SERM Ospemifene Reduces Vestibular Nerve Fiber Sensitivity

A newly published pilot study is the first to show that the selective estrogen receptor modulator (SERM) ospemifene effectively normalizes vestibular innervation sensitivity, in addition to confirming that it relieves postmenopausal vestibular signs and symptoms.

The vulvar vestibule is a thin band of tissue around the introitus that is dense with nerve endings. After menopause, the researchers speculated that the hypoestrogenic state may lead to severe, chronic vestibular neurogenic inflammation, which sensitizes these nerves. They hypothesized that ospemifene, a nonsteroidal synthetic agent with significant estrogenic effects on vaginal epithelium, would reduce this neuroinflammatory action, thus relieving vestibular nerve pain. In previous trials, ospemifene has been shown to improve vaginal trophism and pH, regenerate vaginal cells, improve vaginal lubrication, and reduce dyspareunia. The drug is approved by the Food and Drug Administration to treat moderate to severe dyspareunia related to genitourinary syndrome of menopause (GSM, previously called vulvovaginal atrophy).

The researchers conducted an open-label study of 55 postmenopausal women with GSM who received 60 mg/day of ospemifene orally for 60 days. Inclusion criteria included at least one moderate to severe symptom of GSM such as vaginal dryness, burning, or dyspareunia. Exclusion criteria included obesity, abnormal gynecologic findings other than GSM, or use of hormones, SERMs, or other products with estrogenic or antiestrogenic effects.

Four tests were used to evaluate treatment efficacy: At baseline, women were asked to evaluate their symptoms on a 10-cm visual analog scale, while researchers looked for signs of GSM such as petechiae, pallor, friability, dryness, and redness and rated them on a 4-point scale (0=none to 3=severe). Women who were candidates for the study also received a cotton swab test to evaluate their pain levels in seven areas around the vestibule; the subjects were asked to rate the pain they felt at each of these sites on a scale of 0-3 (0=none, 3=severe). Current perception threshold testing was also performed to quantify the functional integrity of the selected nerve fibers.

Results Encouraging

Fifty-two of the 55 women completed the study. As expected, statistically significantly decreases in mean scores for vaginal dryness, burning, and dyspareunia were reported from baseline. The mean vestibular trophic score also decreased significantly from 11.2 at baseline to 4.2 after 60 days of treatment (P = 0.02). Cotton swab test scores also improved, and current perception threshold values were approximately 40% lower after 2 months of treatment compared to pretreatment values (P < 0.05).

The drug was well-tolerated. The most common side effect was hot flashes: 21% of the women in the study experienced at least one hot flash, and three discontinued ospemifene due to this adverse event.

The researchers explained that vestibular tenderness is a common complaint in many menopausal women with dyspareunia and GSM alone does not adequately explain it. In addition, women with predominantly vestibular symptoms of menopause such as dyspareunia or vestibular dysuria often do not find relief when treated with vaginal estrogen. This study suggests other mechanisms are at play beyond GSM and proves that ospemifene not only can relieve GSM symptoms but can also address vestibular nerve hypersensitivity.

Future Studies

Although this pilot study was the first to examine the effects of ospemifene on vestibular innervation sensitivity after menopause, the small study population and lack of follow-up are limiting factors. A prospective trial with a larger sample size comparing ospemifene to placebo or an emerging GSM therapy (e.g., fractional laser) would be beneficial in further clarifying the neural effects of the drug.