Testosterone after 50 — are men quietly losing strength?

Aim of the study: To review published, randomized trials examining the effect of androgen treatment on muscle strength in older men.

Results: The studies included 38 statistical comparisons. The mean g-index (g(i)) adjusted for sample size was 0.53 (95% confidence interval (CI) = 0.21-0.86). Subanalyses revealed larger effects for measures of lower extremity muscle strength (g(i) = 0.63, 95% CI = 0.03-1.28) than for upper extremity muscle strength (g(i) = 0.47, 95% CI = 0.12-0.84). A larger mean g-index was found for injected (g(i) = 0.95, 95% CI = 0.33-1.58) than topical (g(i) = 0.26, 95% CI = 0.08-0.42) or oral (g(i) = -0.21, 95% CI = -1.40-1.02) administration of testosterone/DHT. Effect sizes were related to study characteristics such as subject attrition and design-quality ratings. Sensitivity analyses revealed that the elimination of one study reduced the mean g-index from 0.53 to 0.23. The results suggest that testosterone/DHT therapy produced a moderate increase in muscle strength in men participating in 11 randomized trials. One study influenced the mean effect size.

Aim of the study: Testosterone increases muscle mass and decreases fat mass by mechanism including androgen receptors. Testosterone induces skeletal muscle fibre hypertrophy and increases the number of satellite cells.

Results: Testosterone induces skeletal muscle fibre hypertrophy and increases the number of satellite cells. It also promotes the differentiation of mesenchymal multipotent cells into myogenic lineage and inhibits their differentiation into the adipogenic lineage. Meta-analyses of clinical trials provide evidence that testosterone treatment, depending on dose, increases the skeletal muscle mass and to some degree also muscle strength. The most frequent adverse effects of testosterone treatment in aging men are an increase of hematocrit and increased risk of prostate events.

Aim of the study: Testosterone treatment increases muscle mass, maximal voluntary muscle strength, aerobic capacity, and some measures of physical function. Activational and epigenetic mechanisms by which androgens improve muscle mass and physical performance and how to apply these anabolic effects to treat functional limitations associated with aging and disease remain incompletely understood.

Results: Testosterone increases blood flow by nongenomic mechanisms involving nitric oxide production and calcium and potassium channels in vascular smooth muscle. The conversion of testosterone to 5α-DHT is not required for mediating its anabolic effects. Mechanisms of testosterone's sexually dimorphic epigenetic and tissue-specific activational effects and roles of α-keto reductase and steroid 5α-reductase and 1-carbon and polyamine metabolism in testosterone's actions remain poorly understood. Strategies to translate testosterone-induced muscle mass and strength gains into patient-important improvements in functional performance and health outcomes are needed to enable its clinical applications to treat functional limitations associated with aging and disease.

Aim of the study: Late-onset hypogonadism is a clinical and biological syndrome associated with advancing age and characterized by typical symptoms and a deficiency in serum testosterone levels. It is a common condition but often underdiagnosed and undertreated.

Results: It is a common condition but often underdiagnosed and undertreated. The main symptoms of hypogonadism are reduced libido/erectile dysfunction, reduced muscle mass and strength, increased adiposity, osteoporosis/low bone mass, depressed mood, and fatigue. Testosterone replacement therapy is only warranted in the presence of both clinical symptoms suggesting hormone deficiency and decreased hormone levels. It improves libido and sexual function, bone density, muscle mass, body composition, mood, erythropoiesis, cognition, quality of life, and cardiovascular disease.

Aim of the study: Sarcopenia refers to the gradual decline in muscle mass and quality noted with advancing age. There is growing evidence linking sarcopenia to functional disability, falls, decreased bone density, glucose intolerance, and decreased heat and cold tolerance in older adults.

Results: Factors implicated in the etiology of sarcopenia include decreased physical activity, malnutrition, increased cytokine activity, oxidative stress, and abnormalities in growth hormone and sex steroid axes. At present, progressive resistance training is the best intervention shown to slow down or reverse this condition. Preliminary studies show that the utilization of several trophic factors, notably testosterone and DHEA, may have a salutary effect on muscle mass and/or strength in older adults. More research is needed, however, before drawing definite conclusion as to the clinical utility of these substances in the management of sarcopenia.

Aim of the study: Testosterone declines by 0.4%-2% annually after the age of 30 and is potentially linked with muscle mass and strength. This study examined how testosterone levels are associated with handgrip strength (HGS) and appendicular lean soft tissue index (ALSTI) in men aged 40-49 and 50-59 years.

Results: In 1001 men aged 40-59 years, higher total testosterone levels were positively associated with higher HGS, with stronger links in the 50- to 59-year-olds (b = 1.35, 95% confidence interval [CI] 0.08-2.62, p < 0.01). In this group, higher testosterone was linked to increased odds ratio (OR) of having higher HGS (OR: 1.73, 95% CI 1.17-2.55, p < 0.01). Per European Association of Urology guidelines, men with testosterone levels above deficiency (≥ 230 ng/dL) had higher odds of increased ALSTI versus those with deficiency (OR: 3.31, 95% CI 1.42-7.74, p < 0.01), while normal testosterone (> 346 ng/dL) versus deficiency showed a significant albeit weaker association (OR: 2.48, 95% CI 1.35-4.57, p < 0.01).