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

Menopause. 2006 Jan-Feb;13(1):37-45. doi: 10.1097/01.gme.0000168061.32917.83.

Abstract

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 muL 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 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Affect / drug effects*
  • Aromatase Inhibitors / pharmacology*
  • C-Reactive Protein / analysis
  • Estradiol / administration & dosage
  • Estradiol / blood
  • Estrogen Replacement Therapy / methods
  • Female
  • Humans
  • Letrozole
  • Lipids / blood
  • Lipoprotein(a) / blood
  • Middle Aged
  • Nitriles / pharmacology
  • Placebos
  • Sexuality / drug effects*
  • Testosterone / administration & dosage*
  • Testosterone / adverse effects
  • Testosterone / blood
  • Triazoles / pharmacology

Substances

  • Aromatase Inhibitors
  • Lipids
  • Lipoprotein(a)
  • Nitriles
  • Placebos
  • Triazoles
  • Testosterone
  • Estradiol
  • Letrozole
  • C-Reactive Protein