . MAIN OUTCOME MEASURE(S ) Mean changes in vaginal maturation index , percentage of parabasal and superficial cells , vaginal pH , and severity of the most bothersome symptom ( MBS ) between baseline and predetermined time points were assessed . Safety and tolerability were evaluated . RESULT ( S ) A total of 310 women ( mean age , 58.6 y ) were enrolled .  Synthetic conjugated estrogens B yielded statistically significantly greater differences in vaginal maturation index and vaginal pH from baseline to the end of treatment . Vaginal dryness ( 44.4 % ) and pain during intercourse ( 30.2 % ) were the symptoms most commonly identified as the MBS . A statistically significant mean reduction in the severity of the MBS was noted for SCE-B. There were no clinical ly significant differences observed between the two groups for findings related to safety . CONCLUSION ( S ) Synthetic conjugated estrogens B ( 0.3 mg/d ) was effective in treating vulvovaginal atrophy in symptomatic postmenopausal women . Significant improvement was seen in vaginal maturation index , vaginal pH , and severity of MBS from baseline to the end of treatment A prospect i ve r and omised double-blind placebo-controlled trial of 17-beta oestradiol 25-mg vaginal tablets or placebo daily for 12 weeks was undertaken in 110 postmenopausal women with urinary frequency , urgency and /or urge incontinence recruited from a tertiary referral urogynaecology clinic . After 3 months the only statistically significant difference was a greater reduction in urinary urgency in those women with sensory urgency treated with 17-beta oestradiol compared to placebo . This may be due to the effective treatment of local vaginal atrophy by low-dose oestrogen rather than any effect on the lower urinary tract Objective : The aim of this study was to determine the patterns and predictors of sexual activity in the Hormone Therapy ( HT )  Trials of the Women 's Health Initiative ( WHI ) . Methods : Sexual activity questions were administered to 27,347 women ages 50 to 79 years at baseline and at year 1 and to a r and om 8.6 % sub sample at years 3 and 6 . The associations with demographic and health characteristics were determined . Results : Sexual activity at baseline was 60.7 % , 44.9 % , and 28.2 % in the 50- to 59- , 60- to 69- , and 70- to 79-year-old age groups , respectively . Most of the participants were satisfied with their current sexual activity ( 63.2 % ) . Of those dissatisfied , 57 % preferred more sexual activity . Vaginal atrophy correlated with sexual inactivity at baseline ( P < 0.001 ) . The correlates associated with stopping sexual activity at year 1 included poor/fair self-rated health , lack of satisfaction with quality of life , depression , and loss of partner ( P < 0.001 ) . The strongest predictor of sexual activity at year 1 was sexual activity at baseline ( odds ratio , 96.71 ; 95 % CI , 81.90 - 114.20 ) . A subset analysis of women adherent with HT or placebo at years 3 and 6 suggested that HT was associated with a higher percentage of participants reporting sexual activity ( P = 0.01 ) . Conclusions : Most women in the WHI HT Trials were satisfied with their sexual activity . Of those who were dissatisfied , the majority preferred more , rather than less , sexual activity . Vaginal atrophy at baseline correlated with sexual inactivity , and sexual activity at baseline was the strongest identified predictor of sexual activity at year 1 . HT use was not predictive of ongoing sexual activity in the intent-to-treat analysis . This report further characterizes the participants in the WHI HT trials and reveals the complexity of factors related to the prevalence of sexual activity and satisfaction Objectives : To evaluate the efficacy and safety of different doses of 17&bgr;‐estradiol for the treatment of vasomotor and vulvovaginal symptoms . Design : This was a r and omized , double‐blind , multicenter , parallel‐group study . One hundred forty‐five subjects , including naturally postmenopausal women aged 40‐60 ( who had not experienced menses for at least 12 months ) , women who had undergone hysterectomy , and women aged 25‐60 who had undergone bilateral oophorectomy with or without hysterectomy were studied . Either placebo or 17&bgr;‐estradiol ( 1 mg or 0.5 mg ) was given orally every day for 12 weeks , and vasomotor symptoms and vaginal epithelial cytology were evaluated . Results : There were significant differences between placebo and the active treatments in the percentage change from baseline in the number of hot flushes ( all hot flushes , 1 mg vs. placebo , p < 0.001 ; 0.5 mg vs. placebo , p = 0.007 ) , with a more substantial proportion of subjects responding in the 1‐mg group ( mean change in mean number of hot flushes of 83.2 % ) . Both doses were also more effective than placebo in increasing the proportion of mature vaginal cells ( end‐of‐treatment mean values of 0 % , 78.5 % , and 21.5 % for parabasal , intermediate , and superficial cells , respectively , in the 1‐mg group ; mean values of 0.3 % , 80.8 % , and 18.9 % in the 0.5‐mg group ; and mean values of 15.2 % , 74.7 % , and 10.2 % in the placebo group ) . The proportion of subjects reporting no vaginal dryness was greatest in the 1‐mg group ( mean percentage of days without dryness of 86.1 % at weeks 9‐12 ) . Conclusions : For the relief of vasomotor and vulvovaginal symptoms , 17&bgr;‐estradiol 1 mg is effective and has an excellent safety profile . ( Menopause 2000;7:310‐317 . © 2000 , The North American Menopause Society . Objective To evaluate the effects of the tissue selective estrogen complex ( TSEC ) pairing bazedoxifene ( BZA ) with conjugated estrogens ( CE ) on sexual function and quality of life in postmenopausal women . Methods In this 12-week , double-blind , placebo-controlled study , postmenopausal , non-hysterectomized women ( n = 652 ) with symptoms of moderate to severe vulvar/vaginal atrophy were r and omized to once-daily treatment with BZA 20 mg/CE 0.45 or 0.625 mg , BZA 20 mg , or placebo . The Arizona Sexual Experiences ( ASEX ) Scale , Menopause-Specific Quality of Life ( MENQOL ) question naire , and Menopause Symptoms Treatment Satisfaction Question naire ( MS-TSQ ) were secondary measures used to assess the effects of BZA/CE on sexual function , menopausal symptoms , and satisfaction with treatment , respectively . Results At week 12 , both BZA/CE doses were associated with significant improvement in ease of lubrication score from baseline compared with placebo ( p < 0.05 ) on the ASEX scale , although there was no difference in the change in total score . The MENQOL question naire results at week 12 showed significant improvements in vasomotor function , sexual function and total scores with both BZA/CE doses vs. placebo or BZA 20 mg ( p < 0.001 ) . The MS-TSQ results showed that BZA/CE-treated subjects reported significantly greater overall satisfaction with treatment , as well as satisfaction with control of hot flushes during the day and night , effect on quality of sleep , and effect on mood or emotions , compared with subjects treated with placebo or BZA 20 mg ( all p < 0.05 ) . Conclusion Treatment with BZA/CE for 12 weeks was shown to significantly improve sexual function and quality -of-life measures in symptomatic postmenopausal women AIMS --To study the effects of ovarian hormone replacement therapy ( HRT ) on bone mineral density and disease activity in postmenopausal women with rheumatoid arthritis ( RA ) . METHOD --A placebo controlled double-blind study was carried out on 62 patients with RA , 22 on placebo and 40 on HRT ( transdermal oestradiol patches twice weekly for 48 weeks plus norithisterone tablets when clinical ly indicated ) . Bone mineral density of spine , hip and wrist was measured at 0 and 48 weeks and clinical and laboratory measures of general well-being and disease activity at 0 , 12 , 24 and 48 weeks . RESULTS --Thirteen of 22 ( 59 % ) of placebo and 31 of 40 ( 78 % ) of the HRT group completed 48 weeks in the study . At entry ,  bone mineral density ( BMD ) values in the lumbar spine and femoral neck were similar to those in age and sex matched controls in both treatment groups , whereas at the distal radius , BMD was significantly reduced to approximately 50 % of control values ( both p < 0.001 from controls ) . In the HRT group , spine BMD increased significantly by a median of + 0.94 % at 48 weeks ( p = 0.024 ) , but did not change significantly in the placebo group . BMD at the femoral neck and distal radius did not change in either group . In the HRT group , there was significant improvement in well being as assessed by the Nottingham Health Care Profile ( p < 0.01 ) and in the articular index ( p < 0.05 ) . There were no significant changes in ESR or CRP in either group . CONCLUSION --Transdermal HRT was well tolerated , increased well being , reduced articular index and increased lumbar spine bone density over a one year period in postmenopausal women with RA . Although no laboratory evidence was found of a disease modifying effect , the symptomatic benefits and improvements in bone density indicate that HRT may be a valuable adjunct to conventional antirheumatic therapy in RA OBJECTIVE To evaluate the feasibility of conducting a large r and omized trial of HRT in symptomatic women with early-stage breast cancer . DESIGN Open r and omized study . SETTING Outpatient clinics at The Royal Marsden and St. George 's Hospitals , London . PATIENT(S ) One hundred postmenopausal women with early-stage breast cancer , experiencing vasomotor symptoms and /or vaginal dryness . INTERVENTION(S ) R and omization ( 1:1 ) to HRT or no HRT for 6 months . MAIN OUTCOME MEASURE(S ) Acceptance , continuance rates , and the reasons eligible women declined study entry . RESULT ( S ) Acceptance ( 38.8 % ) and continuance rates ( > 80 % ) were encouraging . The efficacy of HRT did not appear to be antagonized with concomitant tamoxifen . Seventy-five percent of women continued HRT after the study ended . Three women developed metastatic disease . Two used  HRT .  CONCLUSION ( S ) Despite informed consent , a national UK r and omized trial of HRT should be feasible and has now been planned . Successful implementation necessitates the provision of information about HRT and the estrogen deficiency side effects of breast cancer therapy to health professionals and women with breast cancer OBJECTIVES FM is a condition that preferentially affects women . Sex hormones , and in particular oestrogens , have been shown to affect pain processing and pain sensitivity , and oestrogen deficit has been considered a potentially promoting factor for FM . However , the effects of oestrogen treatment in patients suffering from FM have not been studied . Here , we examined the effect of transdermal oestrogen substitution treatment on experimental as well as self-estimated pain in women suffering from FM . METHODS Twenty-nine post-menopausal women were r and omized to either 8 weeks of treatment with transdermal 17β-oestradiol ( 50 µg/day ) or placebo according to a double-blind protocol . A self-estimation of pain , a set of quantitative sensory tests measuring thresholds to temperature , thermal pain , cold pain and pressure pain , and a cold pressor test were performed on three occasions : before treatment , after 8 weeks of treatment and 20 weeks after cessation of treatment . RESULTS Hormonal replacement treatment significantly increased serum oestradiol levels as expected ( P < 0.01 ) . However , no differences in self-estimated pain were seen between treatment and placebo groups , nor were there any differences between the two groups regarding the results of the quantitative sensory tests or the cold pressor test at any of the examined time points . CONCLUSION Eight weeks of transdermal oestradiol treatment does not influence perceived pain , pain thresholds or pain tolerance as compared with placebo treatment in post-menopausal women suffering from FM . TRIAL REGISTRATION Clinical Trials.gov Registration ; http://www . clinical trials.gov ; NCT01087593 OBJECTIVE To investigate the effects of estrogen and progesterone on sleep in postmenopausal women . METHOD The 33 participants were r and omly assigned to an estrogen or placebo group after undergoing clinical and hormonal assessment s and a polysomnogram , and they underwent the same tests again after 12 weeks . Then , while still taking estrogen or placebo , they all received progesterone for another 12 weeks and underwent a final polysomnogram . RESULTS Estrogen plus progesterone was more effective than estrogen alone in decreasing the prevalence of periodic limb movement ( PLM ) ( 8.1 % vs 2.8 % ) , hot flashes ( 14.2 % vs 0 % ) , and bruxism ( 11.1 % vs 0 % ) at night , or somnolence and attention difficulty during the day . The prevalences of breathing irregularities , arousal from sleep , anxiety , and memory impairment were decreased in both groups following progesterone treatment . CONCLUSION While not significantly affecting sleep quality , hormone therapy decreased the prevalence of arousal in both groups and that of PLM in the group treated with estrogen plus progesterone Objective Pueraria lobata ( PL ) is used as a traditional Chinese herbal remedy for menopausal symptoms , as well as an ingredient in preparations for conditions affecting menopausal women , such as osteoporosis , coronary heart disease , and some hormone-dependent cancers . The scientific basis for its action may be its action as a phytoestrogen . Design To examine the effects of PL in comparison with hormone replacement therapy ( HRT ) on lipid profile , sex hormone levels , bone turnover markers , and indices of cognitive function . For the study , 127 community-living , postmenopausal women aged 50 to 65 years were r and omized to receive HRT ( n = 43 ) , PL ( equivalent to 100 mg isoflavone ; n = 45 ) , or no treatment ( n = 39 ) for 3 months . The following measurements were carried out at baseline and after 3 months for all participants : menopausal symptoms question naire ; neuropsychological tests covering memory , attention , motor speed , and word-finding ability ; quality of life ( SF36 ) ; lipid profile ; urinary deoxypyridinoline ; dietary phytoestrogen intake and urinary phytoestrogen ; estradiol ; follicle-stimulating hormone ; and luteinizing hormone . Results Only participants in the HRT group showed a mean reduction in cholesterol and low-density lipoprotein cholesterol that was significantly different from that of the control group . No significant changes in lipid profile or follicle-stimulating hormone and luteinizing hormone were observed in the PL group compared with the controls . However , both the HRT and PL groups showed an improvement in Mini-Mental State Examination score and attention span compared with the case of participants receiving no treatment . HRT and PL had different effects on cognitive function ;  HRT improved delayed recall , whereas flexible thinking seemed improved in the PL group . Conclusions This study was unable to demonstrate a scientific basis for the use of PL for improving the health of postmenopausal women in general . However , the effect of PL on cognitive function deserves further study OBJECTIVE The primary objective was to detect a difference in time until the first recurrence of urinary tract infection during treatment with an estradiol-releasing silicone vaginal ring ( Estring ; Pharmacia & Upjohn , Inc , Uppsala , Sweden ) compared with no estrogen treatment . The secondary objective was to detect any differences in improvement of urethral and vaginal mucosal atrophy and in the subjective assessment of urogenital symptoms . The study also sought to detect a difference in decrease of vaginal pH to < 5.5 and to record adverse events . STUDY DESIGN This was a multicenter , r and omized , open , parallel-group study with an untreated control group . Postmenopausal women with recurrent symptomatic , bacteriologically confirmed urinary tract infections were r and omly assigned to receive either Estring ( 2 mg estradiol ) or no estrogen treatment . One ring was carried vaginally for 12 weeks . The duration of treatment was 36 weeks for the Estring group and either 36 weeks or until the first recurrence for the control group . Both intent-to-treat and per- protocol analyses were performed to evaluate efficacy , whereas the safety analysis was limited to the intent-to-treat group . The primary variable was analyzed by survival analysis with the Kaplan-Meier method for estimating the survival density function . To compare the survival curves for the 2 treatment groups a log-rank test was performed for time until first recurrence . RESULTS A total of 108 women were r and omly assigned , 53 to the Estring group and 55 to the control group . The cumulative proportion of women remaining free of urinary tract infection was significantly higher in the Estring group than in the control group ( P = .008 ) . After 36 weeks of study the cumulative likelihood of remaining free of disease was approximately 45 % in the women with the vaginal ring compared with approximately 20 % in the control group . Estring lowered vaginal pH , and the time to first recurrence was effectively prolonged by Estring treatment . Vaginal and , to a lesser extent , urethral mucosal cells were significantly more mature in the Estring group . No unexpected adverse events were found . CONCLUSION Estring is useful to prolong the time to next recurrence among postmenopausal women with recurrent urinary tract infection and to decrease the number of recurrences per year . The silicone vaginal ring also has a clinical ly significant ability to alleviate other postmenopausal urogenital symptoms . Estring is safe and well tolerated Objective : To determine the efficacy of three doses of a new , oral formulation of estradiol acetate ( EA ) for alleviation of vasomotor and urogenital symptoms in postmenopausal women . Design : Two separate 12-week studies were undertaken in postmenopausal women with moderate to severe vasomotor symptoms . In the first study , women were r and omly assigned to EA 0.9 mg/day , EA 1.8 mg/day , or placebo  ( study 1 ; N = 293 ) , and in the second study to oral EA 0.45 mg/day or placebo  ( study 2 ; N = 259 ) . Women recorded the frequency and severity of vasomotor symptoms daily and urogenital symptoms weekly on diary cards . Investigators assessed signs of vaginal atrophy . Results : Frequency of moderate to severe vasomotor symptoms decreased significantly versus placebo , starting at week 2 in the EA 1.8-mg group ( P = 0.005 ) , week 3 in the EA 0.9-mg group ( P = 0.003 ) , and week 6 in the EA 0.45-mg group ( P < 0.05 ) . At week 12 , mean percent reduction from baseline in vasomotor-symptom frequency was 91 % , 78 % , and 61 % , respectively . Vasomotor-symptom severity decreased significantly versus placebo , starting at weeks 2 and 3 with EA 1.8 mg and 0.9 mg , respectively , and at week 5 with EA 0.45 mg . Vaginal pH and maturation index improved significantly in all EA groups versus placebo , and some signs and symptoms of vaginal atrophy improved at the EA 0.9- and 1.8-mg doses . Side effects were mild to moderate and consistent with estrogen therapy . Conclusions : Oral EA at all doses was well tolerated and significantly reduced the frequency and severity of postmenopause symptoms versus placebo OBJECTIVE : To evaluate two doses of oral synthetic conjugated estrogens-B tablets compared with placebo on the frequency of awakenings result ing from nocturnal vasomotor symptoms in postmenopausal women over a 12-week treatment period . METHODS : A double-blind , r and omized , placebo-controlled multicenter study enrolled a total of 157 women who were experiencing daytime vasomotor symptoms and a minimum of at least three nocturnal awakenings per night as a result of hot flushes . Participants were evenly r and omized to one of three treatment groups ( 0.3 mg , 0.625 mg , or matching placebo ) and treated for up to 12 weeks . Subjective sleep quality also was assessed . RESULTS : Significantly greater reductions from baseline in the weekly mean frequency of awakenings result ing from hot flushes occurred for participants r and omized to either synthetic conjugated estrogens-B dose relative to placebo ( mean reductions , 3.55 , P=.004 , and 4.65 , P<.001 for 0.3 mg and 0.625 mg , respectively ) . In addition , a significantly greater proportion of participants at either estrogen dose had complete elimination of nocturnal awakenings ( 36.5 % for 0.3 mg , 34 % for 0.625 mg compared with 9.8 % for placebo ; P⩽.002 ) with a general finding of improved sleep based on actigraphy data . No differences were observed in measures of sleep quality or daytime sleepiness . CONCLUSION : In this symptomatic postmenopausal population of women experiencing sleep disruption result ing from nocturnal vasomotor symptoms , a daily dose of synthetic conjugated estrogens-B as low as 0.3 mg appears to be effective in treating nocturnal hot flushes that lead to unwanted awakenings . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00592839 . LEVEL OF EVIDENCE : OBJECTIVE Estrogen or combined hormone ( estrogen-progestin ) therapy is highly efficacious for managing the signs and symptoms of urogenital atrophy . A low , effective estrogen dose may enhance patient acceptance and reduce side effects . METHODS In this r and omized , double-blind , multicenter clinical trial , 71 healthy postmenopausal women with vaginal atrophy ( Vaginal Maturation Index < or = 55 ) received either low-dose synthetic conjugated estrogens , A tablets ( Cenestin ) ( SCE-A ) , 0.3 mg once daily , or placebo for 16 weeks . RESULTS Treatment with SCE-A for 16 weeks result ed in a highly significant ( P<0.0001 ) mean increase of 17.7 in the Vaginal Maturation Index compared to a mean increase of 4.1 with placebo treatment . A significant estrogenic improvement was detected as early as 4 weeks ( mean increase 14.6 ) . Superficial cells were significantly increased from 2.1 % at baseline to 15.9 % at week 16 with SCE-A , and parabasal cells were significantly reduced from 23.0 % at baseline to 1.6 % at week 16 ( P<0.01 between treatments for both ) . Vaginal pH was significantly decreased from 6.2 at week -2 to 5.2 at week 16 with SCE-A compared to placebo ( P<0.0001 ) . There were no significant differences between treatment groups in the incidence of treatment-emergent side effects or other measures of safety , except for urinary tract infection , which occurred more frequently in the placebo group . CONCLUSIONS These results confirm the relatively rapid estrogenic effect and safety of a low-dose ( 0.3 mg/day ) of slow-release SCE-A ( Cenestin ) in the treatment of vaginal atrophy in postmenopausal women OBJECTIVES To determine the effects of ultra-low-dose hormone therapy on muscle mass and physical function in community-dwelling women . DESIGN Double-blind , placebo-controlled trial . SETTING Clinical research center in Connecticut . PARTICIPANTS Healthy , community-dwelling women aged 65 and older ( n=167 ) . INTERVENTION Eligible women were r and omly assigned to treatment with 0.25 mg 17-beta estradiol or placebo for 36 months . All women ( estradiol or placebo ) with an intact uterus received micronized progesterone 100 mg/d for 2 weeks every 6 months . All participants received 1,300 mg elemental calcium with 1,000 IU vitamin D per day . MEASUREMENTS Appendicular skeletal muscle mass ( ASM ) , lean body mass ( LBM ) , and percentage body fat were measured using dual x-ray absorptiometry . Sarcopenia was defined as skeletal muscle mass ( ASM/height2 ) 2 st and ard deviations or less than young , healthy reference population mean . Physical activity ( Physical Activity Scale in the Elderly ( PASE ) ) and performance were measured . Serum estrone , estradiol , and sex hormone-binding globulin were measured . RESULTS The prevalence of sarcopenia at baseline was 13 % . There were no baseline differences between groups except for PASE score and chair rise time , in which the estrogen group had better performance . No changes in ASM , LBM , percentage of body fat , or physical performance were found after 3 years of estrogen therapy . CONCLUSION Sarcopenia was present in 13 % of this group of community-dwelling , postmenopausal older women . Ultra-low-dose estrogen therapy neither improves nor harms ASM . Similarly , no changes in body fat or physical performance were detected Two hundred and forty‐two postmenopausal women between 35 and 65 years of age requiring hormone replacement therapy for climacteric symptoms were blindly and r and omly allocated to treatment either with transdermal estradiol therapy ( Estraderm * 50 μg/24 h ) ( E ) or placebo ( P ) . The patches were changed twice a week and treatment continued for 12 weeks . No progestogen supplement therapy was given during the study . No previous hormone replacement therapy had been given for the last six months and the women had had their last menstruation more than sin months ago . As a part of a larger study assessing women 's quality of life , a Swedish version of ‘ McCoy 's Sex Scale Question naire ’ was administered at the start of treatment and after 12 weeks . This question naire contains nine items regarding different aspects of sexual life . The difference between the scorings at the start of treatment and after 12 weeks were calculated for each item and the values of the E and the P groups were compared . Items regarding ‘ satisfaction with frequency of sexual activity , sexual fantasies . degree of enjoyment . vaginal lubrication and pain during intercourse ’ were positively influenced in the E group compared to the P group . Items not affected were ‘ frequency of orgasm and sexual arousal ’ . A correlation between improved sexual life and quality of life was also found when the results from the McCoy scale were compared with a battery of quality of life question naires OBJECTIVE To test the causal relationship between sex hormones and cognitive skills in postmenopausal women . We hypothesized that testosterone would decrease verbal memory and verbal fluency and increase spatial ability compared with a placebo . For estrogen , we conversely hypothesized that the treatment would increase verbal fluency and verbal memory and decrease spatial ability . DESIGN R and omized , double-blind , placebo-controlled , parallel-group trial . SETTING Women 's health clinical research unit at a university hospital . PATIENT(S ) Two-hundred healthy , naturally postmenopausal women aged 50 - 65 years . INTERVENTION(S ) R and omization to 4 weeks ' treatment with testosterone ( testosterone undecanoate , 40 mg/day ) , estrogen ( oral E2 2 mg/day ) or placebo . MAIN OUTCOME MEASURE(S ) Comparisons in verbal fluency , verbal memory , and spatial ability between the three treatment groups . RESULT ( S ) We found no significant effects of testosterone or estrogen on verbal fluency , verbal memory , or spatial ability . CONCLUSION ( S ) Our results give no support for short-term testosterone or estrogen treatment having any substantial effect on verbal fluency , verbal memory , or spatial ability in healthy postmenopausal women The results of several observational studies suggest that the use of estrogen replacement is associated with better mood , cognitive function and quality of life . Such findings are consistent with those of laboratory-based research showing that estrogen promotes neuronal sprouting , enhances cholinergic activity in the brain , decreases brain and plasma levels of beta-amyloid , increases serotonin postsynaptic responsivity and the turnover of noradrenaline , and inhibits monoamine oxidase activity . However , the findings from the Women 's Health Initiative controlled trial showed that hormone replacement ( estrogen plus progestin ) not only failed to improve mood , cognition and quality of life but also increased the risk of dementia . At present , there is limited information about the effect of unopposed estradiol replacement therapy ( ERT ) on the mental health outcomes of women at increased risk of cognitive decline ( aged 70 years and over ) . We design ed the present r and omized , double-blind , placebo-controlled trial to clarify this issue . One hundred and fifteen women were r and omized to treatment with estradiol ( n=58 ; 2 mg per day ) or placebo for a total period of 20 weeks . The outcomes of interest in this study included changes in the Beck Depression Inventory ( BDI ) scores between baseline and week 20 , as well as changes in quality of life scores ( as measured by the SF-36 ) and cognitive function ( CAMCOG , Block Design , Memory for Faces , California Verbal Learning Test ( CVLT ) and verbal fluency ( VF ) ) .  Nineteen women treated with estradiol  and 10 of those treated with  placebo discontinued the use of the medication during trial , most frequently due to adverse reactions ( OR=4.11 , 95 % CI=1.29 - 15.37 ) . Intention-to-treat analysis showed that the active and placebo groups did not differ in their response to treatment in any of the outcome measures ( p>0.05 ) . A separate analysis restricted to women who completed the 20-week-trial produced similar negative results . The results of this trial indicate that the use of a relatively high dosage of unopposed estrogen replacement for 20 weeks is not associated with significant changes in cognitive function , mood and quality of life . Other more efficacious and safer interventions need to be devised with the aim of improving the mental state and quality of life of older women BACKGROUND The main goals of estrogen replacement therapy ( ERT ) are the prevention of osteoporosis and cardioprotection and the improvement of quality of life ( QL ) . And rogens and tibolone therapy may increase bone mineral density ( BMD ) to a greater extent than ERT and offer an increase in QL . Lipid and cardiovascular effects , however , are still a major concern . AIM To evaluate whether the addition of a weak and rogen to ERT may improve postmenopausal bone loss and sexual activity without adverse effects on lipid pattern and to compare these effects with those observed after tibolone therapy . SUBJECTS AND METHODS This prospect i ve study enrolled 120 surgical postmenopausal women ; of these , 96 completed the 1-year follow-up . Patients were allocated to one of four groups . The first group ( A ; n = 23 ) received 4 mg of estradiol valerate plus 200 mg of enanthate of dihydro and rosterone i m monthly . The second group ( E ; n = 26 ) received 50 microg/day of transdermal 17-b-estradiol continuously ; the third ( T ; n = 23 ) received 2.5 mg of tibolone every day ; and finally , the fourth group ( C ; n = 24 ) constituted a treatment-free control group . Bone mass ( dual X-ray absorptiometry ) , serum total cholesterol , HDL , LDL , triglycerides , apolipoproteins A1 and B and sexual activity were evaluated before starting therapy and at the end of follow-up . RESULTS All active treatment groups showed an increase in BMD . This increase was higher in the A treatment group ( 4.08 % P < 0.01 ) . Sexuality improved significantly with therapy ; however , tibolone and and rogens increased scores to a greater extent than ERT . And rogen therapy was associated with significant increases in total cholesterol , LDL and triglycerides . Cholesterol and LDL fall into groups E and T , HDL into groups A and T and triglycerides in group T only . CONCLUSION The combined regimen of and rogens and ERT increased vertebral bone mass and enhance sexual activity in postmenopausal women equal to that of tibolone and to a greater extent than ERT alone ; its effects on lipids , however , are clearly adverse OBJECTIVE The effect of transdermal estradiol and placebo therapy on the quality of life of postmenopausal women was compared in a r and omized trial over 12 weeks . STUDY DESIGN Two hundred forty-two women were r and omized , and 223 were analyzed for efficacy ( n = 112 for estradiol and n = 111 for placebo ) . The quality of life was assessed by means of a battery of st and ard question naires . RESULTS Quality of life improved after both therapies , but health-related quality of life ( p = 0.0003 ) and well being ( p = 0.003 ) improved more after transdermal estradiol therapy than after placebo . This was also the case for all specific climacteric aspects , including sexual problems ( p < 0.0001 ) and dysfunction ( p = 0.01 ) , at comparison with placebo .  Self-rated symptom relief was more pronounced with estrogen therapy than with placebo ( p < 0.0001 ) . CONCLUSION It was concluded that estradiol therapy was superior to placebo in relieving symptoms and improving quality of life Background Since sex hormones are reported to have important roles in the regulation of immune function , this study was design ed to investigate the effects hormone replacement therapy ( HRT ) and raloxifene ( RAL ) on serum cytokine concentrations in healthy postmenopausal women . Methods Fifty-three healthy postmenopausal women were r and omly assigned and treated by RAL ( Group I , [ RAL 60 mg daily and continuously ] , n = 16 ) , HRT ( Group II , [ 2 mg estradiol valerat + 2 mg dienogest , continuously ] n = 18 ) or placebo ( Group III , n = 19 ) . Two fasting morning blood sample s were obtained from each participant before and 3 months after the treatments . Serum concentration of interleukin (IL)-4 ( as a Th2 cytokine ) and transforming growth factor-beta (TGF-β)1 ( as a Th3 cytokine ) , were measured by using commercially available enzyme-linked immunosorbent assay kits . Kruskal – Wallis analysis of variance , Mann – Whitney U , and Wilcoxon Signed-Ranks Tests were used as necessary . Results At the beginning of the study , the chronological ages , menopausal ages , years of amenorrhea , weights , body mass indexes , and blood pressures were not significantly different between groups ( P < 0.05 ) . RAL treatment caused a significant decrease on serum IL-4 concentration ( P < 0.001 ) . Although HRT caused a 14 % decrease in serum IL-4 concentration , this decrease was not statistically significant ( P > 0.05 ) . Serum TGF-β1 concentrations were significantly decreased by HRT when compared to basal value ( P < 0.001 ) , and to control ( P < 0.05 ) . RAL treatment has no significant effect on serum TGF-β1 concentration ( P > 0.05 ) . Conclusion It seems that RAL treatment might cause a decrease in serum IL-4 concentration while valerate plus dienogest treatment as HRT seems to cause a Th3 tendency in healthy postmenopausal women Objective : To explore whether inhibition of the conversion of testosterone to estradiol modifies the effects of testosterone on cognition in 61 healthy , estrogen-treated postmenopausal women . Design : Seventy-six postmenopausal women using transdermal estrogen for at least 8 weeks , with a serum total testosterone less than 1.2 nmol/L participated in a single-center , double-blind , r and omized , placebo-controlled study . All participants received transdermal testosterone , 400 & mgr;L of a 0.5 % testosterone gel , daily and were r and omized to receive either letrozole 2.5 mg/day or an identical placebo tablet . The main outcome measure was cognition , evaluated using a comprehensive battery of st and ardized neuropsychological tests , at baseline and week 16 . Results : Thirty women in each group completed the study .  Free testosterone increased from baseline in both groups , with no difference between groups . Free testosterone levels achieved were below the 90th centile for young women in 80 % of the participants at week 16 . Serum estradiol and sex hormone-binding globulin levels did not differ from baseline or between groups during the study . No clinical ly significant effects of testosterone treatment were seen for attention and working memory , psychomotor speed , or executive function . Significant improvements were seen for immediate and delayed visual and verbal memory and for simple concentration with testosterone therapy , all of which were unaffected by the aromatase inhibitor . Conclusions : We did not observe any effects of aromatase inhibition on cognition in healthy , estrogen-treated postmenopausal women treated with testosterone . This may be due to insufficient study power or a true lack of effect . However , our findings highlight that the detection of subtle changes in cognition in well women require the development of sensitive instruments and large r and omized , controlled trials Females are disproportionately affected by constipation , which is often aggravated during pregnancy . Bowel function also changes during the luteal phase of the menstrual cycle . The aim was to compare the effects of acute administration of female sex steroids on gastric emptying , small bowel transit and colonic transit in healthy postmenopausal subjects . A second aim was to determine whether withdrawal of the hormones was associated with a change in transit .  Forty-nine postmenopausal females were r and omized to receive for 7 days 400 mg day(-1 ) micronized progesterone , 0.2 mg day(-1 ) oestradiol , combination of the two , or placebo . Treatment groups were balanced on age . Participants underwent whole gut transit measurement by scintigraphy using a 99m-labeled technetium-egg meal and 111-labeled indium-charcoal via a delayed-release capsule . Transit measurement was repeated after withdrawal of the study medications . The primary endpoints were ascending colon ( AC ) emptying half-life time ( t1/2 ) and colonic geometric centre ( GC ) at 24 h. Secondary analysis variables were GC at 4 and 48 h , gastric emptying t1/2 and colonic filling at 6 h. There was a significant overall effect of progesterone on colonic transit with shorter AC emptying t1/2 and significantly greater colonic GC at 48 h. No transit endpoints were altered by oestradiol or combined hormonal treatment relative to placebo . Oestradiol and progesterone result ed in looser stool consistency . Withdrawal of the hormone supplement was not associated with significant alteration in transit .  