Sarcopenia is characterized by loss of muscle strength and physical ability because of aging and/or chronic disease. Supplemental testosterone and other androgenic-anabolic steroids have been ...investigated as countermeasures to ameliorate the negative consequences of sarcopenia; these trials show dose-related improvements in lean body mass, maximal voluntary strength, stair climbing power, aerobic capacity, hemoglobin, and self-reported function, but less consistent improvements in walking speed. Randomized clinical trials with large cohorts and patient-important outcome measures are needed to determine long-term efficacy and safety of testosterone treatment in improving physical function and reducing physical disability, falls, and fractures in older adults with sarcopenia.
Context:
Testosterone's effects on muscle strength and physical function in older men have been inconsistent; its effects on muscle power and fatigability have not been studied.
Objective:
To ...determine the effects of testosterone administration for 3 years in older men on muscle strength, power, fatigability and physical function
Study Design:
In this double-blind, placebo-controlled, randomized trial, healthy men ≥60 years with total testosterone 100–400 ng/dL or free testosterone <50 pg/mL, were randomized to 7.5-g 1% testosterone or placebo gel daily for 3 years.
Outcomes:
Loaded and unloaded stair-climbing power, muscle strength, power, and fatigability in leg press and chest press exercises, and lean mass at baseline, 6, 18, and 36 months.
Results:
The groups were similar at baseline. Testosterone administration for 3 years was associated with significantly greater performance in unloaded and loaded stair-climbing power than placebo (mean (95% CI) estimated between-group difference 10.7W (-4.0,25.5; P=0.026) and 22.4W (4.6,40.3) P=0.027), respectively. Changes in chest press strength (estimated mean difference 16.3N (95% CI 5.5,27.1; P<0.001) and power (mean (95%CI) difference 22.5W (7.5,37.5); P<0.001), and leg press power were significantly greater in men randomized to testosterone than in those randomized to placebo. Lean body mass significantly increased more in the testosterone group.
Conclusion:
Compared to placebo, testosterone replacement in older men for 3 years was associated with modest but significantly greater improvements in stair-climbing power, muscle mass and power. Clinical meaningfulness of these treatment effects and their impact on disability in older adults with functional limitations remains to be studied.
Injuries from falls are major contributors to death and complications in older adults. In this pragmatic, cluster-randomized trial, a multifactorial intervention that was administered by nurses did ...not result in a significantly lower rate of first adjudicated serious fall injury than enhanced usual care.
IMPORTANCE: Testosterone use in older men is increasing, but its long-term effects on progression of atherosclerosis are unknown. OBJECTIVE: To determine the effect of testosterone administration on ...subclinical atherosclerosis progression in older men with low or low-normal testosterone levels. DESIGN, SETTING, AND PARTICIPANTS: Testosterone’s Effects on Atherosclerosis Progression in Aging Men (TEAAM) was a placebo-controlled, double-blind, parallel-group randomized trial involving 308 men 60 years or older with low or low-normal testosterone levels (100-400 ng/dL; free testosterone <50 pg/mL), recruited at 3 US centers. Recruitment took place between September 2004 and February 2009; the last participant completed the study in May 2012. INTERVENTIONS: One hundred fifty-six participants were randomized to receive 7.5 g of 1% testosterone and 152 were randomized to receive placebo gel packets daily for 3 years. The dose was adjusted to achieve testosterone levels between 500 and 900 ng/dL. MAIN OUTCOMES AND MEASURES: Coprimary outcomes included common carotid artery intima-media thickness and coronary artery calcium; secondary outcomes included sexual function and health–related quality of life. RESULTS: Baseline characteristics were similar between groups: patients were a mean age of 67.6 years; 42% had hypertension; 15%, diabetes; 15%, cardiovascular disease; and 27%, obesity. The rate of change in intima-media thickness was 0.010 mm/year in the placebo group and 0.012 mm/year in the testosterone group (mean difference adjusted for age and trial site, 0.0002 mm/year; 95% CI, −0.003 to 0.003, P = .89). The rate of change in the coronary artery calcium score was 41.4 Agatston units/year in the placebo group and 31.4 Agatston units/year in the testosterone group (adjusted mean difference, −10.8 Agatston units/year; 95% CI, −45.7 to 24.2; P = .54). Changes in intima-media thickness or calcium scores were not associated with change in testosterone levels among individuals assigned to receive testosterone. Sexual desire, erectile function, overall sexual function scores, partner intimacy, and health-related quality of life did not differ significantly between groups. Hematocrit and prostate-specific antigen levels increased more in testosterone group. CONCLUSIONS AND RELEVANCE: Among older men with low or low-normal testosterone levels, testosterone administration for 3 years vs placebo did not result in a significant difference in the rates of change in either common carotid artery intima-media thickness or coronary artery calcium nor did it improve overall sexual function or health-related quality of life. Because this trial was only powered to evaluate atherosclerosis progression, these findings should not be interpreted as establishing cardiovascular safety of testosterone use in older men. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00287586
Effects of Testosterone Treatment in Older Men Snyder, Peter J; Bhasin, Shalender; Cunningham, Glenn R ...
