title: Effect of combined implants of oestradiol and testosterone on libido in postmenopausal women. Evaluation of High-Dose Estrogen and High-Dose Estrogen plus Methyltestosterone Treatment on Cognitive Task Performance in Postmenopausal Women Testosterone patch increases sexual activity and desire in surgically menopausal women with hypoactive sexual desire disorder. Comparison of Oral Estrogens and Estrogens Plus Androgen on Bone Mineral Density, Menopausal Symptoms, and Lipid‐Lipoprotein Profiles in Surgical Menopause Androgen levels in adult females: changes with age, menopause, and oophorectomy. Comparative effects of oral esterified estrogens with and without methyltestosterone on endocrine profiles and dimensions of sexual function in postmenopausal women with hypoactive sexual desire. Estrogen and estrogen-androgen replacement in postmenopausal women dissatisfied with estrogen-only therapy. Sexual behavior and neuroendocrine responses. The effect of nandrolone decanoate on bone mineral density, muscle mass, and hemoglobin levels in elderly women with osteoporosis: a double-blind, randomized, placebo-controlled clinical trial. Effects of estradiol with and without testosterone on body composition and relationships with lipids in postmenopausal women Effects of combined estrogen/testosterone therapy on bone and body composition in oophorectomized women Effect of percutaneous androgen replacement therapy on body composition and body weight in postmenopausal women. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. Testosterone patch for the treatment of hypoactive sexual desire disorder in naturally menopausal women: results from the INTIMATE NM1 Study Effect of the combination of methyltestosterone and esterified estrogens compared with esterified estrogens alone on apolipoprotein CIII and other apolipoproteins in very low density, low density, and high density lipoproteins in surgically postmenopausal women. Comparison of the biochemical effects of testosterone and estrogen on bone markers in surgically menopausal women Testosterone enhances estradiol's effects on postmenopausal bone density and sexuality. The endocrine transition around menopause ‐ a five years prospective study with profiles of gonadotropines, estrogens, androgens and SHBG among healthy women Differential effects of oral estrogen versus oral estrogen-androgen replacement therapy on body composition in postmenopausal women. Skeletal effects of oral oestrogen compared with subcutaneous oestrogen and testosterone in postmenopausal women. Effects of testosterone treatment on endometrial proliferation in postmenopausal women. Preliminary Clinical Experience with Androgen Administration for Pre- and Postmenopausal Women with Hypoactive Sexual Desire Effects of androgen supplementation of hormone replacement therapy on the vascular reactivity of cerebral arteries. How many women lose bone mineral density while taking hormone replacement therapy? Results from the Postmenopausal Estrogen/Progestin Interventions Trial. Androgen enhances sexual motivation in females: a prospective, crossover study of sex steroid administration in the surgical menopause. Neuropsychological effects of methyltestosterone in women using menopausal hormone replacement. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial Comparative effects of estrogens plus androgens and tibolone on bone, lipid pattern and sexuality in postmenopausal women. EFFECT OF OESTROGEN AND TESTOSTERONE IMPLANTS ON PSYCHOLOGICAL DISORDERS IN THE CLIMACTERIC Effect of methyl testosterone administration on plasma viscosity in postmenopausal women Vasodilator effects of estrogen are not diminished by androgen in postmenopausal women. SUBCUTANEOUS HORMONE IMPLANTS FOR THE CONTROL OF CLIMACTERIC SYMPTOMS: A Prospective Study Treatment with percutanous testosterone gel in postmenopausal women with decreased libido--effects on sexuality and psychological general well-being. Effects of nandrolone decanoate on bone mass in established osteoporosis. Effects of parenteral administration of estrogen and androgen on plasma hormone levels and hot flushes in the surgical menopause. Acute Influences of Estrogen and Testosterone on Divergent and Convergent Thinking in Postmenopausal Women Combined esterified estrogens and methyltestosterone versus esterified estrogens alone in the treatment of loss of sexual interest in surgically menopausal women Addition of testosterone to estrogen replacement therapy in oophorectomized women: effects on sexuality and well-being Serum lipids in oophorectomized women during estrogen and testosterone replacement therapy. Short‐term testosterone supplementation does not activate GH and IGF‐I production in postmenopausal women Comparison of the effects of estrogen alone and estrogen plus androgen on biochemical markers of bone formation and resorption in postmenopausal women. Differential symptom response to parenteral estrogen and/or androgen administration in the surgical menopause. Testosterone inhibits estrogen/progestogen-induced breast cell proliferation in postmenopausal women PERCEIVED EFFECTS OF TESTOSTERONE REPLACEMENT THERAPY IN PERIMENOPAUSAL AND POSTMENOPAUSAL WOMEN: AN INTERNET PILOT STUDY Esterified estrogens combined with methyltestosterone improve emotional well-being in postmenopausal women with chest pain and normal coronary angiograms Postmenopausal Hormone Use and Secondary Prevention of Coronary Events in the Nurses' Health Study: A Prospective, Observational Study Differential effects of estrogen-androgen and estrogen-only therapy on vasomotor symptoms, gonadotropin secretion, and endogenous androgen bioavailability in postmenopausal women. The benefits of androgens combined with hormone replacement therapy regarding to patients with postmenopausal sexual symptoms. Influence of hormone therapy on the cardiovascular responses to stress of postmenopausal women Efficacy and safety of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a randomized, placebo-controlled trial A Comparison of Esterified Estrogens With and Without Methyltestosterone: Effects on Endometrial Histology and Serum Lipoproteins in Postmenopausal Women Effects of treatment with testosterone alone or in combination with estrogen on insulin sensitivity in postmenopausal women. A longitudinal study of the perimenopausal transition: altered profiles of steroid and pituitary hormones, SHBG and bone mineral density. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. The effect of hormone replacement therapy and route of administration on selected cardiovascular risk factors in post-menopausal women. Sex steroids and affect in the surgical menopause: a double-blind, cross-over study Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. Percutaneous administration of testosterone gel in postmenopausal women – a pharmacological study Hormonal treatments of sexual unresponsiveness in postmenopausal women: a comparative study Effect of estrogen plus progestin on stroke in postmenopausal women: the Women's Health Initiative: a randomized trial. Combined esterified estrogen and methyltestosterone treatment for dry eye syndrome in postmenopausal women. Which androgen replacement therapy for women?
abstract: Our most striking finding was that of the 16 patients monitored by the technique , those with no spontaneous lower oesophageal contractility at any time , but with provoked activity intact , were invariably subsequently diagnosed as brain dead clinical ly after the action ofpancuronium had worn off or been reversed . In this institution brain death is diagnosed using the criteria set out by the royal colleges and faculties of the United Kingdom.3 In addition , carotid arteriography is performed to show cessation ofcerebral circulation . The loss of spontaneous contractility in the presence of continuing provoked activity is explained by the normal physiology of the human oesophagus . The principal nerve supply is derived from the vagus nerve . The lower oesophageal muscle is supplied from intramural and paraoesophageal nerve plexuses . Vagal afferent and efferent fibres connect the oesophageal plexuses with the brain stem nuclei of the vagus nerve , which in turn are connected with higher cortical centres . The mechanisms governing production of non-propulsive activity are unknown , though acoustic stimuli as well as other forms of external stimuli can provoke this response.45 Thus it appears that an intact pathway between the brain and oesophagus is required for non-propulsive activity to occur . By contrast , secondary activity ( peristaltic ) has been recorded in the isolated opossum oesophagus ex vivo and so does not require control by higher centres.2 Hence in brain dead patients spontaneous lower oesophageal contractility would not be expected , whereas provokedcontractility should be intact , as we have found . We conclude that monitoring lower oesphageal contractility may be very useful in the early identification of brain death and may help to predict outcome in patients with head injury Objectives : To investigate the cognitive effects of high-dose oral estrogen alone or in combination with oral methyltestosterone in postmenopausal women . Methods : Participants were tested with a r and omized , double-blind design on the Identical Pictures , Cube Comparisons , Building Memory and Shape Memory tasks before and after 4 months of hormone treatment . Results : Women receiving estrogen and methyltestosterone maintained a steady level of performance on the Building Memory task , whereas those receiving estrogen alone showed a decrease in performance . Conclusions : These results indicate that the addition of testosterone to high-dose estrogen replacement exerts a protective effect on memory performance in postmenopausal women CONTEXT Hypoactive sexual desire disorder ( HSDD ) is one of the most common sexual problems reported by women , but few studies have been conducted to evaluate treatments for this condition . OBJECTIVE The objective of this study was to evaluate the efficacy and safety of a testosterone patch in surgically menopausal women with HSDD . DESIGN The design was a r and omized , double-blind , parallel-group , placebo-controlled , 24-wk study ( the Intimate SM 1 study ) . SETTING The study was performed at private or institutional practice s. PATIENTS The subjects studied were women , aged 26 - 70 yr , with HSDD after bilateral salpingo-oophorectomy who were receiving concomitant estrogen therapy . Placebo ( n = 279 ) or testosterone 300 microg/d ( n = 283 ) was administered . There were 19 patients who withdrew due to adverse events in the placebo group and 24 in the 300 mug/d testosterone group . INTERVENTION Testosterone ( 300 microg/d ) or placebo patches were applied twice weekly . MAIN OUTCOME MEASURE(S ) The primary end point was the change in the frequency of total satisfying sexual activity at 24 wk . Secondary end points included other sexual functioning end points and safety assessment s. RESULTS At 24 wk , there was an increase from baseline in the frequency of total satisfying sexual activity of 2.10 episodes/4 wk in the testosterone group , which was significantly greater than the change of 0.98 episodes/4 wk in the placebo group ( P = 0.0003 ) . The testosterone group also experienced statistically significant improvements in sexual desire and a decrease in distress . The overall safety profile was similar in both treatment groups . CONCLUSION In the Intimate SM 1 study , the testosterone patch improved sexual function and decreased distress in surgically menopausal women with HSDD and was well tolerated in this trial Objective To compare an oral estrogen- and rogen combination with estrogens alone on bone , menopausal symptoms , and lipoprotein profiles in postmenopausal women . Methods Surgically menopausal women received oral esterified estrogens ( 1.25 mg ) , or esterified estrogens ( 1.25 mg ) and methyltestosterone ( 2.5 mg ) daily , for 2 years . Bone mineral density of the lumbar spine and hip , menopausal symptoms , lipoprotein profiles , and biochemical and hematologic indices were evaluated . Results Sixty-six patients were enrolled in the study . Both treatment regimens prevented bone loss at the spine and hip ; combined estrogen- and rogen therapy was associated with a significant increase in spinal bone mineral density compared with baseline ( n = 24 ; mean score ± st and ard error 3.4 ± 1.2 % , P < .01 ) . In the estrogen group , high-density lipoprotein ( HDL ) cholesterol increased significantly and low-density lipoprotein cholesterol decreased significantly . Cholesterol , HDL cholesterol , and triglycerides decreased significantly in the estrogen- and rogen  group . Menopausal symptoms of somatic origin ( hot flashes , vaginal dryness , and insomnia ) were improved significantly by both treatments . Neither adverse hepatic effects nor significant safety or tolerance problems were reported in either group . Conclusion Oral estrogen- and rogen  increased vertebral bone mineral density compared with pre-treatment values and relieved somatic symptoms . Safety indices , including lipoprotein levels , indicated that the combination was well tolerated over the 2 years of treatment CONTEXT Changes in and rogen levels across the adult female life span and the effects of natural menopause and oophorectomy have not been clearly established . OBJECTIVE The objective of this study was to document the effects of age on and rogen levels in healthy women and to explore the effects of natural and surgical menopause . DESIGN , SETTING , AND PARTICIPANTS A cross-sectional study was conducted of 1423 non-healthcare-seeking women , aged 18 - 75 yr , r and omly recruited from the community over 15 months . MAIN OUTCOME MEASURES Serum levels by age of total testosterone ( T ) , calculated free T , dehydroepi and rosterone sulfate , and and rostenedione in a reference group of women free of confounding factors . Women in the reference group had no usage of exogenous steroid therapy ; no history of tubal ligation , hysterectomy , or bilateral oophorectomy ; and no hyperprolactinemia or polycystic ovarian syndrome . The effects of natural and surgical menopause on sex steroid levels were also examined . RESULTS In the reference population ( n = 595 ) , total T , calculated free T , dehydroepi and rosterone sulfate , and and rostenedione declined steeply with age ( P < 0.001 ) , with the decline of each