title: Testosterone for low libido in postmenopausal women not taking estrogen. Testosterone treatment of HSDD in naturally menopausal women: the ADORE study 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. Effects of aromatase inhibition on sexual function and well-being in postmenopausal women treated with testosterone: a randomized, placebo-controlled trial Effect of androgens combined with hormone therapy on quality of life in post-menopausal women with sexual dysfunction Estrogen and estrogen-androgen replacement in postmenopausal women dissatisfied with estrogen-only therapy. Sexual behavior and neuroendocrine responses. Efficacy of vaginally applied estrogen, testosterone, or polyacrylic acid on vaginal atrophy: a randomized controlled trial Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause Androgens as adjuvant treatment in postmenopausal female patients with rheumatoid arthritis. Effects of estradiol with and without testosterone on body composition and relationships with lipids in postmenopausal women Effects of testosterone administration on cognitive function in hysterectomized women with low testosterone levels: a dose–response randomized trial Effects of combined estrogen/testosterone therapy on bone and body composition in oophorectomized 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. Effectiveness of a low dose testosterone undecanoate to improve sexual function in postmenopausal women Effects of androgen supplementation of hormone replacement therapy on the vascular reactivity of cerebral arteries. Genital and subjective measurement of the time course effects of an acute dose of testosterone vs. placebo in postmenopausal women. Clinically relevant changes in sexual desire, satisfying sexual activity and personal distress as measured by the profile of female sexual function, sexual activity log, and personal distress scale in postmenopausal women with hypoactive sexual desire disorder. Effects of testosterone and progressive resistance exercise in healthy, highly functioning older men with low-normal testosterone levels. Androgen enhances sexual motivation in females: a prospective, crossover study of sex steroid administration in the surgical menopause. Effects of physiologic testosterone therapy on quality of life, self-esteem, and mood in women with primary ovarian insufficiency Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. The effect of transdermal testosterone on mammographic density in postmenopausal women not receiving systemic estrogen therapy. Testosterone dose-response relationships with cardiovascular risk markers in androgen-deficient women: a randomized, placebo-controlled trial. Preliminary observations on differing psychological effects of conjugated and esterified estrogen treatments. A randomized trial of the effect of testosterone and estrogen on verbal fluency, verbal memory, and spatial ability in healthy postmenopausal women. Testosterone addition to estrogen therapy – Effects on inflammatory markers for cardiovascular disease Effect of methyl testosterone administration on plasma viscosity in postmenopausal women The Effects of Plasma Estradiol Levels on Increases in Vertebral and Femoral Bone Density Following Therapy With Estradiol and Estradiol With Testosterone Implants Effect of estrogen and testosterone replacement therapy on cognitive fatigue Testosterone dose-response relationships in hysterectomized women with or without oophorectomy: effects on sexual function, body composition, muscle performance and physical function in a randomized trial Treatment with percutanous testosterone gel in postmenopausal women with decreased libido--effects on sexuality and psychological general well-being. Testosterone addition during menopausal hormone therapy: effects on mammographic breast density Evaluation of the clinical relevance of benefits associated with transdermal testosterone treatment in postmenopausal women with hypoactive sexual desire disorder. Effects of parenteral administration of estrogen and androgen on plasma hormone levels and hot flushes in the surgical menopause. Testosterone enhances estradiol's effects on postmenopausal bone density and sexuality. A two-year, double-blind comparison of estrogen-androgen and conjugated estrogens in surgically menopausal women. Effects on bone mineral density, symptoms and lipid profiles. Acute Influences of Estrogen and Testosterone on Divergent and Convergent Thinking in Postmenopausal Women Safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a randomized, placebo-controlled trial. 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. Testosterone inhibits estrogen/progestogen-induced breast cell proliferation in postmenopausal women The benefits of androgens combined with hormone replacement therapy regarding to patients with postmenopausal sexual symptoms. Randomized controlled trial to evaluate transdermal testosterone in female cancer survivors with decreased libido; North Central Cancer Treatment Group protocol N02C3. 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 A double-blind, randomized, placebo-controlled trial of the effect of testosterone cream on the sexual motivation of menopausal hysterectomized women with hypoactive sexual desire disorder Hormonal treatments of sexual unresponsiveness in postmenopausal women: a comparative study Testosterone patch for low sexual desire in surgically menopausal women: a randomized trial. Testosterone therapy in women with chronic heart failure: a pilot double-blind, randomized, placebo-controlled study. Effects of testosterone and estrogen replacement on memory function Effects of the addition of methyltestosterone to combined hormone therapy with estrogens and progestogens on sexual energy and on orgasm in postmenopausal women A comparative study of the effects of local estrogen with or without local testosterone on vulvovaginal and sexual dysfunction in postmenopausal women. Efficacy of vaginally applied estrogen, testosterone, or polyacrylic acid on sexual function in postmenopausal women: a randomized controlled trial.
abstract: BACKGROUND The efficacy and safety of testosterone treatment for hypoactive sexual desire disorder in postmenopausal women not receiving estrogen therapy  are unknown . METHODS We conducted a double-blind , placebo-controlled , 52-week trial in which 814 women with hypoactive sexual desire disorder were r and omly assigned to receive a patch delivering 150 or 300 microg of testosterone per day or placebo .  Efficacy was measured to week 24 ; safety was evaluated over a period of 52 weeks , with a subgroup of participants followed for an additional year . The primary end point was the change from baseline to week 24 in the 4-week frequency of satisfying sexual episodes . RESULTS At 24 weeks , the increase in the 4-week frequency of satisfying sexual episodes was significantly greater in the group receiving 300 microg of testosterone per day than in the placebo group ( an increase of 2.1 episodes vs. 0.7 , P<0.001 ) but not in the group receiving 150 microg per day ( 1.2 episodes , P=0.11 ) . As compared with placebo , both doses of testosterone were associated with significant increases in desire ( 300 microg per day , P<0.001 ; 150 microg per day , P=0.04 ) and decreases in distress ( 300 microg per day , P<0.001 ; 150 microg per day , P=0.04 ) . The rate of and rogenic adverse events - primarily unwanted hair growth - was higher in the group receiving 300 microg of testosterone per day than in the placebo group ( 30.0 % vs. 23.1 % ) . Breast cancer was diagnosed in four women who received testosterone ( as compared with none who received placebo ) ; one of the four received the diagnosis in the first 4 months of the study period , and one , in retrospect , had symptoms before undergoing r and omization . CONCLUSIONS In postmenopausal women not receiving estrogen therapy  , treatment with a patch delivering 300 microg of testosterone per day result ed in a modest but meaningful improvement in sexual function . The long-term effects of testosterone , including effects on the breast , remain uncertain . ( Clinical Trials.gov number , NCT00131495 . Objective To evaluate the efficacy and safety of a transdermal testosterone patch ( TTP , 300 μg/day ) in naturally menopausal women with hypoactive sexual desire disorder ( HSDD ) . Methods A total of 272 naturally menopausal