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Drug Insight: insulin-sensitizing drugs in the treatment of polycystic ovary syndrome—a reappraisal

Abstract

The recognition that insulin resistance has a pivotal role in the pathogenesis of polycystic ovary syndrome (PCOS) revolutionized our understanding of this complex disorder. PCOS causes major metabolic and reproductive morbidities, including substantially increased risk for type 2 diabetes mellitus and the metabolic syndrome. Insulin-sensitizing drugs (ISDs) ameliorate reproductive abnormalities, restore ovulation and regular menses, increase pregnancy rates and reduce androgenic symptoms in affected women with PCOS. Accordingly, ISDs, specifically metformin, have been widely adopted as therapy for this condition. A recent, large, randomized, multicenter, clinical trial that assessed live-birth rates rather than surrogate end points suggested that metformin alone is inferior to clomiphene citrate in treating infertility associated with PCOS. There is, furthermore, no evidence to support the use of metformin during pregnancy to prevent spontaneous abortions or gestational diabetes mellitus in women with PCOS. Renewed safety concerns about thiazolidinediones followed recent studies that reported increased cardiovascular morbidity with these agents. These concerns might preclude thiazolidinedione use in otherwise healthy women with PCOS. Finally, although ISDs improve insulin action and cardiovascular disease risk, there is no evidence that they provide long-term health benefits in PCOS. This article discusses the role of ISDs in PCOS in light of these new data.

Key Points

  • Metformin is the only insulin-sensitizing drug recommended for use in women with polycystic ovary syndrome (PCOS) who do not have type 2 diabetes because of concerns about the cardiovascular safety of thiazolidinediones

  • Metformin is effective at ameliorating glucose intolerance and other features of the metabolic syndrome in women with PCOS

  • For the treatment of infertility in women with PCOS, recent data indicate that the live-birth rate with clomiphene citrate monotherapy is superior to that with metformin monotherapy; there is no evidence that combination therapy is superior to clomiphene citrate alone

  • There is no evidence to support the use of metformin during pregnancy to prevent spontaneous abortions or gestational diabetes mellitus

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Charles P Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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Dunaif, A. Drug Insight: insulin-sensitizing drugs in the treatment of polycystic ovary syndrome—a reappraisal. Nat Rev Endocrinol 4, 272–283 (2008). https://doi.org/10.1038/ncpendmet0787

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