Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Katowice, Poland.
Department of Pediatrics in Bytom, School of Health Sciences in Katowice, Medical University of Silesia, Bytom, Poland.
Pharmacology. 2023;108(3):245-254. doi: 10.1159/000528939. Epub 2023 Feb 15.
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.
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).
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.
The obtained results indicate that statin therapy may enhance gonadotropin-lowering effects of metformin.
二甲双胍可降低升高的 FSH 和 LH 水平。在一些研究中，他汀类药物抑制了促性腺激素的分泌功能。本研究的目的是探讨他汀类药物治疗是否会调节二甲双胍对绝经后妇女下丘脑-垂体-性腺轴活性的影响。
研究人群包括 60 例患有前驱糖尿病的绝经后妇女，其中 40 例由于心血管风险较高，接受了瑞舒伐他汀（每天 20-40mg）治疗。瑞舒伐他汀治疗组的一组妇女（A 组，n=23）和所有他汀类药物未治疗的患者（B 组，n=20）按年龄、葡萄糖稳态标志物和促性腺激素水平进行匹配。在整个研究期间（6 个月），这些妇女接受了二甲双胍治疗。第三组（C 组）包括 17 名拒绝接受二甲双胍治疗的瑞舒伐他汀治疗的妇女。我们评估了基线和随访时的血浆脂质、葡萄糖稳态标志物以及 FSH、LH、促甲状腺激素、催乳素、促肾上腺皮质激素（ACTH）、胰岛素样生长因子-1、雌二醇、孕酮和抗苗勒管激素（在部分患者中）的浓度。
53 名妇女（A 组和 B 组各 18 名，C 组 17 名）完成了研究。在研究开始时，瑞舒伐他汀治疗组和未接受他汀类药物治疗的妇女在总胆固醇、LDL-胆固醇和 ACTH 水平上存在差异。在未接受他汀类药物治疗的妇女中，二甲双胍降低了 FSH 水平，并倾向于降低 LH 水平。在接受瑞舒伐他汀治疗的妇女中，二甲双胍降低了 FSH 和 LH 水平，且这两种作用均强于未接受他汀类药物治疗的妇女。尽管在两组中均观察到，但在未接受他汀类药物治疗的个体中，对葡萄糖稳态标志物的影响更为明显。二甲双胍治疗并未影响血脂、促甲状腺激素、催乳素、ACTH、胰岛素样生长因子-1、雌二醇和抗苗勒管激素的循环水平。在 C 组中，整个研究期间，血浆脂质、葡萄糖稳态标志物和激素水平保持在相似水平。
研究结果表明，他汀类药物治疗可能增强二甲双胍降低促性腺激素的作用。
