Effects of ospemifene on vaginal epithelium of post-menopausal women

Abstract

Ospemifene is a selective estrogen receptor modulator used for the treatment of vulvo-vaginal atrophy (VVA) in post-menopausal women. No direct evidence of its effects on histological features of the human vagina has been reported. To evaluate the effects of ospemifene on histological parameters, glycogen content, proliferation, and estrogen receptor α expression (ERα) of vaginal epithelium in post-menopausal women. Thirty-two post-menopausal women undergoing surgical procedures were enrolled. Sixteen subjects taking ospemifene at the time of inclusion (OSP) were compared to 16 subjects not taking any hormone (CTL). Vaginal biopsies were taken from the proximal and distal vaginal wall during surgery to evaluate histology, Ki-67 and ERα expression. OSP group showed thicker vaginal epithelium (349 ± 64 vs. 245 ± 53 μm, p < .001), higher proliferation index (212 ± 47 vs. 127 ± 28 Ki-67⁺ cells/mm, p < .001), higher epithelial (27.3 ± 3.1 vs. 20.6 ± 2.9 score, p < .001) and stromal (26.6 ± 4.9 vs. 20.6 ± 2.6 score, p < .001) ERα expression when compared to the CTL group. In postmenopausal women affected by VVA, 1 month intake of ospemifene is associated with an increased maturation, and ERα expression of the vaginal mucosa. These changes may partially explain the improvement of symptoms of vaginal atrophy reported with this drug.

Chinese abstract

奥培米芬（Ospemifene）是一种选择性雌激素受体调节剂, 用于治疗绝经后妇女外阴阴道萎缩（VVA）。没有报道过其对人类阴道组织学特征的影响的直接证据。为了评估奥培米芬对绝经后妇女阴道上皮组织学参数, 糖原含量, 增殖和雌激素受体α（ERα）表达的影响。选择三十二名接受外科手术的绝经后妇女入组。将16名在纳入时服用奥培米芬的受试者(OSP)与16名未服用任何激素（CTL）的受试者比较。手术期间从阴道近端和远端取阴道活组织检查以评估组织学, Ki-67和ERα的表达。与CTL 组比较, OSP组显示有较厚的阴道上皮（349 ± 64 vs 245 ± 53μm, p <0.001）, 较高的增殖指数（212 ± 47 vs 127 ± 28 Ki-67⁺细胞/mm, p <0.001）, 较高的上皮（27.3 ± 3.1 vs 20.6 ± 2.9分, p <0.001）和基质（26.6 ± 4.9 vs 20.6 ± 2.6分, p <0.001）Erα表达。在受VVA影响的绝经后妇女中, 摄入奥培米芬1个月与阴道粘膜的成熟及ERα表达的增加有关。这些变化可能一定程度上解释了用该药物后阴道萎缩症状改善的报告。

Keywords:

• Ospemifene
• vulvo-vaginal atrophy
• dyspareunia
• vaginal histology
• vaginal proliferation index

Acknowledgements

We thank Julie Norbury for manuscript language editing.

Disclosure statement

M.C.M. and M.B. has had financial relationships (lecturer) with Shionogi Ltd.