women , predominantly not using hormone therapy , were r and omized in this 6-month , placebo-controlled , double-blind , multicenter study to receive twice weekly either TTP or an identical placebo . Efficacy endpoints measured were the 4-week frequency of satisfying sexual episodes ( SSE ) using the Sexual Activity Log , the sexual desire domain of the Profile of Female Sexual Function and distress by the Personal Distress Scale . Safety was assessed by adverse events , laboratory parameters and hormone levels . Results The TTP group demonstrated significant improvements in SSE ( p = 0.0089 ) as well as in sexual desire ( p = 0.0007 ) and reduced personal distress ( p = 0.0024 ) versus placebo at 6 months ( intent-to-treat analysis , n = 247 ) . The results were significant for all three endpoints in the subgroup ( n = 199 ) not using hormone therapy . Similar numbers of women treated with placebo and TTP discontinued ( n = 39 , 27.5 % vs. n = 26 , 20 % ) , reported adverse events ( including application site reactions ) ( n = 101 , 71.1 % vs. n = 81 , 62.3 % ) and withdrew due to adverse events ( n = 20 , 14.1 % vs. n = 9 , 6.9 % ) . No clinical ly relevant changes were noted in laboratory parameters . Serum free and total testosterone levels increased from baseline in the TTP group ( geometric means 5.65 pg/ml and 67.8 ng/dl , respectively , at week 24 ) within the physiological range ; no changes were seen in estradiol and sex hormone binding globulin levels . Conclusions TTP was effective in treating HSDD and improving sexual function in this study of naturally menopausal women with and without concurrent hormone therapy 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 : The extent to which aromatization of testosterone ( T ) to estradiol is required for the observed effects of testosterone therapy on sexual function and well-being are not known . Therefore , the authors investigated the effects of aromatase enzyme inhibition on sexual function , well-being , and mood in estrogen- and T-replete postmenopausal women in a double-blind , r and omized , placebo-controlled study . Design : Postmenopausal women using transdermal estrogen therapy for at least 8 weeks and reporting low sexual satisfaction ( score < 42 for the Sabbatsberg Sexual Self-rating Scale [ SSS ] ) with a total T value of less than 1.2 nmol/L were treated with 400 μL of a 0.5 % T gel ( total dose 2 mg ) and were r and omly assigned to receive treatment with either 2.5 mg/day of letrozole or an identical placebo tablet . Women were assessed at baseline ( week −2 ) and at 0 , 4 , 8 , and 16 weeks . Sexual function was assessed with the SSS , well-being was assessed with the Psychological General Well-being Index , and mood was assessed with the Beck Depression Inventory at 0 and 16 weeks . Eighty-one women were screened , 76 were r and omly assigned to a treatment group , and 30 in each group completed the study . Because this was a mechanistic study , only the 60 women who completed the study per protocol were included in the final analysis . Results : Total T and calculated free T increased from baseline in both groups , with no difference between groups . At 16 weeks , estradiol , sex hormone-binding globulin , fasting lipids , lipoprotein(a ) , and C-reactive protein did not differ from baseline or between groups . Significant increases in total Sabbatsberg Sexual Self-rating Scale scores , total Psychological General Well-being Index scores , and a reduction in Beck Depression Inventory scores from baseline to 16 weeks was seen for both treatment groups , with no effect of treatment allocation . No adverse treatment effects were reported . Conclusions : Increases in total and free T in the physiologic range in postmenopausal women were associated with improved sexual satisfaction , well-being , and mood . In this study , aromatase inhibition did not influence any of these outcomes . Short-term transdermal T therapy did not modify fasting lipids , lipoprotein(a ) , or C-reactive protein Aim . To evaluate with vali date d instruments changes in quality of life and sexuality in women receiving hormonal replacement therapy ( AHT ) .  Design . R and omised , double-blind , double-dummy study with two parallel treatment arms . Patients and methods . Forty-seven healthy post-menopausal women , aged 45–64 years , were evaluated using the Female Sexual Function Index ( FSFI ) and the menopause-specific quality of life question naire ( MENQOL ) . Of them , 40 diagnosed with sexual dysfunction were r and omised ( 1:1 ) to receive daily 0.625 mg of conjugated estrogens plus 1.25 mg of methyl-testosterone and 100 mg of micronised progesterone or placebo . After 3 months follow-up , FSFI and MENQOL question naires were administered for a second time . Results . Quality of life was unchanged in the placebo group whereas AHT significantly improved scores of vasomotor , psychological , physical and sexual symptoms . As expected , FSFI was not modified in the placebo group while in AHT group the FSFI score improved significantly . In addition , at the end of the study , 68.7 % of subjects of the AHT group did not fit did not fit the criteria for sexual dysfunction as per the FSFI ( p < 0.0001 ) . Conclusions . Adding methyl-testosterone to hormone therapy  improves quality of life and sexuality in post-menopausal women with sexual dysfunction 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 Objective : Vaginal atrophy is a common chronic condition among postmenopausal women that can affect their quality of life . Recent studies have evaluated new treatment alternatives for vaginal atrophy ; however , few therapeutic options have been thoroughly evaluated . This study aim ed to compare the effectiveness and adverse effects of estrogen , testosterone , polyacrylic acid , and placebo lubricant for the treatment of postmenopausal women with vaginal atrophy . Methods : We conducted a r and omized clinical trial with 80 postmenopausal women aged between 40 and 70 years who were being followed up at the Menopause Clinic of CAISM UNICAMP between November 2011 and January 2013 . Women were r and omly assigned to topical vaginal treatment with estrogen , testosterone , polyacrylic acid , and placebo lubricant , three times a week for 12 weeks . We used the vaginal maturation index , pH , vaginal health score , vaginal flora , laboratory tests , and ultrasound to evaluate changes of vaginal atrophy at baseline and after 6 and 12 weeks of treatment . Results : After a 12-week treatment with topical estrogen and testosterone compared with the lubricant , an increased percentage of participants had vaginal pH less than 5 , increased vaginal score , and an increase in the number of lactobacilli . Treatment with topical estrogen improved the vaginal maturation index and showed increased levels of estradiol in three women . No changes were observed in the endometrial evaluation of all treatment groups . Conclusions : After a 12-week treatment with testosterone and estrogen compared with placebo lubrication , there was a significant improvement in vaginal trophism in postmenopausal women with vaginal atrophy Objective : The aim of this study is to confirm the local beneficial effects of intravaginal dehydroepi and rosterone ( DHEA , Prasterone ) on moderate to severe dyspareunia or pain at sexual activity , the most frequent symptom of vulvovaginal atrophy due to menopause or genitourinary syndrome of menopause ( GSM ) . Methods : In a prospect i ve , r and omized , double-blind , and placebo-controlled phase III clinical trial , the effect of daily intravaginal 0.50 % DHEA ( 6.5 mg ) ( Prasterone , EndoCeutics ) was examined on four co primary objectives , namely percentage of parabasal cells , percentage or superficial cells , vaginal pH , and moderate to severe pain at sexual activity ( dyspareunia ) identified by the women as their most bothersome vulvovaginal atrophy symptom . The intent-to-treat population included 157 and 325 women in the placebo and DHEA-treated groups , respectively . Results : After daily intravaginal administration of 0.50 % DHEA for 12 weeks , when compared to baseline by the analysis of covariance test , the percentage of parabasal cells decreased by 27.7 % over placebo ( P < 0.0001 ) , whereas the percentage of superficial cells increased by 8.44 % over placebo ( P < 0.0001 ) , vaginal pH