being greater in the earlier than the later decades . Examination of serum and rogen levels by year in women aged 45 - 54 yr showed no independent effect of menopausal status on and rogen levels . In women aged 55 yr or older , those who reported bilateral oophorectomy and were not on exogenous steroids had significantly lower total T and free T levels than women 55 yr or older in the reference group . CONCLUSIONS We report that serum and rogen levels decline steeply in the early reproductive years and do not vary because a consequence of natural menopause and that the postmenopausal ovary appears to be an ongoing site of testosterone production . These significant variations in and rogens with age must be taken into account when normal ranges are reported and in studies of the role of and rogens in women OBJECTIVE In some women , a decline in sexual interest accompanies a relative and rogen insufficiency after menopause . We sought to characterize the hormonal effects of the combination of oral esterified estrogens and methyltestosterone and to investigate whether this regimen improves hypoactive sexual desire . DESIGN Double-blind r and omized trial . SETTING Healthy volunteers in a multicenter research environment . PATIENT(S ) Postmenopausal women taking estrogen therapy who were experiencing hypoactive sexual desire . INTERVENTION(S ) 4 months of treatment with 0.625 mg of esterified estrogens ( n = 111 ) or the combination of 0.625 mg of esterified estrogens and 1.25 mg of methyltestosterone ( n = 107 ) . MAIN OUTCOME MEASURES Baseline and end-of- study measurements of total and bioavailable testosterone and sex hormone-binding globulin ( SHBG ) , and mean change in level of sexual interest or desire as rated on the Sexual Interest Question naire . RESULT ( S ) Treatment with the combination of esterified estrogens and methyltestosterone significantly increased the concentration of bioavailable testosterone and suppressed SHBG . Scores measuring sexual interest or desire and frequency of desire increased from baseline with combination treatment and were significantly greater than those achieved with esterified estrogens alone . Treatment with the combination was well tolerated . CONCLUSION ( S ) Increased circulating levels of unbound testosterone and suppression of SHBG provide a plausible hormonal explanation for the significantly improved sexual functioning in women receiving the combination of esterified estrogen and methyltestosterone OBJECTIVE To investigate the efficacy of esterified estrogens alone and combined with oral and rogen on sexual function and menopausal symptoms in postmenopausal women . STUDY DESIGN Twenty postmenopausal women dissatisfied with their estrogen or estrogen-progestin therapy volunteered to enter a double-blind , r and omized trial in which they received either oral esterified estrogens or esterified estrogens + and rogen for eight weeks after a single-blind , placebo , lead-in period . Sexual function was assessed with a question naire used in the Yale midlife survey , and plasma levels of estradiol , estrone , sex hormone binding globulin ( SHBG ) and beta-endorphin were measured at two- to four-week intervals . RESULTS Estrogen- and rogen therapy significantly improved sexual sensation and desire after four and eight weeks of double-blind treatment in comparison to previous estrogen therapy and postplacebo baseline assessment s. Plasma levels of estradiol and estrone increased significantly in all patients as compared to the postplacebo baseline and decreased in comparison to circulating estrogen concentrations on previous therapy . Relative proportions of free and bound steroid hormone exhibited contrasting shifts during estrogen and estrogen- and rogen therapy .  SHBG increased in the estrogen group and decreased in the estrogen- and rogen group , leading to lower amounts of free and rogens during estrogen therapy and increased free and rogen levels during estrogen- and rogen therapy . Since proportions of free ( bioavailable ) ovarian steroids would correlate inversely with plasma protein binding capacity , the beneficial effects of oral estrogen- and rogen therapy on sexual sensation and desire may be due either to the administered and rogen or to the increased availability of endogenous and exogenous and rogens , particularly in the central nervous system . CONCLUSION Sexual desire , satisfaction and frequency in postmenopausal women taking hormonal therapy were improved significantly by combined estrogen- and rogen therapy but not by estrogen or estrogen-progestin therapy .  Sexual function improved with estrogen- and rogen therapy even though circulating estrogen levels were lower than those measured during previous estrogen therapy . This leads to the conclusion that and rogens play a pivotal role in sexual function but that estrogens are not a significant factor determining levels of sexual drive and enjoyment METHODS In a r and omized , double-blind , placebo-controlled clinical trial , we evaluated the effect of a 2-year treatment with n and rolone decanoate ( ND ) on bone mineral density ( BMD ) of lumbar spine , femoral neck , and trochanter and on vertebral fracture rate , muscle mass , and hemoglobin levels .  Sixty-five osteoporotic women older than 70 years were studied . Thirty-two patients received injections of 50 mg ND , and 33 received placebos every 3 weeks . All patients received 500 mg calcium tablets daily . RESULTS Compared to baseline , ND increased the BMD of the lumbar spine ( 3.4 % + /- 6.0 and 3.7 % + /- 7.4 ; p < .05 ) and femoral neck ( 4.1 % + /- 7.3 and 4.7 % + /- 8.0 ; p < .05 ) after 1 and 2 years , respectively . The BMD of trochanter increased significantly only after the first year ( 4.8 % + /- 9.3 , p < .05 ) . Compared to the placebo group , the ND group presented with significantly increased BMD of the trochanter and neck . ND significantly reduced incidence of new vertebral fractures ( 21 % vs 43 % in the placebo group ; p < .05 ) . ND showed a significant statistical increase in lean body mass after the first ( 6.2 % + /- 5.8 ; p < .01 ) and second years ( 11.9 % + /- 29.2 ; p < .01 ) . In addition , a 2-year treatment with ND significantly increased hemoglobin levels compared to baseline ( 14.3 % ; p < .01 ) and placebo ( p < .01 ) . CONCLUSIONS ND increased BMD , hemoglobin levels , and muscle mass , and reduced the vertebral fracture rate of elderly osteoporotic women Objective The cardioprotective effects of postmenopausal estrogen replacement therapy are mediated by several mechanisms , including favorable effects on lipids and lipoproteins . The extent to which the latter reflects modification of body fat distribution by sex steroids is not known . Hence , we investigated the relationships between changes in lipids and measures of body composition in postmenopausal women who were administered estrogen therapy with and without testosterone .  Design We r and omized 33 postmenopausal women to treatment with either estradiol 50 mg ( E ) alone or estradiol 50 mg plus testosterone 50 mg implants ( E&T ) administered every 3 months for 2 years in conjunction with  cyclic oral progestins  for women with an intact uterus . Results Both therapies were associated with sustained reductions in total cholesterol and low-density lipoprotein ( LDL ) cholesterol . In women who received E but not E&T , hip ( p < 0.001 ) and abdominal circumferences ( p < 0.05 ) and fat mass : fat-free mass ( FM : FFM ) ratio over the abdomen ( p < 0.05 ) declined . E&T but not E result ed in increased FFM ( p < 0.001 ) and a reduced FM : FFM ratio ( p < 0.05 ) . For E but not E&T , the decrease in LDL cholesterol was significantly related to changes in total and compartmental body fat and to change in the FM : FFM ratio ( p < 0.05 ) . Conclusion Estrogen replacement has effects on body fat distribution in postmenopausal women that are associated with improved lipid parameters . Addition of parenteral testosterone does not negate the favorable effects of estrogen on LDL cholesterol levels but may attenuate the reduction in central ized body fat achieved with E implants Objective . To evaluate the effect of adding testosterone undecanoate 40 mg daily to estrogen therapy on bone markers , bone mineral density and body composition in oophorectomized women . Methods . Fifty women , 45–60 years old , who had undergone a hysterectomy and bilateral salpingo-oophorectomy for benign disorders , were r and omly assigned to oral treatment with testosterone undecanoate 40 mg plus estradiol valerate 2 mg daily or placebo plus estradiol valerate 2 mg daily . Twenty-four weeks later , cross-over was performed to the other treatment regimen . Forty-four women completed the study . Their serum concentrations of insulin-like growth factor (IGF)-I , IGF binding protein (IGFBP)-3 , osteocalcin , carboxyterminal telopeptide aminoterminal ( ICTP ) , of type I collagen propeptide of type I procollagen ( PICP ) and interleukin (IL)-1 receptor antagonist were measured at baseline and after 24 weeks of both treatments , as were also their body mass index ( BMI ) and blood pressure . Bone mineral density of the total body , spine and hip and total body fat , total lean body mass , trunk fat and trunk lean mass were determined by dual-energy X-ray absorptiometry measurements at baseline and after 24 weeks of both regimens . Results . During treatment , the addition of testosterone counteracted the decrease in IGF-I and PICP seen with estrogen therapy alone . Osteocalcin and ICTP were significantly reduced to the same extent by both therapies . No change ocurred in the IL-1 receptor antagonist . A significant increase was seen in total lean body mass with the estrogen/testosterone regimen , but the total fat mass , trunk lean or fat mass remained unchanged after 24 weeks of both treatments . No effect was detected on total , hip or spinal bone mineral density after treatment with estrogen alone or estrogen/testosterone . Likewise , BMI and blood pressure were unaffected . Conclusions . The addition of testosterone to oral estrogen might have positive effects on bone as suggested by the fact that it counteracted the decline in IGF-I and PICP levels . An anabolic effect on muscle was reflected by an increase in the total lean body mass . No adverse effects were noted on BMI , fat distribution or blood pressure during the 6-month treatment with oral testosterone undecanoate OBJECTIVES This study was carried out to assess the effect of topical and rogen replacement therapy on body weight , body composition and fat distribution in postmenopausal women . METHODS 39 healthy postmenopausal women ( 51.4 + /- 2.24 years ) , with increasing body weight , were prospect ively studied for 6 months . Body composition ( fat mass , kg , % ) was measured by means of dual-energy X-ray absorptiometry ( DXA ) . Hormonal and lipid parameters were also measured . Subjects were divided into two groups . An and rogen gel ( group A ) or placebo gel ( group P ) was topically administered to the abdominal and gluteo-femoral regions . DXA was performed before commencement of topical treatment and after 6 months . RESULTS A highly significant total body weight reduction was found in group A ( 68.0 + /- 13.1 to 65.4 + /- 11.8 kg ) . Abdominal fat ( 37.3 + /- 11.2 to 35.1 + /- 9.7 % ) , gluteo-femoral fat ( 46.3 + /- 6.6 to 45.4 + /- 7.7 % ) , total body fat ( 38.2 + /- 7.9 to 36.1 + /- 8.6 % ) and BMI ( 24.8 + /- 4.3 to 23.7 + /- 3.8 ) were also found to have decreased significantly in this group . No significant reduction in body weight ( kg ) and body fat ( % ) could be measured in the placebo group . No influence on lipid parameters was found although total testosterone increased significantly in group A ( 0.29 + /- 0.24 to 0.72 + /- 0.17 ng/ml ) . CONCLUSIONS Topically applied and rogen is capable of reducing abdominal fat accumulations as well as total body weight in postmenopausal women with unexplained weight gain . In contrast to systemic and rogen application , topical administration has no effect on the lipid profile . Gluteal fat , however , is less effectively influenced by and rogens BACKGROUND The ovaries provide approximately half the circulating testosterone in premenopausal women . After bilateral oophorectomy , many women report impaired sexual functioning despite estrogen replacement . We evaluated the effects of transdermal testosterone in women who had impaired sexual function after surgically induced menopause . METHODS Seventy-five women , 31 to 56 years old , who had undergone oophorectomy and hysterectomy received conjugated equine estrogens ( at least 0.625 mg per day orally ) and , in r and om order , placebo , 150 microg of testosterone , and 300 microg of testosterone per day transdermally for 12 weeks each . Outcome measures included scores on the Brief Index of Sexual Functioning for Women , the Psychological General Well-Being Index , and a sexual-function diary completed over the telephone . RESULTS The mean ( + /-SD ) serum free testosterone concentration increased from 1.2+/-0.8 pg per milliliter ( 4.2+/-2.8 pmol per liter ) during placebo treatment to 3.9+/-2.4 pg per milliliter ( 13.5+/-8.3 pmol per liter ) and 5.9+/-4.8 pg per milliliter ( 20.5+/-16.6 pmol per liter ) during treatment with 150 and 300 microg of testosterone per day , respectively ( normal range , 1.3 to 6.8 pg per milliliter [ 4.5 to 23.6 pmol per liter ] ) . Despite an appreciable placebo response , the higher testosterone dose result ed in further increases in scores for frequency of sexual activity and pleasure-orgasm in the Brief index of Sexual Functioning for Women ( P=0.03 for both comparisons with placebo ) . At the higher dose the percentages of women who had sexual fantasies , masturbated , or engaged in sexual intercourse at least once a week increased two to three times from base line . The positive-well-being , depressed-mood , and composite scores of the Psychological General Well-Being Index also improved at the higher dose ( P=0.04 , P=0.03 , and P=0.04 , respectively , for the comparison with placebo ) , but the scores on the telephone-based diary did not increase significantly . CONCLUSIONS In women who have undergone oophorectomy and hysterectomy , transdermal testosterone improves sexual function and psychological well-being Objective : To evaluate the efficacy and safety of a testosterone patch for the treatment of women with