THE ROLE OF ADRENAL HYPERANDROGENISM, INSULIN RESISTANCE, AND OBESITYIN THE PATHOGENESIS OF POLYCYSTIC OVARIAN SYNDROME

Hyperandrogenism, insulin resistance, and obesity are common features of polycystic ovarian syndrome (PCOS). This study was designed to inve stigate the relationship among these factors and how they might contri bute to ovulatory dysfunction in PCOS. Adrenal androgen secretion and insulin resistance were quantified in oligomenorrheic women with PCOS and in three groups of eumenorrheic women: weight-matched hirsute wome n, obese nonhirsute women, and thin nonhirsute women. Adrenal androgen secretion was defined as the androstenedione response to synthetic co rticotropin. Insulin resistance was estimated by calculating the area under the curve for serum insulin levels in response to a 75 g oral gl ucose load. The mean serum androstenedione response (nmol/L) to cortic otropin in PCOS (5.6 +/- 1.3) was greater than that in eumenorrheic hi rsute women (3.4 +/- 0.5; P < 0.10), obese nonhirsute women (1.8 +/- 0 .8; P < 0.05), and lean nonhirsute women (1.9 +/- 0.5; P < 0.05). The serum androstenedione response was not correlated with body mass index (BMI). The area under the curve for serum insulin (mU/L . min/1000) i n PCOS (29.1 +/- 5.3) was greater (P < 0.001) than in eumenorrheic hir sute women (9.1 +/- 1.7), obese nonhirsute women (5.8 +/- 1.0), and le an nonhirsute women (4.5 +/- 0.4). The serum insulin response was high ly correlated with BMI (P < 0.001) in the three groups of obese women, but women with PCOS became significantly more insulin resistant with increasing BMI (P < 0.02). There was no correlation between adrenal an drogen secretion and insulin resistance in any of the groups. We concl ude that adrenal hyperandrogenism and insulin resistance are independe nt predictors of anovulation in hirsute women. These conditions are pr esent in both oligomenorrheic and eumenorrheic hirsute women, but are present to a greater extent in anovulatory women. Obese women with PCO S also differ from eumenorrheic controls by developing a greater degre e of insulin resistance as body mass increases.