decreased by 0.66 pH unit over placebo ( P < 0.0001 ) , and pain at sexual activity decreased by 1.42 severity score unit from baseline or 0.36 unit over placebo ( P = 0.0002 ) . On the other h and , moderate to severe vaginal dryness present in 84.0 % of women improved at 12 weeks by 1.44 severity score unit compared to baseline , or 0.27 unit over placebo ( P = 0.004 ) . At gynecological evaluation , vaginal secretions , epithelial integrity , epithelial surface thickness , and color all improved by 86 % to 121 % over the placebo effect ( P < 0.0001 for all comparisons with placebo ) . Serum steroid levels remained well within the normal postmenopausal values according to the involved mechanisms of intracrinology . The only side effect reasonably related to treatment is vaginal discharge due to melting of the vehicle at body temperature and this was reported in about 6 % of the participants . Conclusions : The daily intravaginal administration of 0.50 % ( 6.5 mg ) DHEA ( Prasterone ) has shown clinical ly and highly statistically significant effects on the four co primary parameters suggested by the US Food and Drug Administration . The strictly local action of Prasterone is in line with the absence of significant drug-related adverse events , thus showing the high benefit-to-risk ratio of this treatment based upon the novel underst and ing of the physiology of sex steroids in women OBJECTIVE : To examine the possible beneficial effect of and rogens in postmenopausal women with active rheumatoid arthritis . METHODS : 107 women participated in a double blind placebo controlled trial to evaluate the effect of 50 mg testosterone propionate intramuscularly every two weeks for one year . RESULTS : An improvement in ESR , Dutch health assessment question naire , and pain was noted . In addition , 21 % of patients treated with testosterone fulfilled the ACR improvement criteria after one year , versus only 4 % of the placebo group . The treatment was well tolerated . CONCLUSIONS : Testosterone may improve the general wellbeing of postmenopausal women with active rheumatoid arthritis 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 Purpose To determine the dose-dependent effects of testosterone administration on cognition in women with low testosterone levels . Methods 71 hysterectomized women with or without oophorectomy with total testosterone < 31 ng/dl and /or free testosterone < 3.5 pg/ml received a st and ardized transdermal estradiol regimen during the 12-week run-in period and were then r and omized to receive weekly intramuscular injections of placebo , 3 , 6.25 , 12.5 , or 25 mg testosterone enanthate for 24 weeks .  Total testosterone  was measured in serum by LC – MS/MS , and free testosterone levels were measured by equilibrium dialysis .  Cognitive function was evaluated using a comprehensive battery of st and ardized neuropsychological tests at baseline and 24 weeks . Results 46 women who had baseline and end-of-treatment cognitive function data constituted the analytic sample . The five groups were similar at baseline . Mean on-treatment nadir total testosterone concentrations were 15 , 89 , 98 , 134 , and 234 ng/dl in the placebo , 3 , 6.25 , 12.5 , and 25 mg groups , respectively . No significant changes in spatial ability , verbal fluency , verbal memory , or executive function were observed in any treatment arm compared to placebo even after adjustment for baseline cognitive function , age , and education . Multiple regression analysis did not show any significant relation between changes in testosterone concentrations and change in cognitive function scores . ConclusionS hort-term testosterone administration over a wide range of doses for 24 weeks in women with low testosterone levels was neither associated with improvements nor worsening of cognitive function 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 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 Background Adding testosterone to hormonal therapy could improve sexual function and general well-being among women during climacteric . We evaluated the effectiveness of testosterone undecanoate on sexual function in postmenopausal women utilizing the st and ardized question naire FSFI score . Methods Postmenopausal women with sexual complaints and Female Sexual Function Index ( FSFI ) ≤ 26.5 were enrolled in to this r and omized , double-blinded , placebo-controlled trial . Participants were r and omly assigned to 8-week treatment with either oral testosterone undecanoate 40 mg or placebo twice weekly with daily oral estrogen .  The FSFI scores before and after treatment were compared to assess any improvement of sexual function . Results Seventy women were recruited of which each group had 35 participants . The baseline characteristics and baseline FSFI scores were comparable between both groups . After 8 weeks of treatment , the FSFI scores significantly improved in both groups when compared to the baseline but the FSFI scores from the testosterone group were significantly higher than in the placebo group post-treatment ( 28.6 ± 3.6 , 25.3 ± 6.7 , respectively , p = 0.04 ) . There was no difference in adverse effect between the two groups Conclusions The twice weekly addition of testosterone undecanoate to daily oral estrogen was associated with a significant improvement in sexual function  among postmenopausal women than the use of the estrogen alone . Trial registration Clinical Trials.gov Identifier NCT01724658 ( February 17 , 2012 ) 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 INTRODUCTION Recent research on the impact of testosterone ( T ) on female sexual function has yielded inconsistent results , and few studies have used physiological measures of genital arousal . AIM This study examined the effects of an acute dose of methyltestosterone ( MT ) on physiological ( genital ) and subjective sexual response in postmenopausal women . MAIN OUTCOME MEASURES Vaginal pulse amplitude ( VPA ) and self-reported sexual response . METHODS R and omized , double-blind , crossover , placebo-controlled trial of 5 mg MT , consisting of two separate 8-hour visits . Participants were 10 postmenopausal women without sexual dysfunction . Participants viewed both neutral and erotic video segments during five post-dose trials while their genital and subjective responses were monitored . RESULTS The Wilcoxon signed rank test indicated a significant difference in VPA between the T ( M = 0.018 , SD = 0.018 ) and placebo ( M = 0.016 , SD = 0.017 ) conditions at 4.5 hours post-dose ( P = 0.03 ) . Higher difference scores were noted for 80 % of subjects during the T condition at 4.5 hours , in contrast with only 50 % of subjects responding to T at the other four time points . No differences were found on VPA relative change scores or subjective sexual arousal scores . When summed across all five time points , genital and subjective measures were correlated regardless of medication condition ( 0.62 and 0.60 for self-reported physical and mental sexual arousal scores , respectively ) . CONCLUSIONS These findings in postmenopausal women combined with those of two previous investigations in premenopausal women demonstrate a probable acute-dose time delay for genital sexual effects of exogenous T with no change in self-reported sexual arousal . Further investigation is needed to determine whether acute dosing of T has a consistent and predictable impact on genital arousal that has promise for the treatment of any subgroup of women with sexual disorders INTRODUCTION Transdermal testosterone patch ( TTP ) treatment produced statistically significant improvements in a satisfying sexual activity ( SSA ) , sexual desire , and personal distress in postmenopausal women suffering from hypoactive sexual desire disorder ( HSDD ) , but clinical significance of these changes was not determined . AIM To quantify the magnitude of change in three principal outcomes measures determined by HSDD patients as associated with the perception of meaningful benefit with TTP therapy . METHODS The criteria for defining responders were determined using anchoring methodology and receiver operating characteristics analysis to establish minimum important differences ( MIDs ) in a representative sub sample of 132 patients in two r and omized , controlled trials in surgically menopausal women with HSDD ( N = 1,094 ) . Perceived benefit