hypoactive sexual desire disorder after natural menopause . Design : A multicenter , r and omized , double-blind , placebo-controlled , parallel-group trial was conducted in naturally menopausal women with hypoactive sexual desire disorder receiving a stable dose of oral estrogen with or without progestin ( N = 549 ) . Women were r and omized to receive testosterone 300 & mgr;g/day or placebo patches twice weekly for 24 weeks . The primary efficacy measure was change from baseline in frequency of total satisfying sexual activity over a 4-week period ( weeks 21 - 24 ) . Results : A total of 483 women ( 88 % ) were included in the primary analysis population ( those with baseline sex hormone binding globulin levels ≤160 nmol/L ) . The change from baseline in number of total satisfying sexual episodes was significantly greater for testosterone compared with placebo ( participants with baseline sex hormone binding globulin levels ≤160 nmol/L , mean change of 2.1 ± 0.28 versus 0.5 ± 0.23 episodes/4 weeks ; P < 0.0001 ; intent-to-treat population , mean change from baseline of 1.9 ± 0.26 versus 0.5 ± 0.21 episodes/4 weeks , P <  0.0001  ) . Testosterone also produced statistically significant improvements  compared with placebo in all secondary efficacy measures , including sexual desire and personal distress . The testosterone patch was well tolerated . Conclusions : Testosterone patch treatment increased the frequency of satisfying sexual activity and sexual desire , decreased personal distress , and was well tolerated in naturally menopausal women with hypoactive sexual desire disorder And rogens are known to lower plasma triglycerides , an independent risk factor for coronary heart disease ( CHD ) . Triglycerides are carried in plasma on very low density ( VLDL ) and low density ( LDL ) lipoprotein particles . Apolipoprotein CIII ( apoCIII ) , a strong predictor of CHD , impairs the metabolism of VLDL and LDL , contributing to increased triglycerides . The objective of this study was to assess the effect of oral methyltestosterone ( 2.5 mg/d ) , added to esterified estrogens ( 1.25 mg/d ) , on concentrations of apolipoproteins and lipoproteins , specifically those containing apoCIII , compared with esterified estrogens alone in surgically postmenopausal women . The women in the methyltestosterone plus esterified estrogen group had significant decreases in total triglycerides , apoCI , apoCII , apoCIII , apoE , and high density lipoprotein ( HDL ) cholesterol compared with those in the esterified estrogen group . The decreases in apoCIII concentrations occurred in VLDL ( 62 % ; P = 0.02 ) , LDL ( 35 % ; P = 0.001 ) , and HDL ( 17 % ; P < 0.0001 ) . There were also decreases in cholesterol and triglycerides concentrations of apoCIII containing LDL , and apoCI concentration of apoCIII containing VLDL . There was no effect on VLDL and LDL particles that did not contain apoCIII or on apoB concentrations . In conclusion , methyltestosterone , when administered to surgically postmenopausal women taking esterified estrogen , has a selective effect to reduce the apoCIII concentration in VLDL and LDL , a predictor of CHD . Methyltestosterone may lower plasma triglycerides through a reduction in apoCIII Twenty-five women with a previous total abdominal hysterectomy with bilateral salpingo – oophorectomy ( TAH BSO ) were given estradiol 50 mg implants at baseline , followed at 16 weeks with the combination of estradiol 50 mg and testosterone 100 mg . Blood sample s were taken at 8-weekly intervals over 32 weeks . Serum levels of estradiol , testosterone , sex hormone binding globulin ( SHBG ) and agents involved in skeletal growth ( growth hormone ( GH ) , insulin-like growth factor 1 ( IGF-1 ) , carboxy terminal pro-peptide of type 1 pro-collagen ( PICP ; a bone formation marker ) and cross-linked carboxy terminal telopeptide ( ICTP ; a marker of bone resorption ) ) were measured . Serum PICP levels increased significantly after estradiol alone ( p = 0.0032 ) but the addition of testosterone had no significant effects on bone markers GH and IGF-1 . These biochemical changes confirm previous studies , which found that the addition of testosterone did not augment the effect of estradiol implants on bone mineral density . Although physiological hormone replacement therapy in oophorectomized women would include replacement of both estradiol and testosterone , this may not to be necessary for prevention of osteoporosis where adequate serum estradiol levels are reached To investigate the role of and rogens in increasing bone density and improving low libido in postmenopausal women , we have studied the long-term effects of estradiol and testosterone implants on bone mineral density and sexuality in a prospect i ve , 2 year , single-blind r and omised trial . Thirty-four postmenopausal volunteers were r and omised to treatment with either estradiol implants 50 mg alone ( E ) or estradiol 50 mg plus testosterone 50 mg ( E&T ) , administered 3-monthly for 2 years . Cyclical oral progestins were taken by those women with an intact uterus . Thirty-two women completed the study .  BMD ( DEXA ) of total body , lumbar vertebrae ( L1-L4 ) and hip area increased significantly in both treatment groups . BMD increased more rapidly in the testosterone treated group at all sites . A substantially greater increase in BMD occurred in the E&T group for total body ( P < 0.008 ) , vertebral L1-L4 ( P < 0.001 ) and trochanteric ( P < 0.005 ) measurements . All sexual parameters ( Sabbatsberg sexual self-rating scale ) improved significantly in both groups . Addition of testosterone result ed in a significantly greater improvement compared to E for sexual activity ( P < 0.03 ) , satisfaction ( P < 0.03 ) , pleasure ( P < 0.01 ) , orgasm ( P < 0.035 ) and relevancy ( P < 0.05 ) . Total cholesterol and LDL-cholesterol fell in both groups as did total body fat . Total body fat-free mass ( DEXA , anthropometry , impedance ) increased in the E&T group only . We concluded that in postmenopausal women , treatment with combined estradiol and testosterone implants was more effective in increasing bone mineral density in the hip and lumbar spine than estradiol implants alone . Significantly greater improvement in sexuality was observed with combined therapy , verifying the therapeutic value of testosterone implants for diminished libido in postmenopausal women . The favourable estrogenic effects on lipids were preserved in women treated with T , in association with beneficial changes in body composition OBJECTIVE The purpose of this study was to investigate the hormonal changes during the menopausal transition in a non- clinical population . METHODS Fifty-nine healthy Norwegian women participated in a five year prospect i ve longitudinal study during the transition from pre- to post-menopause , starting one to four years before menopause , and ending one to four years postmenopausal . None of these women were given hormone replacement therapy ( HRT ) . Blood sample s were collected every 12 months and luteinizing hormone ( LH ) , follicle stimulating hormone ( FSH ) , steroid hormone binding globuline ( SHBG ) , prolactin ( PRL ) , estradiol ( E2 ) , estrone ( E1 ) , testosterone , and rostendione , dehydroepi and rostendione-sulphate ( DHEA-S ) , and thyroid stimulating hormone ( TSH ) were analyzed . RESULTS The serum levels of FSH and LH , E2 and E1 profile essentially confirmed previous data obtained in cross-sectional studies . A continuous increase in serum FSH and LH and a concomitant fall in E2 and E1 were observed in all women before menopause and in the two postmenopausal years . Both and rostendione and testosterone showed a decline three years before menopause . After the menopause , however , there were fluctuations in the testosterone levels . And rostendione correlated positively with both E2 and E1 and testosterone postmenopausally . Body mass index ( BMI ) did correlate with testosterone , but not with and rostendione . BMI correlated negatively with SHBG . No correlation was found between BMI and E2 , E1 , FSH and LH . CONCLUSION This longitudinal prospect i ve study of hormonal changes during the transition from pre- to postmenopause indicates that not only estrogen hormonal changes , but and rogen hormonal changes as well , precedes the menopause by several years Menopause is associated with decreased lean body mass and increased fat due to aging and declining hormone secretion . Estrogens or estrogen-progestins have been used to alleviate vasomotor symptoms . However , estrogen- and rogen ( E/A ) therapy is also used for vasomotor symptom relief and has been shown to increase lean body mass while decreasing fat mass . The objective of this 16-wk , double-blind , r and omized , parallel group clinical trial was to compare esterified estrogen plus methyltestosterone ( 1.25 mg estrogen + 2.5 mg methyltestosterone/d ; E/A group ) vs. esterified estrogen alone ( 1.25 mg/d ; E group ) on body composition . Forty postmenopausal women ( mean age , 57 yr ) participated . Compared with estrogen treatment alone , women in the E/A group increased their total lean body mass and reduced their percentage fat for all body parts ( P < 0.05 ) . After E/A treatment , there were statistically significant increases in lean body mass by 1.232 kg [ 0.181 + /- 0.004 , 0.81 + /- 0.057 , and 0.24 + /- 0.009 kg in the upper body ( P = 0.021 ) , trunk ( P = 0.001 ) , and lower body ( P = 0.047 ) , respectively ] . In the E group , the increase was 0.31 + /- 0.004 , 0.021 + /- 0.03 , and 0.056 + /- 0.05 kg in the upper body , trunk , and lower body , respectively . In the E/A group , body fat was reduced by 0.90 kg ( P = 0.18 for the trunk only ) , and percentage body fat declined by 7.4 % ( P < or = 0.05 for all body parts ) . Lower body strength increased by 23.1 kg ( 51 lb ) in the E/A group vs. only 11 kg ( 24.25 lb ) in the E group ( P = 0.002 between groups ) . A statistically significant increase in weight ( 2.7 + /- 5.1 vs. 0.1 + /- 4.6 lb ; P < 0.05 ) was observed in the E/A group compared with the E group . When subjects were given self-reporting question naires , more improvement was noted in sexual functioning and quality of life in the  E/A  group when compared with patients receiving E alone . There were no noteworthy side effects . In conclusion , E/A replacement therapy can improve body composition , lower-body muscle strength , quality of life , and sexual functioning in postmenopausal women STUDY OBJECTIVE --To compare oral and implanted oestrogens for their effects in preventing  postmenopausal osteoporosis .  DESIGN --Non-r and omised cohort study of postmenopausal women treated with oral or depot oestrogens and postmenopausal controls . SETTING --Gynaecological endocrine clinic in tertiary referral centre . PATIENTS --Oral treatment group of 37 postmenopausal women ( mean age 57.5 years , median 8.75 years from last menstrual period ) , compared with 41 women given oestrogen implants ( mean age 56.2 years , median 9.5 years from last menstrual period ) and 36 controls ( mean age 51.8 years , median 2.0 years from last menstrual period ) . Weight was not significantly different among the groups . INTERVENTIONS --Oral treatment group was given continuous treatment with cyclic oestrogen and progesterone preparations ( Prempak C or Cycloprogynova ) for a median of 8.0 years . Implant group was given subcutaneous implants of oestradiol 50 mg combined with testosterone 100 mg , on average six monthly for a median of 8.5 years . Controls were not treated . END POINT -- Significant increase in bone density . MEASUREMENTS AND MAIN RESULTS --Bone density measured by dual beam photon absorptiometry was 1.02 ( SD 0.13 ) g hydroxyapatite/cm2 in implant group versus 0.89 ( 0.11 ) in oral group ( p less than 0.01 ) and 0.87 ( 0.14 ) in controls ( p less than 0.01 ) . Serum oestradiol concentration in implant group was ( median ) 725 pmol/l versus 170 pmol/l in oral group ( p less than 0.01 ) and 99 pmol/l in controls ( p less than 0.01 ) . Serum follicular stimulating hormone was median 1 IU/l ( range 1 - 11 ) in implant group ( equivalent to premenopausal values ) versus 43 ( 4 - 94 ) IU/l in oral group ( p less than 0.01 ) and 72 ( 28 - 99 ) IU/l in controls ( p less than 0.01 ) . CONCLUSIONS --Subcutaneous oestrogen is more effective than oral oestrogen in preventing osteoporosis , probably owing to the more physiological ( premenopausal ) serum oestradiol concentrations achieved . It also avoids problems of compliance that occur with oral treatment CONTEXT Available data concerning effects of testosterone on endometrium of postmenopausal women are seriously limited . OBJECTIVE Our aim was to compare the influence of treatment with testosterone and /or estrogen on endometrial proliferation in healthy postmenopausal women . DESIGN This was an open , r and omized clinical study with parallel comparison of the groups . SETTING The study was conducted at a women 's health clinical research unit and a research laboratory at a university hospital . PARTICIPANTS Sixty-three women who had experienced natural menopause participated in this study . INTERVENTIONS After r and om assignment , the participants were administered orally testosterone undecanoate ( 40 mg every second day ) , estradiol valerate ( 2 mg daily ) , or both for 3 months . MAIN OUTCOME MEASURES Endometrial thickness was measured , and endometrial proliferation evaluated on the basis of histopathology and expression of Ki-67 , a proliferation marker . RESULTS Endometrial thickness was significantly increased by treatment with estrogen alone or in combination with testosterone but was unaltered by testosterone alone . Among the women receiving estrogen alone , the proportion exhibiting histopathology indicative of proliferation increased significantly to 50 % ( P < 0.05 ) , there was a nonsignificant increase to 28 % with the combined treatment , whereas testosterone alone had no effect at all . Expression of Ki-67 was up-regulated significantly in both gl and s and stroma ( P < 0.05 , respectively ) in both estrogen treatment groups . However , the expression was significantly higher in stroma by estrogen treatment alone than after combined treatment ( P < 0.05 ) . CONCLUSIONS The short-term treatment with testosterone of postmenopausal women does not stimulate endometrial proliferation . In addition , testosterone appears to counteract