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

Patients and Methods


The original study group included 35 patients with PCOS being treated with metformin. Among them, seven patients were specifically selected from the computerized database of our outpatient clinic for being hypothyroid on l-thyroxine substitution treatment. They were affected by chronic autoimmune thyroiditis, and their l-thyroxine substitution dose was stable since at least 6 months. Twenty-eight more patients with PCOS were consecutively recruited from our outpatient clinic. Two of them had subclinical hypothyroidism because of chronic autoimmune thyroiditis and were left untreated. The remaining 26 patients were euthyroid with no detectable thyroid disease. Two patients in this group were excluded from the study during the follow-up: one patient for lack of compliance to metformin treatment and the other one for having missed the scheduled visit plan. Thus, thirty-three patients (seven hypothyroid being treated with l-thyroxine, two untreated with subclinical hypothyroidism and 24 euthyroid) completed the study.

The diagnosis of PCOS was formulated according to the criteria established by the Rotterdam consensus workshop.[14] The mean (±SD) age of patients with PCOS was 25·9 ± 5·9 years, and their mean BMI was 30·7 ± 4·2 Kg/m2. The mean daily dose of metformin in the whole study group was 1·383 ± 539 mg.

Body mass index (BMI) and serum FT4, FT3, TSH were evaluated before and 4 months after starting metformin treatment. Blood samples for assaying FT4, FT3 and TSH were drawn between 08:00 and 09:00 a.m., after an overnight fast. BMI was calculated as the weight (kg) divided by the square of height (m). All subjects gave their informed consent to be included into the study, which was performed in accordance with the guidelines proposed in the Declaration of Helsinki.

Serum Assays

Serum concentrations of free triiodothyronine (FT3, normal range 3·7–7·2 pmol/l), free thyroxine (FT4, normal range 9·0–23·2 pmol/l) and thyroid-stimulating hormone (TSH, normal range 0·4–4·0 mIU/l) were measured using immune-chemiluminescent assays by an automated analyser (Immulite 2000; DPC Cirrus, Los Angeles, CA, USA) employing commercially available kits (all from Diagnostic Products Corporation, Los Angeles, CA, USA). In these assays, the intra-assay coefficient of variation ranged from 4·3% to 8·4% for FT3, from 5·2% to 7·5% for FT4 and from 5·1% to 12·5% to for TSH. The interassay coefficient of variation ranged from 5·4% to 10·0% for FT3, from 7·7% to 9·0% for FT4 and from 6·4% to 12·5% 6·4% for TSH. The analytical sensitivities were 1·54 pmol/l for FT3, 3·9 pmol/l for FT4 and 0·004 mIU/l for TSH (Third-generation TSH assay). Samples were assayed in duplicate. Quality control pools at low, normal and high concentrations for all parameters were present in each assay, respectively.

Statistical Analysis

Statistical analysis was performed using SPSS software (SPSS, Inc., Evanston, IL, USA). All comparisons between groups were performed by Student's t test for unpaired data and Mann–Whitney U test according to the parametric or nonparametric distribution of data. Owing to the nonparametric distribution of the data, pretreatment and on-treatment results were compared by Wilcoxon test. A P-value <0·05 was considered statistically significant.


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