Subclinical Hyperthyroidism Enhances Metformin's Impact on Gonadotropins in Postmenopausal Women: Study Finds

The research examined the impact of metformin on various hormonal levels in postmenopausal women diagnosed with subclinical hyperthyroidism. It found that metformin did not affect the circulating levels of TSH, total and free thyroxine, total and free triiodothyronine, estradiol, prolactin, adrenocorticotropic hormone (ACTH), or insulin-like growth factor-1 (IGF-1).

Metformin treatment reduces elevated levels of anterior pituitary hormones. Considering this, Robert Krysiak, Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Katowice, Poland, and colleagues aim to investigate whether hyperthyroidism modulates the impact of metformin on gonadotroph secretory function in a prospective, cohort study.

For this purpose, the researchers included a study population of 48 postmenopausal women with untreated type 2 diabetes or prediabetes, 24 of whom had coexisting grade 1 subclinical hyperthyroidism. Both groups were matched based on age, insulin sensitivity, and gonadotropin levels. Throughout the study, all participants received metformin treatment at a daily dosage of 2.55 to 3 grams.

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 measured at baseline and again six months later.

The study led to the following findings:

• At baseline, the study groups exhibited differences in TSH and thyroid hormone levels. However, there were no significant disparities in body mass index, blood pressure, glucose homeostasis markers (including fasting glucose, homeostatic model assessment 1 of insulin resistance ratio [HOMA1-IR], and glycated hemoglobin [HbA1c]), or other hormones.
• Both groups showed similar reductions in plasma glucose and HbA1c in response to metformin treatment.
• While metformin decreased HOMA1-IR in both groups, the effect was more pronounced in women with hyperthyroidism, resulting in a reduction of −50 ± 20% compared to −30 ± 15% in those with normal thyroid function.
• A similar pattern was observed for FSH, with decreases of −43 ± 21% in hyperthyroid women versus −21 ± 12% in the other group.
• Only women with hyperthyroidism experienced a significant reduction in LH levels, which decreased by 35 ± 17%.

The results suggest that hyperthyroidism amplifies the gonadotropin-lowering effects of metformin, while also indicating that the drug has a neutral impact on the hypothalamic-pituitary-thyroid axis when it is overactive.

"The study expands the understanding of the role of metformin in hormonal regulation, and emphasizes the importance of comprehensive patient assessments in managing postmenopausal health," the researchers concluded.

Reference:

Krysiak, R., Kowalcze, K., & Okopień, B. Subclinical Hyperthyroidism Enhances Gonadotropin-Lowering Effects of Metformin in Postmenopausal Women. The Journal of Clinical Pharmacology. https://doi.org/10.1002/jcph.6144