Micronized progesterone does not retard colonic transit in postmenopausal females Abstract : Local estrogen substitution has been shown to be more appropriate than any systemic application for the treatment of urogenital symptoms of hormone defiency . The efficacy , safety and acceptability of a new low-dose drug delivery system consisting of an estradiol-releasing silicone vaginal ring was studied in two multicenter trials . In an open-label comparative trial a total of 219 postmenopausal women were r and omized to the estradiol-releasing vaginal ring or to estriol suppositories .  In terms of efficacy both treatment arms were shown to be equivalent ; however , significantly higher rates of acceptability were found for the vaginal ring . In a double-blinded placebo-controlled study a total of 84 patients were r and omized to either treatment arm for a period of 24 weeks . The statistically significant improvement of the vaginal epithelial pH and maturation values demonstrated the efficacy of the estradiol-releasing vaginal ring compared to the placebo ring OBJECTIVE To investigate the effect of pulsed estrogen therapy S21400 ( intranasal 17 beta-estradiol ) on different quality of life ( QoL ) dimensions in early postmenopausal women treated with S21400 150 microg per day , S21400 300 microg per day , or placebo in a double blind , r and omized , controlled 2-year study . STUDY DESIGN QoL was assessed based on the vali date d Women 's Health Question naire design ed for peri- and post-menopausal women . Three hundred and thirty-five healthy , early postmenopausal Danish women , 53 years of age in average , who completed one question naire at baseline and one under study treatment were included in the analysis set . All analyses were performed on an intention-to-treat basis . RESULTS QoL improved significantly in both S21400 groups compared to placebo in the dimensions ' memory/concentration ' , ' vasomotor symptoms ' , ' sleep problems ' and ' sexual behavior ' ( difference in mean change scores being respectively + 7.9 , + 28.3 , + 9.9 and + 10.8 % , p < 0.001 , between the S21400 300 microg and placebo group ) . There were no significant differences between actively treated groups and placebo in the dimensions ' anxiety/depressed mood ' and ' well-being ' . CONCLUSION Pulsed estradiol therapy had a pronounced effect not only on vasomotor symptoms but also a significant and clinical ly relevant improvement in several other QoL dimensions Objective : More than 50 % of all fractures occur in people without osteoporosis . Hormone therapy increases bone density , improves postural balance , and reduces fracture risk in postmenopausal women . It is unclear whether tibolone , a synthetic steroid hormone drug , can improve muscle strength . Thus , the aim of this study was to study the effects of low-dose tibolone therapy on muscle strength in older women . Methods : Eighty healthy women ( 69 completed the study ) 60 years or older were recruited through advertising in the local media . They were r and omly allocated to receive either tibolone 1.25 mg/day or placebo for 6 months . The st and -up test was used to assess leg muscle strength and balance . H and grip and leg muscle strength were measured using JAMAR and modified Cybex dynamometers . Results : Baseline characteristics , including serum estradiol values and muscle strength , were similar in the two groups .  Compliance with the therapy regimen was very high , averaging more than 97 % in both groups . After 6 months , mean values for h and grip strength , knee extensor strength , and average time to perform 10 st and s were improved numerically in both groups compared with values during baseline . However , there were no significant differences in these parameters within or between groups , and differences remained nonsignificant after adjustment for age , serum estradiol , and baseline value . Conclusions : Short-term treatment with low-dose tibolone ( 1.25 mg/d ) seems not to affect muscle strength in older women OBJECTIVE To determine the effects of raloxifene hydrochloride , 60 mg/d , on serum levels of E(2 ) , estrone , sex steroid-binding globulin , thyroxine-binding globulin , and follicle-stimulating hormone ( FSH ) in postmenopausal women . DESIGN R and omized placebo-controlled study at 16 centers in the United States . PATIENT(S ) Ninety three women 42 to 80 years of age who were at least 2 years postmenopausal . INTERVENTION(S ) Raloxifene ( n = 47 ) or placebo ( n = 46 ) for 3 months . MAIN OUTCOME MEASURE(S ) Levels of E(2 ) , estrone , sex steroid-binding globulin , thyroxine-binding globulin , and FSH were measured at baseline and after 3 months of therapy . RESULT ( S ) Raloxifene increased serum levels of sex steroid-binding globulin and thyroxine-binding globulin and decreased FSH levels compared with placebo . Levels of E(2 ) and estrone were unaffected . CONCLUSION ( S ) In postmenopausal women , raloxifene ( 60 mg/d ) did not increase serum estrogen levels ; however , it increased levels of sex steroid-binding globulin and thyroxine-binding globulin and decreased FSH levels OBJECTIVE To evaluate clinical efficacy of multiple regimen combination in treatment of osteoporosis of perimenopausal or postmenopausal women . METHODS From Jul. 2008 to Dec. 2009 , 109 women with low bone mineral density ( BMD ) or osteoporosis treated in Department of Obstetrics and Gynecology , Affiliated Second Hospital , Wenzhou Medical College were enrolled r and omly into 3 group , including 36 women in Group A managed by osteoform 1000 mg/d + alfacalcidol 0.25 µg/bid orally , 40 women in group B managed by osteoform 1000 mg/d + alfacalcidol 0.25 µg/bid + tibolone 1.25 mg/d orally and 33 women in group C managed by osteoform 1000 mg/d + alfacalcidol 0.25 µg/bid + bisphosphonates 70 mg/w orally . After 48 weeks BMD on lumbar 1 - 4 ( L₁₋₄ ) and left femur were detected by X-ray . Bone alkaline phosphatase(BALP ) , cross linked clelopeptide of type I collagen ( CTX ) and 25-hydroxychole calciferol [ 25(OH)D₃ ] was measured by enzyme linked immunosorbent assay ( ELISA ) . RESULT Seven women ( 6.4 % , 7/109 ) were withdrawed form this study , including 2 cases losing follow up in group A , 3 cases stopping treatment in group B , 2 cases giving up treatment due to severe adverse effect ( burning in upper abdomen ) in group C. ( 1 ) Pain relieve : after 48 weeks treatment , women in 3 groups improved symptom of pain significantly , the rates of pain relieve were 85 % ( 29/34 ) in group A , 92 % ( 34/37 ) in group B and 94 % ( 29/31 ) in group C. ( 2 ) BMD : BMD was improved significantly in women in 3 groups after treatment . BMD of L₁₋₄ were ( 0.88 ± 0.15 ) g/cm² in group A , ( 0.89 ± 0.18 ) g/cm² in group B and ( 0.87 ± 0.10 ) g/cm² in group C before treatment , and converted to ( 0.90 ± 0.01 ) g/cm² in group A , ( 0.93 ± 0.09 ) g/cm² in group B and ( 0.91 ± 0.11 ) g/cm² in group C after treatment . BMD of left femur were ( 0.87 ± 0.07 ) g/cm² in group A , ( 0.87 ± 0.07 ) g/cm² in group B and ( 0.85 ± 0.12 ) g/cm² in group C before treatment and converted to ( 0.90 ± 0.03 ) g/cm² in group A , ( 0.91 ± 0.08 ) g/cm² in group B and ( 0.89 ± 0.12 ) g/cm² in group C after treatment . It was shown significantly different BMD between group B or C and group A ( P < 0.01 ) , however , there was no significant different BMD between group B and C ( P > 0.05 ) . ( 3 ) Index of bone metabolism : BALP were ( 26 ± 6 ) µg/L in group A , ( 26 ± 9 ) µg/L in group B and ( 28 ± 7 ) µg/L in group C before treatment and converted to ( 22 ± 5 ) µg/L in group A , ( 20 ± 9 ) µg/L in group B and ( 22 ± 8) µg/L in group C after treatment , which showed statistical difference ( P < 0.05 ) . CTX were ( 0.85 ± 0.20 ) ng/L in group A , ( 0.84 ± 0.47 ) ng/L in group B , and ( 0.88 ± 0.11 ) ng/L in group C before treatment and converted to ( 0.81 ± 0.19 ) ng/L in group A , ( 0.77 ± 0.33 ) ng/L in group B , and ( 0.82 ± 0.14 ) ng/L in group C after treatment , which showed statistical difference ( P < 0.05 ) . CONCLUSIONS Those 3 regimens combination could be used in treatment of osteoporosis by decreasing bone conversion , increasing bone density , decreasing bone absorption . Regimen A was only suitable for basic therapy , the other two regimens could provide better treatment Abstract Rationale : Estrogen concentrations decline with age and menopause is often followed by an acceleration of the age effects on cognition . It is suggested that replacement of estrogen would reinstate , at least in part , cognitive abilities . Effects of estrogens on memory have been reported in studies with women in a clinical setting who either needed or wished to have the estrogen replacement  and are mostly in the perimenopausal age-b and . Objective : The present study investigated the effects of estradiol on memory and on frontal lobe function in elderly female subjects who did not suffer any of the postmenopausal symptoms and had never taken estrogen hormone replacement ( EHR ) previously . Methods : EHR ( Progynova TS , transdermal estradiol ; n=19 ) or placebo ( n=18 ) was given for a period of 3 weeks to elderly healthy female subjects .  Memory , frontal lobe functions ( inhibition and planning ) and visuospatial abilities ( mental rotation ) were tested before and after treatment . Estrogen plasma levels were measured to confirm the result of EHR .  Cortisol plasma levels were also measured before and after cognitive performance in order to evaluate the effects of EHR on the sensitivity of the hypothalamo- pituitary-adrenal ( HPA ) axis to mild mental stress . Results : Plasma estradiol levels in the drug group increased to levels equivalent to that of a fertile woman ( 0.21± 0.5 nmol/l ) . Memory function as well as visuospatial abilities as measured by a mental rotation task improved significantly with EHR . However , there was no effect of EHR on frontal lobe functions . The cognitive effects were not dependent on an improvement in mood or general well-being as may be the case with EHR in women at peri- or post-menopausal stage  . EHR was found to increase the HPA response to task-induced stress , as indicated by an increase in cortisol plasma levels . Conclusions : The present study has provided evidence of a beneficial effect of EHR on cognitive abilities given for first time to healthy elderly women . Furthermore , the present study has demonstrated a differential effect of EHR  on memory , visuospatial abilities and frontal lobe function Objective : To demonstrate the safety and efficacy of tibolone ( 1.25 and 2.5 mg ) in the treatment of moderate to severe vasomotor symptoms and symptoms associated with vaginal atrophy . Design : A placebo-controlled , double-blind , r and omized , multicenter study was conducted on 396 healthy postmenopausal women experiencing a minimum of 7 moderate to severe hot flashes per day ( 60 per week ) . Participants were r and omized to receive tibolone 1.25 or 2.5 mg or placebo once daily for 12 weeks . Assessment s were done at weeks 4 , 8 , and 12 . The severity and frequency of hot flashes were recorded in patient diaries on a daily basis . Results : Tibolone 2.5 mg significantly ( P < 0.001 ) reduced the average number of hot flashes compared with placebo at week 4 ( −7.82 vs −5.27 ) , week 8 ( −9.71 vs −5.86 ) , and week 12 ( −10.14 vs −5.85 ) . The difference between tibolone 1.25 mg and placebo was significant ( P < 0.001 ) at week 8 ( −7.96 ) and week 12 ( −8.32 ) . Findings for the average daily severity of hot flashes were similar , with significantly greater reductions at week 4 ( P < 0.05 ) and weeks 8 and 12 ( P < 0.001 ) for tibolone 2.5 mg versus placebo and at weeks 8 and 12 for tibolone 1.25 mg versus placebo ( P < 0.001 ) . A menopausal atrophic symptom question naire revealed that tibolone 2.5 mg significantly ( P < 0.05 ) reduced nocturia compared with placebo at weeks 4 , 8 , and 12 and urinary urgency at week 4 . Compared with placebo , both doses of tibolone also significantly ( P < 0.001 ) increased the vaginal maturation value from baseline . The overall incidence of adverse events was similar in all treatment groups . Conclusions : Tibolone is effective and well tolerated for the treatment of moderate to severe vasomotor symptoms and the effects of vaginal atrophy associated with menopause OBJECTIVES Determination of the efficacy and safety of vaginally administered low dose ( 25 microg ) micronized 17beta-estradiol in the management of patients with urogenital symptoms . METHODS A total of 1612 patients with urogenital complaints were r and omized to receive 25 microg of micronized 17beta-estradiol ( n=828 ) or placebo ( n=784 ) in a multicenter double-blind placebo-controlled study running for 12 months . Female patients were treated once a day over a period of 2 weeks , and then twice a week for the remaining of the 12 months with an active or placebo tablet . The assessment included full history- question naire , micturition diary , gynecologic and cystometric examination , transvaginal ultrasound , and serum 17beta-estradiol level determination . It was carried out at the beginning , and after 4 and 12 months of treatment . RESULTS The overall success rate of micronized 17beta-estradiol and placebo on subjective and objective symptoms of postmenopausal women with vaginal atrophy was 85.5 % , and 41.4 % , respectively . A significant improvement of urinary atrophy symptoms was determined in vaginal ERT group as compared with the beginning of the study ( 51.9 % vs. 15.5 % , P=0.001 ) . The maximal cystometric capacity ( 290 ml vs. 200 ml , P=0.023 ) , the volume of the urinary bladder at which patients first felt urgency ( 180 vs. 140 , P=0.048 ) , and strong desire to void ( 170 ml vs. 130 ml , P=0.045 ) were significantly increased subsequent to the micronized 17beta-estradiol treatment . The number of patients with uninhibited bladder contractions significantly decreased following micronized 17beta-estradiol as compared with pretreatment values ( 17/30 , P=0.013 ) . Side effects were observed in 61 ( 7.8 % ) patients treated with low dose micronized 17beta-estradiol . Therapy with 25 microg of micronized 17beta-estradiol did not raise serum estrogen level nor stimulated endometrial growth . CONCLUSIONS Local administration of 25 microg of micronized 17beta-estradiol is an effective and a safe treatment option in the management of women with urogenital complaints OBJECTIVES At present the Women 's Health Initiative trial is the only reported r and omised controlled trial study ing the effects of hormone therapy among healthy postmenopausal women . The Women 's Health Initiative reports have been criticized for lacking in generalisability , due to the characteristics of the trial population . We aim ed to compare the health effects of oral continuous combined hormone therapy with a placebo and non-treatment among healthy Estonian women . METHODS Eligible women were r and omised into a blind group of hormone therapy versus placebo and into a non-blind group of open label hormone therapy versus non-treatment .  One thous and seven hundred and seventy-eight postmenopausal women aged 50 - 64 at the time of sampling were recruited in 1999 - 2001 at three clinical centers in Estonia . Participants received conjugated equine oestrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5mg/d , or conjugated equine oestrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 5mg/d , if less than 3 years had passed since menopause at recruitment , or matched placebo or non-treatment . Trial treatment was stopped gradually from 1 January 2004 to 31 May 2004 . RESULTS After a follow-up period from 2.0 to 5.0 years the combined hazard ratio , stratified by blinding and adjusted for age at recruitment and former oral contraceptive use was 1.12 ( 95 % confidence interval [ CI ] : 0.90 - 1.40 ) for coronary heart disease , 1.24 ( 95 % CI : 0.85 - 1.82 ) for cerebrovascular disease , 1.36 ( 95 % CI : 0.73 - 2.52 ) for total cancer , and 0.61 ( 95 % CI : 0.42 to 0.89 ) for bone fractures . CONCLUSIONS The results from the Estonian Postmenopausal Hormone Therapy r and omised trial are consistent with the Women 's Health Initiative findings To test the postulate that sex difference , sex steroids , and peptidyl secretagogues control GH autofeedback , 11 healthy postmenopausal women and 14 older men were each given 1 ) a single iv pulse of GH to enforce negative feedback and 2 ) continuous iv infusion of saline vs. combined GHRH/GHRP-2 to drive feedback escape during pharmacological estradiol ( E(2 ) ; women ) or testosterone ( T ; men ) supplementation vs. placebo in a double-blind , prospect ively r and omized crossover design . By three-way ANCOVA , sex difference , sex hormone treatment , peptide stimulation , and placebo/saline responses ( covariate ) controlled total ( integrated ) GH recovery during feedback ( each P < 0.001 ) . Both sex steroid milieu ( P = 0.019 ) and dual-peptide stimulation ( P < 0.001 ) determined nadir ( maximally feedback-suppressed ) GH concentrations . E(2)/T exposure elevated nadir GH concentrations during saline infusion ( P = 0.003 ) , whereas dual-peptide infusion did so independently of T/E(2 ) and sex difference ( P = 0.001 ) . All three of sex difference ( P = 0.001 ) , sex steroid treatment ( P = 0.005 ) , and double-peptide stimulation ( P < 0.001 ) augmented recovery of peak ( maximally feedback-escaped ) GH concentrations . Peak GH responses to  dual-peptidyl agonists were greater in women than in men ( P = 0.016 ) . E(2)/T augmented peak GH recovery during saline infusion ( P < 0.001 ) . Approximate entropy analysis corroborated independent effects of sex steroid treatment ( P = 0.012 ) and peptide infusion ( P < 0.001 ) on GH regularity . In summary , sex difference , sex steroid supplementation , and combined peptide drive influence nadir , peak , and entropic measurements of GH release under controlled negative feedback . To the degree that the pharmacological sex steroid , GH , and dual-peptide clamps provide prephysiological regulatory insights , these outcomes suggest major determinants of pulsatile GH secretion in the feedback domain Method Twenty-three patients with acroparesthesia were su bmi tted to clinical evaluation and color Doppler analysis of the uterine artery and palmaris superficial branch of the radial artery . Thirteen women ( Group I ) were su bmi tted to hormone treatment with drospirenone 2 mg + + estradiol emidrate 1 mg .  