Female sexual function improved with ospemifene in postmenopausal women with vulvar and vaginal atrophy: results of a randomized, placebo-controlled trial

Abstract

Background: Ospemifene is a non-estrogen, tissue selective estrogen receptor agonist/antagonist, or selective estrogen receptor modulator, recently approved for the treatment of dyspareunia, a symptom of vulvar and vaginal atrophy (VVA), due to menopause. Postmenopausal dyspareunia is often associated with female sexual dysfunction (FSD). In this report, we present data that demonstrate the effect of ospemifene 60 mg/day on FSD assessed by the Female Sexual Function Index (FSFI), a widely used tool with six domains (Arousal, Desire, Orgasm, Lubrication, Satisfaction, and Pain).

Methods: A phase-3, randomized, double-blind, 12-week trial (n = 919) compared the efficacy and safety of oral ospemifene 60 mg/day vs. placebo in postmenopausal women with VVA in two strata based on self-reported, most bothersome symptom of either dyspareunia or dryness. Primary data were published previously. We report herein pre-specified secondary efficacy endpoints analyses, including changes from baseline to Weeks 4 and 12 for FSFI total and domain scores as well as serum hormone levels.

Results: Ospemifene 60 mg/day demonstrated a significantly greater FSFI total score improvement vs. placebo at Week 4 (p < 0.001). Improvement in FSFI scores continued to Week 12 (p < 0.001). At Week 4, the FSFI domains of Sexual Pain, Arousal, and Desire were significantly improved with ospemifene vs. placebo; at Week 12, improvements in all domains were significant (p < 0.05). Changes in serum hormones were minor and uncorrelated with changes in sexual functioning.

Conclusion: In a large, randomized, double-blind, placebo-controlled trial, ospemifene 60 mg/day significantly improved FSD in women with VVA. Consistent effects across FSFI domains were observed.

Keywords: DYSPAREUNIA; FEMALE SEXUAL DYSFUNCTION; MENOPAUSE; OSPEMIFENE; TISSUE-SELECTIVE ESTROGEN AGONIST/ANTAGONIST; VULVAR AND VAGINAL ATROPHY.

Figure 1

Change from baseline to Weeks 4 and 12 (last observation caried forward) in the Female Sexual Function Index (FSFI) total score in the intent-to-treat (ITT) population. ∗∗, p < 0.001 compared with placebo. p Values were computed using ANCOVA where change from baseline was the response variable, baseline assessment was the covariate, and treatment and stratum were fixed effects. The ITT population included all randomized participants who received ≥ one dose of study medication. ANCOVA, analysis of covariance; LS, least squares

Figure 2

Change from baseline to Weeks 4 and 12 (last observation caried forward) in the Female Sexual Function Index (FSFI) total score in the dyspareunia stratum. ∗∗, p < 0.001 compared with placebo; ∗∗∗, p < 0.0001 compared with placebo. p Values were computed using ANCOVA where change from baseline was the response variable, baseline assessment was the covariate, and treatment and center were fixed effects. ANCOVA, analysis of covariance; LS, least squares

Figure 3

Change from baseline to Weeks 4 and 12 (last observation caried forward) in the Female Sexual Function Index (FSFI) domain scores in the intent-to-treat (ITT) population. ∗, p < 0.05 compared with placebo; ∗∗, p < 0.001 compared with placebo. p Values were computed using ANCOVA where change from baseline was the response variable, baseline assessment was the covariate, and treatment and stratum were fixed effects. ANCOVA, analysis of covariance; LS, least squares; W4, Week 4; W12, Week 12

Figure 4

Change from baseline to Weeks 4 and 12 (last observation caried forward) in the Female Sexual Function Index (FSFI) domain scores in the dyspareunia stratum. ∗, p < 0.05 compared with placebo; ∗∗, p < 0.001 compared with placebo; ∗∗∗, p < 0.0001 compared with placebo. p Values were computed using ANCOVA where change from baseline was the response variable, baseline assessment was the covariate, and treatment and center were fixed effects. ANCOVA, analysis of covariance; LS, least squares; W4, Week 4; W12, Week 12

Figure 5

Mean ± standard deviation serum hormone concentrations at baseline and Week 12 in the intent-to-treat population. BL, baseline; FSH, follicle stimulating hormone; LH, luteinizing hormone; SHBG, sex hormone binding globulin; W12, Week 12