Rosuvastatin Potentiates Gonadotropin-Lowering Effects of Metformin in Postmenopausal Women: A Pilot Study

INTRODUCTION: Metformin reduces elevated levels of FSH and LH. In some studies, gonadotroph secretory function was inhibited by statins. The aim of the present study was to investigate whether statin therapy modulates the impact of metformin on hypothalamic-pituitary-gonadal axis activity in postmenopausal women. METHODS: The study population included 60 postmenopausal women with prediabetes, 40 of whom, because of high cardiovascular risk, received rosuvastatin (20-40 mg daily). One group of rosuvastatin-treated women (group A, n = 23) and all statin-naïve patients (group B, n = 20) were matched for age, glucose homeostasis markers, and gonadotropin levels. Over the entire study period (6 months), these women received metformin. The third group (group C) included 17 rosuvastatin-treated women refusing metformin treatment. We assessed baseline and follow-up plasma lipids, glucose homeostasis markers, and concentrations of FSH, LH, thyrotropin, prolactin, adrenocorticotropic hormone (ACTH), insulin-like growth factor-1, estradiol, progesterone, and anti-Müllerian hormone (in selected patients). RESULTS: Fifty-three women (18 in groups A and B and 17 in group C) completed the study. At study entry, rosuvastatin-treated and statin-naïve women differed in levels of total cholesterol, LDL-cholesterol, and ACTH. In statin-naïve women, metformin reduced FSH levels and tended to reduce LH levels. In rosuvastatin-treated women, metformin decreased FSH and LH levels, and both effects were stronger than in statin-naïve women. Although observed in both groups, the impact on glucose homeostasis markers was more pronounced in individuals not receiving statin therapy. Metformin treatment did not affect circulating levels of lipids, thyrotropin, prolactin, ACTH, insulin-like growth factor-1, estradiol, and anti-Müllerian hormone. In group C, plasma lipids, glucose homeostasis markers, and hormone levels remained at a similar level throughout the study period. CONCLUSION: The obtained results indicate that statin therapy may enhance gonadotropin-lowering effects of metformin.