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Metabolic Phenotype in the Brothers of Women with Polycystic Ovary Syndrome

¹ Division of Endocrinology, Metabolism and Molecular Medicine, the Feinberg School of Medicine, Northwestern University, Chicago, Illinois
² Section of Endocrinology, Diabetes, and Nutrition, Boston University, Boston, Massachusetts
³ Division of Endocrinology, Ewha Womans University, Seoul, Korea
⁴ Department of Obstetrics and Gynecology, Pennsylvania State University, Hershey, Pennsylvania

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

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 ( = 0.2, P = 0.009) and LDL cholesterol ( = 0.3, P = 0.001) and triglyceride ( = 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.

Abbreviations: BWH, Brigham and Women's Hospital • DHEAS, dehydroepiandrosterone sulfate • HMC, Pennsylvania State University College of Medicine–Hershey Medical Center • HOMA-IR, homeostatic index of insulin resistance • NU, Northwestern University Feinberg School of Medicine • PCOS, polycystic ovary syndrome • SHBG, sex hormone–binding globulin

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