Vestibular effect of ospemifene: An unexplored field

Abstract

In the treatment of genitourinary syndrome of the menopause (GSM), the targets should be vulval pain and dyspareunia. Research has shown that 95% of menopausal women with dyspareunia also have localized provoked pain in the vestibule, despite hormone supplements being used by just under a third of these women. This is related to differences in nerve density between the vagina and vulvar vestibule. A retrospective analysis of specimens from women with postmenopausal vestibulodynia found significantly less neural hyperplasia and more severe chronic inflammation, compared with premenopausal patients. Hypo-estrogenism may promote a vestibular site-specific inflammation related to pain. SERMs have been shown to exert an anti-neuroinflammatory action. Estradiol decreases the stimulatory effect of lipopolysaccharide on levels of proinflammatory molecules, and ospemifene is more effective than other SERMs in reducing proinflammatory protein levels. A pilot study was conducted in 52 postmenopausal women with ≤1 year of amenorrhea to investigate the vulvar vestibular effects of 60 mg of ospemifene for 60 days. Participants presented with dyspareunia and signs of vestibular atrophy including a thinned, dry, fragile or pale mucosa. Ospemifene was efficacious in improving vestibular signs and symptoms related to GSM. Study participants also underwent current perception threshold (CPT) testing to quantify the sensitivity and functional integrity of specific afferent nerve fibers. Following treatment, there was a marked increase in CPT values for all nerve fibers, particularly C fibers (38.8%), which are mainly responsible for pain perception (higher CPT values after therapy denote that nerve endings are less sensitive, meaning there is less pain). This might reflect an action of ospemifene on inflammation-triggered peripheral sensitization of sensory nerves in the vestibular tissue. In an integrated approach to the treatment of postmenopausal vulval pain that includes preparation with ospemifene, laser treatment has been found to be more effective.