endometrial proliferation induced by estrogen to a certain extent The present study examined effects of testosterone on  hypoactive sexual desire in pre- and postmenopausal women ( treated ) compared with an age-matched reference group ( reference ) . Treated participants received 100 mg of testosterone cypionate in oil injected intramuscularly ( i.m . ) monthly for 3 months . We measured salivary testosterone and scores on the Sexual Desire Inventory pretreatment and posttreatment . Treated and reference participants ' baseline testosterone was equivalent , however , treated participants exhibited higher testosterone levels than did reference participants posttreatment . As expected , treated participants exhibited lower baseline sexual desire than did reference participants and showed a significant increase in sexual desire posttreatment . This research suggests that testosterone may effectively alleviate hypoactive sexual desire , even in women with normal testosterone levels OBJECTIVE To determine the effect of the and rogen supplementation of hormone replacement therapy ( HRT )  on the vascular reactivity of cerebral arteries . DESIGN Open r and omized study . SETTING Healthy volunteers in an academic research environment . PATIENT(S ) Forty postmenopausal women who were treated with sequential HRT ( transdermal E2 50 microg/d + medroxyprogesterone acetate 10 mg/d for 12 days every other month ) for > or = 1 year and < or = 5 years . INTERVENTION(S ) Testosterone undecanoate ( 40 mg/d , p.o . ) was r and omly administered to 20 patients during ongoing HRT ;  the other 20 served as controls . Doppler evaluations of the internal carotid and middle cerebral arteries were performed together with lipid levels assessment s. A visual analogue scale ( VAS ) was used to evaluate various parameters relating to sexual life and well-being . MAIN OUTCOME MEASURE(S ) Pulsatility index ( PI ) of the arteries , VAS assessment of psychophysical well-being . RESULT ( S ) The administration of testosterone undecanoate during HRT induced an increase in the PI of the middle cerebral artery and a reduction of high-density lipoprotein cholesterol . Sexual desire and satisfaction were greatly improved . CONCLUSION ( S ) In postmenopausal women , and rogen supplementation during HRT can partially counteract the beneficial effects of estrogens on cerebral vascular reactivity and lipid profiles , but sexual desire and satisfaction are greatly improved BACKGROUND The frequency of bone loss among women using postmenopausal hormone therapy is unknown . METHODS We used data from the Postmenopausal Estrogen/Progestin Interventions Trial to address the frequency of bone loss among women using postmenopausal hormone replacement therapy .  Of 701 women r and omized to active treatment ( conjugated equine estrogens alone or in combination with 1 of 3 progestins ) , 538 ( 76.7 % ) were adherent and had replicate bone mineral density ( BMD ) measures at baseline , 12 months , and 36 months . Of 174 placebo-assigned women , 132 ( 75.9 % ) were similarly eligible . Replicate BMD measures were used to calculate within-person measurement errors , which were then used to delineate cut points that defined bone losers with 97.5 % , 95.0 % , 90.0 % , or 75.0 % confidence . RESULTS At the lumbar spine , during the first 12 months , 1.5 % of hormone users lost BMD with 97.5 % confidence , corresponding to a decline of -3 % per year ; during months 12 to 36 , only 0.6 % of treated women lost spinal BMD to this degree . An annual loss of -1 % or more was the criterion for spinal bone loss at the 75.0 % confidence level ; 5.1 % and 8.0 % of hormone users met this criterion in the first year and in months 12 to 36 , respectively . For the total hip , during the first 12 months , 2.3 % of hormone-adherent women lost -3.0 % per year or more , the 97.5 % confidence definition of loss ; 0.4 % were so classified during months 12 to 36 . To be 75.0 % confident of hip BMD loss , a -1.0 % per year decline in BMD was required ; using this criterion , 14.5 % and 11.8 % of hormone users lost total hip BMD between 0 to 12 and 12 to 36 months , respectively . Among hormone-adherent women , at the spine and hip , there was virtually no overlap between women classified as bone losers in the first 12 months and those classified as such in the last 24 months . With 95.0 % certainty , corresponding to an approximate loss of -2.5 % at the spine and hip , 31.3 % and 11.7 % of placebo-adherent women lost spinal BMD in the first 12 and last 24 months , respectively . Parallel figures for the hip were 32.3 % and 7.9 % , respectively . CONCLUSION Bone loss while taking postmenopausal hormones is rare , and bone loss among untreated women is far from universal & NA ; Various parameters of sexual functioning were assessed in a prospect i ve , crossover investigation of 53 surgically menopausal women . Patients r and omly received either an estrogen‐ and rogen combined preparation , an estrogen‐alone drug , an and rogen‐alone drug , or a placebo .  Also included were a group of women who had undergone hysterectomy and whose ovaries had been left intact . Two treatment phases , each of 3 months ' duration , were separated by an intervening placebo month . Additionally , plasma levels of total estrogens and testosterone were assayed four times during the study concurrent with monitoring of sexual behaviors . It was clear that exogenous and rogen enhanced the intensity of sexual desire and arousal and the frequency of sexual fantasies in hysterectomized and oophorectomized women . However , there was no evidence that testosterone affected physiologic response or interpersonal aspects of sexual behavior . These findings suggest that the major impact of and rogen in women is on sexual motivation and not on sexual activity per se To observe the effects of and rogen replacement on neuropsychological measures in menopausal women , healthy menopausal women already using replacement estrogen  were studied in a r and omized , double-blind , active placebo-controlled , crossover comparison between two 8-week periods of treatment with ( 1 ) 0.625 mg oral esterified estrogen ( E ) alone and ( 2 ) in combination with 1.25 mg oral methyltestosterone ( meT ) . After an initial baseline session , data were gathered at the end of two treatment periods . Scores on st and ardized psychological tests and computerized reaction times were compared between treatments , as was an overall outcome score that combined all measures . Added meT significantly improved scores on a test of complex information processing , the Switching Attention Test , but not on other tests . Mean outcome score showed no net change and wide variation . Fourteen subjects had outcome scores > 1 SD from the mean , and 21 had no change . In the estrogen alone condition , three measures predicted favorable outcome with added meT : surgically compromised ovarian function , fewer physical symptoms , and higher score on a self-image measure of creativity . Added meT treatment may improve complex information processing . Despite wide disparities in outcome , an increased chance of overall improvement may be predicted by specific pretreatment measures CONTEXT Despite decades of accumulated observational evidence , the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain . OBJECTIVE To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States . DESIGN Estrogen plus progestin component of the Women 's Health Initiative , a r and omized controlled primary prevention trial ( planned duration , 8.5 years ) in which 16608 postmenopausal women aged 50 - 79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993 - 1998 . INTERVENTIONS Participants received conjugated equine estrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5 mg/d , in 1 tablet ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOMES MEASURES The primary outcome was coronary heart disease ( CHD ) ( nonfatal myocardial infa rct ion and CHD death ) , with invasive breast cancer as the primary adverse outcome . A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke , pulmonary embolism ( PE ) , endometrial cancer , colorectal cancer , hip fracture , and death due to other causes . RESULTS On May 31 , 2002 , after a mean of 5.2 years of follow-up , the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits . This report includes data on the major clinical outcomes through April 30 , 2002 . Estimated hazard ratios ( HRs ) ( nominal 95 % confidence intervals [ CIs ] ) were as follows : CHD , 1.29 ( 1.02 - 1.63 ) with 286 cases ; breast cancer , 1.26 ( 1.00 - 1.59 ) with 290 cases ; stroke , 1.41 ( 1.07 - 1.85 ) with 212 cases ; PE , 2.13 ( 1.39 - 3.25 ) with 101 cases ; colorectal cancer , 0.63 ( 0.43 - 0.92 ) with 112 cases ; endometrial cancer , 0.83 ( 0.47 - 1.47 ) with 47 cases ; hip fracture , 0.66 ( 0.45 - 0.98 ) with 106 cases ; and death due to other causes , 0.92 ( 0.74 - 1.14 ) with 331 cases . Corresponding HRs ( nominal 95 % CIs ) for composite outcomes were 1.22 ( 1.09 - 1.36 ) for total cardiovascular disease ( arterial and venous disease ) , 1.03 ( 0.90 - 1.17 ) for total cancer , 0.76 ( 0.69 - 0.85 ) for combined fractures , 0.98 ( 0.82 - 1.18 ) for total mortality , and 1.15 ( 1.03 - 1.28 ) for the global index . Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events , 8 more strokes , 8 more PEs , and 8 more invasive breast cancers , while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures . The absolute excess risk of events included in the global index was 19 per 10 000 person-years . CONCLUSIONS Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women .  All-cause mortality was not affected during the trial . The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases , and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD 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 In a double-blind trial oestradiol , oestradiol/testosterone , or placebo implants were assessed for their effects on psychological symptoms in women attending a menopause clinic . After two months , women receiving active treatment scored better than the placebo group on a self-rating scale of distress , on anxiety , and on depression ( p less than 0.05 ) . Postmenopausal but not perimenopausal women improved after placebo , and at 4 months the scores in the three groups no longer differed significantly background Coronary heart disease ( CHD ) is the leading cause of mortality in women , with an incidence that increases after menopause , hence suggesting a cardioprotective role of oestrogen . Menopause also results in a decline in and rogen levels with result ing symptoms of decreased libido and sexual dysfunction . Recently , there has been a growing interest in the treatment of postmenopausal women with and rogens . However , no data are available on plasma viscosity and fibrinogen levels in postmenopausal women on combined oestrogen/ and rogen therapy OBJECTIVE To compare the effects of estrogen with estrogen- and rogen treatment on vaginal blood flow velocity and fingertip postocclusive hyperemic blood flow response . DESIGN Prospect i ve , r and omized , parallel , double-blind study . SETTING Healthy human volunteers in an academic research environment . PATIENT(S ) Postmenopausal women receiving estrogen replacement therapy for at least 12 months and treated with placebo before this investigation . INTERVENTION(S ) Esterified estrogens or esterified estrogen + methyltestosterone were administered orally ; laser Doppler velocimetry was used to determine vaginal and fingertip blood flow responses at baseline and after 4 and 8 weeks of daily drug administration . MAIN OUTCOME MEASURE(S ) Fingertip postocclusive area under curve ( AUC ) ; vaginal blood flow velocities . RESULT ( S ) The AUC for postocclusive fingertip blood flow and vaginal blood flow increased to a greater extent in the estrogen- and rogen group , but changes were not statistically significant between groups . CONCLUSION ( S ) Estrogen- and rogen treatment does not diminish the vasodilator effects of estrogen treatment in postmenopausal women 55 postmenopausal women on established hormone replacement therapy were treated with either oestradiol and testosterone implants or placebo at the time of return of climacteric symptoms . Their response to therapy was assessed prospect ively . The statistically highly significant levels of symptom relief that followed an oestradiol and testosterone implant were contrasted sharply with the lack of any significant relief with placebo . Despite the success of oestradiol and testosterone implants in relieving symptoms of the climacteric , symptoms returned once the treatment was stopped . Evidence is presented that it is the fall in hormone levels rather than the level itself that provokes the return of climacteric symptoms OBJECTIVES To eluci date if percutanous treatment with 10 mg testosterone per day could enhance sexuality and psychological well-being in postmenopausal women presenting problems with low libido . Secondary to study the influence on blood lipids , hemoglobin and erythropoietin levels . METHODS Fifty-three postmenopausal women participated . As a complement to their already on-going HRT , 10 mg of a testosterone gel ( Testogel , Besins-Iscovesco ) or placebo was administered . Treatment continued for three plus three months in a double blind , r and omized , crossover design . RESULTS The scores concerning " frequency of sexual activity , orgasm and intercourse " , " sexual arousal , fantasies and enjoyment " , " satisfaction with orgasms " , and " interest in sex " were all significally improved for testosterone addition as compared to placebo both before and after crossover . Testosterone levels increased more than 10-fold during treatment while DHT-levels were more than doubled . Estrogen levels were not affected during the addition of testosterone . Liver enzymes , total cholesterol , triglycerides , HDL and LDL revealed no significant differences between any of the periods or groups . Endometrial thickness did not change significantly during treatment . Hemoglobin and erythropoietin remained unchanged . No significant differences in the number of experienced side effects were found . CONCLUSION Testosterone gel of 10 mg had positive effects on several aspects of sexual life such as frequency of sexual activity , orgasm , arousal , fantasies and sexual interest in postmenopausal women