was established based upon the question " Overall , would you say that you experienced a meaningful benefit from the study patches ? " . These data defined responders and established MIDs for changes in sexual desire , SSA , and personal distress . The MIDs were applied to the two trials to establish responder rates in each treatment group . MAIN OUTCOME MEASURES Changes in score that correspond to the MID for sexual desire , SSA , and personal distress , and responder rates in each treatment group based upon these values . RESULTS Increases in frequency of SSA of greater than 1 activity/4 weeks , increases in sexual desire score of > or = 8.9 , and decreases in the personal distress score of > or = 20.0 were identified as threshold improvements best able to differentiate responders and nonresponders . The responder rate was significantly higher ( P < 0.001 ) in the testosterone group vs. placebo for all three outcomes measures ( sexual desire , 50 % vs. 34 % ; SSA , 44 % vs. 30 % ; personal distress , 51 % vs. 39 % ) . CONCLUSIONS Changes in sexual desire , SSA , and personal distress observed with TTP treatment in surgically menopausal women with HSDD were clinical ly significant and were associated with a meaningful treatment benefit CONTEXT Aging in men is associated with reduced testosterone ( T ) levels and physiological changes leading to frailty , but the benefits of T supplementation are inconclusive . OBJECTIVE We studied the effects of T supplementation with and without progressive resistance training ( PRT ) on functional performance , strength , and body composition . DESIGN , SETTING , AND PARTICIPANTS We recruited 167 generally healthy community-dwelling older men ( 66 ± 5 years ) with low-normal baseline total T levels ( 200 - 350 ng/dL ) . INTERVENTION Subjects were r and omized to placebo or transdermal T gel [ 2 doses targeting either a lower ( 400 - 550 ng/dL ) or higher ( 600 - 1000 ng/dL ) T range ] and to either PRT or no exercise for 12 months . MAIN OUTCOME MEASURE The primary outcome was functional performance , whereas secondary outcomes were strength and body composition . RESULTS A total of 143 men completed the study . At 12 months , total T was 528 ± 287 ng/dL in subjects receiving any T and 287 ± 65 ng/dL in the placebo group . In the PRT group , function and strength were not different between T- and placebo-treated subjects , despite greater improvements in fat mass ( P = .04 ) and fat-free mass ( P = .01 ) with T. In the non-PRT group , T did not improve function but improved fat mass ( P = .005 ) , fat-free mass ( P = .03 ) , and upper body strength ( P = .03 ) compared with placebo . There were fewer cardiovascular events in the T-treated groups compared with placebo . CONCLUSIONS T supplementation was well tolerated and improved body composition but had no effect on functional performance . T supplementation improved upper body strength only in nonexercisers compared with placebo & 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 Objective Women with primary ovarian insufficiency ( POI ) display low and rogen levels , which could contribute to mood and behavioral symptoms observed in this condition . We examined the effects of physiologic testosterone therapy added to st and ard estrogen/progestin therapy on quality of life , self-esteem , and mood in women with POI . Methods One hundred twenty-eight women with 46,XX spontaneous POI participated in a 12-month r and omized , placebo-controlled , parallel- design investigation of the efficacy of testosterone augmentation of estrogen/progestin therapy .  Quality of life , self-esteem , and mood symptoms were evaluated with st and ardized rating scales and a structured clinical interview . Differences in outcome measures between the testosterone and placebo treatments were analyzed by Wilcoxon rank sum tests . Results No differences in baseline characteristics , including serum hormone levels ( P > 0.05 ) , were found . Baseline mean ( SD ) Center for Epidemiologic Studies Depression Scale scores were 10.7 ( 8.6 ) and 9.2 ( 7.8 ) for testosterone and placebo , respectively ( P = 0.35 ) . After 12 months of treatment , measures of quality of life , self-esteem , and mood symptoms did not differ between treatment groups . Serum testosterone levels achieved physiologic levels in the testosterone group and were significantly higher compared with placebo ( P < 0.001 ) . Baseline testosterone levels were not associated with either adverse or beneficial clinical effects . Conclusions A 150-&mgr;g testosterone patch achieves physiologic hormone levels in women with POI . Our findings suggest that augmentation of st and ard estrogen/progestin therapy with physiologic testosterone therapy in young women with POI neither aggravates nor improves baseline reports of quality of life or self-esteem and had minimal effects on mood . Other mechanisms might play a role in the altered mood accompanying this disorder IMPORTANCE Rates of testosterone therapy are increasing and the effects of testosterone therapy on cardiovascular outcomes and mortality are unknown . A recent r and omized clinical trial of testosterone therapy in men with a high prevalence of cardiovascular diseases was stopped prematurely due to adverse cardiovascular events raising concerns about testosterone therapy safety . OBJECTIVES To assess the association between testosterone therapy and all-cause mortality , myocardial infa rct ion ( MI ) , or stroke among male veterans and to determine whether this association is modified by underlying coronary artery disease . DESIGN , SETTING , AND PATIENTS A retrospective national cohort study of men with low testosterone levels ( < 300 ng/dL ) who underwent coronary angiography in the Veterans Affairs ( VA ) system between 2005 and 2011 . MAIN OUTCOMES AND MEASURES Primary outcome was a composite of all-cause mortality , MI , and ischemic stroke . RESULTS Of the 8709 men with a total testosterone level lower than 300 ng/dL , 1223 patients started testosterone therapy after a median of 531 days following coronary angiography . Of the 1710 outcome events , 748 men died , 443 had MIs , and 519 had strokes . Of 7486 patients not receiving testosterone therapy  , 681 died , 420 had MIs , and 486 had strokes . Among 1223 patients receiving testosterone therapy , 67 died , 23 had MIs , and 33 had strokes . At 3 years after coronary angiography , the Kaplan-Meier estimated cumulative percentages with events were 19.9%in the no testosterone therapy group vs 25.7%in the testosterone therapy group , with an absolute risk difference of 5.8%(95%CI , -1.4%to 13.1 % ) [corrected].The Kaplan-Meier estimated cumulative percentages with events among the no testosterone therapy group vs testosterone therapy group at 1 year after coronary angiography were 10.1 % vs 11.3 % ; at 2 years , 15.4 % vs 18.5 % ; and at 3 years , 19.9 % vs 25.7 [corrected].There was no significant difference in the effect size of testosterone therapy among those with and without coronary artery disease ( test for interaction , P = .41 ) . CONCLUSIONS AND RELEVANCE Among a cohort of men in the VA health care system who underwent coronary angiography and had a low serum testosterone level , the use of testosterone therapy was associated with increased risk of adverse outcomes . These findings may inform the discussion about the potential risks of testosterone therapy CONTEXT Greater mammographic density is associated with increased breast cancer risk and reduced diagnostic mammographic sensitivity and may be seen with estrogen/progestin therapy ( EPT ) . The effects of testosterone therapy on mammographic density in postmenopausal women not on EPT are not known . OBJECTIVE Our objective was to compare effects of two doses of the testosterone transdermal patch ( TTP ) with placebo in postmenopausal women without concomitant EPT on mammographic density  over 52 wk . DESIGN We conducted a r and omized , double-blind , placebo-controlled , parallel-group , multinational trial . PATIENTS Patients included 279 postmenopausal women participating in a testosterone and sexual function study with paired mammograms for baseline and 52 wk/exit . INTERVENTIONS Patients were r and omized to placebo , TTP 150 microg/d , or TTP 300 microg/d , stratified by menopause type ( natural or surgical ) . MAIN OUTCOME MEASURES Change from baseline to wk 52 in the