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Metformin and the Polycystic Ovary Syndrome

Division of Endocrinology and Metabolism Medical College of Virginia Richmond, Virginia 23298-0111

To the editor:

Moghetti et al. (1) are to be congratulated for their marvelous study assessing the effects of long-term metformin treatment in women with polycystic ovary syndrome (PCOS).

The investigators used a metformin dose of 500 mg t.i.d. (1500 mg daily). It is possible that women who did not respond to metformin at this dose might have responded had the dose been increased to 1000 mg b.i.d. (2000 mg daily). A dose-response study in type 2 diabetic patients has shown that a daily metformin dose of 1500 mg was less effective than 2000 mg, and that 2000 mg daily is the optimal dose (2). Presumably, 2000 mg daily is the dose that maximally improves hepatic and muscle insulin sensitivity.

We have used a metformin dose of 500 mg t.i.d. in all our published studies in PCOS by historical accident (3, 4, 5). Metformin was not available in the United States at the time of our first study (3), and in Europe it was being dosed in this fashion. We maintained this dose in subsequent studies for consistency and to do comparative analyses in the future.

In my own clinical practice, however, I treat women with PCOS with metformin at a dose of 2000 mg daily. Also, it has been my anecdotal experience that some PCOS women who did not respond to metformin at a dose of 1500 mg daily, responded favorably when the dose was subsequently increased to 2000 mg daily.

Received November 12, 2000.

References

1. Moghetti P, Castello R, Negri C, et al. 2000 Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation. J Clin Endocrinol Metab. 85:139–146.[Abstract/Free Full Text]
2. Garber AJ, Duncan TG, Goodman AM, Mills DJ, Rohlf JL. 1997 Efficacy of metformin in type II diabetes: results of a double-blind, placebo-controlled, dose-response trial. Am J Med. 103:491–497.[CrossRef][Medline]
3. Nestler JE, Jakubowicz DJ. 1996 Decreases in ovarian cytochrome P450c17a activity and serum free testosterone after reduction in insulin secretion in women with polycystic ovary syndrome. N Engl J Med. 335:617–623.[Abstract/Free Full Text]
4. Nestler JE, Jakubowicz DJ. 1997 Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17a activity and serum androgens. J Clin Endocrinol Metab. 82:4075–4079.[Abstract/Free Full Text]
5. Nestler JE, Jakubowicz DJ, Evans WS, Pasquali R. 1998 Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med. 337:1876–1880.[Abstract/Free Full Text]

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