Efficacy, tolerability, and endometrial safety of ospemifene compared with current therapies for the treatment of vulvovaginal atrophy: a systematic literature review and network meta-analysis

Abstract

Importance Ospemifene is a novel selective estrogen receptor modulator developed for the treatment of moderate to severe postmenopausal vulvovaginal atrophy (VVA). Objective The aim of the study is to perform a systematic literature review (SLR) and network meta-analysis (NMA) to assess the efficacy and safety of ospemifene compared with other therapies used in the treatment of VVA in North America and Europe. Evidence Review Electronic database searches were conducted in November 2021 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized or nonrandomized controlled trials targeting postmenopausal women with moderate to severe dyspareunia and/or vaginal dryness and involving ospemifene or at least one VVA local treatment were considered. Efficacy data included changes from baseline in superficial and parabasal cells, vaginal pH, and the most bothersome symptom of vaginal dryness or dyspareunia, as required for regulatory approval. Endometrial outcomes were endometrial thickness and histologic classifications, including endometrial polyp, hyperplasia, and cancer. For efficacy and safety outcomes, a Bayesian NMA was performed. Endometrial outcomes were compared in descriptive analyses. Findings A total of 44 controlled trials met the eligibility criteria (N = 12,637 participants). Network meta-analysis results showed that ospemifene was not statistically different from other active therapies in most efficacy and safety results. For all treatments, including ospemifene, the posttreatment endometrial thickness values (up to 52 wk of treatment) were under the recognized clinical threshold value of 4 mm for significant risk of endometrial pathology. Specifically, for women treated with ospemifene, endometrial thickness ranged between 2.1 and 2.3 mm at baseline and 2.5 and 3.2 mm after treatment. No cases of endometrial carcinoma or hyperplasia were observed in ospemifene trials, nor polyps with atypical hyperplasia or cancer after up to 52 weeks of treatment. Conclusions and Relevance Ospemifene is an efficacious, well-tolerated, and safe therapeutic option for postmenopausal women with moderate to severe symptoms of VVA. Efficacy and safety outcomes with ospemifene are similar to other VVA therapies in North America and Europe.

Ospemifene for Genitourinary Syndrome of Menopause: Patient Selection

“…Endometrial thickness ranged between 2.1 and 2.3 mm at baseline and 2.5 and 3.2 mm after treatment. 18 Placebo-controlled trials as well as real-life use of ospemifene have not shown an increase in venous thromboembolism among ospemifene using women when compared to non-ospemifene using women. 16,19…”

“…Preclinical data, clinical data and systematic review have demonstrated ospemifene's antiestrogenic effect and its safety profile with regard to breast tissue, inhibiting tumor growth and possible chemoprotective effect. [17][18][19] Ospemifene is the only therapeutic option approved for use in women with VVA and a history of breast cancer. 26…”

“…Endometrial thickness ranged between 2.1 and 2.3 mm at baseline and 2.5 and 3.2 mm after treatment. 18 …”

Gynecologic Care of Black Breast Cancer Survivors

“…Ospemifene is a selective estrogen receptor modulator that is FDA approved for vaginal atrophy [ 87 , 89 ]. Data in the general population are promising [ 93 , 94 ], along with data that do not demonstrate increased recurrence rates in breast cancer survivors (although not FDA recommended in breast cancer survivors due to lack of data) [ 95 ]. Careful consideration must be given due to ospemifene’s agonist effects on endometrial tissue and increased risk of VTE [ 96 ].…”

Endometrial safety and efficacy of ospemifene

“…Steven R. Goldstein, MD, CCD, NCMP, FACOG, FRCOG(H) I n this month's journal, the article by Simon et al 1 deals with a systematic review of the efficacy and safety of ospemifene compared with current therapies for the treatment of vulvovaginal atrophy. They included 44 controlled trials involving 12,637 participants.…”