Effects of Testosterone Supplementation on Skeletal Muscle Fiber Hypertrophy and Satellite Cells in Community-Dwelling Older Men
Abstract
Objective: In this study, we determined the effects of graded doses of testosterone on muscle fiber cross-sectional area (CSA) and satellite cell number and replication in older men. Participants: Healthy men, 60–75 yr old, received a long-acting GnRH agonist to suppress endogenous testosterone production and 25, 50, 125, 300, or 600 mg testosterone enanthate im weekly for 20 wk. Methods: Immunohistochemistry, light and confocal microscopy, and electron microscopy were used to perform fiber typing and quantitate myonuclear and satellite cell number in vastus lateralis biopsies, obtained before and after 20 wk of treatment. Results: Testosterone administration in older men was associated with dose-dependent increases in CSA of both types I and II fibers. Satellite cell number increased dose dependently at the three highest doses (3% at baseline vs. 6.2, 9.2, and 13.0% at 125, 300, and 600 mg doses, P < 0.05). Testosterone administration was associated with an increase in the number of proliferating cell nuclear antigen+ satellite cells (1.8% at baseline vs. 3.9, 7.5, and 13% at 125, 300, and 600 mg doses, P < 0.005). The expression of activated Notch, examined only in the 300-mg group (baseline, 2.3 vs. 9.0% after treatment, P < 0.005), increased in satellite cells after testosterone treatment. The expression of myogenin (baseline, 6.2 vs. 20.7% after treatment, P < 0.005), examined only in the 300-mg group, increased significantly in muscle fiber nuclei after testosterone treatment, but Numb expression did not change. Conclusions: Older men respond to graded doses of testosterone with a dose-dependent increase in muscle fiber CSA and satellite cell number. Testosterone-induced skeletal muscle hypertrophy in older men is associated with increased satellite cell replication and activation.
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Muscle cells have multiple nuclei and their number increases with muscle hypertrophy.
“Indeed, muscle cells have multiple nuclei and their number increases with muscle hypertrophy [81, 82].”
From Integrating Transwomen and Female Athletes with Differences of Sex Development (DSD) into Elite Competition: The FIMS 2021 Consensus Statement (2021) · cites this paper as [82]
Testosterone has been shown to increase the myonuclear number in men in a dose-dependent manner, alongside muscle fibre CSA being well correlated with the myonuclear number.
“Testosterone has been shown to increase the myonuclear number in men in a dose-dependent manner alongside muscle fibre CSA being well correlated with the myonuclear number [81, 82].”
From Integrating Transwomen and Female Athletes with Differences of Sex Development (DSD) into Elite Competition: The FIMS 2021 Consensus Statement (2021) · cites this paper as [82]
This response may be through a testosterone-induced increase in the number of satellite cells and thus hypertrophy.
“This response may be through a testosterone-induced increase in the number of satellite cells and thus hypertrophy (82, 83).”
From Sex-Based Differences in Skeletal Muscle Kinetics and Fiber-Type Composition (2015) · cites this paper as [83]
Testosterone is a highly studied androgen that is associated with an increase in muscle mass.
“Testosterone is a highly studied androgen that is associated with an increase in muscle mass (66, 83).”
From Sex-Based Differences in Skeletal Muscle Kinetics and Fiber-Type Composition (2015) · cites this paper as [83]
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- Authors
- Sinha-Hikim, I., Cornford, M., Gaytan, H., Lee, M. L., & Bhasin, S.
- Affiliations
- Division of Endocrinology (I.S.-H., H.G., M.L.L., S.B.), Los Angeles, California 90059
- University of California, Los Angeles (US)
- Boston University (US)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2006-08-01
- Volume
- 91
- Issue
- 8
- Pages
- 3024-3033
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2098072804
- Cited by
- 318
- References
- 59
- Citations by year
- 2026: 11 · 2025: 18 · 2024: 13 · 2023: 13 · 2022: 33 · 2021: 13 · 2020: 20 · 2019: 13 · 2018: 12 · 2017: 16 · 2016: 15 · 2015: 22 · 2014: 12 · 2013: 16 · 2012: 21
- FWCI
- 7.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (1R01 AG-14369-01, R01AG014369)
- National Institute of General Medical Sciences (S06GM068510)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK049296, 2R01 DK49296-08, R01DK070534, R01DK059627, 1R01 DK 59627)
- National Center for Research Resources (RR011145, P20RR011145)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- testosterone supplementation, testosterone enanthate, skeletal muscle hypertrophy, satellite cells, muscle fiber cross-sectional area, older men, dose-response relationship, Notch signaling, myogenin, Numb, GnRH agonist, androgen deprivation therapy, vastus lateralis, community-dwelling older men
- MeSH terms
- Aged, Aging, Biopsy, Cell Count, Cell Division, Dose-Response Relationship, Drug, Humans, Hypertrophy, Immunohistochemistry, Male, Microscopy, Electron, Middle Aged, Testosterone, Myogenin, Muscle, Skeletal, Muscle Fibers, Skeletal, Microscopy, Confocal, Proliferating Cell Nuclear Antigen, Satellite Cells, Skeletal Muscle, Receptors, Notch
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