Ten patients refused the treatment and served as controls ( Group II ) . The patients were studied at baseline and after 6 months ' therapy . Results After 6 months of hormone therapy , the resistances of the uterine artery and palmaris superficial branch of the radial artery significantly decreased in Group I patients . This was associated with the complete disappearance of paresthesic symptoms in 12/13 ( 92%% ) of the treated patients . In patients belonging to Group II , the paresthesia remained unchanged . Conclusion Hormone therapy with drospirenone may increase the forearm/h and blood flow , and favor the amelioration of paresthesia Objective To assess the effects of raloxifene , estrogen , and placebo on quality of life in healthy , asymptomatic , postmenopausal women . Methods In a multicenter , double-blind , 12-month study , 398 women were assigned r and omly to one of four groups : raloxifene HCl , 60 ( n = 97 ) or 150 mg/day ( n = 100 ) ; conjugated equine estrogens , 0.625 mg/day ( n = 96 ) ; or placebo ( n = 105 ) . The Women 's Health Question naire , a vali date d quality -of-life instrument for perimenopausal and postmenopausal women , was administered at baseline and 3-month intervals . Results Overall , quality of life from baseline to end point was preserved equally in all treatment groups . Six domains ( depressed mood , somatic symptoms , memory/ concentration , sexual behavior , sleep problems , and perceived attractiveness ) were unchanged in all groups . Three domains ( menstrual symptoms , vasomotor symptoms , and anxiety/fears ) were statistically significantly different among groups . Mean scores for menstrual symptoms significantly worsened and vasomotor symptoms significantly improved from baseline to end point in the estrogen group . Mean scores for vasomotor symptoms did not worsen at any point in the raloxifene 60 mg/day group . Mean anxiety/fears scores improved significantly during raloxifene 60 mg/day administration throughout treatment ( P < .05 ) , irrespective of previous hormone replacement therapy , baseline estradiol ( E2 ) levels , or years postmenopause . Conclusion Most quality -of-life domains were not affected by treatment with estrogen or raloxifene . Estrogen provided relief from vasomotor symptoms but caused menstrual symptoms . Raloxifene 60 mg/day improved anxiety levels in postmenopausal women Aim : This multicenter , open-label , single-arm study evaluated subject satisfaction and improvements in menopausal quality of life among menopausal women using the CombiPatch ® transdermal system consisting of 17β-estradiol 0.05 mg plus norethindrone acetate 0.14 mg in a matrix patch formulation . Methods : The 193 postmenopausal women between the ages of 45 and 65 years who comprised the modified intent-to-treat population ( at least one patch and one efficacy assessment ) were required to have reported at least five daily moderate-to-severe hot flashes and episodes of nocturnal sweating upon study entry for at least 1 month and applied one patch twice a week for 12 weeks . At weeks 0 , 6 , and 12 , the women completed the Menopause-Specific Quality of Life ( MENQOL ) Question naire and , as a secondary study outcome , reported the scale of their application site discomfort . During weeks 1–12 , they also kept diary records of number and severity of hot flashes and four other menopausal symptoms . Skin tolerance and adherence of the transdermal system were evaluated at weeks 6 and 12 by qualified evaluators . At week 6 and the end of the study , both subjects and physicians rated their satisfaction with the system . Results : Among women in the modified intent-to-treat population , transdermal 17β-estradiol plus norethindrone acetate significantly reduced the mean daily number of moderate-to-severe hot flashes experienced by women from 4.1 at week 1 to 0.6 at week 12 ( p < 0.0001 ) . The mean ratings of headache severity , insomnia , and vaginal irritation/dryness also improved significantly by week 6 and were maintained at week 12 . At week 12 , 92.4 % of the subjects and 97.3 % of the physicians reported that they were ‘ satisfied ’ or ‘ very satisfied ’ with the transdermal hormone delivery system . Conclusions : The results of this study compare favorably with previous placebo-controlled studies of transdermal hormone therapy in managing menopausal signs and symptoms . Furthermore , quality of life was significantly improved by the transdermal hormone therapy system , and both subjects and physicians reported high levels of satisfaction BACKGROUND The Women 's Health Initiative ( WHI ) clinical trial of conjugated equine estrogens ( CEEs ) , involving 10,739 postmenopausal women with hysterectomy , aged 50 to 79 years , was stopped early owing to lack of overall health benefit and increased risk of stroke . Because CEE is still prescribed for treatment of menopausal symptoms and prevention of osteoporosis , it is important to underst and the overall impact of this therapy on health-related quality of life ( HRQOL ) . METHODS All participants completed 6 specific measures of quality of life at baseline and 1 year , and a sub sample ( n = 1189 ) also completed the questions 3 years after r and omization . Changes in scores were analyzed for treatment effect . RESULTS R and omization to CEE was associated with a statistically significant but small reduction in sleep disturbance at year 1 compared with baseline ( mean benefit , 0.4 points on a 20-point scale ) and a statistically significant but small negative effect on social functioning ( mean effect , -1.3 points on a 100-point scale ) . There were no significant improvements due to CEE in the areas of general health , physical functioning , pain , vitality , role functioning , mental health , depressive symptoms , cognitive function , or sexual satisfaction at year 1 . A subgroup examined 3 years after baseline had no significant benefits for any HRQOL outcomes . Among women aged 50 to 54 years with moderate to severe vasomotor symptoms at baseline , CEE did not improve any of the HRQOL variables at year 1 . CONCLUSION In this trial of postmenopausal women with prior hysterectomy , oral CEE did not have a clinical ly meaningful effect on HRQOL Summary In this 2-year extension of a 3-year study , bazedoxifene showed sustained efficacy in preventing new vertebral fractures in postmenopausal women with osteoporosis and in preventing non-vertebral fractures in higher-risk women .  Bazedoxifene significantly increased bone mineral density and reduced bone turnover versus placebo and was generally safe and well tolerated . Introduction This study evaluated the efficacy and safety of bazedoxifene for the treatment of postmenopausal osteoporosis over 5 years . Methods A total of 4,216 postmenopausal women with osteoporosis were enrolled in this 2-year extension of a 3-year , r and omized , double-blind , placebo-controlled , phase 3 trial . In the core study ( N = 7,492 ) , subjects received bazedoxifene 20 or 40 mg/day , raloxifene 60 mg/day , or placebo . The raloxifene arm was discontinued after 3 years ; subjects receiving bazedoxifene 40 mg were transitioned to bazedoxifene 20 mg after 4 years . Five-year findings are reported for bazedoxifene 20 and 40/20 mg and placebo . Endpoints included incidence of new vertebral fractures ( primary ) and non-vertebral fractures , and changes in bone mineral density ( BMD ) and bone turnover markers . Results At 5 years , the incidence of new vertebral fractures in the intent-to-treat population was significantly lower with bazedoxifene 20 mg ( 4.5 % ) and 40/20 mg ( 3.9 % ) versus placebo ( 6.8 % ; P < 0.05 ) , with relative risk reductions of 35 % and 40 % , respectively . Non-vertebral fracture incidence was similar among groups . In a subgroup of higher-risk women ( n = 1,324 ; femoral neck T-score ≤−3.0 and /or ≥1 moderate or severe or ≥2 mild vertebral fracture[s ] ) , bazedoxifene 20 mg reduced non-vertebral fracture risk versus placebo ( 37 % ; P = 0.06 ) ; combined data for bazedoxifene 20 and 40/20 mg reached statistical significance ( 34 % reduction ; P < 0.05 ) . Bazedoxifene significantly increased BMD and reduced bone turnover versus placebo ( P < 0.05 ) and was generally safe and well tolerated . Conclusions The findings support a sustained anti-fracture effect of bazedoxifene on new vertebral fractures in postmenopausal osteoporotic women and on non-vertebral fractures in the higher-risk subgroup of women OBJECTIVE To evaluate the effects of combination estrogen/ and rogen therapy on muscle mass , strength and endurance , serum hormone and lipid profiles , and quality of life measures in postmenopausal women . METHODS Prospect i ve , r and omized , placebo-controlled pilot study at a tertiary care medical center . Fifty postmenopausal women were r and omized to a 12-week course of ( 1 ) dehydroepi and rostenedione ( DHEA ) 50 mg daily , ( 2 ) conjugated equine estrogen ( CEE ) 0.625 mg daily , ( 3 ) DHEA 50 mg+CEE 0.625 mg daily , or ( 4 ) placebo . Main outcome measures of lower extremity muscle ( calf ) mass , functional muscle parameters , serum hormone and lipid levels , and quality of life ( QOL ) were obtained at baseline and after treatment . Statistical analysis compared percent change from baseline values and treatment differences among outcomes . RESULTS Significant increases in mean DHEA , DHEA sulfate ( DHEA-S ) , testosterone , and and rostenedione levels were noted with DHEA alone or combined DHEA/CEE treatments when compared with placebo . Compared with no hormone therapy , none of the supplemental hormone groups caused significant changes in muscle mass , muscle strength , muscle endurance , feelings of well-being , sleep , or sexual function . CONCLUSIONS And rogen replacement therapy , with DHEA , to menopausal women increases serum and rogen levels without any appreciable effect on muscle cross-sectional area , muscle strength , muscle function , or improvement in health-related QOL OBJECTIVE To determine the effects of 9 months of hormone replacement therapy ( HRT ) on cognitive performance in women aged 75 years and older . METHODS A 9-month r and omized , double-blinded , placebo-controlled parallel trial . Fifty-two elderly postmenopausal women ( age range 75 - 91 years ) without known contraindications to HRT or evidence of dementia or depression were enrolled . Participants were r and omly assigned in a 1:2 ratio to placebo or conjugated estrogens at 0.625 mg/d plus trimonthly medroxyprogesterone acetate at 5 mg/d for 13 days ( HRT ) . Main outcome measures were change from baseline and rate of change from baseline for the following psychometric tests : Verbal Fluency Test , Weschler Paired Associate Learning and 20 min Delayed Recall , Trailmaking A and B Tests , Cancellation R and om Letter and R and om Form Tests . RESULTS At baseline , women in the HRT group reported a younger age of onset of menopause and a higher prevalence of hysterectomy , but otherwise did not differ from women in the placebo group . After 9 months of treatment , there were no significant group differences for any of the cognitive performance measures . The lack of an observed group-by-time difference for all cognitive tests remained after controlling for age of onset of menopause , education , and previous hysterectomy . CONCLUSIONS Although conclusions are limited by small sample size and the relatively short duration of treatment , results suggest that 9 months of estrogen replacement in combination with trimonthly progestin does not improve cognitive performance in women over 75 years who do not have dementia or depression OBJECTIVE Menopause is linked to an increase in fat mass and a decrease in lean mass exceeding age-related changes , possibly related to reduced output of ovarian steroids . In this study we examined the effect of combined postmenopausal hormone replacement therapy ( HRT ) on the total and regional distribution of fat and lean body mass . RESEARCH METHODS AND PROCEDURES Sixteen healthy postmenopausal women ( age : 55 + /- 3 years ) were studied in a placebo-controlled , crossover study and were r and omized to 17beta estradiol plus cyclic norethisterone acetate ( HRT ) or placebo in two 12-week periods separated by a 3-month washout . Total and regional body composition was measured by DXA at baseline and in the 10th treatment week in both periods . Changes were compared by a paired Student 's t test . RESULTS The change in body weight during HRT was equal to the change during placebo ( -24.6 g vs. -164 g , p = 0.42 ) , but relative fat mass was significantly reduced ( -0.5 % vs. + 1.24 % , p < 0.01 ) . During HRT , compared with during placebo , lean body mass increased ( + 347 g vs. -996 g , p < 0.01 ) and total fat mass decreased ( -400 g vs. + 836 g , p = 0.06 ) . Total bone mineral content increased ( + 28.9 g vs. -4.4 g , p = 0.04 ) and abdominal fat decreased ( -185 g vs. + 253 g , p = 0.04 ) during HRT compared with placebo . DISCUSSION HRT is linked to the reversal of both menopause-related obesity and loss of lean mass , without overall change in body weight . The increase in lean body mass during HRT is likely explained by muscle anabolism , which in turn , prevents disease in the elderly OBJECTIVE Two prospect i ve multicenter , double-blind , r and omized , controlled trials were conducted to examine the safety and efficacy of three once-a-week continuous combined 17beta-estradiol/levonorgestrel ( E2/LNG ) transdermal systems ( E2 0.045 mg/day with 0.015 , 0.030 , and 0.040 mg/day LNG ) for the treatment of vasomotor symptoms and prevention of estrogen-induced endometrial hyperplasia in healthy , postmenopausal women . DESIGN In study 1 , performed in 293 hysterectomized and nonhysterectomized women with moderate to severe hot flushes , transdermal E2/LNG ( E2 0.045 mg/day with 0.030 and 0.040 mg/day LNG ) was compared with placebo for three 28-day treatment cycles . The frequency and severity of hot flushes were recorded daily . In study 2 , performed in 845 women with intact uteri ,  transdermal E2/LNG  ( E2 0.045 mg/day with 0.015 , 0.030 , and 0.040 mg/day LNG ) was compared with transdermal E2 0.045 mg/day monotherapy for thirteen 28-day treatment cycles . Women with endometrial tissue sufficient for evaluation underwent endometrial biopsy assessment at the end of cycle 13 . Bleeding patterns were assessed throughout the study , and the Women 's Health Question naire was used to assess well-being . RESULTS In study 1 , transdermal E2/LNG ( E2 0.045 mg/day with 0.030 and 0.040 mg/day LNG ) significantly decreased the number and severity of hot flushes when compared with placebo .  Symptom relief was seen as early as 2 weeks posttreatment . Similarly , in study 2 , all three doses of transdermal E2/LNG and E2 controlled hot flushes with no differences between groups . In study 2 , no women receiving transdermal E2/LNG developed endometrial hyperplasia compared with 19 ( 12.8 % ) who received transdermal E2 0.045 mg/day ( p < 0.001 for each dose ) . Significant improvements from baseline in scores on the Women 's Health Question naire for vasomotor symptoms , sleep problems , sexual function , cognitive difficulties , and total score were noted at all or most time points with both transdermal E2/LNG and E2 .  Application-site reactions , vaginal hemorrhage , and breast pain were the most common adverse events reported with transdermal E2/LNG . The proportion of women with amenorrhea increased over time in all treatment groups in study 2 . CONCLUSIONS All three doses of this once-a-week combined E2/LNG transdermal system rapidly and effectively control vasomotor symptoms in postmenopausal women while protecting against endometrial hyperplasia . Amelioration of vasomotor symptoms also is accompanied by improvements in aspects of subjective well-being . Once-a-week transdermal E2/LNG , therefore , offers an effective and convenient formulation , the dosing of which can be individualized according to the needs of each patient OBJECTIVE The aim of the study was to confirm the superior efficacy of estriol containing pessaries compared to placebo in the treatment of vaginal atrophy . STUDY DESIGN In a prospect i ve , multicenter , r and omized , placebo-controlled , double-blind study , 436 postmenopausal women with vaginal atrophy ( vaginal maturation index , VMI<40 % ; vaginal pH>5 ; most bothersome symptom , MBS≥65 on visual analogue scale , VAS ) were treated with pessaries containing either 0.2 mg estriol ( N=142 ) or 0.03 mg estriol ( N=147 ) or with a matching placebo ( N=147 ) for 12 weeks . MAIN OUTCOME MEASURES Primary efficacy endpoints included increase in VMI , decrease of the vaginal pH value and decrease in intensity of MBS after 12 weeks of treatment . RESULTS The increase in VMI was significantly greater under 0.2 mg estriol and 0.03 mg estriol ( 46.3±17.0 and 38.4±19.4 , respectively ) compared to placebo ( 23.9±21.5 ; p values<0.001 ) , vaginal pH decreased significantly more ( -1.6±0.8 and -1.4±0.9 , respectively ) compared to placebo ( -0.6±0.8 ; p values<0.001 ) and MBS intensity ( VAS ) declined significantly more ( -52.2±23.7 and -47.1±23.4 , respectively ) compared to placebo ( -31.8±26.3 ; p values<0.001 ) . Adverse events were rare and occurred at similar rates in all three groups . CONCLUSIONS Superiority of estriol containing pessaries over placebo was shown in the local treatment of vaginal atrophy . Even a very low dose of 0.03 mg estriol proved sufficient for local treatment of vaginal atrophy with excellent tolerability The aim of the study was to investigate the effect of 25 micrograms 17 beta-estradiol administered as a small vaginal tablet ( Vagifem , Novo Nordisk A/S ) on the symptoms of the vagina related to atrophy . The study was design ed as a double-blind r and omized placebo controlled study running for 12 weeks . The women were treated once daily for 2 weeks with the active or the placebo tablet . During the subsequent 10 weeks the women were treated twice a week . One hundred and sixty-four women were included . Ten dropped out for minor reasons , most of these due to lack of effect in the placebo group . In the Vagifem group 78.8 % were suffering from moderate to severe atrophy of the vagina , compared with 81.9 % in the placebo group . After 2 weeks the percentages were 14.3 and 35.3 , respectively . After 12 weeks of treatment , 10.7 % in the Vagifem group compared with 29.9 % in the placebo group had moderate to severe atrophy ( P less than 0.0001 ) . A substantial part of the women complained about subjective symptoms such as vaginal dryness and dyspareunia . After 12 weeks of treatment , a significant improvement was found in the Vagifem