Differential symptom response to parenteral estrogen and/or androgen administration in the surgical menopause. EFFECT OF OESTROGEN AND TESTOSTERONE IMPLANTS ON PSYCHOLOGICAL DISORDERS IN THE CLIMACTERIC Effect of androgens combined with hormone therapy on quality of life in post-menopausal women with sexual dysfunction PERCEIVED EFFECTS OF TESTOSTERONE REPLACEMENT THERAPY IN PERIMENOPAUSAL AND POSTMENOPAUSAL WOMEN: AN INTERNET PILOT STUDY Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. Safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a randomized, placebo-controlled trial. Effects of testosterone treatment on endometrial proliferation in postmenopausal women. Estrogen and/or androgen replacement therapy and cognitive functioning in surgically menopausal women Transdermal testosterone therapy improves well-being, mood, and sexual function in premenopausal women Testosterone inhibits estrogen/progestogen-induced breast cell proliferation in postmenopausal women Preliminary Clinical Experience with Androgen Administration for Pre- and Postmenopausal Women with Hypoactive Sexual Desire Androgen enhances sexual motivation in females: a prospective, crossover study of sex steroid administration in the surgical menopause. Testosterone addition during menopausal hormone therapy: effects on mammographic breast density Testosterone enhances estradiol's effects on postmenopausal bone density and sexuality. Testosterone enhances estradiol's effects on postmenopausal bone density and sexuality. Hormonal treatments of sexual unresponsiveness in postmenopausal women: a comparative study Testosterone patch for low sexual desire in surgically menopausal women: a randomized trial.
The investigation of estrogen and /or and rogen administration on physical and psychological symptoms in the surgical menopause was carried out in a prospect i ve , double-blind , crossover design . When patients who received either a combined estrogen- and rogen drug or and rogen alone  were compared with those who received estrogen alone or placebo , energy level , well-being , and appetite were increased ( p less than 0.01 ) . The and rogen-containing preparations also induced lower somatic , psychological , and total scores on the menopausal index . Superior functioning in the and rogen-treated groups occurred in association with higher plasma testosterone levels during the treatment phases ( p less than 0.01 ) . These data suggest that reduced levels of circulating testosterone subsequent to bilateral oophorectomy may play an important role in the development of physical and psychological symptoms that are frequent sequelae of this surgical procedure In a double-blind trial oestradiol , oestradiol/testosterone , or placebo implants were assessed for their effects on psychological symptoms in women attending a menopause clinic . After two months , women receiving active treatment scored better than the placebo group on a self-rating scale of distress , on anxiety , and on depression ( p less than 0.05 ) . Postmenopausal but not perimenopausal women improved after placebo , and at 4 months the scores in the three groups no longer differed significantly 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 Women experience somatic , mood , energy , and libido changes during menopause .  Testosterone replacement therapy is being prescribed in conjunction with estrogen replacement therapy ( ERT ) for these symptoms . Little is known about women ’s perceptions of the benefits and risks of testosterone , so an Internet survey was conducted to elicit women ’s perceptions of the effects on mood , energy , sexuality , and somatic symptoms .  A sample of 61 women primarily from the United States and Canada participated in the survey ; one woman from Germany and one from Sweden also took part in the survey . Participants reported significantly improved sexuality and improved mood and vigor , with a decline in fatigue . Of the 7 somatic complaints assessed , improvements were noted in 5 ( sleep disturbances , hot flashes , night sweats , vaginal dryness , and appetite ) . A prospect i ve clinical trial is needed to confirm these results 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 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 CONTEXT Available data concerning effects of testosterone on endometrium of postmenopausal women are seriously limited . OBJECTIVE Our aim was to compare the influence of treatment with testosterone and /or estrogen on endometrial proliferation in healthy postmenopausal women . DESIGN This was an open , r and omized clinical study with parallel comparison of the groups . SETTING The study was conducted at a women 's health clinical research unit and a research laboratory at a university hospital . PARTICIPANTS Sixty-three women who had experienced natural menopause participated in this study . INTERVENTIONS After r and om assignment , the participants were administered orally testosterone undecanoate ( 40 mg every second day ) , estradiol valerate ( 2 mg daily ) , or both for 3 months . MAIN OUTCOME MEASURES Endometrial thickness was measured , and endometrial proliferation evaluated on the basis of histopathology and expression of Ki-67 , a proliferation marker . RESULTS Endometrial thickness was significantly increased by treatment with estrogen alone or in combination with testosterone but was unaltered by testosterone alone . Among