Ovarian hyperandrogynism as a result of congenital adrenal virilizing disorders: evidence for perinatal masculinization of neuroendocrine function in women
Abstract
Women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency often have a polycystic ovary-like syndrome, consisting of hyperandrogynism, infertility, menstrual irregularities, and elevated LH levels. This is generally considered secondary to poor control of the congenital adrenal hyperplasia. However, our experience led us to suspect that ovarian hyperandrogenism occurs even when congenital adrenal hyperplasia is well controlled on glucocorticoid therapy. Therefore, we tested the hypothesis that congenital adrenal virilizing disorders result in ovarian hyperandrogenism. We studied eight women with congenital adrenal virilizing disorders, seven with well controlled classic 21-hydroxylase deficiency and one with congenital virilizing adrenal carcinoma removed at 1.7 yr of age. We also studied six women with late-onset 21-hydroxylase deficiency, without signs of congenital virilization. An ovarian source of androgens was assessed after suppressing adrenal function with dexamethasone and then testing pituitary-ovarian function by a GnRH agonist (nafarelin) test. Five women with congenital adrenal virilizing disorders (four with classic 21-hydroxylase deficiency and one with congenital virilizing adrenal carcinoma) and one women with late-onset 21-hydroxylase deficiency had ovarian hyperandrogenism as determined by subnormal suppression of free testosterone after dexamethasone and/or by increased 17-hydroxyprogesterone response to nafarelin while on dexamethasone. A…
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A transient perinatal androgen excess in female rodents, nonhuman primates, and even humans can masculinize their metabolism and reprogram their genetic predisposition to obesity and metabolic syndrome in adulthood without any alteration in adult sex hormone levels.
“Further, a transient perinatal androgen excess in female rodents, nonhuman primates, and even humans can masculinize their metabolism and reprogram their genetic predisposition to obesity and metabolic syndrome in adulthood without any alteration in adult sex hormone levels [31, 65–71].”
From Sex differences in metabolic homeostasis, diabetes, and obesity (2015) · cites this paper as [68]
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- Authors
- Barnes, R. B., Rosenfield, R. L., Ehrmann, D. A., Cara, J. F., Cuttler, L., Levitsky, L. L., & Rosenthal, I. M.
- Affiliations
- University of Chicago (US)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1994-11
- Volume
- 79
- Issue
- 5
- Pages
- 1328-1333
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2110269109
- Cited by
- 304
- References
- 1
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 8 · 2022: 8 · 2021: 8 · 2020: 12 · 2019: 11 · 2018: 10 · 2017: 7 · 2016: 15 · 2015: 11 · 2014: 16 · 2013: 20 · 2012: 9
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Center for Research Resources (RR-00055, RR-00055-28SL)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 06308, R01HD006308)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- ovarian hyperandrogenism, congenital adrenal hyperplasia, 21-hydroxylase deficiency, hypothalamic-pituitary axis, dexamethasone suppression, free testosterone, glucocorticoid therapy
- MeSH terms
- Adolescent, Adrenal Gland Diseases, Adrenal Gland Neoplasms, Adult, Child, Dexamethasone, Female, Humans, Hydrolases, Luteinizing Hormone, Neurosecretory Systems, Ovarian Diseases, Sex Characteristics, Testosterone, Virilism, Nafarelin, Hyperandrogenism
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