percentage of dense tissue ( PD ) on digital mammograms . RESULTS A total of 250 women with paired mammograms for study baseline and wk 52 were included in the primary analysis . Mean age was 54.6 yr , baseline body mass index was 27.5 kg/m(2 ) , and 78 % were naturally menopausal . There were no baseline differences between groups . Mean changes from baseline ( + /-SEM ) in PD for placebo , TTP 150 microg/d and TTP 300 microg/d were small ( 0.05 + /- 0.16 , 0.06 + /- 0.19 , and 0.21 + /- 0.17 % ) and not significantly different . There were no statistically significant differences from placebo for total dense or nondense area and no significant relationships between hormone levels and PD after adjustment for body mass index . CONCLUSION TTP therapy over 52 wk appears to have no significant effect on digitally quantified absolute or percent dense mammographic area in postmenopausal women not using EPT OBJECTIVE To determine dose-dependent effects of T administration on cardiovascular risk markers in women with low T levels . METHODS Seventy-one hysterectomized women with or without oophorectomy with total T < 31 ng/dL and /or free T < 3.5 pg/mL received a st and ardized transdermal estradiol regimen during the 12-week run-in period and were then r and omized to receive weekly i m injections of placebo or 3- , 6.25- , 12.5- , or 25-mg T enanthate for 24 weeks . Total and free T levels were measured by liquid chromatography-t and em mass spectrometry and equilibrium dialysis , respectively . Insulin resistance and inflammatory markers were measured at baseline and 24 weeks . In a subset of women , magnetic resonance imaging of the abdomen was performed to quantify abdominal fat volume . RESULTS Fifty-nine women who completed the 24-week intervention were included in the final analysis . The five groups were similar at baseline . Mean on-treatment nadir total T concentrations were 14 , 79 , 105 , 130 , and 232 ng/dL in the placebo group and the 3- , 6.25- , 12.5- , and 25-mg groups , respectively . No significant changes in fasting glucose , fasting insulin , homeostatic model assessment of insulin resistance , high sensitivity C-reactive protein , adiponectin , blood pressure , and heart rate were observed at any T dose when compared to placebo . Similarly , no dose- or concentration-dependent changes were observed in abdominal fat on magnetic resonance imaging . CONCLUSION Short-term T administration over a wide range of doses for 24 weeks in women with low T levels was not associated with worsening of cardiovascular risk markers During a double-blind comparison of menopausal replacement therapy with estrogen alone compared with estrogen plus methyltestosterone ( meT ) , subjects who had been on conjugated equine estrogen ( CEE ) said they felt better when placed on esterified estrogen ( EE ) . We , therefore , tested whether these estrogen treatments differed in their neuropsychological effects .  Subjects were 34 healthy menopausal respondents to advertisements younger than age 66 who were on CEE at baseline . Each was r and omized into the EE condition , either immediately after baseline or after they first took EE plus added meT for 8 weeks . We compared neuropsychological measures between these two conditions . Data included cognitive performance test results and symptom self-ratings . Multivariate techniques were used to adjust for the effects of treatment order . Compared with prior CEE treatment , EE treatment was associated with significantly improved scores on the Zung Self-Rated Depression Scale and on Switching Attention Test performance . Further investigation is warranted to determine if different forms of estrogen replacement induce different neuropsychological effects OBJECTIVE To test the causal relationship between sex hormones and cognitive skills in postmenopausal women . We hypothesized that testosterone would decrease verbal memory and verbal fluency and increase spatial ability compared with a placebo . For estrogen , we conversely hypothesized that the treatment would increase verbal fluency and verbal memory and decrease spatial ability . DESIGN R and omized , double-blind , placebo-controlled , parallel-group trial . SETTING Women 's health clinical research unit at a university hospital . PATIENT(S ) Two-hundred healthy , naturally postmenopausal women aged 50 - 65 years . INTERVENTION(S ) R and omization to 4 weeks ' treatment with testosterone ( testosterone undecanoate , 40 mg/day ) , estrogen ( oral E2 2 mg/day ) or placebo . MAIN OUTCOME MEASURE(S ) Comparisons in verbal fluency , verbal memory , and spatial ability between the three treatment groups . RESULT ( S ) We found no significant effects of testosterone or estrogen on verbal fluency , verbal memory , or spatial ability . CONCLUSION ( S ) Our results give no support for short-term testosterone or estrogen treatment having any substantial effect on verbal fluency , verbal memory , or spatial ability in healthy postmenopausal women Objective . To analyze the effects of testosterone addition to estrogen therapy in comparison with estrogen alone on cardiovascular risk factors in postmenopausal women . Methods . Fifty surgically postmenopausal women were included in this double-blind , placebo-controlled and r and omized study to receive daily oral treatment with estradiol valerate 2 mg + placebo ( E/P ) or estradiol valerate 2 mg + testosterone undecanoate 40 mg ( E/T ) for 24 weeks and then switched to the other regimen for another 24 weeks . Sex hormones , High sensitivity CRP ( hsCRP ) , Interleukin-6 ( IL-6 ) , Tissue necrosis factor (TNF)-α , Insulin-like growth factor binding globulin ( IGFBP-1 ) , vascular cell adhesion molecule (VCAM)- 1 , and homocysteine were analyzed at baseline and after 6 and 12 months . Results . Estradiol and and rogens increased as expected during the treatments . After 6 months of E/P , increases of hsCRP and IGFBP-1 and a decline of VCAM were recorded , whereas IL-6 , TNF-α , and homocysteine were unchanged . When testosterone was added to estrogen , the increase of IGFBP-1 and decline in VCAM was similar as with estrogen treatment alone . However , testosterone addition counteracted the estrogen-induced rise in hsCRP but had no effects on IL-6 , TNF-α , and homocysteine . Conclusion . Data suggest that testosterone addition to estrogen treatment in postmenopausal women has a modest influence on inflammatory markers and there were no apparent adverse effects . On the contrary , the estrogen-induced increase in hsCRP was suppressed 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 Percutaneous estradiol ( E2 ) implants effectively preserve bone density in postmenopausal women . However , these implants are often given with testosterone , which may itself have an anabolic effect on bone . To determine whether testosterone confers any additional bone-sparing effect , we studied 50 postmenopausal women r and omly allocated to receive E2  ( 75 mg ) alone or with testosterone ( 100 mg ) every 6 months for 1 year . Women with an intact uterus received cyclic norethindrone ( 5 mg ) for 10 days of each calendar month . Twenty-five untreated women were recruited to act as a reference group . Bone density was measured at the lumbar spine and proximal femur by dual x-ray densitometry . By 1 year , bone density at the lumbar spine had fallen by 1.8 % in the reference group . In the women treated with E2 alone , it increased significantly by 7.8 % ( P < .0001 ) and in those receiving E2 with testosterone , it increased by 6.3 % ( P < .0001 ) . At the femoral neck , bone density decreased by 3 % in the controls and increased by approximately 4 % in both treated groups ( P < .0001 ) . The increase in bone density at these sites was unrelated to the woman 's chronological age , menopausal age , or initial bone density . However , it correlated significantly with the serum E2 levels attained after 1 year of therapy . In no treated patients did bone density decrease significantly . These data show that testosterone confers no additional bone-sparing effect in postmenopausal women Both estrogen and testosterone insufficiency has been associated with reduced psychological well-being including fatigue . However , hormonal replacement studies on fatigue are rare . Therefore , we wanted to study the effect of testosterone and estrogen replacement therapy on cognitive fatigue