Evidence for metabolic and reproductive phenotypes in mothers of women with polycystic ovary syndrome

Abstract

Dyslipidemia is a feature of polycystic ovary syndrome (PCOS), but its pathogenesis remains controversial. We performed this study of mothers of women with PCOS to test the hypothesis that dyslipidemia is a heritable trait in families of women with PCOS and to investigate the impact of age on reproductive and metabolic phenotypes. Fasting blood was obtained in 215 non-Hispanic white mothers of women with PCOS and 62 control women. The prevalence of metabolic syndrome was compared with that in non-Hispanic white women of comparable age from the National Health and Nutrition Examination Survey III. Mothers had higher total (P < 0.001) and low-density lipoprotein (LDL) cholesterol levels (P = 0.007), whereas high-density lipoprotein and triglyceride levels did not differ compared with control women. The only predictors of LDL levels in mothers were their daughters' LDL levels (r2 = 0.11, P < 0.001) and their own unbound testosterone levels (r2 = 0.04, P = 0.03). The prevalence of metabolic syndrome was increased in obese (body mass index > or = 30 kg/m2) mothers compared with obese non-Hispanic white women from the National Health and Nutrition Examination Survey III (P = 0.04). Thirty-one percent of mothers reported a history of menstrual irregularity. These mothers had higher androgen levels, markers of insulin resistance, and LDL levels than mothers with regular menses. LDL levels are increased in mothers of women with PCOS, suggestive of a heritable trait. A history of menstrual irregularity identifies mothers with features of PCOS. Obese mothers have a very high prevalence of metabolic syndrome. These findings suggest that both the reproductive and metabolic abnormalities persist with age in PCOS.

Fig. 1.

Mothers with irregular menses had higher total T, uT, and fasting glucose levels compared with mothers with regular menses (P = 0.007 for total T, P = 0.01 for uT, and P = 0.02 for fasting glucose) and compared with control women (P = 0.002 for total T, P < 0.001 for uT, and P < 0.001 for fasting glucose). Mothers with irregular menses had higher HOMA IR compared with control women (P = 0.001). Black bars, mothers with irregular menses; gray bars, mothers with regular menses; white bars, control women.

Fig. 2.

The prevalence of metabolic syndrome is shown in mothers of women with PCOS compared with women from NHANES III after stratification based on BMI. Obese mothers had higher prevalence of metabolic syndrome compared with obese women from NHANES III (P = 0.04). Black bars, mothers of women with PCOS; gray bars, women from NHANES III.