Insulin administration alters gonadal steroid metabolism independent of changes in gonadotropin secretion in insulin-resistant women with the polycystic ovary syndrome.
Open accessAbstract
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, gonadotrope 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 microU/ml PCO vs. 907 +/- 92 microU/ml normal, P less than or equal to 0.01). Insulin acutely increased mean delta (6 h minus prestudy) levels of androstenedione (A) (P less than or equal to 0.001) and estradiol (E2) (P less than or equal to 0.05) and decreased mean plasma pool (0-6 h) levels of testosterone (T) (P less than 0.05), nonsex hormone binding globulin-bound T (P less than 0.05), and dihydrotestosterone (P less than or equal to 0.01) in the PCO women. Insulin also decreased mean plasma 6 h A to estrone (E1) ratios and increased 6 h E1 levels (both P less than or equal to 0.05) in the PCO women. There were significant sequence effects (insulin + day) in the PCO women on T/E2 ratios, indicating a carryover 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 less than or equal to 0.01). There were significant spontaneous decreases in mean luteinizing hormone (p less than 0.05) and follicle-stimulating hormone levels (p less than or equal to 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-resistent 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.
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References 47 · Cited by 204
Research works printed but not linked: 2
- Pearson, B., M. D. Murphy, W. Engelberg, and C. J. Patte. 1963. Simple method for the determination of plasma corticoids. J. Clin. Endocrinol. & Metab. 23:293-300.
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- Authors
- Dunaif, A., & Graf, M.
- Affiliations
- City University of New York (US)
- ORCID
- Dunaif, A
- Venue
- Journal of Clinical Investigation
- Published
- 1989-01-01
- Volume
- 83
- Issue
- 1
- Pages
- 23-29
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC303638
- OpenAlex
- W2079672855
- Cited by
- 204
- References
- 47
- Citations by year
- 2026: 2 · 2025: 4 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 6 · 2016: 6 · 2015: 7 · 2014: 3 · 2013: 8 · 2012: 6
- FWCI
- 12.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Charles H. Revson Foundation
- National Institutes of Health
- National Center for Research Resources (RR‑00071)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-00608)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- polycystic ovary syndrome, insulin resistance, hyperinsulinemia, gonadal steroidogenesis, gonadotropin secretion, follicle-stimulating hormone, androstenedione, estradiol, testosterone, dihydrotestosterone, sex hormone-binding globulin, estrone, insulin infusion, androgen deprivation therapy, ovulation
- MeSH terms
- Adolescent, Adult, Blood Glucose, Female, Gonadotropins, Humans, Hyperinsulinism, Insulin, Insulin Resistance, Polycystic Ovary Syndrome, Sex Hormone-Binding Globulin, Gonadal Steroid Hormones, Steroids
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