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.
Level 4 - case-series / case-control
Small non-randomized experimental physiological study without a parallel control group
PubMed 2946716 · doi:10.1210/jcem-64-1-180
What was done
Five normal women and one woman with hyperandrogenism, insulin resistance, and acanthosis nigricans underwent a hyperinsulinemic-euglycemic clamp. Participants received a 0.1 U/kg insulin bolus followed by a continuous 10 mU/kg·min insulin infusion for 12 to 16 hours. In normal women, mean serum insulin reached 1832 ± 292 µU/ml with blood glucose clamped at 116 ± 5 mg/dl. Serum testosterone, progesterone, dehydroepiandrosterone sulfate (DHEA-S), cortisol, and prolactin were measured.
What was found
Serum testosterone did not increase in any participant during insulin infusion and decreased in one woman. Serum progesterone fell by 20% of basal levels within the first 2 hours in normal women and stabilized thereafter. Serum DHEA-S decreased progressively by 39% after 12 hours of infusion in normal women and by 31% at 14 hours in the woman with hyperandrogenism. The DHEA-S reduction did not correlate with serum cortisol changes and was not caused by prolactin suppression.
Why it matters
Acute high-dose hyperinsulinemia does not stimulate circulating testosterone or DHEA-S and instead lowers DHEA-S, indicating that hyperandrogenism in insulin-resistant conditions is not driven by rapid insulin-mediated steroid secretion.
Limits
The study is limited by an extremely small sample size (five normal controls and one patient) and lack of a parallel control group. The infused insulin levels were supraphysiological (likely engaging IGF-I receptors), and the 12- to 16-hour duration cannot evaluate chronic trophic effects of hyperinsulinemia.
Cited by
- contradicts When blood sugar rises, insulin rises, which directly leads to an increase in testosterone levels.