Effects of aromatase inhibition on sexual function and well-being in postmenopausal women treated with testosterone: a randomized, placebo-controlled trial

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, randomized, 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 mu L of a 0.5% T gel (total dose 2 mg) and were randomly 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 randomly 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 Wellbeing 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.