Krysiak Robert, Kowalcze Karolina, Okopień Bogusław
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, Katowice, Poland.
J Clin Pharmacol. 2025 Mar;65(3):318-327. doi: 10.1002/jcph.6144. Epub 2024 Oct 3.
Metformin treatment decreases elevated concentrations of anterior pituitary hormones. The aim of this prospective, cohort study was to investigate whether hyperthyroidism modulates the impact of metformin on gonadotroph secretory function. The study population included 48 postmenopausal women with untreated type 2 diabetes or prediabetes, 24 of whom had coexisting grade 1 subclinical hyperthyroidism. Both groups were matched for age, insulin sensitivity, and gonadotropin levels. Over the entire study period, all participants were treated with metformin (2.55-3 g daily). Plasma glucose, insulin, thyroid-stimulating hormone (TSH), total and free thyroid hormones, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin, adrenocorticotropic hormone (ACTH), and insulin-like growth factor-1 (IGF-1) were assayed at entry and 6 months later. At baseline, the study groups differed in levels of TSH and thyroid hormones but not in body mass index, blood pressure, glucose homeostasis markers (fasting glucose, homeostatic model assessment 1 of insulin resistance ratio [HOMA1-IR], and glycated hemoglobin [HbA]), and the remaining hormones. There were no differences between both groups in the degree of reduction in plasma glucose and HbA in response to metformin treatment. Although metformin decreased HOMA1-IR in both groups, this effect was stronger in women with hyperthyroidism than with normal thyroid function (-50 ± 20% vs -30 ± 15%). Similar relationships were observed for FSH (-43 ± 21% vs -21 ± 12%). Only in hyperthyroid women did the drug reduce LH concentration (by 35 ± 17%). Metformin did not affect circulating levels of TSH, total and free thyroxine, total and free triiodothyronine, estradiol, prolactin, ACTH, and IGF-1. The obtained results indicate that hyperthyroidism enhances the gonadotropin-lowering effects of metformin, as well as the fact that this agent has a neutral effect on the hypothalamic-pituitary-thyroid axis in case of its overactivity.
二甲双胍治疗可降低垂体前叶激素升高的浓度。这项前瞻性队列研究的目的是调查甲状腺功能亢进是否会调节二甲双胍对促性腺激素分泌功能的影响。研究人群包括48名未经治疗的2型糖尿病或糖尿病前期的绝经后女性，其中24人同时患有1级亚临床甲状腺功能亢进。两组在年龄、胰岛素敏感性和促性腺激素水平方面相匹配。在整个研究期间，所有参与者均接受二甲双胍治疗（每日2.55 - 3克）。在入组时和6个月后测定血浆葡萄糖、胰岛素、促甲状腺激素（TSH）、总甲状腺激素和游离甲状腺激素、促卵泡激素（FSH）、促黄体生成素（LH）、雌二醇、催乳素、促肾上腺皮质激素（ACTH）和胰岛素样生长因子-1（IGF-1）。在基线时，研究组在TSH和甲状腺激素水平上存在差异，但在体重指数、血压、血糖稳态指标（空腹血糖、胰岛素抵抗比的稳态模型评估1 [HOMA1-IR]和糖化血红蛋白[HbA]）以及其余激素方面无差异。两组在二甲双胍治疗后血浆葡萄糖和HbA的降低程度上没有差异。虽然二甲双胍在两组中均降低了HOMA1-IR，但这种作用在甲状腺功能亢进的女性中比甲状腺功能正常的女性更强（-50±20%对-30±15%）。FSH也观察到类似的关系（-43±21%对-21±12%）。仅在甲状腺功能亢进的女性中，该药物降低了LH浓度（降低了35±17%）。二甲双胍不影响TSH、总甲状腺素和游离甲状腺素、总三碘甲状腺原氨酸和游离三碘甲状腺原氨酸、雌二醇、催乳素、ACTH和IGF-1的循环水平。获得的结果表明，甲状腺功能亢进增强了二甲双胍降低促性腺激素的作用，以及该药物在甲状腺功能亢进情况下对下丘脑-垂体-甲状腺轴具有中性作用这一事实。
