Exogenous testosterone does not influence 11-oxygenated C19 steroid concentrations in healthy postmenopausal women
Open accessAbstract
Abstract Context 11β-Hydroxyandrostenedione (11OHA4), 11β-hydroxytestosterone (11OHT), and their respective peripheral derivatives, 11-ketoandrostenedione (11KA4) and 11-ketotesosterone (11KT), have been implicated in androgen-related physiopathology. Little is known of these steroids in postmenopausal women or whether exogenous testosterone therapy influences their levels. Objective The impact of exogenous testosterone on serum levels of 11-oxygenated steroids was determined in healthy postmenopausal women. Participants and Methods Levels of 19-carbon (C19) steroids were measured by liquid chromatography–tandem mass spectrometry in serum obtained at baseline and at 12 and 26 weeks from 73 healthy postmenopausal women, aged 55 to 65 years, who participated in a randomized, double-blind, placebo-controlled clinical trial assessing the effects of transdermal testosterone on cognitive performance. Results Of the 11-oxygenated androgens, 11OHA4 was the most abundant (median, 6.46 nmol/L; range, 1.51 to 23.82 nmol/L), with concentrations several fold greater than its precursor androstenedione (median, 1.38 nmol/L; range, 0.52 to 2.92 nmol/L). Baseline median (range) testosterone and 11KT levels were similar [0.56 (0.23 to 1.48) nmol/L; 0.85 (0.25 to 2.86) nmol/L, respectively). 11OHT was closely correlated with 11KT (Spearman rank correlation coefficient, 0.79; P < 0.001) and 11OHA4 correlated with 11KA4 (Spearman rank correlation coefficient, 0.73; P < 0.001). Testosterone therapy resulted in an increase in serum testosterone level, whereas all 11-oxygenated androgens remained unchanged throughout the 26 weeks of treatment. Conclusion After menopause, the adrenal production of 11-oxygenated derivatives of androstenedione and testosterone contributes importantly to the total circulating androgen pool. Exogenous testosterone does not influence the circulating levels 11-oxygenated C19 steroids.
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Addition of exogenous testosterone does not lead to increased 11-oxygenated androgen output, confirming that only locally produced substrates (primarily A4) can be 11β-hydroxylated.
“Notably, the addition of exogenous testosterone does not lead to increased 11-oxygenated androgen output, thereby confirming that only locally produced substrates (primarily A4) can be 11β-hydroxylated [68].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [68]
Although multiple studies have measured circulating concentrations of 11-oxygenated androgens in healthy control groups, there are significant variations in the levels reported and no reference ranges have been established to date.
“However, although multiple studies have measured the circulating concentrations of 11-oxygenated androgens in healthy control groups, there are significant variations in the levels reported and as such, no reference ranges have been established to date [39,41,68,69,289].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [68]
11KA4 is the next most abundant 11-oxygenated androgen precursor in circulation.
“11KA4 is the next most abundant 11-oxygenated androgen precursor in circulation (Table 2) [39,41,68,69,289].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [68]
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- Authors
- Davis, S. R., Turcu, A. F., Robinson, P. J., & Bell, R. J.
- Affiliations
- Monash University (AU)
- University of Michigan (US)
- Corresponding author
- Davis, Susan R
- Venue
- Journal of the Endocrine Society
- Publisher
- The Endocrine Society
- Published
- 2019-02-04
- Volume
- 3
- Issue
- 3
- Pages
- 670-677
- ISSN
- 2472-1972 (ISSN-L)
- PMC
- PMC6397421
- OpenAlex
- W2913841406
- Cited by
- 10
- References
- 24
- Citations by year
- 2022: 2 · 2021: 2 · 2020: 3 · 2019: 3
- FWCI
- 2.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of the Endocrine Society (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Monash University Research Portal (Monash University) (submittedVersion, cc-by-nc-nd)
- Funders
- National Health and Medical Research Council (1135843)
- Judith Jane Mason and Harold Stannett Williams Memorial Foundation
- Biosante Pharmaceuticals
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- 11β-hydroxyandrostenedione, 11β-hydroxytestosterone, 11-ketoandrostenedione, exogenous testosterone, postmenopausal women, adrenal androgen production, androstenedione, serum steroid levels
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