Metabolic phenotype in the brothers of women with polycystic ovary syndrome.
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.


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 (rho = 0.2, P = 0.009) and LDL cholesterol (rho = 0.3, P = 0.001) and triglyceride (rho = 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.
Sam
Susan
S
Division of Endocrinology, Metabolism and Molecular Medicine, the Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Coviello
Andrea D
AD
Sung
Yeon-Ah
YA
Legro
Richard S
RS
Dunaif
Andrea
A
D000293:Adolescent; D000328:Adult; D000728:Androgens / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D006706:Homeostasis; D006801:Humans; D034321:Hyperamylasemia / Q000097:blood / Q000235:genetics*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D018579:Patient Selection; D010414:Pennsylvania; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D012016:Reference Values; D035781:Siblings; D044465:White People
D000728:Androgens; D001786:Blood Glucose; D007328:Insulin