on HRT . Several psychological variables were positively influenced . The given dose result ed in too high serum levels . Even if no negative effects were observed , monitoring of serum levels and a decreased dose should be considered in future studies A double-blind , r and omized , placebo-controlled study was conducted in 46 postmenopausal women with established osteoporosis in order to assess the long-term effects of n and rolone decanoate on the bone mineral density ( BMD ) of the lumbar vertebrae and of the distal third of the radius and on the biochemical markers of bone turnover . The patients received intramuscular injections of placebo or 50 mg n and rolone decanoate every 3 weeks for 18 months . Thirty-two of the initial 46 patients completed 1 year of study and 25 completed the whole study period of 18 months . Overall , vertebral BMD increased by 2.9 % in the n and rolone decanoate group and fell by 2.3 % in the placebo group . Radial BMD showed a slight but transient improvement , with a subsequent return to basal levels in the n and rolone decanoate group , whereas there was a progressive decrease in the placebo group . Patients treated with n and rolone decanoate also complained less of bone pain . Urinary hydroxyproline decreased significantly in treated patients , whereas osteocalcin tended to increase , but the change was not significant . HDL cholesterol concentrations decreased only slightly and haemoglobin increased significantly in the n and rolone decanoate group . Two patients treated with n and rolone decanoate withdrew from the study because of hirsutism and hoarseness . The results indicate that n and rolone decanoate exerts positive effects on vertebral BMD and on bone pain in patients with established postmenopausal osteoporosis In a prospect i ve , double-blind , crossover study , it was found that surgically menopausal women who received an estrogen drug alone and those who were given a combined estrogen- and rogen preparation  reported a significantly reduced frequency of hot flushes compared to a placebo group ( p less than 0.01 ) coincident with their higher total plasma estrogen levels ( p less than 0.01 ) . The administration of testosterone alone , however , was ineffective in alleviating hot flushes , even though these patients had plasma estrogen values that were not different from those of women with intact ovaries . It was proposed that , in women with very low levels of endogenous estrogens , changes in sex hormone-binding globulin ( SHBG ) concentrations induced by exogenous testosterone may reduce the amount of non-SHBG-bound estrogens , thereby obviating estrogenic effects on hot flushes Previous studies indicated an enhanced capability of divergent creative thinking in young women during the ovulatory phase , which expressed itself also by an increased dimensional complexity of ongoing electroencephalographic ( EEG ) activity . Considering the enhanced plasma levels of estrogen and testosterone characterizing the ovulatory phase , we tested whether short-term administration of estrogen or testosterone in postmenopausal women with constantly low levels of gonadal steroids induces similar changes in divergent thinking . In two placebo-controlled cross-over studies , healthy postmenopausal women ( n=12 , in each study , mean age 58 years , range 47–65 years ) were treated transdermally over 3 days with estrogen and testosterone , respectively , at doses inducing plasma hormone concentrations comparable with those observed in young women around ovulation . Capabilities of divergent thought and convergent analytical thought , performance on motor perseveration , and verbal memory were examined . EEG activity  was recorded while subjects performed on tasks of thinking and during mental relaxation . Estrogen impaired divergent thinking ( p<0.01 ) and enhanced convergent thinking , motor perseveration , and memory for the initial word list ( p<0.05 for all tests ) . In parallel , EEG dimensional complexity was reduced ( p<0.05 ) . Overall , these changes indicate an estrogen-induced shift from a ‘ divergent ’ towards a more ‘ convergent ’ mode of processing . However , overall less consistent , effects of testosterone were opposite to those of estrogen . It increased performance on some of the divergent thinking tasks ( p<0.05 ) , and tended to increase EEG dimensional complexity during divergent thinking . Data indicate a differential sensitivity of modes of thinking to short-term treatment with estrogen and testosterone in postmenopausal women Objective : To compare the effect of esterified estrogens and methyltestosterone versus esterified estrogens alone on diminished sexual interest in surgically menopausal women . Design : This r and omized , double-blind study compared the effect of combined esterified estrogens ( 1.25 mg ) and methyltestosterone ( 2.5 mg ) ( EE/MT ) versus esterified estrogens ( 1.25 mg ) alone ( EE ) for 8 weeks . Several different sexual function question naires were used to measure response to therapy . Changes from baseline in sexual interest/function and hormone levels were evaluated after 4 and 8 weeks of treatment . Results : A total of 102 women were r and omized into the study ; 52 ( age range , 32 - 61 years ) to EE/MT and 50 ( age range , 33 - 62 years ) to EE .  After 8 weeks , significant differences between treatments were not seen in the Changes in Sexual Functioning Question naire ( CSFQ-F-C ) sexual desire/interest subscale score , the primary efficacy variable . In contrast statistically significant between-treatment differences were found for several secondary efficacy variables including Menopausal Sexual Interest Question naire ( MSIQ ) sexual interest/desire score , CSFQ-F-C arousal/erection subscale score and Women 's Health Question naire sexual functioning subscale score . The mean serum concentration of bioavailable and free testosterone significantly increased , approximately doubling between baseline and the end of the study in patients receiving EE/MT , with a significant ( P < 0.001 ) between-treatment difference . The mean serum concentration of sex hormone-binding globulin significantly decreased to less than one third of the pretreatment levels in patients receiving EE/MT ( P < 0.001 ) . Both treatments were well tolerated . Conclusions : The mixed results seen with the different sexual function question naires may be due to the CSFQ-F-C 's lack of specificity for this population . Increased levels of bioavailable and free testosterone paralleled the improved MSIQ item scores . Both the EE and EE/MT treatments were well tolerated Objective : To evaluate the effect of adding testosterone undecanoate 40 mg daily to estrogen replacement on sexual function , psychological well-being and self-esteem in surgically postmenopausal women . Methods : A letter of invitation to participate in the study was mailed to women who had undergone hysterectomy and bilateral oophorectomy for benign disorders during 1990 - 98 . Fifty women , 45 - 60 years old , were consecutively recruited and r and omly assigned to oral treatment with testosterone undecanoate 40 mg plus estradiol valerate 2 mg daily or placebo plus estradiol valerate 2 mg daily for 24 weeks . A double-blind design was chosen , with cross-over to the other regimen for another 24 weeks of treatment . Forty-four women completed the study . Outcome included scores on McCoy 's sex scale question naire , the Psychological General Well-Being index and a self-esteem question naire , at baseline and after 24 weeks of either treatment . Serum concentrations of total testosterone , sex hormone binding globulin , free testosterone , dihydrotestosterone , and rostenedione , estradiol , follicle stimulating hormone and luteinizing hormone were analyzed at baseline and after 24 weeks of both treatment regimens . Results : After 24 weeks , both treatment regimens had significantly improved some of the sexual variables . The addition of testosterone had a significantly better effect on the sex variables ' enjoyment of sex ' , ' satisfaction with frequency of sexual activity ' and ' interest in sex ' . The total McCoy score was significantly increased by both treatments , but there was a stronger effect when testosterone was also given . Although both regimens improved psychological well-being and self-esteem , we found no significant differences between testosterone-estrogen or estrogen alone at 24 weeks . Serum levels of all and rogens , with considerable individual variation , increased significantly from baseline after 24 weeks of testosterone-estrogen treatment . Supraphysiological levels were achieved in a significant proportion of the women . Increases in estradiol and sex hormone binding globulin were less marked when testosterone was also given . Both treatments reduced gonadotropin levels . Conclusions : The addition of testosterone undecanoate improved specific aspects of sexual function more than treatment with estrogen alone . Improvements in well-being and self-esteem were similar for both treatments . If testosterone undecanoate 40 mg daily should be used for clinical treatment , regular monitoring of and rogen serum levels is needed OBJECTIVE To evaluate the effects of giving testosterone undecanoate ( TU ) in addition to estrogen replacement on serum lipids in oophorectomized women . METHOD Women with surgically induced menopause ( n = 50 ) were r and omly assigned to oral treatment with 2 mg of estradiol valerate in combination with 40 mg of TU or placebo for 24 weeks . The study was double-blind with cross-over to the other regimen for further 24 weeks of treatment . Forty-four women completed the study . Their serum concentrations of total , high density lipoprotein (HDL)- and low density lipoprotein (LDL)-cholesterol , triglycerides , lipoprotein-(a ) ( Lp-(a ) ) , total testosterone , estradiol and sex hormone-binding globulin ( SHBG )  were analyzed at baseline and after 24 weeks of each treatment . RESULTS Serum levels of total testosterone increased markedly from a baseline mean of 0.8 - 4.9 nmol/l during testosterone addition . The levels of free testosterone significantly increased during the combined treatment and fell when given estrogen alone . Total and LDL-cholesterol levels were significantly reduced by both treatments as also were those of Lp-(a ) although the difference was not significant . We found a 13 % reduction in HDL-cholesterol levels when testosterone was added , but no change with estrogen alone . Triglyceride levels were increased by estrogen treatment , but not affected by the combination of estrogen plus testosterone . CONCLUSIONS These findings suggest that 40 mg of TU can be given in addition to estrogen replacement with only little side-effects on the pattern of circulating lipids . Although supraphysiological concentrations of testosterone were induced a significant reduction in total and LDL-cholesterol levels occurred Background  Testosterone ( Te ) , oestradiol , GH and IGF‐I concentrations fall in postmenopausal women The present study was undertaken to determine whether the addition of an and rogen to estrogen therapy in postmenopausal women would alter the skeletal response as determined by measurements of markers of bone formation and resorption .  Postmenopausal women were treated for 9 weeks with either a combination of 1.25 mg esterified estrogen and 2.5 mg methyltestosterone ( E+A ) or 1.25 mg conjugated equine estrogen ( CEE ) . Both groups showed a similar decrease in urinary excretion of the bone resorption markers , deoxypyridinoline , pyridinoline , and hydroxyproline . Patients treated with CEE showed decreases in the serum markers of bone formation , bone-specific alkaline phosphatase , osteocalcin , and C-terminal procollagen peptide . In contrast , subjects treated with E+A showed increases in these markers of bone formation . CEE increased , and E+A decreased serum levels of sex hormone-binding globulin as well as triglycerides and high density lipoprotein levels . Only CEE significantly reduced low density lipoproteins . Both regimens were effective in reducing postmenopausal somatic symptoms , but only E+A had a significant effect on psychological symptoms . We conclude that short term administration of and rogen with estrogen may reverse the inhibitory effects of estrogen on bone formation . Long term studies are needed to determine the relative benefits and risks of the combination of estrogen and and rogen and whether this results in greater increases in bone mass and strength The investigation of estrogen and /or and rogen administration on physical and psychological symptoms in the surgical menopause was carried out in a prospect i ve , double-blind , crossover design . When patients who received either a combined estrogen- and rogen drug or and rogen alone  were compared with those who received estrogen alone or placebo , energy level , well-being , and appetite were increased ( p less than 0.01 ) . The and rogen-containing preparations also induced lower somatic , psychological , and total scores on the menopausal index . Superior functioning in the and rogen-treated groups occurred in association with higher plasma testosterone levels during the treatment phases ( p less than 0.01 ) . These data suggest that reduced levels of circulating testosterone subsequent to bilateral oophorectomy may play an important role in the development of physical and psychological symptoms that are frequent sequelae of this surgical procedure Objective : During the past few years serious concern has been raised about the safety of combined estrogen/progestogen hormone therapy , in particular about its effects on the breast . Several observations suggest that and rogens may counteract the proliferative effects of estrogen and progestogen in the mammary gl and . Thus , we aim ed to study the effects of testosterone addition on breast cell proliferation during postmenopausal estrogen/progestogen therapy . Design : We conducted a 6-month prospect i ve , r and omized , double-blind , placebo-controlled study . A total of 99 postmenopausal women were given continuous combined estradiol 2 mg/norethisterone acetate 1 mg and were equally r and omly assigned to receive additional treatment with either a testosterone patch releasing 300 & mgr;g/24 hours or a placebo patch . Breast cells were collected by fine needle aspiration biopsy at baseline and after 6 months , and the main outcome measure was the percentage of proliferating breast cells positively stained by the Ki-67/MIB-1 antibody . Results : A total of 88 women , 47 receiving active treatment and 41 in the placebo group , completed the study . In the placebo group there was a more than fivefold increase ( P < 0.001 ) in total breast cell proliferation from baseline ( median 1.1 % ) to 6 months ( median 6.2 % ) . During testosterone addition , no significant increase was recorded ( 1.6 % vs 2.0 % ) . The different effects of the two treatments were apparent in both epithelial and stromal cells . Conclusions : Addition of testosterone may counteract breast cell proliferation as induced by estrogen/progestogen therapy in postmenopausal women Women experience somatic , mood , energy , and libido changes during menopause .  