the women receiving estrogen alone , the proportion exhibiting histopathology indicative of proliferation increased significantly to 50 % ( P < 0.05 ) , there was a nonsignificant increase to 28 % with the combined treatment , whereas testosterone alone had no effect at all . Expression of Ki-67 was up-regulated significantly in both gl and s and stroma ( P < 0.05 , respectively ) in both estrogen treatment groups . However , the expression was significantly higher in stroma by estrogen treatment alone than after combined treatment ( P < 0.05 ) . CONCLUSIONS The short-term treatment with testosterone of postmenopausal women does not stimulate endometrial proliferation . In addition , testosterone appears to counteract endometrial proliferation induced by estrogen to a certain extent The effect of estrogen and /or and rogen replacement therapy on several aspects of cognitive functioning in surgically menopausal women was tested in a prospect i ve , crossover design . Women who received either a combined estrogen- and rogen preparation , estrogen alone , or and rogen alone had scores on two tests of short-term memory , a test of long-term memory and a test of logical reasoning that were not different during the postoperative treatment phase compared to their preoperative performance . However , oophorectomized women who received placebo had lower scores on all four measures of cognitive functioning postoperatively , coincident with their significantly lower concentrations of plasma estradiol and testosterone .  Patients who had a hysterectomy but whose ovaries were retained showed stability both in cognitive performance and in circulating sex steroid concentrations . These findings suggest that the drastic change in endocrine milieu following surgical menopause may have a direct , albeit modest , effect on aspects of cognitive functioning . Possible mechanisms of action of the sex hormones on cognitive functioning in women are discussed Objective Circulating testosterone in women declines during the late reproductive years such that otherwise healthy women in their 40s have approximately half the testosterone level as women in their 20s . Despite this , research showing the benefits of and rogen replacement has been limited to the postmenopausal years . In view of the known premenopausal physiological decline in testosterone , we have evaluated the efficacy of transdermal testosterone therapy on mood , well-being , and sexual function in eugonadal , premenopausal women presenting with low libido . Design Premenopausal women with low libido participated in a r and omized , placebo-controlled , crossover , efficacy study of testosterone cream ( 10 mg/day ) with two double-blind , 12-week , treatment periods separated by a single-blind , 4-week , washout period . Results Thirty-four women completed the study per protocol , with 31 women ( mean age 39.7 ± 4.2 years ; serum testosterone 1.07 + 0.50 nmol/L ) providing complete data  . Testosterone therapy result ed in statistically significant improvements in the composite scores of the Psychological General Well-Being Index [ + 12.9 ( 95 % CI , + 4.6 to + 21.2 ) , P = 0.003 ] and the Sabbatsberg Sexual Self-Rating Scale [ + 15.7 ( 95 % CI , + 6.5 to + 25.0 ) , P = 0.001 ] compared with placebo . A mean decrease in the Beck Depression Inventory score approached significance [ −2.8 ( 95 % CI , −5.7 to + 0.1 ) , P = 0.06 ] . Mean total testosterone levels during treatment were at the high end of the normal range , and estradiol was unchanged . No adverse effects were reported . Conclusions Testosterone therapy  improves well-being , mood , and sexual function in premenopausal women with low libido and low testosterone . As a substantial number of women experience diminished sexual interest and well-being during their late reproductive years , further research is warranted to evaluate the benefits and safety of longer-term intervention 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 The present study examined effects of testosterone on  hypoactive sexual desire in pre- and postmenopausal women ( treated ) compared with an age-matched reference group ( reference ) . Treated participants received 100 mg of testosterone cypionate in oil injected intramuscularly ( i.m . ) monthly for 3 months . We measured salivary testosterone and scores on the Sexual Desire Inventory pretreatment and posttreatment . Treated and reference participants ' baseline testosterone was equivalent , however , treated participants exhibited higher testosterone levels than did reference participants posttreatment . As expected , treated participants exhibited lower baseline sexual desire than did reference participants and showed a significant increase in sexual desire posttreatment . This research suggests that testosterone may effectively alleviate hypoactive sexual desire , even in women with normal testosterone levels & 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 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 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 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 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
Some studies suggest that testosterone therapy has additional effects , which include increased bone mineral density and decreased serum high-density lipoprotein ( HDL ) cholesterol .
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 .