Thyroidal Effect of Metformin Treatment in Patients With Polycystic Ovary Syndrome

Mario Rotondi; Carlo Cappelli; Flavia Magri; Roberta Botta; Rosa Dionisio; Carmelo Iacobello; Pasquale De Cata; Rossella E. Nappi; Maurizio Castellano; Luca Chiovato


Clin Endocrinol. 2011;75(3):378–381 

In This Article

Abstract and Introduction


Objective Metformin is widely used for the treatment of type 2 diabetes. Growing evidence supports the beneficial effects of metformin also in patients with polycystic ovary syndrome (PCOS). It was recently reported that metformin has a TSH-lowering effect in hypothyroid patients with diabetes being treated with metformin.
Design Aim of this study was to evaluate the effect of metformin treatment on the thyroid hormone profile in patients with PCOS.
Patients and measurements Thirty-three patients with PCOS were specifically selected for being either treated with levothyroxine for a previous diagnosis of hypothyroidism (n = 7), untreated subclinically hypothyroid (n = 2) or euthyroid without levothyroxine treatment (n = 24) before the starting of metformin. The serum levels of TSH and FT4 were measured before and after a 4-month period of metformin therapy.
Results Thyroid function parameters did not change after starting metformin therapy in euthyroid patients with PCOS. In the 9 hypothyroid patients with PCOS, the basal median serum levels of TSH (3·2 mIU/l, range = 0·4–7·1 mIU/l) significantly (P < 0·05) decreased after a 4-month course of metformin treatment (1·7 mIU/l, range = 0·5–5·2 mIU/l). No significant change in the serum levels of FT4 was observed in these patients. The TSH-lowering effect of metformin was not related to the administered dose of the drug, which was similar in euthyroid as compared with hypothyroid patients with PCOS (1406 ± 589 vs 1322 ± 402 mg/day, respectively; NS).
Conclusions These results indicate that metformin treatment has a TSH-lowering effect in hypothyroid patients with PCOS, both treated with l-thyroxine and untreated.


Metformin is a widely used drug for the treatment of type 2 diabetes. Metformin is commonly regarded as safe drug, because no clinically relevant pharmacologic interaction was described with most of the commonly used drugs, with the exception of folate and vitamin B12.[1–3] With specific regard to polycystic ovary syndrome (PCOS), metformin is not licensed for the treatment of this condition in any country to date.[4] Nevertheless, in the last few years, growing evidence supported beneficial effects of metformin in PCOS.[5,6] These studies prompted consensus statements and recommendations for the use of metformin in patients with PCOS.[7–10]

Despite the fact that metformin was introduced nearly 50 years ago in the clinical practice for the treatment of diabetes, only recently has this drug was reported to modify the thyroid hormone profile,[11–13] producing a significant decrease in the serum levels of TSH. Vigersky et al.[11] described four patients with primary hypothyroidism, being euthyroid on l-thyroxine (LT4), in whom the administration of metformin led to a significant fall in the serum levels of TSH. In these patients, the serum levels of FT4 were unchanged, and no clinical sign of thyrotoxicosis was observed. The effect of metformin was found to be reversible, because drug withdrawal was accompanied by a significant rise in serum TSH levels, which returned to the premetformin serum concentration.[11] More recently, it was demonstrated that the TSH-lowering effect of metformin is also observed in primary hypothyroid patients with diabetes and primary hypothyroidism, who are not treated with L-T4 replacement therapy.[13]

Despite the clinical relevance of these findings, the mechanisms by which metformin produces a TSH-lowering effect remain largely unknown. To further characterise the effect of metformin treatment on circulating thyroid function parameters, we investigated the impact of metformin treatment on the serum levels of thyroid hormones and TSH in a cohort of patients with PCOS, both euthyroid or hypothyroid


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