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.