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Metabolic and other effects of pioglitazone as an add-on therapy to metformin in the treatment of polycystic ovary syndrome (PCOS)

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Abstract

Insulin resistance is a key pathogenic defect of the clustered metabolic disturbances seen in polycystic ovary syndrome (PCOS). Metformin is an insulin sensitizer acting in the liver and the peripheral tissues that ameliorates the metabolic and reproductive defects in PCOS. In addition, pioglitazone is an insulin sensitizer used in diabetes mellitus type 2 (T2DM), improving insulin resistance (IR) in adipose tissue and muscles. In T2DM, these drugs are also used as a combined treatment due to their “add-on effect” on insulin resistance. Although the beneficial role of troglitazone (a member of the thiazolidinediones (TZDs) family) in PCOS has been shown in the past, currently only pioglitazone is available in the market. A few small randomized controlled trials have directly compared the effectiveness of pioglitazone in women with PCOS, while there are a limited number of small studies that support the beneficial metabolic add-on effect of pioglitazone on metformin-treated PCOS women as compared to metformin or pioglitazone monotherapy. These findings suggest a potentially promising role for combined pioglitazone/metformin treatment in the management of PCOS in metformin-resistant patients. In view of recent concerns regarding pioglitazone usage and its associated health risk, we aim to compare the pros and cons of each drug regarding their metabolic and other hormonal effects in women with PCOS and to explore the possible beneficial effect of combined therapy in certain cases, taking into consideration the teratogenic effect of piogl-itazone. Finally, we discuss the need for a randomized controlled trial that will evaluate the metabolic and other hormonal effects of combined metformin/pioglitazone treatment in PCOS with selective treatment targets.

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Authors and Affiliations

  1. Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire, Warwick Medical School, Coventry, UK

    Georgios Valsamakis, Kostas Lois & Sudhesh Kumar

  2. Endocrine Unit, Aretaieion University Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece

    Georgios Valsamakis & George Mastorakos

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  1. Georgios Valsamakis
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  2. Kostas Lois
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  3. Sudhesh Kumar
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  4. George Mastorakos
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Correspondence to Georgios Valsamakis.

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Valsamakis, G., Lois, K., Kumar, S. et al. Metabolic and other effects of pioglitazone as an add-on therapy to metformin in the treatment of polycystic ovary syndrome (PCOS). Hormones 12, 363–378 (2013). https://doi.org/10.1007/BF03401302

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