Testosterone replacement therapy is being prescribed in conjunction with estrogen replacement therapy ( ERT ) for these symptoms . Little is known about women ’s perceptions of the benefits and risks of testosterone , so an Internet survey was conducted to elicit women ’s perceptions of the effects on mood , energy , sexuality , and somatic symptoms .  A sample of 61 women primarily from the United States and Canada participated in the survey ; one woman from Germany and one from Sweden also took part in the survey . Participants reported significantly improved sexuality and improved mood and vigor , with a decline in fatigue . Of the 7 somatic complaints assessed , improvements were noted in 5 ( sleep disturbances , hot flashes , night sweats , vaginal dryness , and appetite ) . A prospect i ve clinical trial is needed to confirm these results Objective The cardiac syndrome X is described as the triad of angina pectoris , a positive exercise test for myocardial ischemia , and angiographically smooth coronary arteries . Although syndrome X does not result in an increased risk of cardiovascular mortality , the symptoms are often troublesome and unresponsive to conventional antianginal therapy . The majority of patients are postmenopausal , and estrogen therapy can alleviate anginal symptoms . We investigated the effect of esterified estrogens combined with methyltestosterone ( Estratest ) on quality of life in postmenopausal women with syndrome X. Design Patients were withdrawn from  antianginal therapy . Sublingual nitrates were allowed for treatment of anginal episodes . Patients underwent treadmill testing , and quality of life was assessed by using the Short Form-36 and Cardiac Health Profile question naires after the women had received 8 weeks of Estratest or identical placebo in a r and omized , double-blind , cross-over study . Results Nineteen patients were r and omized , and 16 patients completed the protocol .  Plasma 17&bgr;-estradiol concentrations were significantly increased by Estratest ; however , total testosterone levels were not . The “ emotional ” score of the Cardiac Health Profile question naire was significantly improved after Estratest use compared with placebo ( p = 0.03 ) ; however , there was no significant change in the Short Form-36 question naire for any variable . Estratest significantly increased systolic blood pressure and rate pressure product at rest but had no effect on exercise parameters . Time to onset of chest pain during exercise was also unaffected . Conclusions We have demonstrated a beneficial effect of Estratest on emotional well-being in postmenopausal women with cardiological syndrome X. There was no significant treatment effect on exercise parameters , including time to onset of chest pain The Heart and Estrogen/progestin Replacement Study ( HERS ) was a r and omized clinical trial of postmenopausal hormone  use in 2763 women ( 1 ) . Unlike previous observational studies , it included only women with previous coronary heart disease , and hormone therapy was exclusively oral conjugated estrogen plus progestin . In HERS , overall rates of recurrent coronary heart disease did not differ between the treated and nontreated groups . However , in additional , unplanned analyses , the results of HERS were not uniformly null . A marked and statistically significant trend toward decreasing risk was observed with increasing duration of hormone use ( 1 ) ; in the first year , the rate of major coronary events was 52 % higher in the treatment group . In the second year , rates were equal , but during the final fourth and fifth years , women assigned to hormone therapy had a 33 % lower risk for coronary events . The overall results of HERS and the apparent changes in risk over time were both unexpected . Since no previous investigations have examined the relation between duration of hormone use or combined hormone treatment to secondary prevention of coronary heart disease events , it remains unclear whether the time trend was authentic and whether the observations in HERS are limited to that hormone regimen ( 2 ) . In addition , we were interested in underst and ing how women 's use of hormone therapy before their initial coronary disease event might affect the outcome of their hormone use after that event . In HERS , duration of hormone therapy before trial entry was necessarily disregarded ( although 23 % of participants had previously taken hormones ) ; thus , it remains unknown how , or whether , to account for hormone use or duration of use before a patient 's initial coronary event . To further examine the effects of duration of hormone therapy and to explore the effect of different hormone regimens , we investigated the relation between  postmenopausal hormone use and secondary prevention of major coronary events in 2489 women with established coronary disease in the Nurses ' Health Study , a large observational cohort . Methods The Nurses ' Health Study Cohort The Nurses ' Health Study began in 1976 , when 121 700 female nurses 30 to 55 years of age completed a mailed question naire about  postmenopausal hormone use and medical history , including cardiovascular disease and its risk factors . Every 2 years , we mail follow-up question naires to the original participants to up date information on risk factors and to identify newly diagnosed cases of major illnesses . The total follow-up for the cohort to date exceeds 92 % . Sample for Analysis For this analysis , we limited the cohort to postmenopausal women who reported a previous myocardial infa rct ion or documented coronary atherosclerosis ( coronary artery bypass graft surgery , percutaneous coronary revascularization , or angiographic evidence of 70 % occlusion of one or more major coronary arteries ) . Such women were identified on the baseline question naire in 1976 ; postmenopausal women who reported one of these conditions on a subsequent follow-up question naire were added to the sample at that time . Women ranged in age from 34 to 73 years at entry into the sample for analysis ; 60 % of women had a natural menopause . These criteria closely parallel those used in HERS ( 1 ) ; however , in HERS , women with hysterectomy were excluded , occlusion was defined as at least 50 % , and participants ranged in age from 44 to 79 years . We classified women as postmenopausal from the time of natural menopause or hysterectomy with bilateral oophorectomy .  Women who underwent hysterectomy without bilateral oophorectomy were considered postmenopausal when they reached the age at which natural menopause had occurred in 90 % of the cohort ( 54 years for smokers and 56 years for nonsmokers ) ( 3 ) . The women 's reports of age at menopause and type of menopause were highly accurate ( 4 ) . In HERS , women with a history of breast or endometrial cancers were excluded . In the current study , we excluded women who reported stroke or cancer ( except nonmelanoma skin cancer ) on the 1976 baseline question naire at the outset and excluded women from further follow-up if they reported these diseases on a subsequent biennial question naire . This was done to avoid potential bias , in which major diseases such as stroke or cancer may have caused women to alter their hormone use and may be related to risk for coronary heart disease . This type of bias could not have occurred in a r and omized trial , such as HERS . Two hundred forty-eight postmenopausal women with coronary disease entered the analysis in 1976 , and 2241 postmenopausal women were added during follow-up as they reported heart disease ; thus , 17 239 person-years accrued during up to 20 years of follow-up from 1976 to 1996 . Ascertainment of Hormone Use In 1976 , women were asked about current and past use and duration of hormone therapy ;  this information was up date d on each biennial question naire . Beginning in 1978 and on each subsequent question naire , we collected information on type of hormone used . For the period 19761978 , we assigned women to the type of hormone reported on the 1978 question naire . If no data were available on hormone therapy for a given 2-year period , those women were assigned to a missing category for that period . In the HERS trial , women who had taken hormones in the 3 months before their screening visit were excluded ( although 23 % to 24 % of the enrolled participants had previously used hormones ) . Because this study is observational , we could not impose a 3-month washout period ; thus , we could not duplicate that aspect of the HERS protocol . We analyzed duration of hormone use in two different ways . In the main analysis , we performed a HERS replication and used a method similar to that in HERS to calculate duration of use . In HERS , duration of hormone therapy began to accrue at r and omization ( regardless of previous hormone use ) ; r and omization occurred sometime after the participant 's initial coronary disease event . Therefore , in our main analysis , we began accruing duration of hormone use for each participant immediately after her initial coronary disease event ( regardless of hormone use before this event ) . For example , if a woman began hormone therapy in 1984 and had a revascularization procedure in 1986 , her duration of use in 1990 would be 4 years . In an alternative analysis , we considered the women 's full experience with hormone therapy ( both before and after the initial coronary disease event ) . Thus , duration of hormone use accumulated continuously from start to termination of therapy . For example , if a woman began hormone therapy in 1984 and had a revascularization procedure in 1986 , her duration of use in 1990 would be 6 years . Similar to HERS participants , 29 % of the nurses had taken hormones before their first coronary disease event . Identification of Second Coronary Disease Events Similar to HERS , in our study the category of recurrent major coronary heart disease included nonfatal myocardial infa rct ion and fatal coronary disease that occurred between the return of the 1976 question naire and 1 June 1996 . Nurses who reported a nonfatal infa rct ion were asked for permission to review their medical records . Nonfatal myocardial infa rct ions were confirmed by hospital records if they met the World Health Organization criteria ( 5 ) ( symptoms , plus either elevated cardiac enzyme levels or diagnostic electrocardiograms ) . Infa rct ions requiring hospitalization and corroborated by interview or letter , but for which medical records were unobtainable , were included as probable . Most deaths were reported by the participants ' families . Every 2 years , we search the National Death Index ( 6 ) to identify deaths among nonrespondents ; follow-up for death remains more than 98 % complete to date . For all deaths possibly attributable to cardiovascular causes , we requested permission from relatives ( subject to state regulations ) to review the medical records . Deaths were considered due to coronary disease if medical records or autopsy findings confirmed a fatal myocardial infa rct ion . Cases in which coronary disease was listed on the death certificate as the underlying cause of death and another , more plausible cause could not be discerned were included as probable cases , since the nurse was known to have had coronary disease before death . The investigators conducted all interviews and medical record review s without knowledge of participants ' hormone use status . In separate analyses , results for probable cases of coronary disease ( 20 % ) were almost identical to those for confirmed cases ( 80 % ) ; thus , we present data from analyses in which confirmed and probable cases are combined . Statistical Analysis For each participant , person-months were allocated to hormone categories according to the baseline data and were up date d every 2 years according to information received on follow-up question naires . Examination of type of hormone therapy was limited to users of oral conjugated estrogen with or without oral medroxyprogesterone acetate , as this was the most common hormone regimen . If information on hormone use was missing during a follow-up period , then person-time was assigned to a missing category for that time period . So that the study would be prospect i ve , we established hormone status during each 2-year follow-up period from women 's reports at the start of the time period ; thus , we probably underestimate duration of use by an average of 1 year in both the main analysis and the alternate analysis . Follow-up for a participant ended with diagnosis of myocardial infa rct ion , death , or 1 June 1996 , whichever came first . The analysis is based on incidence rates , using person-months of follow-up as the denominator . We used relative risk as the measure of association , defined as the incidence of second major coronary events among women in various categories of hormone use divided by the rate among women who never used hormones 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 OBJECTIVE To evaluate the benefits and risks of hormone replacement therapy ( HRT ) combined with methyltestosterone ( MT ) in postmenopausal women with sexual dysfunction .  