Polycystic ovary syndrome (PCOS) is associated with hyperinsulinemia, insulin resistance (IR), increased risk of glucose intolerance, and type 2 diabetes. Family studies have indicated a genetic susceptibility to PCOS. The aims of this study were 1) to assess glucose tolerance status, gonadotropins, and androgens in first degree relatives of patients with PCOS; and 2) to assess IR in normal glucose tolerant (NGT) family members. One hundred two family members of 52 patients with PCOS [MothersPCOS (n = 34; mean age, 46.5 yr; mean body mass index (BMI), 28.8 kg/m2), FathersPCOS (n = 24; mean age, 50.4 yr; mean BMI, 27.5 kg/m2), SistersPCOS (n = 19; mean age, 25.1 yr; mean BMI, 22.9 kg/m2), and BrothersPCOS (n = 25; mean age, 23.7 yr; mean BMI, 22.5 kg/m2)] and 82 unrelated healthy control subjects without a family history of diabetes or PCOS (4 age- and weight-matched subgroups, i.e. ControlMothersPCOS, ControlFathersPCOS, ControlSistersPCOS, and ControlBrothersPCOS) were studied. Glucose and insulin (at baseline and during a 75-g, 2-h oral glucose tolerance test) were measured. IR was assessed by fasting insulin (FI), fasting glucose to insulin ratio (FGI), homeostatic model assessment (HOMA IR), and area under the curve for insulin during the oral glucose tolerance test (AUCinsulin) in NGT MothersPCOS, FathersPCOS, SistersPCOS, BrothersPCOS, and matched control subgroups. Including the prestudy-diagnosed 3 mothers and 2 fathers with diabetes, diabetes and impaired glucose tolerance (IGT) were noted in 16% and 30% of MothersPCOS and 27% and 31% of FathersPCOS, respectively. There was no diabetes in SistersPCOS and BrothersPCOS. IGT was found in 5% of SistersPCOS. Impaired fasting glucose was found in 3% of MothersPCOS and 4% of BrothersPCOS. The analysis of NGT family members showed that MothersPCOS had higher FI (P < 0.05), HOMA IR (P < 0.05), and AUCinsulin (P < 0.01) and lower FGI (P < 0.05) than ControlMothersPCOS, whereas all IR parameters were comparable between FathersPCOS and their matched control subgroup. SistersPCOS had higher FI (P < 0.05), HOMA IR (P < 0.01), and AUCinsulin (P < 0.05) and lower FGI (P < 0.01), and BrothersPCOS had higher AUCinsulin (P < 0.01) than their matched control subgroups, respectively. MothersPCOS had higher testosterone levels than ControlMothersPCOS (P < 0.01 and P < 0.05 for pre- and postmenopausal women, respectively). SistersPCOS had higher LH (P < 0.01), testosterone (P < 0.001), androstenedione (P < 0.01), and dehydroepiandrosterone sulfate (P < 0.05) levels than ControlSistersPCOS. There was no difference in gonadotropin and androgen levels in FathersPCOS compared with ControlFathersPCOS or in BrothersPCOS compared with ControlBrothersPCOS.
Our results suggest that 1) first degree relatives of patients with PCOS may be at high risk for diabetes and glucose intolerance; 2) NGT female family members have insulin resistance; and 3) mothers and sisters of PCOS patients have higher androgen levels than control subjects. We propose that the high risks of these impairments warrant screening in first degree relatives of patients with PCOS.