Hyperandrogenism and hyperinsulinism in children of women with polycystic ovary syndrome: a controlled study

Abstract

Objective: Hyperandrogenia and insulin resistance are heritable family traits, likely to cluster in children of polycystic ovary syndrome (PCOS) mothers.

Design: We performed a case control study of PCOS children (n = 32) compared with children from control women (n = 38) for reproductive and metabolic abnormalities, stratifying results by three Tanner stage groupings. The children underwent history and physical examinations, a 3-h timed urine collection, a 2-h oral glucose tolerance test, and abdominal ultrasound examination (females only). Serum was obtained in older children (age > 8 yr) who consented.

Results: Urine LH levels were significantly lower in the Tanner IV-V PCOS girls compared with controls (P = 0.04). Urine testosterone levels were significantly elevated in Tanner II-III PCOS boys compared with controls (P = 0.007). There were no significant differences in dehydroepiandrosterone levels. We validated the correlation between salivary and serum levels of insulin (insulin areas under the curve) in an adult population [n =30, Pearson correlation coefficient (r) = 0.67; P < 0.0001], which also replicated in the children (2-h insulin r = 0.57; P = 0.0004). Mean area under the curve salivary insulin levels were significantly higher in the Tanner IV-V PCOS girls in the later stages of puberty when compared with controls (3625 +/- 1372 vs. 1766 +/- 621 min x muU/ml, 95% confidence interval 475-3242; P < 0.02).

Conclusions: Hyperinsulinism may be a familial characteristic of PCOS children (or at least girls) but does not appear until the later stages of puberty. Other reproductive abnormalities that characterize PCOS may develop later.

Figure 1

Correlation between salivary and serum insulin in children from the study. A, Fasting insulin (n = 32 children). B, One hundred twenty minute insulin (n = 30 children). The Pearson correlation coefficient (r) and associated 95% confidence interval (CI) are reported in each panel.

Figure 2

Urinary reproductive hormones by Tanner stage in females. A, LH. B, FSH. C, Testosterone. D, DHEA. On the horizontal axis, P denotes PCOS child, and C denotes control child. The mean and se are plotted. An asterisk (*) beside a Tanner stage on the horizontal axis denotes a P < 0.05 for comparing PCOS to control.

Figure 3

Urinary reproductive hormones by Tanner stage in males. A, LH. B, FSH. C, Testosterone. D, DHEA. On the horizontal axis, P denotes PCOS child, and C denotes control child. The mean and se are plotted. An asterisk (*) beside a Tanner stage on the horizontal axis denotes a P < 0.05 for comparing PCOS to control.

Figure 4

Salivary insulin levels during an OGTT by Tanner stage and group. A, Tanner stage 0–I. B, Tanner stage II–III. C, Tanner stage IV–V, combined male and female data. The mean and se are plotted. There were no significant differences for any of the individual time points.