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The role of hyperinsulinemia in the pathogenesis of ovarian hyperandrogenism
Open accessAbstract
The evidence that supports the hypothesis that insulin and LH both regulate ovarian androgen production was presented. The most dramatic clinical example of the association between hyperinsulinemia and hyperandrogenism is the HAIR-AN syndrome. Our hypothesis is that, in the HAIR-AN syndrome, the severe insulin resistance causes a compensatory hyperinsulinemia, which stimulates ovarian androgen production if adequate LH is present. The acanthosis nigricans is an epiphenomenon of the syndrome. Acanthosis nigricans is a dermatologic manifestation of severe insulin resistance. In vitro evidence suggests that insulin and IGF-I stimulate androgen production in incubations of human stroma and theca. The stromatropic effects of insulin may sensitize the stroma to the stimulatory effects of LH. In some hyperandrogenic-insulin-resistant women, a glucose load appears to produce an acute rise in circulating androgens. The magnitude of the rise in circulating androgens is proportional to the magnitude of the insulin response to the glucose load. These data suggest that hyperinsulinemia may play a central role in the development of ovarian hyperandrogenism.
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“Insulin suppresses hepatic SHBG secretion and acts on the ovary to promote thecal cell androgen synthesis 58 with the net effect of increasing circulating free testosterone concentrations.”
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Diamond, M. P., GRAINGER, D. A., LAUDANO, A. J., Starick-Zych, K., & DeFronzo, R. A. (1991) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-72-4-883 · Cited by 74
Roles of LH and insulin resistance in lean and obese polycystic ovary syndrome
Grulet, H., Hécart, A. C., Delemer, B., Gross, A., Sulmont, V., Leuténegger, M., & Caron, J. (1993) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1993.tb02144.x · Cited by 73
Stadtmauer, L. A. (2002) · Human Reproduction · doi:10.1093/humrep/17.12.3016 · Cited by 73
Thomson, R. L., Buckley, J. D., & Brinkworth, G. D. (2011) · Obesity Reviews · doi:10.1111/j.1467-789x.2010.00758.x · Cited by 70
“IR and compensatory hyperinsulinemia act on ovarian tissue, disturbing ovarian hormone regulation and the menstrual cycle, resulting in infertility (5,23,24) and contribute directly to hyperandrogenemia by stimulating thecal cell androgen production (2,25,26).”
BackgroundSlowinska-Srzednicka, J., Zgliczyński, S., Wierzbicki, M., Srzednicki, M., Stopińska-Głuszak, U., Zgliczyński, W., Soszynski, P. A., Chotkowska, E., Bednarska, M., & Sadowski, Z. (1991) · Journal of Endocrinological Investigation · doi:10.1007/bf03346870 · Cited by 70
Polycystic ovaries and the polycystic ovary syndrome phenotype in women with active acromegaly
Kaltsas, G., Androulakis, I. I., Tziveriotis, K., Papadogias, D., Tsikkini, A., Makras, P., Dimitriou, K., Stathopoulou, A., & Piaditis, G. P. (2007) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2007.02987.x · Cited by 69
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Upper Body Obesity and Hyperinsulinemia Are Associated with Anovulation
Morán, C., Hernández, E., Ruíz, J. E., Fonseca, M. E., BERMUDEZ, J. A., & Zárate, A. (1999) · Gynecologic and Obstetric Investigation · doi:10.1159/000010052 · Cited by 66
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Ovarian morphology and insulin sensitivity in women with bulimia nervosa
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“85) have moderate to severe insulin resistance and chronic hyperinsulinaemia and this may cause an increase in ovarian androgen production (Barbieri et al., 1988).”
BackgroundInsulin resistance/hyperinsulinemia and reproductive disorders in infertile women
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“Insulin, by acting via its receptor, appears to promote ovarian and adrenal androgen biosynthesis [35, 36], amplifying luteinizing hormone (LH)-induced androgen production by theca cells and resulting in hyperandrogenemia [37, 38].”
BackgroundFerredoxin 1 regulates granulosa cell apoptosis and autophagy in polycystic ovary syndrome
Xing, J., Qiao, G., Luo, X., Liu, S., Chen, S., Ye, G., Zhang, C., & Yi, J. (2023) · Clinical Science · doi:10.1042/cs20220408 · Cited by 59
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“Further, insulin resistance can lead to elevated androgen and estrogen concentrations because insulin stimulates ovarian steroid secretion [33, 37, 38].”
BackgroundLiepa, G. U., Sengupta, A. M., & Karsies, D. (2008) · Nutrition in Clinical Practice · doi:10.1177/011542650802300163 · Cited by 58
Hyperinsulinaemic androgen excess in adolescent girls
Ibáñez, L., Ong, K. K., López-Bermejo, A., Dunger, D. B., & de Zegher, F. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.58 · Cited by 56
Metadata
- Authors
- Wallach, E. E., Barbieri, R. L., Smith, S., & Ryan, K. J.
- Affiliations
- Brigham and Women's Hospital (US)
- Venue
- Fertility and Sterility
- Publisher
- Elsevier BV
- Published
- 1988-08
- Volume
- 50
- Issue
- 2
- Pages
- 197-212
- ISSN
- 0015-0282 (ISSN-L)
- OpenAlex
- W194639418
- Cited by
- 348
- References
- 108
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 3 · 2023: 9 · 2022: 9 · 2021: 8 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 7 · 2016: 6 · 2015: 5 · 2014: 7 · 2013: 4 · 2012: 2
- FWCI
- 10.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Fertility and Sterility (publishedVersion)
- PubMed (publishedVersion)
- 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 › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- hyperinsulinemia, ovarian hyperandrogenism, polycystic ovary syndrome, androgen overproduction, PCOS pathogenesis, insulin resistance, hypothalamic-pituitary-ovarian axis, adrenal androgen production
- MeSH terms
- Acanthosis Nigricans, Androgens, Female, Humans, Hyperinsulinism, Insulin Resistance, Ovary, Polycystic Ovary Syndrome, Syndrome
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