Insulin Resistance in the Sisters of Women with Polycystic Ovary Syndrome: Association with Hyperandrogenemia Rather Than Menstrual Irregularity

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Abstract
This study was performed to determine whether the sisters of women with polycystic ovary syndrome (PCOS) have evi- dence for insulin resistance. Three hundred and thirty-six women with PCOS, 307 sisters of these probands, and 47 con- trol women were studied. The sisters were grouped by phe- notypes: PCOS (hyperandrogenemia (HA) with chronic oligo- or amenorrhea, n 39), HA with regular menses (n 36), unaffected (UA; n 122), and unknown (n 110). The analyses were adjusted for age and body mass index. PCOS and HA sisters of women with PCOS had similar and significantly elevated fasting insulin levels (P 0.001) as well as similar and significantly decreased fasting glucose/insulin ratios (P < 0.001) suggestive of insulin resistance compared with UA sis- ters and control women. Markers of insulin resistance were associated with hyperandrogenemia and not with menstrual irregularity. PCOS sisters also had decreased levels of SHBG (P 0.02) suggestive of higher ambient insulin levels. PCOS sisters had increased levels of proinsulin (P 0.04) compared with control women, which suggested pancreatic -cell dys- function in this group of sisters. The magnitude of obesity also differed significantly among the groups of sisters. The PCOS sisters were significantly more obese than all the other groups, and the HA sisters were more obese than the UA sis- ters. We conclude that markers of insulin resistance are as- sociated with hyperandrogenemia rather than menstrual ir- regularity in the sisters of women with PCOS. Menstrual irregularity may be related to the magnitude of insulin sen- sitivity or insulin secretion or to other factors associated with obesity. (J Clin Endocrinol Metab 87: 2128 -2133, 2002)

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