Insulin administration alters gonadal steroid metabolism independent of changes in gonadotropin secretion in insulin-resistant women with the polycystic ovary syndrome

A. Dunaif, M. Graf

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151 Scopus citations

Abstract

We have investigated the hypothesis that hyperinsulinemia may cause the polycystic ovary syndrome (PCO) by directly stimulating gonadal steroidogenesis and/or gonadotropin secretion. 10 insulin-resistant women with PCO and 5 age- and weight-matched ovulatory normal women had pulsatile gonadotropin release, gonadotropin sensitivity to gonadotropin releasing hormone, and sex hormone levels studied on two consecutive study days, basally and during the infusion of insulin (mean ± SEM steady state insulin levels, 1,254 ± 63 μU/ml PCO vs. 907 ± 92 μU/ml normal, P ≤ 0.01). Insulin acutely increased mean delta (6 h minus prestudy) levels of androstenedione (A) (P ≤ 0.001) and estradiol (E2) (P ≤ 0.05) and decreased mean plasma pool (0-6 h) levels of testosterone (T) (P < 0.05), nonsex hormone binding globulin-bound T (P < 0.05), and dihydrotestosterone (P < 0.01) in the PCO women. Insulin also decreased mean plasma 6 h A to estrone (E1) ratios and increased 6 hE1 levels (both P ≤ 0.05) in the PCO women. There were no significant sequence effects (insulin + day) in the PCO women on T/E2 ratios, indicating a carry-over action of insulin. Insulin had no effects on gonadotropin release in the PCO women. In the normal women, the only significant change was an insulin or study day effect that increased mean 6 h E2 levels (P ≤ 0.01). There were significant spontaneous decreases in mean luteinizing hormone (P < 0.05) and follicle-stimulating hormone levels (P ≤ 0.01) in the PCO but not the normal women on the second day of study. This study indicates that insulin can directly alter peripheral sex hormone levels independent of changes in gonadotropin release in insulin-resistant PCO women. Insulin decreased the levels of potent androgens in PCO women and did not increase androgen levels in normal women, arguing against a simple, direct causal relationship between hyperinsulinemia and hyperandrogenism in PCO.

Original languageEnglish (US)
Pages (from-to)23-29
Number of pages7
JournalJournal of Clinical Investigation
Volume83
Issue number1
DOIs
StatePublished - 1989

ASJC Scopus subject areas

  • Medicine(all)

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