Ospemifene, a novel selective estrogen receptor modulator for treating dyspareunia associated with postmenopausal vulvar and vaginal atrophy Original paper

What was studied?

The study investigated the efficacy, safety, and tolerability of ospemifene, a selective estrogen receptor modulator (SERM), for treating vulvar and vaginal atrophy (VVA) in postmenopausal women with moderate to severe dyspareunia (pain during sexual intercourse). This multicenter phase 3 study compared ospemifene (60 mg/day) with a placebo over a 12-week treatment period. The study assessed multiple efficacy endpoints, including vaginal cytology (percentage of parabasal and superficial cells) and vaginal pH, along with the severity of dyspareunia. The goal was to determine if ospemifene could alleviate VVA symptoms without causing significant systemic estrogenic effects, especially in the context of breast cancer survivors who cannot use estrogen-based treatments.

Who was studied?

The study involved 605 postmenopausal women, aged 40 to 80 years, who reported moderate to severe dyspareunia associated with VVA. These women were diagnosed with VVA, as defined by having less than 5% superficial cells in the vaginal smear and a vaginal pH higher than 5. They were randomized to receive either ospemifene 60 mg/day (303 participants) or a placebo (302 participants) for 12 weeks. Participants were excluded if they had certain health conditions, such as high blood pressure, significant gynecological disorders, or any history of estrogen-sensitive cancers. The study participants were primarily white (90%) and had body mass index (BMI) values ranging from 16.7 to 37.1 kg/m².

Most important findings

The study found that ospemifene significantly improved the key endpoints compared to placebo. After 12 weeks of treatment, the ospemifene group showed a 40.2% decrease in the percentage of parabasal cells and a 12.3% increase in superficial cells, whereas the placebo group showed no significant changes. Additionally, vaginal pH decreased by 0.94 in the ospemifene group, compared to just a 0.07 reduction in the placebo group. The most critical outcome, dyspareunia severity, was significantly reduced in the ospemifene group, with a decrease of 1.5 points on the severity scale, compared to a 1.2-point reduction in the placebo group. Furthermore, more women in the ospemifene group reported improvement in vaginal pain, with 38% experiencing no vaginal pain or mild pain after 12 weeks, compared to 28% in the placebo group. The safety profile of ospemifene was generally favorable, with hot flushes being the most reported treatment-related adverse event (6.6% vs 3.6% in the placebo group).

Key implications

The findings suggest that ospemifene is an effective treatment option for alleviating symptoms of VVA, particularly dyspareunia, in postmenopausal women. This is particularly important for women with estrogen-sensitive conditions who cannot use traditional estrogen therapies. Ospemifene offers a non-estrogenic alternative that targets the vaginal tissues and reduces the severity of VVA without inducing significant systemic estrogen effects, which could potentially harm breast or uterine tissue. The study also suggests that ospemifene could reduce reliance on vaginal lubricants, offering women an effective, long-term solution for managing vaginal dryness and discomfort. However, further research is necessary to fully assess the long-term safety of ospemifene, especially concerning its potential impact on the endometrium and breast tissue.