Krysiak Robert, Kowalcze Karolina, Ott Johannes, Burgio Sofia, Zaami Simona, Okopień Bogusław
Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medyków 18, 40-752 Katowice, Poland.
Department of Pediatrics in Bytom, Faculty of Health Sciences in Katowice, Medical University of Silesia, Stefana Batorego 15, 41-902 Bytom, Poland.
Pharmaceuticals (Basel). 2025 Aug 1;18(8):1149. doi: 10.3390/ph18081149.
The effect of metformin on the secretory function of thyrotropic cells is sex-dependent. The current study aimed to investigate whether the impact of this drug on activity of the hypothalamic-pituitary-thyroid axis in women is impacted by the androgen status of patients. The study population included 48 levothyroxine-naïve reproductive-aged women with subclinical hypothyroidism and prediabetes receiving 3.0 g of metformin daily. Women with ( = 24) and without ( = 24) polycystic ovary syndrome were matched for age, insulin sensitivity, TSH, and reasons for thyroid hypofunction. Circulating levels of glucose, glycated hemoglobin, insulin, TSH, thyroid hormones, gonadotropins, androgens, estradiol, SHBG, prolactin, ACTH, and IGF-1 were measured before metformin treatment and six months later. At entry, women with and without polycystic ovary syndrome differed in LH, LH/FSH ratio, androgens, and estradiol. The decrease in TSH, fasting glucose and glycated hemoglobin, and the improvement in insulin sensitivity were less pronounced in women with than in women without polycystic ovary syndrome. In each group, there were no differences in the impact on TSH and thyroid hormones between patients with subclinical hypothyroidism of autoimmune and non-autoimmune origin. The changes in TSH inversely correlated with total testosterone and free androgen index. Only in women with coexisting polycystic ovary syndrome, did metformin slightly reduce LH, LH/FSH ratio, testosterone, and free androgen index. The results suggest that concurrent polycystic ovary syndrome attenuates metformin action on TSH secretion, which can be explained by increased androgen production. Moreover, the drug seems to alleviate PCOS-associated changes in the activity of the reproductive axis.
二甲双胍对促甲状腺细胞分泌功能的影响存在性别差异。本研究旨在调查该药物对女性下丘脑 - 垂体 - 甲状腺轴活性的影响是否受患者雄激素状态的影响。研究人群包括48名未接受左甲状腺素治疗的育龄期亚临床甲状腺功能减退和糖尿病前期女性，她们每天服用3.0克二甲双胍。患有（n = 24）和未患有（n = 24）多囊卵巢综合征的女性在年龄、胰岛素敏感性、促甲状腺激素（TSH）以及甲状腺功能减退原因方面进行了匹配。在二甲双胍治疗前及治疗六个月后，测量了血糖、糖化血红蛋白、胰岛素、TSH、甲状腺激素、促性腺激素、雄激素、雌二醇、性激素结合球蛋白（SHBG）、催乳素、促肾上腺皮质激素（ACTH）和胰岛素样生长因子 - 1（IGF - 1）的循环水平。在入组时，患有和未患有多囊卵巢综合征的女性在促黄体生成素（LH）、LH/FSH比值、雄激素和雌二醇方面存在差异。与未患有多囊卵巢综合征的女性相比，患有该综合征的女性TSH、空腹血糖和糖化血红蛋白的降低以及胰岛素敏感性的改善不那么明显。在每组中，自身免疫性和非自身免疫性起源的亚临床甲状腺功能减退患者对TSH和甲状腺激素的影响没有差异。TSH的变化与总睾酮和游离雄激素指数呈负相关。仅在同时患有多囊卵巢综合征的女性中，二甲双胍略微降低了LH、LH/FSH比值、睾酮和游离雄激素指数。结果表明，并发多囊卵巢综合征会减弱二甲双胍对TSH分泌的作用，这可以通过雄激素生成增加来解释。此外，该药物似乎减轻了多囊卵巢综合征相关的生殖轴活性变化。