and the relation between sex hormone levels and cognitive fatigue in oophorectomized women . Fifty women with surgically induced menopause ( mean age : 54.0 ± 2.9 years ) were r and omly assigned to treatment with estradiol valerate in combination with testosterone undecanoate or placebo for 24 weeks in a double-blind cross-over study . Neuropsychological tests and question naires were used to assess cognitive fatigue and psychological well-being . Cognitive fatigue was significantly associated to poor self-rated health and higher body mass index but not to general psychological well-being or sex hormone levels . Treatment with testosterone + estrogen had no significant effect on cognitive fatigue but the results indicated a curvilinear relation for hormonal levels . The estrogen/testosterone ratio was more related to functions rather than high or low hormone levels per se . We found that cognitive fatigue is frequent in oophorectomized women and negatively associated to self-perceived health and positively associated to BMI . A well-balanced ratio between estrogen and testosterone levels may be important for cognitive fatigue Objective This study aims to determine the dose-dependent effects of testosterone on sexual function , body composition , muscle performance , and physical function in hysterectomized women with or without oophorectomy . Methods Seventy-one postmenopausal women who previously underwent hysterectomy with or without oophorectomy and had total testosterone levels less than 31 ng/dL or free testosterone levels less than 3.5 pg/mL received a st and ardized transdermal estradiol regimen during the 12-week run-in period and were r and omized to receive weekly intramuscular injections of placebo or 3 , 6.25 , 12.5 , or 25 mg of testosterone enanthate for 24 weeks .  Total and free testosterone levels were measured by liquid chromatography – t and em mass spectrometry and equilibrium dialysis , respectively . The primary outcome was change in sexual function measured by the Brief Index of Sexual Functioning for Women . Secondary outcomes included changes in sexual activity , sexual distress , Derogatis Interview for Sexual Functioning , lean body mass , fat mass , muscle strength and power , and physical function .  Results Seventy-one women were r and omized ; five groups were similar at baseline . Sixty-two women with analyzable data for the primary outcome were included in the final analysis . The mean on-treatment total testosterone concentrations were 19 , 78 , 102 , 128 , and 210 ng/dL in the placebo , 3-mg , 6.25-mg , 12.5-mg , and 25-mg groups , respectively . Changes in composite Brief Index of Sexual Functioning for Women scores , thoughts/desire , arousal , frequency of sexual activity , lean body mass , chest-press power , and loaded stair-climb power were significantly related to increases in free testosterone concentrations ; compared with placebo , changes were significantly greater in women assigned to the 25-mg group , but not in women in the lower-dose groups . Sexual activity increased by 2.7 encounters per week in the 25-mg group . The frequency of and rogenic adverse events was low . Conclusions Testosterone administration in hysterectomized women with or without oophorectomy for 24 weeks was associated with dose and concentration-dependent gains in several domains of sexual function , lean body mass , chest-press power , and loaded stair-climb power . Long-term trials are needed to weigh improvements in these outcomes against potential long-term adverse effects 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 Objective To study the effect on mammographic breast density of testosterone addition during combined estrogen/progestogen therapy in postmenopausal women . Methods A prospect i ve , r and omized , double-blind , placebo-controlled trial . A total of 99 women were given 2 mg 17β-estradiol and 1 mg norethisterone acetate in combination with either a testosterone patch ( 300 μg/24 h ) or a placebo patch . Mammographic breast density at baseline and after 6 months was assessed by visual classification scales and by digitized quantification . A st and ardized question naire was used to quantify subjective breast symptoms . Results Visual classifications showed an increase in mammographic density in 18–30 % of the women , with no significant differences between the treatment groups . The mean increase of the area of dense breast during treatment according to digitized assessment was 7.4 % in the placebo group and 5.4 % in the testosterone group . Breast symptoms showed a positive association with the increase in density ( rs = 0.34 ; p < 0.01 ) . Symptoms were most pronounced at 2 months of treatment . Density , both at baseline ( rs = −0.35 ; p < 0.01 ) and change during treatment ( rs = −0.28 ; p < 0.01 ) showed a negative association with free testosterone levels . Conclusion The addition of testosterone does not appear to influence mammographic breast density in women concurrently treated with a common oral estrogen/progestogen regimen for a period of 6 months INTRODUCTION Postmenopausal women with hypoactive sexual desire disorder ( HSDD ) experienced statistically significant improvements in the frequency of satisfying sexual activity , sexual desire , and distress with testosterone treatment in phase III trials , but it was not known whether the magnitude of these effects was clinical ly meaningful . The clinical relevance study was design ed to answer this question . AIM To evaluate the clinical relevance of the treatment benefits . METHODS This study involved a representative sample of 132 surgically postmenopausal women with HSDD who were enrolled in two r and omized , placebo-controlled trials ( N = 1094 ) assessing the efficacy and safety of transdermal testosterone treatment ( 300 mcg/day ) for 6 months . At the end of the studies , prior to unblinding , a sample of women ( 12 % ) was interviewed concerning their experiences with the treatment . MAIN OUTCOME MEASURES Women were asked " Overall , would you say that you experienced a meaningful benefit from the study patches ? " Changes in the efficacy end points in the double-blind studies were compared for the women who did and did not experience an overall meaningful benefit . RESULTS Overall , 33 of 64 women ( 52 % ) who received testosterone reported experiencing a meaningful treatment benefit , compared with 21 of 68 women ( 31 % ) who received placebo ( P = 0.025 ) . Among the women who identified themselves as experiencing a meaningful benefit , the mean ( SE ) change from baseline in 4-week frequency of satisfying sexual activity was 4.4 ( 0.76 ) , in desire score was 21.0 ( 2.78 ) , moving from " seldom " to " sometimes " feeling sexual desire , and in distress score was -36.5 ( 3.96 ) , moving from " often " to " seldom " being distressed . Among the women who identified themselves as not experiencing a meaningful benefit , the mean ( SE ) change from baseline in 4-week frequency of satisfying sexual activity was 0.5 ( 0.31 ) , in desire score was 2.9 ( 1.42 ) , and in distress score was -8.8 ( 2.23 ) . CONCLUSIONS Surgically menopausal women with HSDD in these studies received clinical ly meaningful benefits , including improvements in satisfying sexual activity , sexual desire , and personal distress 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 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 To compare the effects of two doses of conjugated equine estrogen ( CEE ) and two of esterified estrogen plus methyltestosterone ( E + A ) in surgically menopausal women . STUDY DESIGN A two-year , parallel-group , double-blind study of 311 women who were r and omly assigned to one of four regimens : ( 1 ) CEE , 0.625 mg/d ; ( 2 ) CEE , 1.25 mg/d ; ( 3 ) esterified estrogens , 0.625 mg , + methyltestosterone , 1.25 mg/d ; or ( 4 ) esterified estrogens , 1.25 , + methyltestosterone , 2.5 mg/d .  