Sex differences in 11-oxygenated androgen patterns across adulthood
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CONTEXT: The gonads are the major source of sex steroids during reproductive ages. The gonadal function declines abruptly in women and gradually in men. The adrenals produce 11-oxygenated androgens (11-oxyandrogens), which start rising during adrenarche. Following menopause, 11-oxyandrogens levels remain similar to reproductive ages. OBJECTIVE: To compare the circulating 11-oxyandrogen concentrations in men and women across adult ages. METHODS: We used mass spectrometry to measure testosterone (T), androstenedione (A4), 11β-hydroxytestosterone (11OHT), 11-ketotestosterone (11KT), 11β-hydroxyandrostenedione (11OHA4), 11-ketoandrostenedione (11KA4), cortisol, and cortisone in morning sera obtained from adults in outpatient setting. We performed double immunofluorescence of 3β-hydroxysteroid dehydrogenase type 2 and cytochrome b5 in adrenal tissue from 19 men, age 23-78 years. RESULTS: We included 590 patients (319 men), aged 18 to 97 years, and 84% white. 11KT and 11KA4 were stable across ages in women, but they declined in men (0.21 and 0.06 ng/dL/year, respectively; P < 0.05). 11OHA4 and 11OHT increased modestly with age in women (0.6 and 0.09 ng/dL/year, respectively; P < 0.01), and both remained stable across ages in men. As body mass index (BMI) increased, 11KA4 decreased in women, and 11KT increased in men, both suggesting higher 17β-hydroxysteroid dehydrogenase activity in obese individuals. A4 and T declined with age and A4 with BMI in both sexes; T declined with BMI in men. Adrenal androgenic enzyme expressions in aging men were similar to those observed in women. CONCLUSIONS: In contrast with traditional androgens, the production of 11OHA4 and 11OHT is sustained with aging in both sexes. The bioactive androgen 11KT declines in aging men but not in women.
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The 11-oxo-androgens (and 21-deoxycortisol) correlate better with adrenal size than traditional biomarkers of short-term disease control, such as androstenedione and 17OHP.
“The 11-oxo-androgens (and 21-deoxycortisol), correlate better with adrenal size than traditional biomarkers of short-term disease control, such as androstenedione and 17OHP (129).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [129]
Elevated 11-oxo-androgens are predictive of menstrual irregularity in women and of TARTs in men with CAH.
“Elevated 11-oxo-androgens are also predictive of menstrual irregularity in women and of TARTs in men with CAH (129).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [129]
In contrast, 11KT is inversely proportional to testosterone in men and in boys Tanner stage 3-5 with 21OHD.
“In contrast, 11KT is inversely proportional to testosterone in men (123) and in boys Tanner stage 3-5 (129) with 21OHD.”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [129]
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- Authors
- Davio, A., Woolcock, H., Nanba, A. T., Rege, J., O’Day, P., Ren, J., Zhao, L., Ebina, H., Auchus, R., Rainey, W. E., & Turcu, A. F.
- Affiliations
- University of Michigan (US)
- Tohoku University (JP)
- Corresponding author
- Turcu, Adina F
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2020-06-04
- Volume
- 105
- Issue
- 8
- Pages
- e2921-e2929
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC7340191
- OpenAlex
- W3034089088
- Cited by
- 76
- References
- 28
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 15 · 2023: 12 · 2022: 10 · 2021: 20 · 2020: 3
- FWCI
- 8.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Glenn Foundation for Medical Research (N024780-00)
- NIDDK (1K08DK109116)
- Michigan Institute for Clinical and Health Research (U064177)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- sex differences, 11-oxygenated androgens, 11-ketotestosterone, 11β-hydroxytestosterone, 11-ketoandrostenedione, 11β-hydroxyandrostenedione, androstenedione, testosterone, aging, adrenarche, menopause, body mass index, 17β-hydroxysteroid dehydrogenase type 2, cytochrome b5, adrenal androgen production
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Androgens, Androstenedione, Female, Humans, Hydroxytestosterones, Male, Middle Aged, Sex Factors, Testosterone, Cohort Studies, Young Adult
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