DESIGN This study was a r and omized , double-blind , placebo-controlled and crossover trial . Eighty-five women using HRT  were divided into four treatment groups : GI-HRT plus placebo for 4 months ; GII-HRT plus MT 2.5mg/day for 4 months ; GIII-HRT plus placebo for 2 months and then replaced with HRT plus MT 2.5mg/day for 2 months ; GIV-HRT plus MT 2.5mg/day and then replaced with HRT plus placebo for 2 months . Blood was collected at baseline , after 2 months ( T1 ) and 4 months ( T2 ) of treatment for hormone determinations of estradiol , FSH , total and free testosterone , GOT , GPT , glucose , total and fractions of cholesterol and triglycerides . All participants answered clinical questions and a vali date d question naire of modified McCoy 's sex scale . RESULTS The association of HRT with MT 2.5mg/day did not significantly change liver enzymes or increase cardiovascular risk factors . The patients of GII , GIIII and GIV when using MT presented amelioration of sex symptoms , mainly satisfaction and desire ( p<0.01 ) ; however , GIII at T1 ( 1.3+/-0.3 ) presented similar problem score results as compared to GIII at T2 ( 1.5+/-0.6 ) . CONCLUSION All data suggest that combined HRT- and rogen therapy may be beneficial for postmenopausal women receiving HRT who continue to complain of sexual difficulties or for postmenopausal women with sexual complaints who are not undergoing estrogen therapy Epidemiological and psychophysiological data suggest that groups that differ in reproductive hormones and stress responses also differ in risk for cardiovascular disease . To evaluate the effects of hormone therapy on women 's cardiovascular responses to laboratory stressors , 89 healthy postmenopausal women were tested twice , before and after exposure for about 8 weeks to one of the five conditions : placebo , Estratab ( primarily estrone ) , Estratab plus Prometrium ( micronized progesterone ) , Estratab plus Provera ( synthetic progestin ) , and Estratest ( same estrogen as in Estratab plus methyltestosterone ) . Results showed that women assigned to Estratab plus Prometrium and Estratest had diminished systolic blood pressure responses to stress upon retesting , whereas the other groups did not change in the level of their responses . Women assigned to Estratab plus Prometrium had diminished diastolic blood pressure responses during a speech stressor upon retesting , whereas women assigned to Estratab plus Provera increased . Our findings show that hormone therapy does affect women 's stress responses , but they do not provide a simple explanation as to why groups at high and low risk for cardiovascular disease differ in reproductive hormones and stress responses Objective : Evaluation of the use of testosterone therapy for hypoactive sexual desire disorder ( HSDD ) after oophorectomy has mostly involved women treated with oral estrogen preparations . We investigated the efficacy and safety of a testosterone patch in surgically menopausal women receiving concurrent transdermal estrogen . Design : Women with HSDD after oophorectomy , for whom this was a concern , who were using transdermal estrogen , were recruited to a 24-week , r and omized , double-blind , placebo-controlled  trial in Europe and Australia . Patients were r and omly allocated to placebo ( n = 40 ) or testosterone 300 & mgr;g/day ( n = 37 ) treatment . Primary endpoints were changes in sexual desire measured by the sexual desire domain of the Profile of Female Sexual Function and the frequency of satisfying sexual activity at 24 weeks . Results : Sixty-one women ( 79 % ) completed the trial . All subjects who received at least one application of study medication were included in analysis . The testosterone-treated group experienced a significantly greater change from baseline in the domain sexual desire score compared with placebo ( change from baseline , 16.43 versus 5.98 ; P = 0.02 ) . The domain scores for arousal , orgasm , decreased sexual concerns , responsiveness , and self-image as well as decreased distress were also significantly greater with testosterone therapy than placebo . The frequency of satisfactory sexual events increased but was not statistically different between treatment groups ( P = 0.06 ) Adverse events occurred with similar frequency in both groups , and no serious risks of therapy were observed Conclusions : In this study , transdermal testosterone therapy via a skin patch improved sexual desire and other sexual function domains . It was well tolerated in these oophorectomized women with HSDD receiving concomitant transdermal estrogen Objective : To compare the efficacy and safety of esterified estrogens with and without methyltestosterone . Methods : Twenty-six women participated in a doubleblind r and omized trial for 6 months . Outcome measures included serum total and lipoprotein-bound cholesterol , vasomotor symptoms , vaginal cytology and endometrial histology , and chemistry values . Analysis of variance and t test statistics were used to assess differences . Results : After 6 months of therapy , the treatment groups were comparable with regard to symptom scores , vaginal cytology and endometrial histology scores , and clinical laboratory test values . Treatment with esterified estrogens plus methyltestosterone significantly decreased total cholesterol , high-density lipoprotein cholesterol ( HDL ) , HDL2 , HDL3 , and apolipoprotein Al compared to esterified estrogens alone . Conclusions : Esterified estrogens with or without methyltestosterone were effective at reducing menopausal symptoms and were well tolerated over 6 months of continuous treatment . A significant decrease in cholesterol and apolipoproteins in the estrogen plus methyltestosterone group suggests a potentially adverse impact on the beneficial effect normally imparted by estrogen therapy OBJECTIVE Little is known about metabolic effects of testosterone treatment in postmenopausal women . The aim of the study was to compare the treatment effects of testosterone , estrogen , and testosterone plus estrogen on insulin sensitivities , body compositions , and lipid profiles in healthy postmenopausal women . DESIGN An open , r and omized clinical study with parallel group comparison . SETTING Women 's health clinical research unit at a university hospital . PATIENT(S ) Sixty-three naturally postmenopausal women participated in the study . INTERVENTION(S ) The participants were r and omly assigned to 3 months of treatment with testosterone undecanoate ( 40 mg every second day ) , estradiol valerate ( 2 mg daily ) , or the combination of both . MAIN OUTCOME MEASURE(S ) Insulin sensitivity assessed by euglycemic hyperinsulinemic clamp , body composition , and serum lipids . RESULT ( S ) Insulin-induced glucose disposal was reduced by approximately 20 % after treatment with testosterone alone , and after the combined treatment , but not by estrogen alone . Body weight , but not total body fat , increased significantly by about 1 kg in all groups . Lean body mass was significantly increased in the group of combined treatment and tended to be increased by testosterone alone . High-density lipoprotein (HDL)-cholesterol decreased significantly by testosterone treatment . In contrast , HDL-cholesterol increased , whereas low-density lipoprotein (LDL)-cholesterol and lipoprotein-(a ) [ Lp(a ) ] decreased with estradiol treatment . CONCLUSION ( S ) We conclude that 3 months of treatment with testosterone undecanoate in postmenopausal women induces insulin resistance and an adverse serum lipid profile but may increase lean body mass From a longitudinal prospect i ve study , 160 women with spontaneous menopause and without steroid medication were followed during the transition from pre- to  postmenopause  . After 12 years 152 women were still participating in the study . Blood sample s were drawn every 6 months until 1 year after the menopause and every 12 months thereafter . Measurements of bone mineral density ( BMD ) on the forearm were performed every second year . All women routinely completed a question naire concerning symptoms frequently attributed to the climacteric period . All data were grouped around the onset of the menopause , thereby allowing longitudinal evaluation of the changes in the variables from the premenopausal to the postmenopausal period . The beginning of the perimenopausal period was characterized by transitory elevations of follicle-stimulating hormone ( FSH ) . A significant increase in serum levels of gonadotropins was observed for both FSH and luteinizing hormone ( LH ) from about 5 years before the menopause . Within the 6 month period around the menopause there was a further increase which culminated within the first postmenopausal year for LH and 2 - 3 years postmenopause for FSH . Thereafter , a continuous decrease in LH occurred over the following 8 years . With respect to FSH , there was a slight decline starting about 4 years postmenopause . During the premenopausal period an increasing frequency of inadequate luteal function or anovulation occurred and , in the postmenopausal years , the serum levels of progesterone ( P ) were invariably low . Gradually , the ratio between estrone ( E1 ) and 17-beta-estradiol ( E2 ) increased , reflecting the declining follicular steroidogenesis . A marked decrease in estrogen levels occurred during the 6 month period around the menopause , most pronounced in E2 . During the next 3 years , the levels of E2 and E1 showed an essentially parallel , moderate decline . Around the menopause , serum levels of testosterone ( T ) , delta 4- and rostenedione ( A ) and sex hormone-binding globulin ( SHBG ) showed small but significant decreases . From about 3 years postmenopause , the levels were relatively constant over the following 5 years . A decrease in BMD was observed in the postmenopause , and from about 3 years postmenopause , estradiol correlated positively with BMD . Before , as well as after the menopause , body mass index ( BMI ) showed an inverse correlation with SHBG . Postmenopausal and rostenedione correlated positively with E1 , E2 and T. BMI correlated positively with E1 and E2 . The concentrations of the free fraction of E2 and T are dependent on the levels of SHBG , which in turn has a negative correlation with BMI . The impact of this will influence the severity of symptoms , the degree of bone loss and the need for supplementary therapy CONTEXT Despite decades of use and considerable research , the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain . OBJECTIVE To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States . DESIGN , SETTING , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled disease prevention trial ( the estrogen-alone component of the Women 's Health Initiative [ WHI ] ) conducted in 40 US clinical centers beginning in 1993 . Enrolled were 10 739 postmenopausal women , aged 50 - 79 years , with prior hysterectomy , including 23 % of minority race/ethnicity . INTERVENTION Women were r and omly assigned to receive either 0.625 mg/d of conjugated equine estrogen ( CEE ) or placebo . MAIN OUTCOME MEASURES The primary outcome was coronary heart disease ( CHD ) incidence ( nonfatal myocardial infa rct ion or CHD death ) . Invasive breast cancer incidence was the primary safety outcome . A global index of risks and benefits , including these primary outcomes plus stroke , pulmonary embolism ( PE ) , colorectal cancer , hip fracture , and deaths from other causes , was used for summarizing overall effects . RESULTS In February 2004 , after review ing data through November 30 , 2003 , the National Institutes of Health ( NIH ) decided to end the intervention phase of the trial early . Estimated hazard ratios ( HRs ) ( 95 % confidence intervals [ CIs ] ) for CEE vs placebo for the major clinical outcomes available through February 29 , 2004 ( average follow-up 6.8 years ) , were : CHD , 0.91 ( 0.75 - 1.12 ) with 376 cases ; breast cancer , 0.77 ( 0.59 - 1.01 ) with 218 cases ; stroke , 1.39 ( 1.10 - 1.77 ) with 276 cases ; PE , 1.34 ( 0.87 - 2.06 ) with 85 cases ; colorectal cancer , 1.08 ( 0.75 - 1.55 ) with 119 cases ; and hip fracture , 0.61 ( 0.41 - 0.91 ) with 102 cases . Corresponding results for composite outcomes were : total cardiovascular disease , 1.12 ( 1.01 - 1.24 ) ; total cancer , 0.93 ( 0.81 - 1.07 ) ; total fractures , 0.70 ( 0.63 - 0.79 ) ; total mortality , 1.04 ( 0.88 - 1.22 ) , and the global index , 1.01 ( 0.91 - 1.12 ) . For the outcomes significantly affected by CEE , there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years . The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years . CONCLUSIONS The use of CEE increases the risk of stroke , decreases the risk of hip fracture , and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years . A possible reduction in breast cancer risk requires further investigation . The burden of incident disease events was equivalent in the CEE and placebo groups , indicating no overall benefit . Thus , CEE should not be recommended for chronic disease prevention in postmenopausal women BACKGROUND There is increasing use of hormone replacement therapy ( HRT ) by post-menopausal women . Observational epidemiological studies have shown reductions in cardiovascular risk factors in  HRT users in the USA , but no r and omized controlled trials of HRT have been carried out in the primary practice setting . Previous studies of cardiovascular risk factors have shown a variety of responses according to type of progestagen and oral or topical administration . None has examined the effect of route using an identical progestagen . OBJECTIVES Our aim was to establish differences , if any , in alteration in cardiovascular risk factors with HRT in post-menopausal women according to route of administration of HRT , oral , transdermal and implant , using first oestrogen alone then oestrogen plus norethisterone , or testosterone for implant . METHODS Subjects were recruited by letter of invitation to women aged 50 - 65 years from lists in general practice s local to the Charing Cross Hospital Lipid Clinic in West London . Their menopausal status was confirmed and they were r and omized to one of three treatment groups or acted as controls . They attended for three visits ; at baseline , HRT was initiated as oestrogen alone , oral or transdermal . At the 3-month visit , HRT with the progestagen , norethisterone , was given cyclically , continuously or transdermally until the final visit at 6 months . A separate group of women from the menopause clinic at Chelsea and Westminster Hospital were studied on oestrogen implant then on implanted oestrogen and testosterone . The outcome measures studied were the separate effects of the four regimes as compared with controls on lipoproteins , glucose , insulin , fibrinogen , factor VII and E-selectin , together with weight , waist : hip ratio and blood