Androgens and Selective Androgen Receptor Modulators to Treat Functional Limitations Associated With Aging and Chronic Disease
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Testosterone, many steroidal androgens, and nonsteroidal ligands that bind to androgen receptor and exert tissue-specific transcriptional activity (selective androgen receptor modulators [SARMs]) are being developed as function-promoting therapies to treat functional limitations associated with aging and chronic diseases. This narrative review describes preclinical studies, mechanisms, and randomized trials of testosterone, other androgens, and nonsteroidal SARMs. Sex differences in muscle mass and strength and empiric use of anabolic steroids by athletes to increase muscularity and athletic performance provide supportive evidence of testosterone's anabolic effects. In randomized trials, testosterone treatment increases lean body mass, muscle strength, leg power, aerobic capacity, and self-reported mobility. These anabolic effects have been reported in healthy men, hypogonadal men, older men with mobility limitation and chronic diseases, menopausal women, and HIV-infected women with weight loss. Testosterone has not consistently improved walking speed. Testosterone treatment increases volumetric and areal bone mineral density, and estimated bone strength; improves sexual desire, erectile function, and sexual activity; modestly improves depressive symptoms; and corrects unexplained anemia in older men with low testosterone levels. Prior studies have not been of sufficient size or duration to determine testosterone's cardiovascular and prostate safety. The efficacy of testosterone in reducing physical limitations, fractures, falls, progression to diabetes, and correcting late-onset persistent depressive disorder remains to be established. Strategies to translate androgen-induced muscle mass and strength gains into functional improvements are needed. Future studies should evaluate the efficacy of combined administration of testosterone (or a SARM) plus multidimensional functional exercise to induce neuromuscular adaptations required for meaningful functional improvements.
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SARMs indirectly affect non-muscle androgen receptor pathways mediated by muscle fibroblasts and, in some but not all studies, have been shown to increase muscle mass and physical function.
“SARMs indirectly affect non-muscle androgen receptor pathways mediated by muscle fibroblasts and, in some but not all studies have been shown to increase muscle mass and physical function216.”
From Sarcopenic obesity in older adults: a clinical overview (2024) · cites this paper as [216]
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- Authors
- Bhasin, S., Krishnan, V., Storer, T. W., Steiner, M., & Dobs, A. S.
- Affiliations
- Brigham and Women's Hospital (US)
- Eli Lilly (United States) (US)
- Veru Inc. (United States) (US)
- Johns Hopkins University (US)
- Corresponding author
- Bhasin, Shalender
- Venue
- The Journals of Gerontology: Series A
- Publisher
- Oxford University Press (OUP)
- Published
- 2023-06-01
- Volume
- 78
- Issue
- Supplement_1
- Pages
- 25-31
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- PMC
- PMC10272983
- OpenAlex
- W4380869393
- Cited by
- 36
- References
- 68
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 9 · 2023: 2
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journals of Gerontology Series A (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (R01NR014502, 5R01AG060539)
- Boston Claude D. Pepper Older Americans Independence Center (P30 AG31679)
- National Institute on Aging
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Keywords
- testosterone, selective androgen receptor modulators, androgens, aging, functional limitations, muscle strength, lean body mass, bone mineral density, hypogonadism, menopause, mobility (physical function), anabolic effects, sex differences, exercise training, chronic disease
- MeSH terms
- Aged, Aging, Androgen Antagonists, Androgens, Chronic Disease, Female, Humans, Male, Receptors, Androgen, Testosterone, Anabolic Agents
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