group ( P less than 0.002 ) . Before treatment 53.1 % in the treatment group and 41.0 % in the placebo group were suffering from urological symptoms . After 2 weeks , 60.5 % of the women in the Vagifem group underwent a change for the better compared to 35.3 % in the placebo group . After 12 weeks of treatment the percentages in the two groups feeling an improvement were 62.8 % and 32.4 % . In this study local low-dose treatment with 25 micrograms 17 beta-estradiol was found to have a significant effect on the  postmenopausal urogenital symptoms related to atrophy BACKGROUND In perimenopause many women complain of psychogenic and organic disorders often connected with initial and increasing levels of hypoestrogenism . In this study we evaluated the effects of hormone replacement therapy ( HRT ) in symptomatic women in perimenopause . METHODS We enrolled 100 healthy and symptomatic women who were r and omly distributed to two groups for a 12-month study . Group A : 50 patients received HRT with estradiol valerate and cyproterone acetate ( Pausene(R ) ) ; Group B : 50 patients were used as a control group ( treated with Cacit Vitamin D30(R ) ) . A number of clinical and instrumental tests were performed at 0 , 6 and 12 months to evaluate any changes in vasomotor and urogenital symptoms , bone and serum homeostasis and possible sexual disorders . The statistical analysis was performed using the c2 test . RESULTS The group of women receiving HRT showed a significant reduction in vasomotor clinical symptoms ( p<0.001 ) and sexual disorders ( p<0.002 ) ; this was not reflected in the control group where libido decreased steadily with apparent slight improvements only at the end of the study . The urogenital disorders disappeared almost completely in Group A , whereas they diminished in Group B. HRT patients also showed a slight increase ( p<0.001 ) in the initial value of BMD ( bone mineral density ) , a reduction in the marker for bone turnover and an improved lipid profile ( p<0.05 ) . These changes were unfortunately not noted in Group B. CONCLUSIONS On the basis of these results we conclude that HRT appeared to have a beneficial effect on perimenopausal clinical symptoms over the 12-month period , leading to marked improvements in the psychophysical wellbeing of symptomatic women in perimenopause OBJECTIVE : To investigate safety and efficacy and identify the lowest effective dose of a new transdermal estradiol ( E2 ) gel for relief of menopausal symptoms in a population of postmenopausal women . METHODS : This study was a r and omized , double-blind , placebo-controlled , multicenter , parallel-group study . Postmenopausal women with at least 60 hot flushes per week applied 0.87 g/d ( n=136 ) , 1.7 g/d ( n=142 ) , or 2.6 g/d ( n=69 ) E2 gel or placebo gel ( n=137 ) topically for 12 weeks . The changes from baseline in hot flush frequency and severity at 4 and 12 weeks and changes from baseline in vaginal atrophy symptoms at 12 weeks were examined . RESULTS : With increasing E2 doses , mean trough serum E2 increased from 17 to 29 pg/mL. By weeks 3–5 , E2 gel reduced moderate-to-severe hot flush rate by at least seven hot flushes per day ( P<.001 ) and reduced the severity score ( P<.01 ) . The numbers needed to treat for benefit for an 80 % and 100 % decrease in hot flush number were 3.2 and 6.3 for the 0.87-g/d group and 1.3 and 2.3 for the 2.6-g/d group . At week 12 , vaginal pH was more acidic and vaginal maturation index more mature compared with placebo ( P<.001 ) . The lowest dose improved most bothersome vulvovaginal atrophy symptoms ( P<.05 ) . Estradiol gel was well tolerated at the site of application and produced no unexpected adverse effects . The 0.87 g/d dose produced fewest adverse events . CONCLUSION : The 0.87 g/d dose of this new transdermal E2 gel , which delivers an estimated 0.0125 mg E2 daily , delivered the lowest effective dose for treatment of vasomotor symptoms and vulvovaginal atrophy in a population of postmenopausal women . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00391417 LEVEL OF EVIDENCE : OBJECTIVE To assess the effect of raloxifene compared with placebo on sexual function in older postmenopausal women undergoing therapy for the treatment of osteoporosis . METHODS A subset ( 12 % ) of English-speaking women in the United States and Canada participating in the Multiple Outcomes of Raloxifene Evaluation Trial were asked to complete a sexual function question naire at baseline and after 36 months of treatment . The Multiple Outcomes of Raloxifene Evaluation Trial is a multicenter , r and omized , blinded , placebo-controlled clinical trial , in which 7705 postmenopausal women with osteoporosis were r and omly assigned to one of three groups : raloxifene hydrochloride 60 mg per day or 120 mg per day or placebo . In this sub study , 943 women completed the sexual function question naire at both visits . Because preliminary analyses showed no differences by raloxifene dose ( n = 302 for 60 mg per day ; n = 322 for 120 mg/day ) , the two groups were combined and compared with the placebo group ( n = 319 ) . For the given sample size , we had 80 % power ( & agr ; = .05 , two-sided , ratio of raloxifene to placebo = 2:1 ) to detect a 10%–16 % difference in the proportion of women experiencing no change in sexual function between placebo and treatment groups . RESULTS Overall , sexual function and changes in sexual function from baseline to study end between the raloxifene and placebo groups did not differ . In particular , there were no differences in sexual desire or frequency of sexual activity between the groups . Among sexually active women , there were no differences in enjoyment , satisfaction , orgasm , or reported sexual problems . CONCLUSION Sexual function in older postmenopausal women with osteoporosis is not affected by treatment with raloxifene Objective : To determine the effects of lower doses of conjugated estrogens ( CE ) alone or in combination with medroxyprogesterone acetate ( MPA ) on body weight and to evaluate the influence of body mass index ( BMI ) on the effect of lower-dose CE or CE/MPA on vasomotor symptoms , vaginal atrophy , bone mineral density ( BMD ) , endometrial safety , and side effects such as endometrial bleeding and breast pain . Design : In this large clinical trial [ the Women 's Health , Osteoporosis , Progestin , Estrogen ( Women 's HOPE ) study ] , 2,673 healthy , postmenopausal women with intact uteri were r and omized for 1 year of CE 0.625 , CE 0.625/MPA 2.5 , CE 0.45 , CE 0.45/MPA 2.5 , CE 0.45/MPA 1.5 , CE 0.3 , CE 0.3/MPA 1.5 ( all doses mg/d ) , or placebo .  Weight , BMI , number and severity of hot flushes , vaginal atrophy ( as determined by the vaginal maturation index ) , bleeding profiles , breast pain , and endometrial biopsies were evaluated . A subset of 822 women was r and omized into a 2-year sub study to evaluate changes in BMD with lower-dose CE or CE/MPA regimens . Results : After 1 year of treatment , a small but significant ( P < 0.05 ) gain in body weight from baseline was observed in all arms of the study , the largest increase in body weight occurring in the placebo group [ 1.15 ± 0.21 ( SE ) kg ] . Body mass index had no significant effect on changes from baseline for vasomotor symptoms , bleeding patterns , vaginal atrophy , BMD , endometrial safety , or breast pain when analyzed both by analysis of covariance with baseline BMI as covariate or when participants were grouped into BMI less than 25 kg/m2 and BMI of 25 kg/m2 or greater . In placebo-treated women , vaginal atrophy was significantly greater ( P < 0.05 ) in women with a BMI less than 25 kg/m2 compared with a BMI of 25 kg/m2 or greater . Conclusions : Lower- and st and ard-dose regimens of CE or CE/MPA are not associated with greater weight gain  than placebo . In addition , BMI does not seem to influence effects of these regimens on vasomotor symptoms , vaginal atrophy , bleeding profiles , BMD , endometrial safety , or breast pain Aims : To compare the effects of 3 months ' tibolone treatment with the effects of placebo on sexual function ( in particular , vaginal blood flow , and sexual desire and arousability ) and climacteric symptoms in postmenopausal women . Methods : A r and omized , double-blind , cross-over study was conducted in 38 postmenopausal women who received tibolone 2.5 mg/day and placebo .  Vaginal blood flow during erotic stimulation by fantasy and film was measured using a vaginal photoplethysmograph and subjects completed sexual function question naires and daily diaries . Results : Tibolone significantly increased baseline vaginal pulse amplitude ( VPA ) levels compared with placebo . There were significant treatment differences in VPA in favor of tibolone during fantasy periods but not during erotic film stimulation . Tibolone was associated with significant increases in sexual desire , and the frequency of arousability and of sexual fantasies compared with those with placebo .  Vaginal lubrication was significantly improved on tibolone . Twenty-five of 38 ( 66 % ) subjects correctly guessed when they were on active treatment . Tibolone was well tolerated . Conclusions : Tibolone was associated with significant improvements in sexual function  in postmenopausal women , reflecting both its estrogenic and and rogenic properties . There were significantly greater increases in vaginal blood flow with tibolone in response to erotic fantasy but not film , suggesting two possible pathways of female sexual response Objective The aim of this study was to determine the efficacy , safety , and lowest practical dose of a transdermal estradiol gel in the treatment of symptomatic postmenopausal women . Methods Healthy postmenopausal women with seven or more moderate to severe hot flushes per day or 50 to 60 or more per week were r and omized to transdermal gel containing 1.5 mg ( n = 73 ) or 0.75 mg ( n = 75 ) estradiol ( EstroGel 0.06 % ) or placebo ( n = 73 ) in a phase 3 study , or to 0.375 mg ( n = 119 ) or 0.27 mg ( n = 118 ) estradiol ( 0.03 % gel ) or placebo ( n = 114 ) in a phase 4 study . Results The frequency of moderate to severe hot flushes and severity of all hot flushes significantly decreased versus placebo at weeks 4 and 12 with 1.5 , 0.75 , and 0.375 mg estradiol . Overall participant responder rates were generally lower in the phase 4 study than those in the phase 3 study with the approved 0.75-mg estradiol dose . Vaginal maturation index ( VMI ) shifts from baseline to week 12 were significant ( P < 0.001 ) with 0.75 and 1.5 mg estradiol versus placebo ;  VMI improved ( P < 0.001 ) , superficial cells increased ( P = 0.005 ) , and parabasal cells decreased ( P = 0.002 ) with 0.375 mg estradiol vs placebo but not with 0.27 mg estradiol . The most frequently reported treatment-emergent adverse events , although not necessarily treatment related , were headache , infection , breast pain , and nausea ( phase 3 study ) and insomnia and headache ( phase 4 study ) . No serious adverse events were related to treatment ; no deaths occurred . Conclusion A transdermal gel with 0.75 mg estradiol was the lowest practical dose that effectively reduced the frequency and severity of moderate to severe hot flushes , improved VMI , and was well tolerated ABSTRACT Objectives To determine the efficacy and safety of low-dose maintenance therapy with transdermal estradiol ( E2 ) gel in Japanese women with climacteric disorder and estrogen deficiency symptoms . Methods Women ( n = 209 ) aged 37–59 years who had climacteric disorder or estrogen deficiency symptoms received a st and ard dose of transdermal E2 gel ( 1.8 g/day , containing E2 1.08 mg/day ) for 8 weeks as induction treatment . A total of 177 women in whom the number of daily hot flushes had decreased to less than one-third of the baseline value ( marked improvement ) at week 8 were double-blindly r and omized to receive low-dose E2 ( n = 88 , 0.9 g/day , containing E2 0.54 mg/day ) or E2-free placebo ( n = 89 ) for 16 weeks . Results Improvement rates in the number of daily hot flushes at the final evaluation ( primary endpoint ) in the low-dose E2 group ( marked 90.8 % , moderate 6.9 % , mild 1.1 % , no change 1.1 % , worsening 0 % ) were significantly greater than in the placebo group ( marked 77.0 % , moderate 10.3 % , mild 4.6 % , no change 2.3 % , worsening 5.7 % ) ( p = 0.0097 ) , showing an inhibitive effect on the flare-up of climacteric symptoms . The incidence of treatment-related adverse events in the low-dose group ( 21.6 % ) was similar to that in the placebo ( 22.5 % ) but was lower than that in the st and ard-dose treatment ( 32.5 % ) . Conclusions Low-dose maintenance therapy that was half the st and ard dose of transdermal E2 gel ( 0.9 g/day ) applied to women who had achieved marked improvement in the number of hot flushes at the st and ard dose ( 1.8 g/day ) was demonstrated to be effective ( inhibition of recurrence ) and safe for the treatment of climacteric disorder and estrogen deficiency symptoms Objective : To evaluate the effects of combined vaginal and oral low-dose estrogen plus progestogen therapy ( EPT ) on the frequency and severity of dyspareunia , sexual function , and quality of life in recently postmenopausal women . Methods : This outpatient , double-blind , r and omized , placebo-controlled trial enrolled 285 healthy , sexually active postmenopausal women aged 45 to 65 years . Women received either one daily oral low-dose conjugated estrogens ( 0.45 mg)/medroxyprogesterone ( 1.5 mg ) tablet for six 28-day cycles along with 1 g conjugated estrogens vaginal cream ( 0.625 mg ) , intravaginally for the first 6 weeks of the trial or a placebo cream and placebo tablet .  Efficacy was evaluated using the McCoy Female Sexuality Question naire , self-reported daily diary cards , the Brief Index of Sexual Functioning-Women ( BISF-W ) , and the Women 's Health Question naire . Results : The EPT group had a significant decrease in the frequency of dyspareunia compared with baseline and placebo in an analysis of responses to the McCoy Female Sexuality Question naire . Also , EPT was associated with a significant improvement in a woman 's level of sexual interest , frequency of orgasm , and pleasure of orgasm . There was no effect of EPT use on coital frequency . The EPT group had significant improvement in receptivity/initiation and relationship satisfaction , although not in other BISF-W domains , versus placebo ( BISF-W analysis ) and significant improvement versus placebo on most Women 's Health Question naire responses . Conclusions : EPT provided a statistically significant improvement compared with placebo in dyspareunia , sexual experience , and quality of life as measured in this study . In general , EPT also improved self-reported sexual perception and enjoyment significantly compared with placebo OBJECTIVE : To evaluate the efficacy of ultra – low-dose 10-microgram 17&bgr;-estradiol ( E2 ) vaginal tablets for treatment of  vaginal atrophy .  METHODS : Postmenopausal women ( N=309 ) were r and omly assigned to 10-microgram E2 or placebo vaginal tablets for 52 weeks in a multicenter , double-blind study . Primary efficacy endpoints included change from baseline to week 12 in vaginal cytology , vaginal pH , and most bothersome urogenital symptoms score . Grading of vaginal health was a secondary efficacy assessment . Safety assessment s included endometrial biopsy , physical and gynecologic examinations , and recording adverse events . RESULTS : At week 12 , the change from baseline for 10 micrograms E2 compared with placebo demonstrated significant improvement in vaginal Maturation Index ( proportion of parabasal cells : –37 % compared with –9 % ; superficial cells : 13 % compared with 4 % ; intermediate cells : 24 % compared with 5 % ; P<.001 for each ) , Maturation Value ( 25.0 compared with 6.5 , P<.001 ) , grading of vaginal health ( –0.91 compared with –0.51 , P<.001 ) , vaginal pH grade ( –1.3 compared with –0.4 , P<.001 ) , and most bothersome symptoms score ( –1.23 compared with –0.87 , P=.003 ) . For each component of vaginal Maturation Index , vaginal Maturation Value , grading of vaginal health , and vaginal pH , treatment effects were statistically different from placebo after 2 weeks of treatment . For most bothersome symptoms , treatment effect became apparent after 4 weeks and reached statistical significance at week 8 of therapy . All treatment effects were statistically significant at week 52 . There were no major safety findings regarding physical , gynecologic , or laboratory assessment s. CONCLUSION : After 12 weeks of treatment , an ultra – low-dose 10-microgram E2 vaginal tablet , compared with placebo , demonstrated significant improvement for the primary endpoints : vaginal cytology and pH and most bothersome urogenital symptoms score . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , http:// clinical trials.gov , NCT00108849 LEVEL OF EVIDENCE : OBJECTIVE Selective estrogen receptor modulators ( SERMs ) are drugs that exhibit both estrogen agonistic and antagonistic effects that are tissue-specific . Ospemifene ( FC-1271a ) is a novel SERM compound , which has been shown in animal models to have estrogen-like effects on bone and the cardiovascular system , while having antiestrogen-like effects in uterus and breast . In this study , we investigated the effects of ospemifene on the uterine endometrium , vaginal maturation index and hormonal status in healthy postmenopausal women . METHODS The study was conducted as a double-blind , placebo-controlled phase I study , where 40 healthy postmenopausal women volunteers were r and omized to receive daily oral doses of ospemifene either 25 , 50 , 100 or 200 mg or placebo for 12 weeks . Vaginal ultrasonography and endometrial biopsy were performed and vaginal maturation index determined at baseline and at 12 weeks ' visit . Serum concentrations of estradiol , luteinizing hormone , follicle stimulating hormone ( FSH ) , sex-hormone binding globulin ( SHBG ) , parathyroid hormone and prolactin were determined from sample s taken at baseline , at 4 days and at 4 , 12 , and 16 weeks ' visits . Climacteric symptoms were assessed using 12 visual analogue scales ( VAS ) at baseline and at the end of the study . RESULTS No clinical ly significant changes were seen in endometrial thickness at any dose level . Ospemifene exerted a very weak estrogenic effect on endometrial histology . On the other h and , it induced a clear estrogenic effect on vaginal epithelium . Among the endocrine parameters only FSH and SHBG showed significant dose dependent changes ; FSH decreased and SHBG increased during the treatment . In general , ospemifene was well tolerated . The 25 and 50 mg doses tended to reduce climacteric symptoms , but no statistically significant differences were observed between different doses of ospemifene and placebo . The highest dose level ( 200 mg ) induced more subjective adverse reactions , especially hot flushes , than lower doses . CONCLUSION Our study suggests that a safe and well tolerated dose of ospemifene for potential clinical use may be between 25 and 100 mg . Further studies are needed to substantiate the results of this Phase I pilot study BACKGROUND Vasomotor symptoms and bone loss are complications frequently induced by adjuvant treatment for breast cancer .  