pressure . RESULTS The continuous combined oestrogen-progestagen therapy had similar effects on cardiovascular risk factors as oestrogen with cyclical progestagen . All regimes lowered low-density lipoprotein cholesterol , the oral route being more potent than the parenteral ; the effect of transdermal HRT was similar to the implant . Lp(a ) was reduced only with the oral route . Reductions in factor VII and E-selectin were observed in both the oral and transdermal routes . There was no increase in body mass index , waist : hip ratio , blood pressure or glucose and insulin levels with any of the HRT regimes used . Systolic blood pressure was reduced with the transdermal route . CONCLUSIONS This study supports the evidence that oestrogen-progestagen HRT , both oral and transdermal , although attenuating some of the benefit of oestrogen alone on fibrinogen and high-density lipoprotein , significantly reduces cardiovascular risk factors , which should diminish post-menopausal risk of coronary disease The effect of estrogen and /or and rogen on mood in surgically menopausal women was investigated with a prospect i ve , double-blind , cross-over design . Oophorectomized women who received either estrogen ( E ) , and rogen ( A ) , or a combined estrogen- and rogen preparation ( E-A ) parenterally attained lower depression scores during both treatment phases compared to a placebo group ( PL ) , coincident with their higher plasma estrogen and testosterone levels . When steroids were withdrawn , depression scores of all oophorectomized women were significantly higher than those of a hysterectomized control group with intact ovaries ( CON ) . The A group also had higher hostility scores than the E , PL , and CON groups . These data provide evidence of a covariation between circulating levels of estrogen and testosterone and certain affects in healthy women CONTEXT Observational studies have suggested that postmenopausal hormone treatment may improve cognitive function , but data from r and omized clinical trials have been sparse and inconclusive . The Women 's Health Initiative Memory Study ( WHIMS ) is an ancillary study of the Women 's Health Initiative ( WHI ) hormone therapy trials . On July 8 , 2002 , the estrogen plus progestin therapy in the WHI trial was discontinued because of certain increased health risks for women . OBJECTIVE To determine whether estrogen plus progestin therapy protects global cognitive function in older postmenopausal women . DESIGN , SETTING , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled clinical trial , WHIMS is an ancillary study of geographically diverse , community-dwelling women aged 65 years or older from 39 of 40 clinical centers within the WHI estrogen plus progestin trial that started in June 1995 . Of 4894 eligible postmenopausal women aged 65 years or older and free of probable dementia at baseline , 4532 ( 92.6 % ) were enrolled in the estrogen plus progestin component of WHIMS . A total of 4381 participants ( 96.7 % ) provided at least 1 valid cognitive function score between June 1995 and July 8 , 2002 . INTERVENTIONS Participants received either 1 daily tablet containing 0.625 mg of conjugated equine estrogen with 2.5 mg of medroxyprogesterone acetate ( n = 2145 ) or matching placebo ( n = 2236 ) . MAIN OUTCOME MEASURE Global cognitive function measured annually with the Modified Mini-Mental State Examination . RESULTS The Modified Mini-Mental State Examination mean total scores in both groups increased slightly over time ( mean follow-up of 4.2 years ) . Women in the estrogen plus progestin group had smaller average increases in total scores compared with women receiving placebo ( P = .03 ) , but these differences were not clinical ly important . Removing women by censoring them after adjudicated dementia , mild cognitive impairment , or stroke , and nonadherence to study protocol , did not alter the findings . Prior hormone therapy use and duration of prior use did not affect the interpretation of the results , nor did timing of prior hormone therapy initiation with respect to the final menstrual period . More women in the estrogen plus progestin group had a substantial and clinical ly important decline ( > or = 2 SDs ) in Modified Mini-Mental State Examination total score ( 6.7 % ) compared with the placebo group ( 4.8 % ) ( P = .008 ) . CONCLUSIONS Among postmenopausal women aged 65 years or older , estrogen plus progestin did not improve cognitive function when compared with placebo . While most women receiving estrogen plus progestin did not experience clinical ly relevant adverse effects on cognition compared with placebo , a small increased risk of clinical ly meaningful cognitive decline occurred in the estrogen plus progestin group We wished to investigate if a testosterone gel administered percutaneously to postmenopausal women could result in stable serum levels of the hormone and which dose was required to produce levels within the normal premenopausal range . Fifteen postmenopausal women , mean age 55.3 years ( range 45–70 years ) , volunteered to participate in the study and were divided into three groups . They received 10 , 20 or 30 mg of testosterone as a 1 % testosterone hydroalcoholic gel at 09.00 hours daily for 14 days . The gel was applied in a thin layer on the outside of the thigh each morning , over an area of approximately 15 cm2 . Blood sample s were collected hourly between 09.00 and 17.00 hours on days 1 and 14 , and also at 08.00 hours on days 3 , 5 , 11 , 12 , 13 and finally day 16 , i.e. 2 days after termination of treatment . The mean basal serum level of testosterone was 1.1 ± 0.9 nmol/l and for 5α-dihydrotestosterone 208 ± 143 pmol/l . There was a clear increase from the 10 mg to the 20 mg treatment ( mean testosterone level during treatment 3.2 and 7.2 nmol/l , respectively ) while serum testosterone values after 30 mg showed very little further increase ( mean 7.5 nmol/l ) . Values for days 3–5 were quite similar to those for days 13–14 . The present study suggests that adequate and acceptable serum levels of testosterone can be achieved with 10 mg testosterone applied transdermally Summary . Forty postmenopausal women , referred for hormone replacement therapy and all of whom reported a significant concern about a decline in their sexual interest , were r and omly allocated to one of two hormone implant  treatment groups : either oestradiol ( 50 mg ) alone , or oestradiol ( 50 mg ) and testosterone ( l00 mg ) . Comparison between the two groups as a whole revealed no significant differences on any measure , both treatments being associated with a significant reduction in the severity of psychological , somatic and vasomotor symptoms , and with a significant improvement in sexual interest and responsiveness . Similar effects were also observed in patients who denied , pretreatment , any concurrent dyspareunia .  Although it is not possible to identify the reasons for change , the results indicate no advantages of supplementary testosterone administration over oestradiol alone for sexually unresponsive postmenopausal women CONTEXT The Women 's Health Initiative ( WHI ) trial of estrogen plus progestin was stopped early because of adverse effects , including an increased risk of stroke in the  estrogen plus progestin group . OBJECTIVE To assess the effect of estrogen plus progestin on ischemic and hemorrhagic stroke and in subgroups , and to determine whether the effect of estrogen plus progestin was modified by baseline levels of blood biomarkers . DESIGN Multicenter double-blind , placebo-controlled , r and omized clinical trial involving 16 608 women aged 50 through 79 years with an average follow-up of 5.6 years . Baseline levels of blood-based markers of inflammation , thrombosis , and lipid levels were measured in the first 140 central ly confirmed stroke cases and 513 controls . INTERVENTIONS Participants received 0.625 mg/d of conjugated equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOME MEASURES Overall strokes and stroke subtype and severity were central ly adjudicated by stroke neurologists . RESULTS One hundred fifty-one patients ( 1.8 % ) in the estrogen plus progestin and 107 ( 1.3 % ) in the placebo groups had strokes . Overall 79.8 % of strokes were ischemic . For combined ischemic and hemorrhagic strokes , the intention-to-treat hazard ratio ( HR ) for estrogen plus progestin vs placebo was 1.31 ( 95 % confidence interval [ CI ] , 1.02 - 1.68 ) ; with adjustment for adherence , the HR was 1.50 ( 95 % CI , 1.08 - 2.08 ) . The HR for ischemic stroke was 1.44 ( 95 % CI , 1.09 - 1.90 ) and for hemorrhagic stroke , 0.82 ( 95 % CI , 0.43 - 1.56 ) . Point estimates of the HRs indicate that excess risk of all stroke was apparent in all age groups , in all categories of baseline stroke risk , and in women with and without hypertension , prior history of cardiovascular disease , use of hormones , statins , or aspirin . Other risk factors for stroke , including smoking , blood pressure , diabetes , lower use of vitamin C supplements , blood-based biomarkers of inflammation , higher white blood cell count , and higher hematocrit levels did not modify the effect of estrogen plus progestin on stroke risk . CONCLUSIONS Estrogen plus progestin increases the risk of ischemic stroke in generally healthy postmenopausal women .  Excess risk for all strokes attributed to estrogen plus progestin appeared to be present in all subgroups of women examined PURPOSE To determine whether systemic replacement with combined esterified estrogen ( EE ) and methyltestosterone ( MT ) ( EE + MT ) would reduce symptoms and promote clinical improvement in postmenopausal women with dry eye syndrome ( DES ) . DESIGN Retrospective , noncomparative , interventional case series . METHODS Investigators review ed the charts of 11 postmenopausal women treated within the last 3 years with EE + MT .  RESULTS The mean patient age was 65.2 years ( st and ard deviation [ SD ] 11.4 , range 48 - 84 years ) . The mean treatment duration was 12.2 months ( SD 6.2 months , range 4 - 24 months ) . Ten ( 91 % ) of 11 patients reported improvement in dry eye symptoms while receiving treatment . For these 10 , relief occurred after an average of 4.1 months of treatment ( SD 3.2 , range , 1 - 9 months ) . CONCLUSIONS Treatment with EE + MT may be efficacious for DES of various etiologies . A r and omized placebo-controlled trial is planned to further evaluate these encouraging findings Although the postmenopausal ovary remains an important source of testosterone ( T ) production , there is nevertheless a decline in total circulating and rogen levels with age . A role for and rogen replacement in addition to estrogens in some postmenopausal , particularly ovariectomized , women is increasingly gaining acceptance . We have compared the pharmacokinetics of two existing testosterone preparations , oral testosterone undecanoate ( TU ) and sc testosterone implants , with a new matrix transdermal delivery system for T. In study 1 , three different doses of TU ( 40 mg , two 20-mg doses 6 h apart and two 10-mg doses 6 h apart , orally ) were investigated in 10 postmenopausal women .  Median peak levels of 18 nmol/L ( range , 5.8 - 64.0 nmol/L ; 40 mg ) , 12.3 nmol/L ( range , 5.7 - 29.2 nmol/L ; 20 mg ) , and 9.7 nmol/L ( range , 7.8 - 28.7 nmol/L ; 10 mg ) were observed , but T levels varied considerably within and between subjects regardless of the dose used . In study 2 , 30 women receiving s.c . estradiol therapy were r and omized to receive either a 100-mg T implant or placebo . In the T-treated group , levels peaked at 8.9 + /- 1.7 nmol/L 1 month after insertion and then declined gradually to 2.9 + /- 0.4 nmol/L at 6 months . In study 3 , a novel matrix transdermal delivery system for T was investigated in 6 females . Estimated daily delivery rates of 840 ( TD 1 ) , 1100 ( TD2 ) , and 3000 microg ( TD3 ) T/24 h were investigated . T rose rapidly after a single application of TD 1 and TD2 and were relatively constant for the next 18 h , at which time peaks of 2.3 + /- 1.0 and 4.1 + /- 1.6 nmol/L , respectively , at 24 h were seen . T concentrations fell to baseline levels within 6 h after patch removal . When TD2 was applied for 7 days , a T level of 4.3 + /- 0.7 nmol was seen 24 h after application , falling gradually to 2.8 + /- 0.7 nmol/L by day 7 . During twice weekly application of TD2 , stable T concentrations were maintained , and all peak levels were similar ( peak level , 4.2 + /- 0.3 nmol/L 24 h post-TD application ) as were predose troughs ( 3.2 + /- 0.3 nmol ) . Twice weekly application of TD3 produced a similar pattern of T , and the mean peak and trough levels were 7.5 + /- 0.9 and 4.0 + /- 0.4 nmol/L , respectively . In conclusion , TU produced inappropriate high T levels at all doses , with wide variations between subjects , confirming that TU is unpredictably absorbed and unlikely to be satisfactory for use in women . Subcutaneous testosterone implants produce unphysiological T levels for at least 1 - 2 months . The transdermal matrix delivery system maintained relatively stable T levels within narrow ranges with little within- and between-subject variation . We conclude that such transdermal systems may be of value for and rogen therapy in postmenopausal women because they provide a highly controllable way of delivering T noninvasively and reliably , and achieve mean physiological levels not possible with existing methods
target: The pooled estimate from the studies suggested that the addition of testosterone to HT regimens improved sexual function scores for postmenopausal women .
  A significant adverse effect was a decrease in high-density lipoprotein ( HDL ) cholesterol levels .
  However , there is evidence that adding testosterone to HT has a beneficial effect on sexual function in postmenopausal women .
  There was a reduction in HDL cholesterol associated with the addition of testosterone to the HT regimens .
  It is , therefore , difficult to estimate the effect of testosterone on sexual function in association with any individual hormone treatment regimen
background: BACKGROUND : The value of adding testosterone to hormone therapy ( HT ) for the management of peri- and postmenopausal women is controversial and has not been systematic ally review ed .
  OBJECTIVES : To determine the benefits and risks of testosterone therapy for peri- and postmenopausal women taking hormone therapy .