Study parameters were symptoms , lipids , bone mineral density , side effects and safety . RESULTS All treatments prevented loss of bone in the spine and hip . The higher E + A dose increased spine and hip BMD more than other treatments ( P < .002 ) . All treatments improved menopausal symptoms , with non-significantly greater improvements in well-being and sexual interest in the E + A groups . Similar and significant decreases in low-density lipoprotein were observed in all groups , but high-density lipoprotein and triglycerides were increased only in the unopposed estrogen groups ( P < .05 ) . Hirsutism was uncommon and similar in all groups at two years . Discontinuation rates and reasons for withdrawal from the study were similar in both groups . No clinical ly significant side effects or laboratory test abnormalities were seen . CONCLUSION As compared to estrogen alone , E + A significantly improved BMD and was well tolerated in surgically menopausal women 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 BACKGROUND Oophorectomy reduces serum testosterone levels . We studied the efficacy and safety of transdermal testosterone in treating hypoactive sexual desire disorder in surgically menopausal women . METHODS A 24-week , r and omized , double-blind , placebo-controlled , parallel-group , multicenter trial was conducted in women ( aged 24 - 70 years ) who developed distressful low sexual desire after bilateral salpingo-oophorectomy and hysterectomy and who were receiving oral estrogen therapy .  Women were r and omized to receive placebo ( n = 119 ) or testosterone patches in dosages of 150 microg/d ( n = 107 ) , 300 microg/d ( n = 110 ) , or 450 microg/d ( n = 111 ) twice weekly for 24 weeks . Sexual desire and frequency of satisfying sexual activity were primary efficacy outcome measures . RESULTS Of the 447 women r and omized , 318 ( 71 % ) completed the trial . Compared with placebo , women receiving the 300-microg/d testosterone patch had significantly greater increases from baseline in sexual desire ( 67 % vs 48 % ; P = .05 ) and in frequency of satisfying sexual activity ( 79 % vs 43 % ; P = .049 ) . The 150-microg/d group showed no evidence of a treatment effect . The 450-microg/d group also was not statistically different from the 300-microg/d or placebo groups . Marginally significant linear dose-response trends were observed for total satisfying sexual activity and sexual desire at 24 weeks ( P = .06 and .06 , respectively ) . Adverse events occurred with similar frequency in both groups ; no serious safety concerns were observed . CONCLUSIONS The 300-microg/d testosterone patch increased sexual desire and frequency of satisfying sexual activity and was well tolerated in women who developed hypoactive sexual desire disorder after surgical menopause 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 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 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 BACKGROUND Decreased libido is one of several changes in sexual function that are often experienced by female cancer patients .  Transdermal testosterone therapy has been associated with increased libido among estrogen-replete women who report low libido . METHODS In a phase III r and omized , placebo-controlled crossover clinical trial , we evaluated whether transdermal testosterone would increase sexual desire in female cancer survivors . Postmenopausal women with a history of cancer and no current evidence of disease were eligible if they reported a decrease in sexual desire and had a sexual partner . Eligible women were r and omly assigned to receive 2 % testosterone in Vanicream for a testosterone dose of 10 mg daily or placebo Vanicream for 4 weeks and were then crossed over to the opposite treatment for an additional 4 weeks . The primary endpoint was sexual desire or libido , as measured using the desire subscales of the Changes in Sexual Functioning Question naire , as assessed at baseline and at the end of 4 and 8 weeks of treatment . Serum levels of bioavailable testosterone were measured at the same times . All statistical tests were two-sided . RESULTS We enrolled 150 women . Women who were on active testosterone cream had higher serum levels of bioavailable testosterone than women on placebo ( mean change from baseline , testosterone versus placebo , week 4 , 11.57 % versus 0 % , difference = 11.57 % , 95 % confidence interval [ CI ] = 8.49 % to 14.65 % ; week 8 , 10.21 % versus 0.28 % , difference = 9.92 % , 95 % CI = 5.42 % to 14.42 % ; P<.001 for all ) . However , the average intrapatient libido change from baseline to weeks 4 and 8 was similar on both arms . CONCLUSION Increased testosterone level did not translate into improved libido , possibly because women on this study were estrogen depleted 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 Objectives To assess the safety and efficacy of 10 mg topical testosterone therapy daily ( 2 cm And ro-Feme ® cream ) as a treatment for low sexual desire in postmenopausal hysterectomized women who were already on transdermal estrogen . Methods A double-blind , r and omized , placebo-controlled , cross-over study ( each period being of 3 months ' duration ) was performed in the research center of a tertiary referral women 's hospital . Thirty-six menopausal healthy women were recruited who had undergone a hysterectomy , who were not depressed , were in a stable relationship and who fulfilled diagnostic criteria for low sexual desire , as measured by the Brief Index of Sexual Function for Women ( BISF-W ) . Main outcome measures The primary outcome measure was improvement in the sexuality score as measured by a vali date d tool ( BISF-W ) ; secondary measures were sub-scores of the BISF-W , effect on mood and energy , lipids and testosterone levels .  Results Testosterone cream significantly improved sexual desire , frequency of sex , receptivity and initiation as measured by the BISF-W score . It did not change mood , energy , lipids , blood pressure or weight over the study period . Conclusions Testosterone cream significantly improved sexual scores in menopausal women with low sexual desire . It was effective , easy to use and had no side-effects over the 3-month period of active treatment . It offers a novel and acceptable method of administering testosterone to menopausal women 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 OBJECTIVE To assess the efficacy and safety of a 300 mug/d testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women on concomitant estrogen therapy . METHODS Five hundred thirty-three women with hypoactive sexual desire disorder who had undergone previous hysterectomy and bilateral oophorectomy were enrolled in a 24-week , multicenter , double-blind , placebo-controlled trial . Patients were r and omly assigned to receive placebo or the testosterone patch twice weekly . The primary efficacy endpoint was change from baseline at week 24 in the frequency of total satisfying sexual activity , measured by the Sexual Activity Log . Secondary measures included sexual desire using the Profile of Female Sexual Function and personal distress as measured by the Personal Distress Scale . Hormone levels , adverse events , and clinical laboratory measures were review ed . RESULTS Total satisfying sexual activity significantly improved in the testosterone patch group compared with placebo after 24 weeks ( mean change from baseline , 1.56 compared with 0.73 episodes per 4 weeks , P = .001 ) . Treatment with the testosterone patch also significantly improved sexual desire ( mean change , 10.57 compared with 4.29 , P < .001 ) and decreased personal distress ( P = .009 ) . Serum free , total , and bioavailable testosterone concentrations increased from baseline . Overall , adverse events were similar in both groups ( P > .05 ) . The incidence of and rogenic adverse events was higher in the testosterone group ; most and rogenic adverse events were mild . CONCLUSION In surgically menopausal women with hypoactive sexual desire disorder , a 300 mug/d testosterone patch significantly increased satisfying sexual activity and sexual desire , while decreasing personal distress , and was well tolerated through up to 24 weeks of use OBJECTIVES The primary objective of this study was to assess the effect of a 6-month testosterone supplementation therapy on functional capacity and insulin resistance in female patients with chronic heart failure ( CHF ) . BACKGROUND Patients with CHF show decreased exercise capacity and insulin sensitivity . Testosterone supplementation improves these variables in men with CHF . No study has evaluated the effects of testosterone supplementation on female patients with CHF . METHODS Thirty-six elderly female patients with stable CHF , ( ejection fraction 32.9 ± 6 ) were r and omly assigned ( 2:1 ratio ) to