Sexual function in women on estradiol or venlafaxine for hot flushes: a randomized controlled trial

Abstract

Objective: To evaluate sexual function in midlife women taking low-dose oral estradiol or venlafaxine for hot flushes.

Methods: In an 8-week randomized controlled trial among women aged 40-62 years, sexual function was compared between 0.5 mg oral estradiol per day or 75 mg venlafaxine per day (both compared with a placebo). Measures included composite and six domain scores from the Female Sexual Function Index and sexually related personal distress.

Results: Participants were aged 54.6 years (standard deviation [SD] 3.8) years, 59% white, with 8.1 (SD 5.3) daily hot flushes. Median composite baseline Female Sexual Function Index score was 16.3 (SD 11.9, n=256) for all women and 21.7 (SD 9.3, n=198) among sexually active women. Composite mean Female Sexual Function Index change from baseline to week 8 was 1.4 (95% confidence interval [CI] -0.4 to 3.2) for estradiol, 1.1 (95% CI -0.5 to 2.7) for venlafaxine, and -0.3 (95% CI -1.6 to 1.0) for placebo. Composite Female Sexual Function Index and sexually related distress change from baseline did not differ between estradiol and placebo (P=.38, P=.30) or venlafaxine and placebo (P=.79, P=.48). Among sexually active women, Female Sexual Function Index domain score change from baseline differences (active compared with placebo) in desire was 0.3 (95% CI 0.0-0.6) for estradiol, -0.6 (95% CI -1.2 to 0.0) in orgasm for venlafaxine, and 0.9 (95% CI 0.2-1.6) in penetration pain for venlafaxine. No women reported adverse events related to sexual dysfunction.

Conclusion: Overall sexual function among nondepressed midlife women experiencing hot flushes did not change over 8 weeks with low-dose oral estradiol or venlafaxine (compared with placebo), although a subtle increase in desire (estradiol) and decreases in orgasm and pain (venlafaxine) may exist.

Clinical trial registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01418209.

Level of evidence: I.

Figure 1

Randomization and data collection. FSFI, Female Sexual Function Index.

Figure 2

Change in composite Female Sexual Function Index scores among all women from baseline to 4 and 8 weeks: estradiol, venlafaxine and placebo. Y axis: Mean Composite Female Sexual Function Index score with standard deviation, ranges 2 (not sexually active and no desire) to 36. Analysis consisted of the treatment group estimated contrast from a linear regression model summarizing composite Female Sexual Function Index score at 4 and 8 weeks as a function of group, clinical site, time point and baseline sexual function score.