Safety and efficacy of ospemifene for the treatment of dyspareunia associated with vulvar and vaginal atrophy due to menopause

Abstract

During the menopausal transition, women experience a number of symptoms due to declining estrogen levels, including vasomotor symptoms and vulvar and vaginal atrophy (VVA). Unlike vasomotor symptoms, vaginal dryness and dyspareunia, the main symptoms of VVA, typically worsen without treatment and can significantly impact the quality of life. Up to 60% of postmenopausal women may be affected by VVA, but many women unfortunately do not seek treatment due to embarrassment or other factors. After 20+ years in development, ospemifene (Osphena™) was approved by the US Food and Drug Administration in 2013 for treatment of moderate-to-severe dyspareunia associated with VVA due to menopause. As the first non-hormonal alternative to estrogen-based products for this indication, the approval of ospemifene represents a significant milestone in postmenopausal women’s health. Ospemifene is a non-steroidal estrogen receptor agonist/antagonist, also known as a selective estrogen receptor modulator (SERM), from the same chemical class as the breast cancer drugs tamoxifen and toremifene. Unlike other selective estrogen receptor modulators, ospemifene exerts a strong, nearly full estrogen agonist effect in the vaginal epithelium, making it well suited for the treatment of dyspareunia in postmenopausal women. Results of Phase III clinical trials showed that ospemifene significantly improved the vaginal maturation index (decreased parabasal cells and increased superficial cells), decreased vaginal pH, and decreased severity of the self-identified most bothersome symptom (dyspareunia or vaginal dryness) compared to placebo. Long-term safety studies revealed that 60 mg ospemifene given daily for 52 weeks was well tolerated and was not associated with any endometrium or breast-related safety concerns. This review discusses the preclinical and clinical data supporting the use of ospemifene for the treatment of dyspareunia associated with VVA due to menopause and provides an overview of its clinical safety.

No increase in incidence or risk of recurrence of breast cancer in ospemifene-treated patients with vulvovaginal atrophy (VVA)

“…Ospemifene-treated VVA patients did not have a higher incidence of breast cancer or breast cancer recurrence than postmenopausal women with VVA without any prescribed VVA-related treatment. This analysis further supports the findings of prior evidence reporting no increased risk for breast cancer-related safety concerns among patients receiving ospemifene [14][15][16][17][18]20]. Additional efforts should be made to educate both physicians and patients of the safety of ospemifene as a treatment option for postmenopausal women with VVA who have had or may be at risk for breast cancer.…”

“…Step 2 randomly matched with two untreated controls on age at index VVA date, Charlson Comorbidity Index (CCI) categories at index VVA date [18], year of index VVA, US region, and follow up month from index VVA to the last record.…”

Genitourinary syndrome of menopause: Common problem, effective treatments

“…Long-term safety studies suggested no adverse effects on the endometrium or breast for at least 52 weeks. 32 These studies also noted that ospemifene improved the vaginal maturation index (decreased parabasal cells and increased superfi cial cells) and decreased vaginal pH. It has Nonhormonal over-the-counter therapies provide relief for most women with mild symptoms…”

Randomized, Double‐Blind, Placebo‐Controlled Study of Modified Erzhi Granules in the Treatment of Menopause‐Related Vulvovaginal Atrophy

“…VVA is mainly due to decreased estrogen levels after menopause, which reduces the thickness of epithelial tissues in the female reproductive tract, smooth muscle function, and collagen and hyaluronic acid levels; this results in decreased vaginal wall elasticity, increased mucosal fragility, imbalanced local flora, and increased pH. The clinical manifestations include vaginal dryness, painful sexual intercourse, vaginal burning, postcoital bleeding [ 3 ]. Vaginal wall atrophy, flattened villi, loss of folds, and pale pink petechiae are occasionally found in gynecologic examination.…”