Tuesday, September 27, 2011

Thyroidal Effects of Metformin Treatment in Patients with PCOS

(click the title above to get to the paper)
Mario Rotondi et al.
Clin Endocrinol. 2011;75(3):378–381

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.
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.
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).
These results indicate that metformin treatment has a TSH-lowering effect in hypothyroid patients with PCOS, both treated with l-thyroxine and untreated.

Essentially it apears from this study (and another by R. Vigersky) that hypothyroid patients given metformin will end up with lower TSH levels, but not free T4. This study looked at patients with PCOS (by Rotterdam criteria) specifically. Interestingly the change occured in the hypothyroid patients that were taking levothyroxine as well as those that were not.

For euthyroid PCOS patients given metformin, there was no significant change in TSH or free T4 levels after 4 months.

This is one of those studies, I think, where you can vascillate between thinking "interesting" on the one hand and "who cares" on the other. I suppose that I find it interesting, because I generally approach PCOS as a metabolic disorder first and treat with diet exercise and usually metformin first line. However I often find that TSH levels are in the upper end of the TSH reference range or above and find myself concurrently prescribing levothyroxine. The somewhat interesting question is that, if one does prescribe both and then monitor TSH levels say 3 months later, what has contributed to the TSH change? And also, if TSH could return to "normal" levels with metformin alone, is there a need for levothyroxine in newly diagnosed "sublcinical hypothyroid" patients.

I try to aim for weight loss so the combination of diet, exercise, metformin and levothyroxine with a bordeline high TSH seems appealing. But maybe I need to rethink this?

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