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瑞舒伐他汀可增强二甲双胍对非自身免疫性亚临床甲状腺功能减退和糖尿病前期男性的促甲状腺激素降低作用。

Rosuvastatin potentiates the thyrotropin-lowering effect of metformin in men with non-autoimmune subclinical hypothyroidism and prediabetes.

作者信息

Krysiak Robert, Kowalcze Karolina, Okopień Bogusław

机构信息

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.

出版信息

J Clin Pharm Ther. 2022 Dec;47(12):2030-2040. doi: 10.1111/jcpt.13746. Epub 2022 Jul 28.

Abstract

WHAT IS KNOWN AND OBJECTIVE

Metformin treatment decreases thyrotropin levels in individuals with hypothyroidism and this effect seems to be mediated by the 5'-adenosine monophosphate-activated protein kinase pathway in the pituitary. The activity of this pathway is also stimulated by statins. The current study was aimed at investigating whether the impact of metformin on hypothalamic-pituitary-thyroid axis activity is affected by statin use.

METHODS

The study included three matched groups of men with non-autoimmune hypothyroidism and prediabetes: patients treated for at least 6 months with high-intensity rosuvastatin therapy (20-40 mg daily) [groups A (n = 24) and C (n = 19)] and men not receiving statin therapy [group B (n = 24)]. Over the entire study period (6 months), groups A and B received metformin (2.55-3 g daily). Moreover, groups A and C continued rosuvastatin therapy. The lipid profile, glucose homeostasis markers, and plasma concentrations of thyrotropin, total and free thyroid hormones, prolactin, FSH, LH, ACTH and insulin-like growth factor-1 were determined at baseline and 6 months later.

RESULTS AND DISCUSSION

Fifty-nine patients completed the study. There were differences between groups A and C and group B in baseline values of total cholesterol, LDL-cholesterol, gonadotropins and ACTH. Although observed in both groups of metformin-treated patients, the effect on thyrotropin levels was more pronounced in group A than in group B. The impact on fasting glucose and insulin sensitivity was stronger in group B than group A. In turn, only in group A metformin tended to reduce gonadotropin levels. There were no differences between follow-up and baseline values of lipids, total and free thyroid hormones, prolactin, ACTH and insulin-like growth factor-1 in both these groups. In group C, all assessed variables remained at a similar level.

WHAT IS NEW AND CONCLUSION

The results of the current study suggest that rosuvastatin potentiates the inhibitory effect of metformin on thyrotrope secretory function.

摘要

已知信息与研究目的

二甲双胍治疗可降低甲状腺功能减退患者的促甲状腺激素水平,且该作用似乎由垂体中的5'-单磷酸腺苷激活蛋白激酶途径介导。他汀类药物也可刺激该途径的活性。本研究旨在调查他汀类药物的使用是否会影响二甲双胍对下丘脑-垂体-甲状腺轴活性的影响。

方法

该研究纳入了三组匹配的患有非自身免疫性甲状腺功能减退和糖尿病前期的男性:接受高强度瑞舒伐他汀治疗(每日20 - 40mg)至少6个月的患者[组A(n = 24)和组C(n = 19)]以及未接受他汀类药物治疗的男性[组B(n = 24)]。在整个研究期间(6个月),组A和组B接受二甲双胍治疗(每日2.55 - 3g)。此外,组A和组C继续接受瑞舒伐他汀治疗。在基线和6个月后测定血脂谱、血糖稳态标志物以及促甲状腺激素、总甲状腺激素和游离甲状腺激素、催乳素、促卵泡生成素、促黄体生成素、促肾上腺皮质激素和胰岛素样生长因子-1的血浆浓度。

结果与讨论

59名患者完成了研究。组A和组C与组B在总胆固醇、低密度脂蛋白胆固醇、促性腺激素和促肾上腺皮质激素的基线值方面存在差异。虽然在两组接受二甲双胍治疗的患者中均观察到了这种情况,但组A对促甲状腺激素水平的影响比组B更明显。组B对空腹血糖和胰岛素敏感性的影响比组A更强。反过来,仅在组A中,二甲双胍有降低促性腺激素水平的趋势。在这两组中,血脂、总甲状腺激素和游离甲状腺激素、催乳素、促肾上腺皮质激素和胰岛素样生长因子-1的随访值与基线值之间没有差异。在组C中,所有评估变量均保持在相似水平。

新发现与结论

本研究结果表明,瑞舒伐他汀可增强二甲双胍对促甲状腺细胞分泌功能的抑制作用。

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