KatCarney

Insulin resistance in the sisters of women with polycystic ovary syndrome: association with hyperandrogenemia rather than menstrual irregularity

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in women and is defined by hyperandrogenic chronic anovulation with the exclusion of secondary causes, such as congenital adrenal hyperplasia or an androgen secreting tumor. PCOS women are uniquely insulin resistant. It is estimated that 5% of the female population is affected. The underlying genetic defect in insulin action is unknown. Obesity aggravates the underlying predisposition to insulin resistance. Diagnostic criteria which focus on menstrual irregularity are more likely to identify insulin resistant women. About 40% of PCOS women display glucose intolerance (either impaired glucose tolerance or type 2 diabetes) in response to an oral glucose challenge. The study was performed to determine whether the sisters of women with polycystic ovary syndrome have evidence for insulin resistance. Three hundred and thirty-six women with PCOS, 307 sisters of these probands, and 47 control women were studied. The sisters were grouped by phenotypes: 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 sisters 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 beta-cell dysfunction 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 sisters. It is concluded that markers of insulin resistance are associated with hyperandrogenemia rather than menstrual irregularity in the sisters of women with PCOS. Insulin resistance per se does not cause menstrual irregularities, however, menstrual irregularity may be related to the magnitude of insulin sensitivity or insulin secretion or to other factors associated with obesity.

Reference

Legro RS, Bentley-Lewis R, Driscoll D, Wang SC, Dunaif A. (2002) Insulin resistance in the sisters of women with polycystic ovary syndrome: association with hyperandrogenemia rather than menstrual irregularity. J Clin Endocrinol Metab. 87:2128-2133.

Legro, R.S. (2002) Polycystic ovary syndrome. Long term sequelae and management. Minerva Ginecol. 54:97-114

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