Systematic indirect comparison of ospemifene versus local estrogens for vulvar and vaginal atrophy.

In the absence of a direct head-to-head study, we performed an indirect historical comparison of ospemifene 60 mg (Senshio ^® ) vs. local vaginal estrogens in moderate or severe vulvar and vaginal atrophy (VVA). A literature search was carried out of clinical efficacy/safety trials of local vaginal estrogens in VVA approved in Europe. For efficacy comparison, studies had to be placebo-controlled and of 12 weeks' duration. For safety comparison, studies had to be ≥40 weeks' duration. Efficacy endpoints were the difference between active and placebo in change from baseline to week 12 for symptoms, vaginal pH, and maturation value (MV). Safety endpoints were endometrial safety, breast safety, thrombosis, and adverse events. The 12-week improvement over placebo in symptom score was not different for ospemifene 60 mg and 17β-estradiol 10 μg and for ospemifene 60 mg and estriol gel. After 12 weeks, the percentages with vaginal pH <5.0 and <5.5 were better for ospemifene 60 mg than 10 μg 17β-estradiol. Week-12 pH changes were comparable with estriol pessaries or gel and ospemifene 60 mg. The 12-week MV improvements over placebo were similar or better with ospemifene 60 mg compared with 10 μg 17β-estradiol and with estriol pessaries or gel. There was no increased vaginal bleeding, endometrial hyperplasia, or carcinoma (including breast cancer) relative to placebo and no signal for increased risk of venous thromboembolism with ospemifene 60 mg or 10 μg 17β-estradiol, but the confidence intervals for both products do not exclude an increased risk. This historical indirect comparison suggests that ospemifene 60 mg has an efficacy, safety, and tolerability profile comparable to or better than local vaginal estrogens in the treatment of VVA.