Overall Safety of Ospemifene in Postmenopausal Women from Placebo-Controlled Phase 2 and 3 Trials

OBJECTIVE To evaluate the safety of daily oral ospemifene 60 mg, estrogen agonist/antagonist, used to treat moderate-to-severe dyspareunia due to postmenopausal vulvovaginal atrophy, which is part of genitourinary syndrome of menopause. METHODS Post hoc analysis of safety data (treatment-emergent adverse events [TEAEs]) pooled from six phase 2 and 3 randomized, double-blind, multicenter placebo-controlled studies, evaluating the effects of ospemifene 60 mg on the breast, cardiovascular system, and bone in postmenopausal women. RESULTS At least one TEAE was reported by 67.6% (840/1242) and 54.1% (518/958) of women taking ospemifene 60 mg and placebo, respectively. Most TEAEs were mild or moderate and occurred within 4 to 12 weeks. The most commonly reported TEAEs with ospemifene were hot flush (8.5% vs. 3.3% for placebo) and urinary tract infection (6.5% vs. 4.8%). Discontinuation due to TEAEs was 7.6% with ospemifene and 3.8% with placebo. Most women discontinued treatment due to adverse events (AEs): hot flushes, muscle spasms, headache, and vaginal discharge. Serious AEs occurred infrequently (ospemifene, 2.6%; placebo, 1.8%); most were not considered related to treatment. Breast cancer and other breast-related TEAE incidences were comparable between ospemifene (2.5%) and placebo (2.2%), and cardiovascular TEAE incidence, including deep vein thrombosis, was low with ospemifene (0.3%) and placebo (0.1%). CONCLUSION No unexpected safety signals were reported, and discontinuation due to TEAEs was low, with use of ospemifene 60 mg versus placebo in six phase 2 and 3 trials, suggesting a lack of detrimental effects on the breast, bone, and cardiovascular health of postmenopausal women when ospemifene is used to effectively treat moderate-to-severe postmenopausal dyspareunia.