Early Decline of Androgen Levels in Healthy Adult Men: An Effect of Aging Per Se? A Prospective Cohort Study
Open accessAbstract
Context: Androgen levels have been shown to decline in aging men. However, there is no consensus on the effect of aging, (changes in) body mass index (BMI), lifestyle factors, and intercurrent disease. Objective: Investigating longitudinal changes in serum androgen levels in healthy men in relation to body composition, lifestyle factors, and intercurrent disease. Design, Setting, and Participants: Longitudinal, population-based sibling pair study at a university research center. 999 healthy men aged 24 to 46 years of whom 691 were reevaluated after a mean period of 12 years. Main outcome measures: Serum SHBG, LH, and FSH levels measured using immuno-assays. Testosterone (T), estradiol (E2), dihydro-testosterone (DHT), and androstenedione (Adione) measured using liquid chromatography-tandem mass spectometry, free T calculated (cFT). Results: Baseline age was 34 ± 6 years. Mean BMI increased by 1.19 kg/m2, T levels decreased by 14.2% (20.8 nmol/L vs. 17.8 nmol/L), cFT by 19.1% (392 pmol/L vs. 317 pmol/L), DHT by 15.6% (1.5 nmol/L vs.1.3 nmol/L), and Adione by 10.7% (3.7 nmol/L vs. 3.3 nmol/L; all P < 0.001). E2 did not change over time. SHBG increased by 3.0% (39.8 nmol/L vs. 41.0 nmol/L), LH by 5.8% (4.6 U/L vs. 4.9 U/L) and FSH by 14.7% (4.3 U/L vs. 5.1 U/L) (all P < 0.001). For T, cFT, DHT, Adione, and SHBG, these longitudinal changes persisted after adjustment for confounders (all P < 0.001). Conclusion: Serum androgen levels start declining early during adult life and independently from changes in BMI and other lifestyle factors, suggesting that aging per se leads to an altered sex steroid status. Given the concurrent rise in gonadotropin levels, the decline in androgen status most likely arises from primary decrease in testicular function.
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Age is an important contributor to variance in total T, free T and SHBG.
“In conclusion, age is an important contributor to variance in total T, free T as well as SHBG [61, 62].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [62]
Decreased androgen levels and increased SHBG have been confirmed in the longitudinal SIBEX study.
“These observations of decreased androgen levels and increased SHBG have been confirmed in the longitudinal Siblos Extension Study (SIBEX) [62].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [62]
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- Authors
- Banica, T., Verroken, C., Reyns, T., Mahmoud, A., T’Sjoen, G., Fiers, T., Kaufman, J.-M., & Lapauw, B.
- Affiliations
- Ghent University Hospital (BE)
- Department of Endocrinology, Ghent University Hospital, Ghent, Belgium
- Corresponding author
- Banica, Thiberiu
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2020-12-31
- Volume
- 106
- Issue
- 4
- Pages
- e1074-e1083
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W3114512714
- Cited by
- 32
- References
- 6
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 6 · 2023: 3 · 2022: 8 · 2021: 1 · 2020: 1
- FWCI
- 2.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Funders
- Fund for Scientific Research—Flanders (G.0876.11)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- androgen decline, aging, healthy men, testosterone, free testosterone, dihydrotestosterone, androstenedione, sex hormone-binding globulin, gonadotropins, luteinizing hormone, follicle-stimulating hormone, estradiol, body mass index, lifestyle factors, intercurrent illness, longitudinal change, young men
- MeSH terms
- Adult, Aging, Androgens, Health Status, Humans, Longitudinal Studies, Male, Middle Aged, Prospective Studies, Testosterone, Cohort Studies, Young Adult, Healthy Volunteers
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