Tibolone prevents both side-effects , but its effect on cancer recurrence is unknown . The aim of this study was to show non-inferiority of tibolone to placebo regarding risk of recurrence in breast-cancer patients with climacteric complaints . METHODS Between July 11 , 2002 , and Dec 20 , 2004 , women surgically treated for a histologically confirmed breast cancer ( T(1 - 3)N(0 - 2)M(0 ) ) with vasomotor symptoms were r and omly assigned to either tibolone 2.5 mg daily or placebo at 245 centres in 31 countries . R and omisation was done by use of a central ised interactive voice response system , stratified by centre , with a block size of four . The primary endpoint was breast-cancer recurrence , including contralateral breast cancer , and was analysed in the intention-to-treat ( ITT ) and per- protocol population s ; the margin for non-inferiority was set as a hazard ratio of 1.278 . This study is registered with Clinical Trials.gov , number NCT00408863 . FINDINGS Of the 3148 women r and omised , 3098 were included in the ITT analysis ( 1556 in the tibolone group and 1542 in the  placebo group ) . Mean age at r and omisation was 52.7 years ( SD 7.3 ) and mean time since surgery was 2.1 years ( SD 1.3 ) . 1792 of 3098 ( 58 % ) women were node positive and 2185 of 3098 ( 71 % ) were oestrogen-receptor positive . At study entry , 2068 of 3098 ( 67 % ) women used tamoxifen and 202 of 3098 ( 6.5 % ) women used  aromatase inhibitors  . The mean daily number of hot flushes was 6.4 ( SD 5.1 ) . After a median follow-up of 3.1 years ( range 0.01 - 4.99 ) , 237 of 1556 ( 15.2 % ) women on tibolone had a cancer recurrence , compared with 165 of 1542 ( 10.7 % ) on placebo ( HR 1.40 [ 95 % CI 1.14 - 1.70 ] ; p=0.001 ) . Results in the per- protocol population were similar ( 209 of 1254 [ 16.7 % ] women in the tibolone group had a recurrence vs 138 of 1213 [ 11.4 % ] women in the placebo group ; HR 1.44 [ 95 % CI 1.16 - 1.79 ] ; p=0.0009 ) . Tibolone was not different from placebo with regard to other safety outcomes , such as mortality ( 72 patients vs 63 patients , respectively ) , cardiovascular events ( 14 vs 10 , respectively ) , or gynaecological cancers ( 10 vs 10 , respectively ) . Vasomotor symptoms and bone-mineral density improved significantly with tibolone , compared with placebo . INTERPRETATION Tibolone increases the risk of recurrence in breast cancer patients , while relieving vasomotor symptoms and preventing bone loss . FUNDING Schering-Plough ( formerly NV Organon , Oss , Netherl and s ) This study reports some of the effects of oestrogen and progestogen therapy .  forty-nine women who had undergone hysterectomy and bilateral salpingo-oophorectomy took part in a double blind crossover study during which they received ethinyl oestradiol 50 micrograms/day , norgestrel 250 micrograms/day , the combination of these substances " Nordiol " and placebo .  Somatic complaints were assessed at monthly interviews and weight and blood pressure recorded . The addition of norgestrel to ethinyl oestradiol therapy result ed in less dryness of skin but significantly increased mastalgia and breast size . There were no significant differences between drugs on amount of facial hair , acne , arthralgia , pruritus vulvae , vaginal discharge , vaginal odour , dyspareunia , weight or blood pressure . There was a significant reduction of diastolic blood pressure with the time duration of the study Abstract Objective : This study aim ed to evaluate the effects of monophasic estrogen-progestogen therapy on the sexuality and climacteric symptoms of postmenopausal women . Patients and methods : A prospect i ve , r and omised , double-blind , crossover , placebo-controlled , single-centre study was carried out over a total of 12 consecutive months in 40 postmenopausal women with an intact uterus who had no contraindications to hormone therapy . Patients received 17β-estradiol 2 mg in combination with norethisterone acetate 1 mg ( Cliane ® ) daily for 6 months or one placebo tablet daily for 6 months . The tablets were identical in appearance . After 6 months , the groups were crossed over and the patients were followed up for another 6 months . The groups were homogenous with respect to age , height , bodyweight , body mass index and race . For the statistical analysis , the group receiving hormone therapy was referred to as group A and the placebo group was design ated group B , irrespective of the placebo/hormone therapy sequence . Results : In group A there were fewer hot flashes ( F = 22.85 , p < 0.01 ) and an improvement in sexual interest ( F = 5.55 , p < 0.05 ) . The sequence in which the medication was received result ed in a statistically significant difference with respect to dyspareunia ( F = 9.65 , p < 0.01 ) and satisfaction with the duration of penetration ( F = 6.58 , p < 0.05 ) . In the intrapatient analysis of variation with respect to orgasmic capability and the presence of dialogue with partner regarding the couple ’s sexual life , whether the placebo was taken prior to or following hormone therapy was significant ( F = 17.12 , p < 0.001 and F = 7.10 , p < 0.05 , respectively ) . Conclusions : Monophasic estrogen-progestogen therapy has a beneficial effect on sexuality and on hot flashes in postmenopausal women OBJECTIVES To study the effects of hormonal replacement on hot flushes , other symptoms linked to menopause , and blood pressure . METHODS The study included 1006 early postmenopausal women aged 45 - 58 years , participating in the Danish Osteoporosis Prevention Study ( DOPS ) r and omised to Hormonal replacement therapy ( HRT )  ( n=502 ) or no HRT  ( n=504 ) in an open label trial . Symptom scores were recorded at baseline , after 6 month , 1 , 2 , and 5 years on a modified Greene scale ( range 0 - 4 with 0 equalling no symptoms , and 4 maximal symptoms ) . RESULTS HRT efficiently alleviated hot flushes ( mean+/-S.E.M. score 0.48+/-0.04 in HRT vs. 0.83+/-0.05 in no HRT after 5 years , P<0.01 by repeated measures ANOVA ) , sleeping difficulties associated with hot flushes ( 0.21+/-0.60 vs. 0.37+/-0.86 , P<0.01 ) , vaginal dryness ( 0.45+/-0.04 vs. 0.73+/-0.05 , P<0.01 ) , dyspareunia ( 0.27+/-0.04 vs. 0.39+/-0.04 , P<0.01 ) , and libido ( 0.48+/-0.05 vs. 0.59+/-0.05 , P=0.08 ) . In the untreated group the occurrence of mood swings ( from 0.77+/-0.05 at baseline to 0.45+/-0.04 after 5 years , 2P<0.01 ) and oedemas ( from 0.59+/-0.04 to 0.43+/-0.04 , 2P=0.02 ) decreased with age while the occurrence of incontinence increased ( from 0.43+/-0.03 to 0.52+/-0.04 , 2P<0.01 ) . These changes were not influenced by HRT . Furthermore , HRT had no influence on presence of headache ( 0.54+/-0.05 vs. 0.58+/-0.05 after 5 years ) , voiding pattern ( 0.49+/-0.04 vs. 0.53+/-0.04 ) , or blood pressure ( mean systolic pressure 123+/-18 vs. 123+/-19 , diastolic pressure 77+/-10 vs. 77+/-11 ) . CONCLUSIONS HRT is efficient in controlling hot flushes and vaginal dryness , and symptoms related to these conditions . However , no effect on blood pressure or other menopause symptoms was recorded Objective To determine the prevalence of endometrial hyperplasia and endometrial cancer in postmenopausal women with endometrial thickness of 4.1–8 mm on transvaginal ultrasound scan . Design Prospect i ve observational study carried out in the Heart of Engl and NHS Trust Teaching Hospital in the West Midl and s , UK , in a population of 58 women with postmenopausal bleeding . Method Prospect i ve analysis of all women referred to the Rapid Access Clinic in the Heart of Engl and Hospital with a history of postmenopausal bleeding over a 12-month period ( April 2007–April 2008 ) .  Endometrial histology was taken as the final diagnosis . The main outcome measure was endometrial histology in women with postmenopausal bleeding with endometrial thickness of 4.1–8 mm . Results All women ( n = = 58 ) diagnosed with endometrial thickness of 4.1–8 mm on transvaginal sonography were included in the analysis .  Pipelle endometrial biopsy  could only be performed in 22 women ( 37.9%% ) .  Hysteroscopy  was performed in 45 women ( 77.5%% ) . Out of these , a histological diagnosis was available in 28 women ( 62.2%% ) . In the remaining 17 women , the endometrium was observed as atrophic on hysteroscopy . In these 17 cases , either no or insufficient endometrial sample was obtained . In total , two ( 3.4%% ) women were diagnosed with complex endometrial hyperplasia and two ( 3.4%% ) women were diagnosed with endometrial carcinoma . Conclusion There was a significant prevalence of endometrial hyperplasia and endometrial cancer in postmenopausal women with a history of postmenopausal bleeding and who had endometrial thickness of 4.1–8 mm . Therefore , the current recommendation of histological assessment on all women with endometrial thickness > 4 mm should remain unchanged Objective : To evaluate the effects of hormone therapy ( HT ) on cognition and subjective quality of life ( QoL ) in recently postmenopausal women with cognitive complaints . Methods : Cognitive Complaints in Early Menopause Trial ( COGENT ) was a r and omized , double-blind , placebo-controlled , multicenter , pilot study of 180 healthy postmenopausal women aged 45 to 55 years , r and omly assigned to receive either placebo or conjugated equine estrogen 0.625 mg/medroxyprogesterone acetate 2.5 mg for 4 months . Outcome measures included memory , subjective cognition , QoL , sexuality , and sleep , which were assessed at baseline and month 4 . Results : The study was terminated before the expected final sample size of 275 due to a decrease in enrollment coinciding with the publication of findings from the Women ’s Health Initiative . There were no differences between groups on any cognitive or QoL measures , except for an increase in sexual interest and thoughts with HT . Modest negative effects on short- and long-term verbal memory approached significance ( p < 0.10 ) . Women with baseline vasomotor symptoms ( VMS ) showed a decrease in VMS and an improvement in general QoL , but no cognitive benefit vs placebo . Conclusions : With the power to detect an effect size of ≥0.45 , this study suggests potential modest negative effects on verbal memory that are consistent with previous hormone therapy trials in older women . GLOSSARY : BTA = Brief Test of Attention ; BVRT = Benton Visual Retention Test ; COGENT = Cognitive Complaints in Early Menopause Trial ; CRT = Educational Testing Service Card Rotation Test ; CVLT = California Verbal Learning ; FAS = Letter Fluency Test ; HERS = Heart and Estrogen/progestin Replacement Study ; HT = hormone therapy ; MFSQ = McCoy Female Sexuality Scale Question naire ; MFQ = The Memory Functioning Question naire ; PANAS = Positive and Negative Affect Scale ; PSQI = The Pittsburgh Sleep Quality Index ; QoL = subjective quality of life ; SWAN = Study of Women ’s Health Across the Nation ; UQoL = Utian Quality of Life ; VMS = vasomotor symptoms Test ; WHI = Women ’s Health Initiative ; WHISCA = WHI Study of Cognitive Aging ; WMS-R/DGT-F , MS-R/DGT-B = Digit Span Forward and Backward Subtests of the Wechsler Memory Scale – Revised Objective : To investigate the effect of ultralow-dose transdermal estradiol on postmenopausal symptoms and side effects in a cohort of largely asymptomatic postmenopausal women aged 60 to 80 years . Design : This secondary analysis used data from the UltraLow-dose Transdermal estRogen Assessment trial , a r and omized , placebo-controlled , double-blind trial in postmenopausal women to determine the skeletal effects and safety of ultralow-dose transdermal estradiol .  Four hundred seventeen postmenopausal women , aged 60 to 80 years , were r and omly assigned to receive either unopposed transdermal estradiol at 0.014 mg/d ( n = 208 ) or placebo ( n = 209 ) . Participants were queried at each clinic visit about postmenopausal symptoms and side effects purported to be associated with estrogen therapy using a st and ardized question naire . Results : At baseline , 16 % of women reported hot flashes , 32 % reported vaginal dryness , and 35 % reported trouble sleeping . Women who received ultralow-dose estradiol were no more likely to report improvement of hot flashes , vaginal dryness , or sleep difficulties than those who received placebo . Treatment with ultralow-dose estradiol did not cause breast tenderness , uterine bleeding , or other symptoms often attributed to estrogen , but vaginal discharge was more common in women who received estradiol compared with those who received placebo . Conclusion : In this population of older , largely asymptomatic women , ultralow-dose transdermal estradiol did not improve postmenopausal symptoms and did not cause side effects other than vaginal discharge . Further study is needed to determine whether this dose of transdermal estradiol is effective in treating symptoms of postmenopause in younger , more symptomatic women Objective : To evaluate whether the frequency of overactive bladder ( OAB ) symptoms increases in menopause patients after a tension-free vaginal tape ( TVT ) procedure  , and to determine if topical estrogen therapy can help prevent these symptoms . Design : After undergoing a preoperative assessment , enrolled patients were r and omly allocated to receive TVT plus postoperative vaginal estrogen therapy ( ET group ) or TVT without adjunctive medical treatment ( No ET group ) . The pre- and postoperative assessment s included : acquisition of a urogynecologic history with st and ardized questions regarding urinary function ( including a 10- grade visual analogue scale score ) , urogynecologic clinical examination , and urodynamic assessment . Follow-up assessment s were performed at 1 , 3 , and 6 months after surgery . Results : Fifty-six of 59 patients were evaluable ; 28 received topic vaginal estrogen after surgery ( ET group ) and 28 did not receive adjunctive medical treatment ( No ET group ) . The overall OAB syndrome rate in menopause patients ( No ET group ) was 7 % ( 2 of 28 patients ) at baseline and 32 % ( 9 of 28 patients ) 6 months after surgery ( P = 0.04 ) . At the 6-month follow-up assessment , the incidence of urinary urgency was 4 % ( 1 of 28 patients ) and 29 % ( 8 of 28 patients ) in the ET and No ET groups , respectively ( P = 0.01 ) . Differences in frequency and nocturia were not statistically significant . Analysis of the visual analogue scale scores revealed that at the 6-month follow-up assessment , urgency significantly improved in the ET group compared with the No ET group ( 0.23 ± 1.0 vs 2.30 ± 3.7 , respectively ; P = 0.02 ) . Conclusions : The TVT procedure seems to increase the frequency of OAB syndrome  in menopause patients .  Vaginal estriol therapy significantly reduces symptoms of urinary urgency , has a high rate of patient satisfaction , and can be used to treat postmenopausal women for at least 6 months after a TVT procedure CONTEXT GH negatively regulates its own secretion . How gender , sex steroids , and secretagogues modulate GH autofeedback is not known . HYPOTHESIS/ OBJECTIVE Supplementation with sex steroids and /or a peptidyl secretagogue will enhance the escape of GH from autoinhibition , thus framing a mechanism for amplifying pulsatile GH secretion . SUBJECTS AND SETTING Ten healthy postmenopausal women and 10 comparably aged men participated at the Clinical -Translational Science Unit . DESIGN / INTERVENTIONS R and omly ordered , double-blind , prospect i ve crossover treatment with placebo vs. testosterone ( men ) or placebo vs. estradiol ( women ) . Autofeedback was imposed by an iv pulse of GH .  Recovery of feedback inhibition was quantified during constant infusion of saline , GHRH , or GH-releasing peptide-2 ( three peptide categories ) . OUTCOMES / RESULTS During negative feedback , total ( integrated ) GH recovery depended upon gender ( P = 0.017 ) , sex hormone ( P < 0.001 ) , and peptide category ( P < 0.001 ) . Mechanistic analysis revealed that feedback-suppressed nadir GH concentrations were determined by sex-steroid treatment ( P = 0.018 ) but not by gender ( P = 0.444 ) . Peak GH escape was controlled by both treatment ( P = 0.004 ) and gender ( P = 0.003 ) . Nadir GH and peak GH during feedback were enhanced by GHRH or GHRP-2 ( P < 0.001 for both ) . Gender × peptide ( P = 0.012 for nadir GH ) , treatment × peptide ( P < 0.001 total and peak GH ) , and gender × treatment ( P = 0.017 nadir GH ) regulated GH recovery interactively . CONCLUSION Gender , sex-steroid supplementation , and secretagogue type confer distinct feedback-rescuing effects , introducing a new level of complexity in the control of pulsatile GH regulation Objective To study the impact of low-dose unopposed esterified estrogens on menopausal symptoms and quality of life . Methods In a long-term , 2-year , r and omized , double-blind , placebo-controlled study , 204 postmenopausal women were treated with esterified estrogens 0.3 mg daily or placebo . Menopausal symptoms were assessed with a modified Kupperman index at baseline , 3 , 6 and thereafter every 6 months . In a second 12-week , open-label , short-term pilot study , 25 postmenopausal women with moderate to severe vasomotor symptoms were treated with esterified estrogens 0.3 mg daily for 12 weeks . Vasomotor symptoms and quality of life were assessed using the Greene scale and Quality of Life Menopause Scale ( QUALMS ) . Results In the long-term study , significant ( p < 0.05 ) reductions in total symptom scores were observed at each time point with esterified estrogens compared with placebo .  