The New England journal of medicine,
02/2016, Letnik:
374, Številka:
7
Journal Article
Recenzirano
Odprti dostop
In this study, men 65 years of age or older with low serum testosterone and symptoms of hypoandrogenism received testosterone or placebo for a year. Testosterone had a moderate benefit in sexual ...function and some benefit in mood but no benefit in vitality or walking distance.
Testosterone concentrations in men decrease with increasing age.
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Many symptoms and conditions similar to those that are caused by low testosterone levels in men with pituitary or testicular disease become more common with increasing age. Such symptoms include decreases in mobility, sexual function, and energy. These parallels suggest that the lower testosterone levels in older men may contribute to these conditions.
Previous trials of testosterone treatment in men 65 years of age or older, however, have yielded equivocal results. Although testosterone treatment consistently increased muscle mass and decreased fat mass,
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effects on physical performance,
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sexual function, . . .
Physical performance measures, including cardiopulmonary exercise testing (CPXT), are widely used in geriatric practice and aging research. Theoretically, research participants and study personnel ...could get infected in the closed environment of the exercise laboratory by contact with respiratory droplets from an infected person, by breathing virus‐laden aerosols, or by touching fomites. Older adults are at increased risk of developing more severe disease and of dying from SARS‐CoV‐2 infection. This special article offers guidance—informed by a synthesis of scientific data and recommendations of the CDC and WHO—on procedures that can be implemented in exercise laboratories to minimize risk of SARS‐CoV‐2 and other respiratory infections. Most tests of physical function (e.g., gait speed, Short Physical Performance Battery) are not aerosol‐generating and are associated with only a small increase in minute ventilation; in contrast, CPXT markedly increases minute ventilation and is potentially aerosol‐generating. Researchers should evaluate the benefit‐to‐risk ratio of information gained from the laboratory assessment versus the risk of SARS‐CoV2 infection. Risk mitigation strategies described here fall into four categories: personal hygiene and the use of personal protective equipment; standardized screening; reconfiguration of laboratory space; and optimization of laboratory ventilation. The proposed safety measures are not intended to replace institutional policy, state, or federal guidelines; they may not apply to all settings and are expected to evolve as more definitive information becomes available. These practical measures to maximize protection against SARS‐CoV2 infection can help maximize participant and staff safety, reduce anxiety, and facilitate protocol adherence, and study integrity.
See related Letter by Tamara Konetzka et al. and Special article Cohen et al.
Aging and exercise have opposing effects on mnemonic discrimination task performance, which putatively taxes pattern separation mechanisms reliant on the dentate gyrus (DG) subfield of the ...hippocampus. In young adults, increasing cardiorespiratory fitness (CRF) has been shown to improve mnemonic discrimination task performance and increase left anterior DG/CA3 volume. It is unknown how these variables interact in cognitive aging, yet this knowledge is critical, given the established effects of aging on hippocampal plasticity. To investigate these relationships, 65 older adults (aged 55–85 years) completed a submaximal treadmill test to estimate CRF, a mnemonic discrimination task, and a high‐resolution MRI scan to determine hippocampal subfield volumes. Our older adult sample demonstrated the lowest task accuracy in the condition with the greatest stimuli similarity and left DG/CA3 body volume significantly predicted accuracy in this condition. Our results did not provide support for relationships between CRF and task accuracy or CRF and DG/CA3 volume as evidenced in studies of young adults. Instead, CRF predicted bilateral subiculum volume in older adult women, not men. Altogether, these findings provide further support for a role of the DG in behavioral pattern separation in humans and suggest that CRF may have differential effects on hippocampal subfield integrity in older adult men and women. ClinicalTrials.gov identifiers: (a) Neuroimaging Study of Exercise and Memory Function, NCT02057354; (b) The Entorhinal Cortex and Aerobic Exercise in Aging, NCT02775760; (c) Physical Activity and Cognition Study, NCT02773121.
Sixty‐five older adults (aged 55–85 years) completed a submaximal treadmill test to estimate cardiorespiratory fitness, a mnemonic discrimination task, and a high‐resolution MRI scan to determine hippocampal subfield volumes. Left dentate gyrus/CA3 body volume predicted accuracy in the task condition with greatest stimuli similarity, and cardiorespiratory fitness predicted bilateral subiculum volume in older adult women, not men. Altogether, these findings provide further support for a role of the dentate gyrus in behavioral pattern separation in humans and suggest that cardiorespiratory fitness may have differential effects on hippocampal subfield integrity in older adult men and women.
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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