Efficacy and safety of ospemifene in postmenopausal women with moderate-to-severe vaginal dryness: a phase 3, randomized, double-blind, placebo-controlled, multicenter trial

Menopause. 2019 Jan 28;26(6):611-621. doi: 10.1097/GME.0000000000001292.


Objective: To evaluate the safety and efficacy of ospemifene for the treatment of moderate to severe vaginal dryness in postmenopausal women with vulvovaginal atrophy (VVA).

Methods: This 12-week, multicenter, double-blind phase 3 study randomized postmenopausal women (aged 40-80 years) with VVA and moderate to severe vaginal dryness as their most bothersome symptom to daily oral ospemifene 60 mg or placebo. Coprimary efficacy endpoints included changes from baseline to week 12 in percentages of vaginal parabasal and superficial cells, vaginal pH, and vaginal dryness severity with ospemifene versus placebo; other secondary endpoints were evaluated (weeks 4, 8, and 12). Safety was assessed by treatment-emergent adverse events (TEAEs) and endometrial biopsies.

Results: Women (n = 631; ospemifene [n = 316], placebo [n = 315]) had a mean age of 59.8 years, a mean body mass index of 27.2 kg/m, and most were white. Ospemifene significantly improved (P < 0.0001) the percentages of parabasal and superficial cells, vaginal pH, and severity of vaginal dryness severity compared with placebo at week 12; significant between-group differences were noted by week 4. Secondary endpoints of dyspareunia (P < 0.001), maturation value (P < 0.0001), and the Female Sexual Function Index (P < 0.05) also significantly improved with ospemifene versus placebo at week 12. Significantly more women responded (31.5% vs 6.0%; P < 0.0001) or were satisfied (49.2% vs 33.8%; P = 0.0007) with ospemifene versus placebo at week 12. No unexpected TEAEs, treatment-related serious TEAEs, thrombotic events, or endometrial hyperplasia or carcinoma were observed.

Conclusions: Ospemifene was effective and well tolerated for the treatment of moderate-to-severe vaginal dryness in postmenopausal women with VVA.

Trial registration: ClinicalTrials.gov NCT02638337.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Atrophy / drug therapy
  • Double-Blind Method
  • Dyspareunia / drug therapy
  • Female
  • Hot Flashes / etiology
  • Humans
  • Middle Aged
  • Patient Satisfaction
  • Postmenopause / physiology*
  • Selective Estrogen Receptor Modulators / administration & dosage
  • Selective Estrogen Receptor Modulators / adverse effects*
  • Selective Estrogen Receptor Modulators / therapeutic use*
  • Severity of Illness Index*
  • Tamoxifen / administration & dosage
  • Tamoxifen / adverse effects
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / therapeutic use
  • Treatment Outcome
  • Vagina / pathology*
  • Vaginal Diseases / drug therapy*
  • Vulva / pathology*


  • Selective Estrogen Receptor Modulators
  • Tamoxifen
  • Ospemifene

Associated data

  • ClinicalTrials.gov/NCT02638337