Insulin resistance and abnormal ovarian responses to human chorionic gonadotropin in chronically anovulatory women

We studied the interrelationships between insulin resistance, obesity, and abnormal ovarian androgen secretion in chronically anovulatory women with clinical or biochemical evidence of hyperandrogenism. Four groups of six subjects each were studied: (1) normal weight (within 10% ideal body weight) anovulatory, (2) obese (>120% ideal body weight) anovulatory, (3) normal weight eumenorrheic, and (4) obese eumenorrheic. After dexamethasone suppression, human chorionic gonadotropin (2000 IU/1.5m² body surface area intramuscularly) was administered to each subject. Serum testosterone levels were subsequently determined hourly for 17 hours. On a separate occasion, an oral glucose tolerance test was administered to five subjects from each group. Serum glucose and immunoreactive insulin levels were determined before and after the ingestion of a standard 100 gm glucose load. As a group, the anovulatory women had higher (p < 0.05) basal testosterone levels (1005 ± 97 pg/ml) than did the ovulatory women (241 ± 21 pg/ml) (values ± SE). Obesity per se was not associated with increased basal testosterone levels. Testosterone levels rose in response to human chorionic gonadotropin (p < 0.005) only in obese anovulatory women, reached maximal levels after 3 hours, and subsequently remained stable. Basal immunoreactive insulin levels were elevated (p < 0.05) only in obese anovulatory women (52.4 ± 20 µU/ml) compared with obese eumenorrheic (8.7 ± 1.0 µU/ml), normal weight anovulatory (5.8 ± 2.4 µU/ml), and normal weight eumenorrheic (4.6 ± 0.4 µU/ml) women. Similarly, maximal increases in immunoreactive insulin levels after glucose ingestion were significantly greater (p < 0.01) in obese anovulatory women compared with other groups. Of note is the observation that maximal changes in testosterone observed within the first 3 hours after human chorionic gonadotropin and maximal changes in insulin were correlated (r = 0.91, p < 0.01). These data suggest that (1) both insulin resistance and an abnormal acute response to human chorionic gonadotropin are seen only in obese anovulatory women and (2) the degree to which these two abnormalities are manifested is clearly correlated. The mechanism(s) responsible for this interrelationship, as well as the underlying cause(s) of these biochemical defects, remain to be elucidated.