The Effects of Hyperinsulinemia on Serum Testosterone, Progesterone, Dehydroepiandrosterone Sulfate, and Cortisol Levels in Normal Women and in a Woman with Hyperandrogenism, Insulin Resistance, and Acanthosis Nigricans*

Publisher Website
Google Scholar
Abstract
Insulin may mediate the hyperandrogenism that frequently occurs in patients with insulin-resistant states. To test this hypothesis, we studied five normal women and one woman with hyperandrogenism, insulin resistance, and acan-thosis nigricans with the hyperinsulinemic-euglycemic clamp technique. Each woman received a 0.1 U/kg insulin bolus dose, followed by a 10 mU/kg·min insulin infusion for 12–16 h. In the normal women, an average insulin level of 1832 ± 292 (±sem) μU/ml was achieved; serum glucose was clamped at 116 ± 5 mg/dl. At this level, insulin may bind to the insulin-like growth factor I receptor as well as to its own receptor. Contrary to our working hypothesis, a rise in serum testosterone did not occur in any woman during insulin infusion, and in one woman, serum testosterone levels decreased. When analyzed as a percentage of the basal value, serum progesterone levels fell 20% in the normal women within the first 2 h of insulin infusion, but did not change thereafter. Dehydroepiandrosterone sulfate (DHEA-S) levels, however, uniformly and progressively decreased by 39% after 12 h of insulin infusion in the normal women and by 31% at 14 h in the woman with hyperandrogenism, insulin resistance, and acanthosis nigricans. The fall in serum DHEA-S levels was not due to diurnal rhythmicity, as the changes in serum DHEA-S levels did not correlate with those in serum cortisol. Suppression of PRL release also was excluded as a cause of the fall in DHEA-S levels. These results indicate that acute hyperinsulinemia of 12- to 16-h duration does not increase serum testosterone or DHEA-S concentrations and, indeed, can cause a decline in serum DHEA-S levels in both normal women and the single woman studied with hyperandrogenism, insulin resistance, and acanthosis nigricans.