Androgens and Selective Androgen Receptor Modulators to Treat Functional Limitations Associated With Aging and Chronic Disease.
Shalender BhasinVenkatesh KrishnanThomas W StorerMitchell SteinerAdrian S DobsPublished in: The journals of gerontology. Series A, Biological sciences and medical sciences (2023)
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.
Keyphrases
- replacement therapy
- bone mineral density
- late onset
- middle aged
- depressive symptoms
- smoking cessation
- weight loss
- hiv infected
- physical activity
- high intensity
- mental health
- small molecule
- prostate cancer
- body composition
- cardiovascular disease
- postmenopausal women
- transcription factor
- gene expression
- adipose tissue
- skeletal muscle
- mesenchymal stem cells
- early onset
- bone marrow
- antiretroviral therapy
- roux en y gastric bypass
- cell therapy
- endothelial cells
- community dwelling
- iron deficiency
- heat shock protein
- human immunodeficiency virus
- glycemic control
- urinary tract infection
- stress induced