receive testosterone transdermal patch ( T group , n = 24 ) or placebo ( P group , n = 12 ) , both on top of optimal medical therapy . At baseline and after 6 months , patients underwent  6-min walking test  ( 6MWT ) , cardiopulmonary exercise test , echocardiogram , quadriceps maximal isometric voluntary contraction , dynamic quadriceps isokinetic strength ( peak torque ) , and insulin resistance assessment by homeostasis model . RESULTS Distance walked at 6MWT as well as peak oxygen consumption significantly improved in the T group , whereas they were unchanged in the P group ( p < 0.05 for all comparisons ) . The homeostasis model was significantly reduced in the T group in comparison with the P group ( -16.5 % vs. + 5 % , respectively ; p < 0.05 ) . Maximal voluntary contraction and peak torque increased significantly in the T group but did not change in the P group . Increase in distance walked at 6MWT was related to the increase in free testosterone levels ( r = 0.593 , p = 0.01 ) . No significant changes in echocardiographic parameters were observed in either group . No side effects requiring discontinuation of T were detected . CONCLUSIONS Testosterone supplementation improves functional capacity , insulin resistance , and muscle strength in women with advanced CHF .  Testosterone seems to be an effective and safe therapy for elderly women with CHF Objective : Testosterone insufficiency has been associated with psychosexual problems , reduced psychological well-being , and negative metabolic consequences , whereas less is known about the effects on cognition . The aim of this study was to investigate the effect of adding testosterone to estrogen therapy on memory functions in oophorectomized women . Methods : In a r and omized , double-blind , placebo-controlled design , women with surgically induced menopause ( n = 50 ; mean [ SD ] age , 54.0 [ 2.9 ] y ) received estradiol valerate in combination with testosterone undecanoate or placebo . The women were assessed with a self-report question naire regarding memory and neuropsychological tests for verbal and spatial episodic memory and incidental learning at baseline , at the time of crossover , and after completion of treatment . Results : Testosterone undecanoate 40 mg added to estrogen therapy had a negative effect on immediate but not delayed verbal memory at 24 weeks . Subjective and objective memory showed some correspondence as the women in the estrogen + placebo treatment group rated decreased everyday memory problems at 24 weeks compared with baseline . This was not observed in the women in the estrogen + testosterone treatment . Verbal attention span deteriorated from baseline with estrogen + placebo treatment but not with the estrogen + testosterone treatment . However , there was no significant treatment effect between the two groups . Conclusions : Adding testosterone to estrogen treatment deteriorated immediate verbal memory compared with estrogen + placebo , while other memory functions were unaffected Objective To evaluate the effect of the addition of methyltestosterone to estrogen and progestogen therapy on postmenopausal sexual energy and orgasm . Methods Sixty postmenopausal women in a stable relationship with a partner capable of intercourse , and presenting sexual complaints that appeared after menopause , were r and omly divided into two groups : EP ( n = 29 ) received one tablet of equine estrogens ( CEE ) 0.625 mg plus medroxyprogesterone acetate ( MPA ) 2.5 mg and one capsule of placebo ; EP + A ( n = 31 ) received one tablet of CEE 0.625 mg plus MPA 2.5 mg and one capsule of methyltestosterone 2.0 mg ; The treatment period was 12 months . The effects of treatment on sexual energy were assessed using the Sexual Energy Change Scale . The ability to reach orgasm in sexual relations with the partner was verified through monthly calendars and by calculating the ratio between monthly frequency of orgasms in sexual relations and monthly sexual frequency . Results There was a significant relationship between improvement in level of sexual energy and the addition of methyltestosterone to CEE/MPA treatment ( p = 0.021 ) . No significant effect on orgasmic capacity was noted after the treatment period . Conclusion Addition of methyltestosterone to CEE/MPA therapy may increase sexual energy , but might not affect the ability to obtain orgasm in sexual relations INTRODUCTION A significant number of postmenopausal women suffer from distressing problems because of urogenital atrophy secondary to the decline in circulating estrogen levels . Treatment with topical hormones may provide relief in such women when used judiciously . AIM To study the effects of local estrogen with or without local testosterone on urogenital and sexual health in postmenopausal women . METHODS Seventy-five postmenopausal women symptomatic for urogenital atrophy and sexual dysfunction were r and omly divided into two study groups and one control group . The women in study group 1 received local estrogen cream ; study group 2 received local estrogen and testosterone cream ; the control group received nonhormonal lubricant KY gel for 12 weeks . The urogenital and sexuality score , along with the vaginal health index and the vaginal maturation index ( VMI ) , was calculated at the beginning of therapy and 12 weeks later . MAIN OUTCOME MEASURES Changes in the urogenital and sexuality score along with vaginal health index and VMI . RESULTS After 12 weeks of therapy , there was a significant improvement in all the four study parameters , which correlated well with the improvement in symptoms of urogenital atrophy and sexual dysfunction in both the study groups as compared with the control group . Improvement in sexuality score was greatest with combined estrogen- and rogen therapy . There were no adverse effects and the therapies were well accepted without any compliance issue . CONCLUSION Local estrogen either alone or with and rogen is highly effective in relieving symptoms of urogenital atrophy and in improving sexual function in symptomatic postmenopausal women INTRODUCTION Female libido is multifactorial and complex . Declining estrogen levels in postmenopausal women affects vaginal function . AIM The aim of this study was to evaluate female sexual function after using topical estrogen , testosterone , or polyacrylic acid as vaginal lubricants with K-Y jelly as a placebo lubricant . METHODS This was a r and omized controlled clinical trial on 80 postmenopausal women between 40 and 70 years of age with follow-up at the Menopause Clinic of the CAISM Unicamp . The women were r and omized to treatment with topical vaginal estrogen , testosterone , polyacrylic acid , or oil lubricant alone , three times a week for a period of 12 weeks from November 2011 to January 2013 . MAIN OUTCOME MEASURE We used the Female Sexual Function Index ( FSFI ) to assess changes in sexual response at baseline , and after 6 and 12 weeks . RESULTS After 12 weeks of treatment , polyacrylic acid and topical testosterone produced improvements in the FSFI domains of sexual desire , lubrication , satisfaction , reduced pain during intercourse , and total score compared with lubricant alone . Treatment with topical estrogen in comparison with lubricant alone showed an improvement in the FSFI field of desire . The intragroup analysis over the time of the treatment showed improvements in the fields of desire , lubrication , and reduced pain for polyacrylic acid , testosterone , and estrogen . Furthermore , women who used testosterone showed improvements over time in the fields of arousal , orgasm , and satisfaction . CONCLUSIONS Treatment of postmenopausal women with symptoms of vaginal atrophy with polyacrylic acid , testosterone , and estrogen for 12 weeks produced improvements in self-reported female sexual function when compared with a placebo lubricant
target: Some studies suggest that testosterone therapy has additional effects , which include increased bone mineral density and decreased serum high-density lipoprotein ( HDL ) cholesterol .
background: The clinical sequelae of oestrogen deficiency during menopause are undoubted .
  However , the pathophysiological role of testosterone during the menopause is less clear .
  Several r and omized , placebo-controlled clinical trials suggest that testosterone therapy improves sexual function in postmenopausal women .