Vaginal metabolites in postmenopausal women with or without vulvo-vaginal atrophy at baseline and after ospemifeme and systemic hormone treatment

Objectives: Vulvo-vaginal atrophy (VVA) is a highly prevalent chronic condition affecting the lives of postmenopausal women. Ospemifene and systemic hormone therapy (HT) improve vaginal health. This study aims to characterize the vaginal metabolic profile of women with VVA at baseline and after ospemifene and systemic HT. Study design: Sixty postmenopausal women, 32 of whom were affected by VVA, were consecutively enrolled. The vaginal metabolic profile of women with and without VVA at baseline and after three months of ospemifene or HT treatment was assessed. Main outcome measures: The following parameters were evaluated: (i) the Vaginal Health Index; (ii) the Vaginal Maturation Index; and (iii) vaginal metabolic profile, by means of 1H NMR spectroscopy. Results: The vaginal metabolome of postmenopausal women with VVA was different from that of postmenopausal women without VVA, including a more profound decrease in the levels of lactate and several amino acids, typically found in eubiosis, together with an enrichment of molecules derived from anaerobes and gut microbes. After 3 months, ospemifene and HT had modified the vaginal metabolome of the women with VVA, specifically by increasing the levels of beneficial molecules (e.g., lactate, leucine, glycine) and reducing those involved in dysbiosis (e.g., formate). HT improved the vaginal metabolome to a lesser extent. Conclusions: The vaginal metabolic profile of postmenopausal women with VVA differs from that of postmenopausal women without VVA. Our preliminary data show that both ospemifene and HT treatment increase the levels of molecules beneficial for vaginal health and reduce the levels of those involved in dysbiosis. HT improves the vaginal metabolic profile to a lower extent than ospemifene over the course of three months.