Structure of Epithelial and Stromal Compartments of Vulvar and Vaginal Tissue From Women With Vulvo-Vaginal Atrophy Taking Ospemifene.

INTRODUCTION: Vulvo-vaginal atrophy affects the daily lives of most post-menopausal women. We know that ospemifene intake can induce vaginal epithelial improvements within a few weeks; however, direct evidence of the effects of ospemifene on the human vulva and on connective tissue of both the vagina and vulva are lacking. AIM: To evaluate the changes induced by ospemifene on epithelium thickness, glycogen content proliferation index, collagen content, and type I/III collagen ratio in vulvar and vaginal tissue of post-menopausal women. METHODS: 20 women who attended our gynecologic clinic for planned surgery were recruited for the study. 11 subjects were taking ospemifene at the time of inclusion, and 9 subjects who were not taking ospemifene were selected as control group. Vaginal and vulvar biopsies were taken during surgery. Histological features and glycogen content were evaluated by standard hematoxylin-eosin and periodic acid-Schiff staining, total collagen and collagen type I/III ratio were evaluated by hydroxyproline assay and Sirius red staining, while the expression of Ki67 was evaluated by immunohistochemistry. MAIN OUTCOME MEASURE: We analyzed histological features of the epithelial and stromal layer of the vaginal and vulvar vestibule mucosa. RESULTS: Vaginal and vulvar biopsies from women taking ospemifene showed an increased epithelium thickness, glycogen content, and proliferation index compared with the control group. Collagen content was also higher in women taking ospemifene, while an increased ratio between type I and III collagen fibers was found only at vaginal level. CLINICAL IMPLICATIONS: Our study shows that the effectiveness of ospemifene on vaginal tissue also extends to the vulvar vestibule. STRENGTH & LIMITATIONS: This study provides direct evidence of the impact of ospemifene on vaginal and vulvar tissue. A specifically designed longitudinal study may further support our findings. CONCLUSION: Ospemifene intake is associated with a marked improvement of various morphological and physiological features of both vaginal and vulvar vestibule epithelium, including the collagen content of the tissues