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 androgen 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 randomized, placebocontrolled, 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 resulted 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.

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Thus, the capacity of adipose tissue to produce estrogen seems to increase significantly with age at the time of menopause and to be unaltered by exogenous estrogen therapy. This difference in extragonadal estrogen production with age may play a pivotal role in the increase in estrogen-dependent malignancies in the postmenopausal years.

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