Metabolic Phenotype in the Brothers of Women with Polycystic Ovary Syndrome

  1. Susan Sam, MD1,
  2. Andrea D. Coviello, MD2,
  3. Yeon-Ah Sung, MD3,
  4. Richard S. Legro, MD4 and
  5. Andrea Dunaif, MD1
  1. 1Division of Endocrinology, Metabolism and Molecular Medicine, the Feinberg School of Medicine, Northwestern University, Chicago, Illinois
  2. 2Section of Endocrinology, Diabetes, and Nutrition, Boston University, Boston, Massachusetts
  3. 3Division of Endocrinology, Ewha Womans University, Seoul, Korea
  4. 4Department of Obstetrics and Gynecology, Pennsylvania State University, Hershey, Pennsylvania
  1. Corresponding author: Andrea Dunaif, MD, Division of Endocrinology, Metabolism and Molecular Medicine, the Feinberg School of Medicine, Northwestern University, 303 E. Chicago Ave., Tarry 15709, Chicago, IL 60611. E-mail: a-dunaif{at}northwestern.edu

Abstract

OBJECTIVE—Hyperandrogenemia, insulin resistance, and dyslipidemia demonstrate familial aggregation in the female first-degree relatives of women with polycystic ovary syndrome (PCOS), suggesting that these defects are heritable. Hyperandrogenemia also appears to be the male reproductive phenotype. We performed this study to test the hypothesis that brothers of women with PCOS have metabolic defects similar to those of their proband sisters.

RESEARCH DESIGN AND METHODS—This was a prospective case-control study performed at four academic medical centers in the U.S. Fasting blood was obtained from 196 non-Hispanic white brothers of women with PCOS and 169 control men of age, BMI, and ethnicity comparable to those of brothers. A separate analysis was performed by study site to assess potential regional variations in metabolic parameters.

RESULTS—Overall, brothers of women with PCOS had significantly higher total (P = 0.001) and LDL cholesterol (P = 0.01) as well as triglyceride levels (P = 0.01) compared with control men, although there were regional variations in these differences. There were significant positive correlations between brothers and their sisters with PCOS for total (ρ = 0.2, P = 0.009) and LDL cholesterol (ρ = 0.3, P = 0.001) and triglyceride (ρ = 0.2, P = 0.05) levels. Brothers also had significantly higher fasting insulin levels and homeostatic index of insulin resistance (P = 0.02 for both comparisons) compared with control men.

CONCLUSIONS—Brothers of women with PCOS have dyslipidemia as well as evidence for insulin resistance similar to that of their proband sisters with PCOS. These findings are consistent with the hypothesis that some metabolic abnormalities in PCOS are heritable and are not sex specific.

Footnotes

  • Published ahead of print at http://care.diabetesjournals.org on 10 March 2008. DOI: 10.2337/dc07-2190.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted March 3, 2008.
    • Received November 16, 2007.
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  1. Published online before print March 10, 2008, doi: 10.2337/dc07-2190 Diabetes Care June 2008 vol. 31 no. 6 1237-1241
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