Somatic symptom scores ( hot flushes , night sweats , vaginal dryness ) decreased significantly ( p < 0.01 ) in patients treated with esterified estrogens 0.3 mg compared to baseline and placebo . In the short-term , open-label pilot study , the incidence of vasomotor symptoms was significantly ( p < 0.01 ) reduced with esterified estrogens 0.3 mg from week 4 until the study end . Significant ( p < 0.05 ) improvements versus baseline were seen in the somatic and vasomotor/sleep domains and in the total quality -of-life score . Conclusions Esterified estrogens 0.3 mg given daily provide adequate menopausal symptom relief and improved quality of life in postmenopausal women Summary A double-blind cross-over study with Org OD 14 was done in 35 post-menopausal patients aged 48–69 years who had hot flushes and other associated symptoms . Patients were r and omly allocated to Org OD 14 or to placebo as first treatment . Each period of treatment lasted for 6 weeks and there were no intervals between treatments . Tablets containing 2.5 mg of Org OD 14 or placebo tablets of identical appearance were supplied . Patients took one Org OD 14 tablet or one placebo tablet per day . Data on the following variables were obtained and analyzed statistically : hot flushes , sweating , dizziness , palpitation , tiredness , headache , insomnia , irritability , breathlessness , backache , loss of libido , and mood . Assessment was daily in the case of hot flushes and weekly for the other variables . Org OD 14 was statistically significantly more effective in controlling hot flushes , sweating and headache and tended to be better than the placebo tablets for the other variables Estrogen treatment of postmenopausal women has been suggested to improve mood and psychological function . However , this remains controversial because previous studies involved heterogeneous groups , were not double blind , and included women who were also experiencing somatic symptoms that were relieved by estrogen .  A r and omized double-blind study was carried out comparing the effects of placebo and conjugated equine estrogens ( 0.625 and 1.25 mg ) on psychological function over 3 months in 36 asymptomatic women , aged 45 - 60 . The tests included the Minnesota Multiphasic Personality Inventory-168 , the Profile of Adaptation to Life , and the Beck Depression Inventory . Memory was assessed directly by the Wechsler Adult Intelligence Scales , measuring both digit span and digit symbol . All women were well-adjusted psychologically . The income management scale of the Profile of Adaptation to Life improved ( P<.05 ) with estrogen , as did the Beck Depression Inventory ( P<.05 ) , but these results were not dose-related . Memory assessed prospect ively by the Wechsler Adult Intelligence Scales was not affected significantly . These results suggest that estrogen use may improve the overall quality of life in postmenopausal women AIM The effect of hormone replacement therapy ( HRT ) on the quality of life in women with hypertension is still not clear . Thus , the aim of the study was to assess the effect of hormone replacement therapy on quality of life in postmenopausal women with essential hypertension by using a battery of st and ardized question naires . MATERIAL AND METHODS The study population consisted of 53 women ( mean age 50.9 + /- 6.3 years ) with mild and moderate essential hypertension ( mean duration 6.4 + /- 6.4 years ) . The postmenopausal status was defined as the absence of menstrual blood loss during > 6 months and blood estradiol concentration < 50 pg/ml , accompanied by follicle-stimulating hormone ( FSH ) levels > 21 U/I. Twenty seven women were blindly r and omised to transdermal hormone replacement therapy ( HRT ) and received 17-beta-estradiol and noretisterone acetate , TTS .  Twenty six women were r and omly selected as controls . The subjects were evaluated at baseline ( after 2 weeks ' wash-out from hypotensive drug period ) and after three months of HRT using self-administered st and ardized quality of life question naires : the Psychological General Well-being Index ( PGWB ) and the Subjective Symptoms Assessment Profile ( SSA-P ) . RESULTS No differences were found in blood pressure values , heart rate , body mass index and distribution of body fat tissue between women receiving HRT and controls at baseline and after 3 months of follow-up . There were no significant differences in the baseline total PGWB score as well as in its subscale between two groups . Similarly , the frequency and intensity of subjective symptoms assessed by SSA-profile were the same in both groups at baseline . After 3 months , a significant improvement in PGWB total score was observed in women receiving HRT . This effect was due to improvement in anxiety , positive well-being and vitality . Moreover , emotional distress , symptoms of flushing , sweating and trembling h and s also diminished and sexual capacity improved in women treated with HRT . CONCLUSION A three-month hormone replacement therapy in hypertensive postmenopausal women slightly improves the general well-being , seems to decrease emotional tension , increase sexual capacity and markedly relieves some vasomotor symptoms CONTEXT Lower-than-commonly-prescribed doses of conjugated equine estrogens ( CEEs ) with medroxyprogesterone acetate ( MPA ) improve vasomotor symptoms and vaginal atrophy , provide acceptable bleeding and lipid profiles , and afford endometrial protection . This lower-dose therapy 's protection against loss of bone mineral density ( BMD ) associated with menopause has not been thoroughly investigated . OBJECTIVE To determine the effects of lower doses of CEEs only or CEEs-MPA on spine and hip BMD , total body bone mineral content ( BMC ) , and biochemical markers of bone turnover in postmenopausal women . DESIGN AND SETTING Two-year r and omized , double-blind , placebo-controlled sub study of the Women 's Health , Osteoporosis , Progestin , Estrogen trial , conducted at 19 US centers between August 1995 and October 2000 . PARTICIPANTS Eight hundred twenty-two healthy postmenopausal women aged 40 to 65 years who were within 4 years of their last menstrual period . INTERVENTIONS Patients were r and omly assigned to receive CEEs , 0.625 ; CEEs , 0.625 and MPA , 2.5 ; CEEs , 0.45 ; CEEs , 0.45 and MPA , 2.5 ; CEEs , 0.45 and MPA , 1.5 ; CEEs , 0.3 ; CEEs 0.3 and MPA , 1.5 ( all doses in mg/d ) ; or placebo for 2 years . All participants also received elemental calcium at 600 mg/d . MAIN OUTCOME MEASURES Changes from baseline in spine and total hip BMD , total body BMC , and biochemical markers of bone turnover ( serum osteocalcin and urinary cross-linked N-telopeptides of type I collagen ) , assessed at 6-month intervals and compared among treatment groups with a modified intention-to-treat approach . RESULTS At 24 months , women assigned to all of the active treatment groups had significant gains from baseline ( P<.001 ) in spine and hip BMD and total body BMC ( except total body BMC in the group receiving CEEs , 0.3 mg/d ) . These changes were significantly different from those in the placebo group , in which losses of bone mass in spine and total body were evident over the course of the study ( P<.001 ) . The loss in hip BMD from baseline in the placebo group was significant at 18 ( P = .02 ) but not at 24 months ( P = .06 ) . Osteocalcin and N-telopeptides of type I collagen were significantly reduced from baseline ( P<.001 ) for all active treatment groups at all time points ; no changes were found for the placebo group . For women treated with CEEs alone , the gains in spine BMD for the group taking CEEs , 0.625 mg/d , were significantly higher than those of the group taking CEEs , 0.3 mg/d ( P = .02 ) , but not the group treated with CEEs , 0.45 mg/d ( P = .48 ) . CONCLUSIONS Doses of CEEs or CEEs-MPA lower than 0.625 mg/d effectively increase BMD and BMC in early postmenopausal women OBJECTIVE This study was undertaken to examine the effect of ultralow-dose transdermal estradiol on sexual function in postmenopausal women . STUDY DESIGN Analysis of data from a multicenter , r and omized , double-blind , placebo-controlled trial of a 0.014 mg/day transdermal estradiol patch in 417 women aged 60 to 80 years . Sexual function was assessed by self-administered question naires at baseline and 4 , 12 , and 24 months . A linear effects model was used to assess treatment effects using data from all on- study assessment s. RESULTS Women r and omly assigned to estradiol had a 4.3 point greater improvement in the vaginal pain/dryness domain relative to placebo ( 95 % CI = 0.3 - 8.4 , P = .04 ) . No significant differences in frequency of sexual activity or other sexual function domains ( desire , satisfaction , problems , or orgasm ) were observed between treatment groups ( P > or = .10 for all ) . CONCLUSIONS Ultralow-dose estradiol result ed in modest improvement in sexual function related to vaginal pain and dryness , but not in other domains of sexual function OBJECTIVE To investigate somatic symptom relief , gonadotropin secretion , and endogenous and rogen bioavailability ( protein-bound and free ) during 3 months of estrogen- and rogen therapy or matched estrogen-only replacement therapy . DESIGN Ninety-three naturally menopausal out patients with 6 or more months of amenorrhea , who were experiencing mild-to-moderate vasomotor symptoms , were r and omized to receive one of five treatments : oral esterified estrogens ( 0.625 mg or 1.25 mg ) , oral esterified estrogens combined with methyltestosterone ( 0.625 mg combined with 1.25 mg methyltestosterone or esterified estrogens 1.25 mg combined with 2.5 mg methyltestosterone ) , or placebo for 12 weeks . All treatments were preceded by a 4-week placebo lead-in period . RESULTS Patients receiving the lower dose of estrogen- and rogen therapy had fewer somatic menopausal symptoms than patients receiving the lower dose estrogen ( 0.625 mg ) , and they experienced somatic symptom relief similar to those patients receiving the higher dose of estrogen ( 1.25 mg ) . Significantly greater luteinizing hormone suppression ( p < or = 0.03 ) occurred in estrogen- and rogen groups compared to estrogen groups , suggesting that added and rogen might mediate a more pronounced negative feedback on the hypothalamic-pituitary axis . Sex hormone-binding globulin increased significantly in both estrogen-treated groups ( p < or = 0.01 ) , whereas decreases occurred in both estrogen- and rogen groups ( p < or = 0.006 ) . The higher dose estrogen-only preparation significantly reduced and rostenedione ( p < or = 0.01 ) and dehydroepi and rosterone sulfate ( p < or = 0.005 ) . CONCLUSION The extent of relief with lower dose estrogen- and rogen therapy was similar to higher dose estrogen-only treatment . The greater efficacy of combination therapy on somatic symptoms could be mediated by the same mechanism responsible for the suppressive effects of estrogen- and rogen therapy on luteinizing hormone secretion . The marked differences in circulating levels of sex hormone building globulin , which were increased by estrogen and decreased by estrogen- and rogen , and the result ing impact on bioavailable and rogens and estrogens could also explain the differential somatic relief with both treatments . Endogenous adrenal and rogens were lower in women treated with esterified estrogens 1.25 mg/day , suggesting that estrogen therapy can produce a significant hypo and rogenic state by inhibiting production or accelerating clearance of adrenal and rogens Out of a sample of 162 early post-menopausal women , aged 45 - 54 yr , 131 completed a placebo-controlled study to investigate the effect of  sex hormones on mild climacteric symptoms  with special reference to the dose-response relationship and withdrawal effects . The women were followed up for 42 mth under four different study programmes . All the women were examined every 3 mth and a blind assessment made of the menopausal index estimated according to Kupperman et al. The data revealed a highly significant reduction in climacteric symptoms in the hormone-treated women as compared with the placebo group ( P less than 0.001 ) , a highly significant dose relationship between climacteric symptoms and treatment with 4 , 2 and 1 mg oestradiol , respectively ( P less than 0.001 ) , a highly significant and dose-dependent rebound phenomenon after withdrawal of hormone treatment ( P less than 0.001)--which levelled off after 6 mth following withdrawal-- and complete relief of hot flushes with the two highest doses of oestradiol ( 4 and 2 mg oestradiol ) . It is concluded that sex hormones have a beneficial effect in post-menopausal women with even mild symptoms Objective : Phase 3 studies of postmenopausal women with or at risk for osteoporosis reported that , compared with placebo , bazedoxifene increased the incidence of hot flushes . The current study evaluated the vasomotor effects of bazedoxifene in healthy nonflushing postmenopausal women . Methods : In this phase 2 study , nonflushing postmenopausal women ( n = 494 ) were r and omized to daily treatment with bazedoxifene 5 , 10 , or 20 mg ; raloxifene 60 mg ; or placebo for 12 weeks . The primary endpoint was the percentage of women reporting hot flushes at any time during the study ; secondary endpoints included the mean number and severity of hot flushes and the mean number of days with hot flushes . Effects on bone turnover markers and lipid parameters were also evaluated . Results : Over the 12-week study , 25.5 % of placebo-treated women reported hot flushes . The incidence of hot flushes with bazedoxifene 5 , 10 , and 20 mg and raloxifene 60 mg was 26.0 % , 33.7 % , 27.6 % , and 21.4 % , respectively , with no significant differences from that with placebo . The active treatment groups showed no significant differences from placebo in the mean number or severity of hot flushes during week 12 or any 4-week period . Bazedoxifene and raloxifene showed beneficial effects on lipid parameters and markers of bone turnover . All doses of bazedoxifene were generally well tolerated and did not increase endometrial thickness , vaginal bleeding , or breast pain compared with placebo over 12 weeks of therapy . Conclusions : Data from this phase 2 clinical trial suggest that bazedoxifene does not increase the incidence of hot flushes relative to placebo in nonflushing postmenopausal women In order to analyse both sexual desire after menopause and its response to treatment with tibolone , a r and omized placebo/tibolone trial has been design ed with 28 postmenopausal patients . They were asked to answer a question naire design ed by us to obtain quantitative measurements to describe changes in sexual desire . After selection , the patients were r and omly assigned to two groups as follows : 14 in the group treated with 2.5 mg/day of tibolone and 14 in the placebo group treated with 500 mg/day of calcium . The patients were monitored after 3 , 6 and 12 months . Before joining this study , they had signed a written consent . It was observed that the sexual desire after menopause underwent a significant fall , with decline in arousability and intercourse . The comparative results show that the patients treated with tibolone experience an improvement after the third month of treatment and this improvement was maintained until the end of treatment . We conclude that the question naire proposed here is a useful non-parametric method to diagnose a patient 's sexuality status at the baseline assessment and a valuable tool for monitoring various therapies . Furthermore , tibolone proved to be effective in managing reduced sexual desire which appears in postmenopausal patients BACKGROUND This study focus on the effect of 6 months transdermal estradiol therapy ( TTS ) on the sexual behaviour and the quality of life in early menopausal women , complaining of uncomfortable menopausal symptoms . METHODS Three hundred and sixty-two postmenopausal women , aged 48 - 56 , participated in this study . One hundred and seventy-one of them were given continuous solid matrix patch TTS 50 mg/day for 6 months . Sexual behaviour , menopausal symptoms and well-being were evaluated through a self-rating method . We used a structured question naire with three obligatory answers ( less/same/more ) for each question --sexual life , hot flushes , touchiness , insomnia , blood pressure , work willing , memory loss , well-being -- filled in by the women themselves or by the medical equipe after a telephone interview . RESULTS Seventy five per cent of women aged 51 - 53 and 84 % aged 54 - 56 , who had been treated for 6 months with TTS showed a fall of sexual drive , if compared with , respectively , 62 % and 48 % of untreated subjects . Relief of hot flushes , touchiness and insomnia occurred in 80 % of treated women , with slight differences among the various groups while 61 % showed increase of well-being . CONCLUSIONS The results of our study demonstrate that continuous TTS for 6 months decreased sexual drive in 69 % of women , improved menopausal symptoms in 80 % women but increased well-being only in 61 % of women . These differences suggest that women 's well-being does not seem linked only to the relief of menopausal symptoms and the impairment of their sexual life can play a negative role The purpose of this study was to investigate the value of tibolone in the treatment of psychosomatic symptoms in menopause . Forty-two menopausal women ( aged 46 - 63 , mean 53.9 ) with nightly perspiration , vasomotor flushes , disturbance of libido , dyspnea and other psychosomatic symptoms  were assigned to one of two treatment groups for three months : 1st group ) 21 users of tibolone ; 2nd group ) 21 users of placebo . At the end of the trial disturbance of libido was observed in 4 ( 19.0 % ) cases tin the 1st group and 11 ( 52.4 % ) cases in the 2nd ( p < 0.05 ) and nightly perspiration was observed in 3 cases ( 14.3 % ) in the 1st group and 9 cases ( 42.9 % ) in the 2nd ( p < 0.05 ) . Although vasomotor flushes were observed in only 3 ( 14.3 % ) cases in the 1st group and 7 cases ( 33.3 % ) in the 2nd group , this difference was not significant ( p > 0.05 ) . There was no significant effect of tibolone or placebo in dyspnea , vertigo and headache . From the results it can be concluded that tibolone can have a beneficial effect on some psychosomatic symptoms in postmenopausal women Objectives : The primary objective of the Selective estrogen Menopause And Response to Therapy 3 ( SMART-3 ) trial was to compare the efficacy and safety of two doses of bazedoxifene (BZA)/conjugated estrogens ( CE ) versus placebo for the treatment of moderate to severe vulvar/vaginal atrophy ( VVA ) associated with menopause . Methods : This was a phase 3 , multicenter , double-blind , r and omized , placebo-controlled , and active comparator-controlled study . Healthy postmenopausal women ( n = 664 ; aged 40 - 65 y ) were r and omized to BZA 20 mg/CE 0.625 mg , BZA 20 mg/CE 0.45 mg , BZA 20 mg , or placebo once daily for 12 weeks . Changes in vaginal maturation , vaginal pH , and severity of the most bothersome symptom of VVA from baseline were assessed at screening and at weeks 4 and 12 . Adverse events were recorded throughout the study . Results : BZA 20 mg/CE 0.625 or CE 0.45 mg significantly ( P < 0.01 ) increased superficial cells and decreased parabasal cells compared with placebo . Vaginal pH and most bothersome symptom significantly improved with BZA 20 mg/CE 0.625 mg compared with placebo ( P < 0.05 ) . Improvements in vaginal dryness were also observed with both BZA/CE doses ( P < 0.05 ) . The incidence of treatment-related adverse events were similar across treatment groups . Conclusions : BZA/CE is effective in treating moderate to severe VVA and vaginal symptoms . These data further support the use of a tissue-selective estrogen complex containing BZA/CE as a new menopausal therapy for postmenopausal women OBJECTIVE The purpose of this study was to assess the urogenital effects of raloxifene , tamoxifen , conjugated equine estrogen , and placebo in healthy postmenopausal women . STUDY DESIGN This r and omized , double-blind , placebo-controlled study compared the urogenital effects of 0.625 mg of conjugated equine estrogen ( n = 15 women ) , 20 mg of  tamoxifen ( n = 14 women ) , 60 mg of raloxifene  , ( n = 15 women ) , and placebo  ( n = 13 women ) . Evaluations at baseline and evaluations after 20 weeks receiving the drug included a pelvic examination with cytologic evaluation of vagina and urethra , pelvic organ prolapse quantitation , and urethral axis deflection by cotton swab test ( only in patients with incontinence [ 33 % ] ) . RESULTS Conjugated equine estrogen increased the maturation value of both urethral and vaginal cytologic condition ( P = .002 , P = .032 , respectively ) . There was a decrease in vaginal maturation value in the raloxifene group ( not significant ) . Two of 8 women in the conjugated equine estrogen group showed evidence of worsening prolapse by pelvic organ prolapse quantitation ; the condition of 2 of 8 women improved . In the raloxifene , tamoxifen , and placebo groups 8 of 12 women , 4 of 13 women , and 2 of 11 women had worsening in prolapse scores , respectively , whereas none of the women had improvement . Increased cotton swab deflection was found in 3 of 5 women in the raloxifene group , in 5 of 8 women in the tamoxifen group , in 0 of 4 women in the placebo group , and in 0 of 2 women in the conjugated equine estrogen group . Seventy-five percent of the patients who received raloxifene and 60 % of the patients who received tamoxifen had increases in prolapse by any measure ( ie , pelvic organ prolapse quantitation or cotton swab or clinical assessment ) compared with 18 % of the patients in the placebo group and 22 % of the patients in the conjugated equine estrogen group ( P = .015 ) , although symptoms did not differ among groups . CONCLUSION Neither raloxifene nor tamoxifen improve cytohormonal effects in the vagina or urethra , whereas conjugated equine estrogen does . Raloxifene and tamoxifen appear to show worsening prolapse compared with conjugated equine estrogen and placebo . The clinical relevance of these effects is unknown and requires investigation Objective The aim of this study was to assess the safety of ospemifene , a novel selective estrogen receptor modulator , for the treatment of vulvar and vaginal atrophy in postmenopausal women with a uterus . Methods In this multicenter , r and omized , double-blind , placebo-controlled , long-term safety extension study , nonhysterectomized women aged 40 to 80 years ( n = 180 ) received daily oral doses of placebo , ospemifene 30 mg/day , or ospemifene 60 mg/day for 40 weeks ( continued as blinded treatments from the initial 12-week pivotal efficacy study of ospemifene ) . The total treatment period was 52 weeks . Safety assessment s included adverse events , cervical Papanicolaou tests , endometrial histology , endometrial thickness , gynecological examination , breast palpation , mammography , physical examination , and clinical safety laboratory assessment s. Results No clinical ly significant adverse changes in safety assessment s were observed in any treatment group . Most treatment-emergent adverse events were mild or moderate in severity . Hot flushes , the most frequently occurring treatment-emergent adverse event related to the study drug , had a low discontinuation rate ( 1.6 % ) . No study participants discontinued because of endometrial or cervical pathology ; no endometrial findings were clinical ly meaningful . On week 52 , more than 95 % of endometrial biopsy sample s either were classified as atrophic or inactive or had insufficient tissue for diagnosis . There were no treatment-emergent adverse events of pelvic organ prolapse or venous thromboembolism . No cases of endometrial hyperplasia or carcinoma were observed . Only three participants ( 1.7 % ) taking ospemifene experienced vaginal bleeding or spotting , which was self-limiting . Conclusions Daily doses of ospemifene 30 mg and ospemifene 60 mg yielded few treatment-emergent adverse events and demonstrated no significant endometrial changes during the 1-year treatment of vulvar and vaginal atrophy in postmenopausal women with a uterus INTRODUCTION Sexual dysfunction is more prevalent in postmenopausal women . AIMS To prospect ively evaluate and compare the effects of hormone therapy ( HT ) regimens , oral and vaginal estradiol , estradiol + drospirenone and tibolone , on  sexual function in healthy postmenopausal women . METHODS The study included 169 consecutive healthy postmenopausal women , and the women were divided into two groups : 111 women received HT , and 58 women received no treatment and served as a control group . As an HT , 23 women with surgically induced menopause received oral 17-beta estradiol . The rest of the women with natural menopause were prospect ively r and omized : 22 received oral 17-beta estradiol + drospirenone daily , 42 received oral tibolone , and 24 received vaginal 17-beta estradiol .  Sexual function was evaluated with a detailed 19-item question naire , the female sexual function index , including sexual desire , arousal , lubrication , orgasm , satisfaction , and pain . MAIN OUTCOME MEASURES The differences in sexual function were compared before and 6 months after the treatment in all women . RESULTS Total sexual function score increased from 19.81 + /- 7.15 to 22.9 + /- 6.44 in the HT group and decreased from 21.6 + /- 8.69 to 17.6 + /- 5.7 in the control group , revealing a significant difference from baseline to post-treatment between the two groups ( P = 0.000 ) . The highest improvement in total score and arousal was achieved with the oral 17-beta estradiol ( P = 0.000 and P = 0.000 , respectively ) . The highest improvement in lubrication was achieved with the oral and vaginal 17-beta estradiol groups ( P = 0.000 ) . The highest improvement in orgasm was achieved with the tibolone group ( P = 0.000 ) . The highest improvement in pain was achieved with the oral and vaginal 17-beta estradiol groups ( P = 0.000 ) . CONCLUSIONS HT provided significant improvement in sexual function compared to women receiving no treatment , and therefore , HT regimens should be suggested for improvement in sexual functioning of postmenopausal women Objective To evaluate the effect of estrogen replacement therapy on cognitive functioning . Methods The study consisted of two 3-month treatment periods , one with estrogen and one with the placebo , in r and om order , separated by a 1-month wash-out period . The study group comprised 70 healthy postmenopausal women , aged 47–65 years , with previous hysterectomy . Sixty-two women completed the study .  Cognitive speed and accuracy , attention , and memory were evaluated . Serum estradiol ( E2 ) and FSH levels were controlled at the end of the estrogen , placebo , and wash-out periods . Results Most of the cognitive tests correlated with age : older women were slower and made errors than younger women . Estrogen replacement therapy was not superior to the placebo in any test of cognitive performance . In two out of ten visual detection tasks , recognition thresholds were longer with estrogen than with the placebo ( P < .001 and P = .004 ) . On the most dem and ing test of working memory , the reaction times ( P = .045 ) and error rates ( P = .043 ) differed between treatments , yet this finding proved to be an effect of learning rather than treatment . There was no correlation between cognitive performance and serum E2 levels . Conclusion Cognitive performance decreased with age . Short-term estrogen replacement therapy did not provide any advantage over the placebo in terms of improving the performance Objective To compare the effect of different formulations of continuous combined hormone therapy on sexual performance in naturally postmenopausal women . Material and methods A total of 158 postmenopausal women were enrolled and prospect ively r and omized to the single-blind study . Fifty-four women received tibolone 2.5 mg , 53 received 2 mg estradiol and 2 mg dienogest ( E2/dienogest ) , and 51 did not receive any menopausal therapy . The patients were monitored after 6 months . Attitudes of sexuality were evaluated by using the Rosen 's female sexual function index . Results Compared with E2/dienogest and the control group , tibolone treatment was associated with more improvement of sexual performance , including sexual desire , sexual arousal and satisfaction . Both of the hormone therapies decreased frequencies of vaginal dryness and painful intercourse . Conclusions Tibolone has more positive effects on the sexual dysfunction of postmenopausal women and may be an alternative to the E2/dienogest preparation in postmenopausal women with sexual dysfunction OBJECTIVE The potential therapeutic utility of estrogens in schizophrenia is increasingly being recognized . Raloxifene , a selective estrogen receptor modulator , appears to act similarly to conjugated estrogens on dopamine and serotonin brain systems and may be a better option since it lacks the possible negative effects of estrogen on breast and uterine tissue . In this study , we assess the utility of raloxifene as an adjunctive treatment for negative symptoms and other psychotic symptoms in postmenopausal women with schizophrenia . METHOD This was a 12-week , double-blind , r and omized , placebo-controlled study . Patients were recruited from both the inpatient and outpatient departments of Parc Sanitari Sant Joan de Déu , Barcelona , Spain , and Corporació Sanitària Parc Taulí , Sabadell , Spain . Thirty-three postmenopausal women with schizophrenia ( DSM-IV criteria ) who exhibited prominent negative symptoms were r and omized to either adjunctive raloxifene ( 16 women ; mean age = 60.14 years , SD = 6.41 years ) or adjunctive placebo  ( 17 women ; mean age = 62.66 years , SD = 4.54 years ) for 12 weeks . The period of recruitment lasted from January 2005 through June 2009 . Psychopathological symptoms were assessed at baseline and weeks 4 , 8 , and 12 by means of the Positive and Negative Syndrome Scale . RESULTS The addition of raloxifene ( 60 mg/d ) to regular antipsychotic treatment significantly reduced negative ( P = .044 ) , positive ( P = .031 ) , and general psychopathological ( P = .045 ) symptoms during the 12-week trial as compared with women receiving placebo . CONCLUSIONS Raloxifene as an adjuvant treatment in postmenopausal women with schizophrenia who exhibit prominent negative symptoms appears to be useful in improving negative , positive , and general psychopathological symptoms . If more extensive and longer-term studies confirm and exp and upon these positive results , the use of raloxifene could be recommended in postmenopausal patients with schizophrenia . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01041092 Objective The aim of this study was to evaluate the efficacy and safety of a new low-concentration estriol formulation ( 0.005 % estriol vaginal gel ) , providing an ultra low dose of estriol per application ( 50 & mgr;g ) , for the local treatment of postmenopausal vaginal atrophy . Methods Postmenopausal women with symptoms and signs of vaginal atrophy were enrolled in a prospect i ve , double-blind , placebo-controlled study . Women received either 1 g of vaginal gel containing 50 & mgr;g of estriol or placebo gel , daily for 3 weeks and then twice weekly up to 12 weeks . A cytological vaginal study , evaluation of vaginal pH , and assessment of symptoms and signs of vaginal atrophy were performed , and changes between baseline and weeks 3 and 12 were assessed . Adverse events were recorded . Results A total of 167 women were included ( 114 received estriol and 53 received placebo ) . After 12 weeks of therapy , a superiority of estriol compared with placebo gel was shown in the change in maturation value and vaginal pH ( P < 0.001 and P < 0.001 , respectively ) . The superiority of estriol was well demonstrated in improvement of vaginal dryness ( P = 0.001 ) and the Global Symptom Score ( P = 0.018 ) . Estriol gel proved also superior in the improvement of several of the most outst and ing vaginal signs of vaginal atrophy evaluated . After 3 weeks , estriol gel also showed a superiority over the placebo gel in most symptoms and signs evaluated . Treatment-related adverse events were similar among groups . Conclusions 0.005 % Estriol vaginal gel , a new formulation providing an ultra low dose of estriol per application , was shown to be safe and effective in the treatment of postmenopausal vaginal atrophy Objective : The objective of this study was to evaluate the efficacy and safety of three doses of estradiol gel 0.1 % ( Divigel , a novel formulation consisting of 1 mg estradiol per 1 g transdermal gel ) to reduce the frequency and severity of vasomotor symptoms and signs of vulvar and vaginal atrophy associated with menopause . Design : A total of 488 postmenopausal women were evaluated in a 12-week study comparing placebo with estradiol gel 0.1 % at doses of 1.0 , 0.5 , and 0.25 mg/day , with estimated daily deliveries of 0.027 , 0.009 , and 0.003 mg of estradiol , respectively . Primary endpoints were the change from baseline in daily frequency and severity of moderate to severe vasomotor symptoms . Change from baseline in the signs of vulvar and vaginal atrophy ( vaginal pH and percentage of superficial cells ) was also assessed . Results : Treatment with estradiol gel 0.1 % showed statistically significant reductions in frequency and severity of vasomotor symptoms from baseline compared with placebo as early as Week 2 that were maintained throughout treatment . Signs of vulvar and vaginal atrophy were also significantly improved from baseline with all three doses of estradiol gel 0.1 % compared with placebo . Conclusions : Low-dose transdermal estradiol gel 0.1 % is an effective treatment for relief of vasomotor symptoms , as well as signs of vulvar and vaginal atrophy , associated with menopause . Estradiol gel 0.1 % offers multiple dosing options to individualize patient therapy , including the lowest available effective dose ( 0.25 mg estradiol , delivering 0.003 mg/d estradiol ) to treat the vasomotor symptoms of menopause Objective : The aim of this study was to investigate the effectiveness of microdose transdermal 17&bgr;-estradiol ( E2 ) therapy in postmenopausal women with moderate to severe vulvovaginal symptoms . Methods : This report is based on a subset of 121 women who reported most bothersome moderate or severe vulvovaginal symptoms at baseline , from a previous r and omized , double-blind , placebo-controlled , multicenter study of 425 healthy , symptomatic , postmenopausal women . Recruits had experienced at least 7 moderate or severe hot flushes daily for at least 1 week or at least 50 moderate or severe hot flushes per week for at least 1 week . Effects on co primary efficacy variables have been reported previously . Participants received low-dose transdermal E2 plus levonorgestrel ( n = 43 ; nominal delivery 0.023 mg/d E2/0.0075 mg/d levonorgestrel ) , microdose E2 ( n = 42 ; nominal delivery 0.014 mg/d ) , or placebo ( n = 36 ) for 12 weeks . Secondary efficacy variables reported herein include mean change from baseline in vaginal pH and vaginal maturation index , the proportion of women with symptoms of vulvar and vaginal atrophy at baseline and week 12 , and the proportion of women with moderate-to-severe symptoms of vulvar and vaginal atrophy . Results : Microdose transdermal E2 treatment was associated with a consistent benefit versus placebo in women with vulvovaginal atrophy . There was a statistically significant difference between both E2 versus placebo for changes in vaginal pH and vaginal maturation index . Conclusions : Microdose transdermal E2 offers a useful addition to the therapeutic armamentarium for postmenopausal women in whom vulvovaginal symptoms are particularly troublesome Objective : The aim of this study was to evaluate low-dose synthetic conjugated estrogens A ( SCE-A ) cream administered twice weekly for the treatment of moderate to severe vulvovaginal atrophy ( VVA ) in a symptomatic postmenopausal population . Methods : In a multicenter , double-blind , r and omized , placebo-controlled study , 305 women with symptoms of VVA were treated with either 1 g SCE-A cream ( n = 150 ) or matching placebo ( n = 155 ) for a period of up to 12 weeks . Participants had to have a vaginal pH of greater than 5 , less than or equal to 5 % superficial cells on a vaginal smear , and at least one of five symptoms of VVA ( dryness , soreness , irritation , pain with intercourse , and bleeding after intercourse ) that was moderate or severe in intensity . Women had to select one moderate or severe symptom as the most bothersome . Results : Efficacy was assessed at 2 , 3 , 4 , 8 , and 12 weeks and included the change from baseline in the severity of the most bothersome symptom ( MBS ) , maturation index , and pH. Most women identified vaginal dryness as the MBS ( 48 % ) followed by pain with intercourse ( 31.3 % ) . A statistically significant increase in the maturation index and significant decreases in pH and severity of the MBS were observed for those treated with SCE-A vaginal cream compared with placebo . Conclusions : A low dose ( 1 g = 0.625 mg ) of SCE-A vaginal cream administered twice weekly was shown to be effective compared with placebo in treating VVA in postmenopausal women for the three co primary efficacy measures of maturation index , pH , and severity of the MBS
target: HT treatment with estrogens alone or in combination with progestogens was associated with a small to moderate improvement in sexual function , particularly in pain , when used in women with menopausal symptoms or in early postmenopause ( within five years of amenorrhoea ) , but not in unselected postmenopausal women .
  The current evidence does not suggest an important effect of tibolone or of SERMs alone or combined with estrogens on sexual function .
background: BACKGROUND The perimenopausal and postmenopausal periods are associated with many symptoms , including sexual complaints .
  OBJECTIVES To assess the effect of hormone therapy ( HT ) on  sexual function in perimenopausal and postmenopausal women .