Effect of testosterone supplementation on sarcopenic components in middle-aged and elderly men: A systematic review and meta-analysis (original) (raw)
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Testosterone Supplementation for Aging-Associated Sarcopenia
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2003
Aging of humans is associated with a loss of muscle mass and function, and an increase in fat mass. Epidemiologic studies have demonstrated a correlation between bioavailable testosterone concentrations and fat-free mass and muscle strength. Testosterone replacement in older men with low testosterone levels increases fat-free mass and muscle strength, and decreases fat mass. However, we do not know whether testosterone replacement improves physical function and other health-related outcomes, or reduces the risk of disability, falls, or fractures in older men with low testosterone levels. The long-term risks and benefits of testosterone supplementation in older men are not known.
Does testosterone supplementation improve health and function in elderly men?
Nature Clinical Practice Endocrinology & Metabolism, 2008
BACKGROUND-Low serum testosterone levels are associated with age-related changes in physical and cognitive function. Replacement therapy could, therefore, help alleviate symptoms of aging. OBJECTIVE-To determine whether 6 months' supplementation with testosterone improved signs of aging in a population of elderly men with low-normal testosterone levels. DESIGN AND INTERVENTION-This was a double-blind, randomized, placebo-controlled trial of testosterone supplementation conducted at a single center in the Netherlands between January 2004 and April 2005. Participants were recruited by direct mailing. Inclusion criteria included age 60-80 years and a serum testosterone level below the 50 th percentile of the study population-based testosterone distribution (cutoff 13.7 nmol/l). Exclusion criteria included myocardial infarction, heart failure, malignancy, serious liver or renal disease, epilepsy, diabetes mellitus, elevated prostatespecific antigen, use of corticosteroids, and use of testosterone esters within the previous 60 days. Eligible participants were randomly allocated to receive either 80 mg oral testosterone undecenoate or placebo twice daily for 6 months. Functional ability was measured with the timed 'get up and go' test, the Stanford Health Assessment Questionnaire, an isometric handgrip strength test, and a maximal voluntary isometric leg strength test. Cognitive parameters assessed included verbal episodic memory, cognitive and perceptual speed, attention and mental flexibility, extrapersonal spatial perception, and visuospatial performance. BMD and total body composition were measured by dual-energy X-ray absorptiometry. Quality of life was assessed with the Short-Form 36 Health Survey (SF-36) and the Questions on Life Satisfaction Modules questionnaires. OUTCOME MEASURES-The main outcome measures were functional mobility, cognitive function, BMD, anthropometry, body composition, biochemical measures, quality of life, and safety parameters. RESULTS-The study enrolled 113 men in the testosterone group (mean age 67.1 years; mean serum testosterone level 11.0 nmol/l) and 110 men in the placebo group (mean age 67.4 years; mean serum testosterone level 10.4 nmol/l). Treatment adherence was >90% for both groups. When compared with the placebo group, treatment with testosterone was associated with increased lean body mass, decreased body fat mass and decreased body fat percentage (P <0.001 for all comparisons); however, no significant changes in parameters of functional ability were observed in either group. Total cholesterol and HDL cholesterol decreased in the testosterone group, whereas insulin and glucose concentrations and measures of insulin resistance increased in the placebo group.
Testosterone Supplementation Therapy for Older Men: Potential Benefits and Risks
Journal of the American Geriatrics Society, 2000
Serum testosterone levels decline gradually and progressively with aging in men. Many manifestations associated with aging in men, including muscle atrophy and weakness, osteoporosis, reduced sexual functioning, and increased fat mass, are similar to changes associated with testosterone deficiency in young men. These similarities suggest that testosterone supplementation may prevent or reverse the effects of aging. A MEDLINE search was performed to identify studies of testosterone supplementation therapy in older men. A structured, qualitative review was performed of placebo-controlled trials that included men aged 60 and older and evaluated one or more physical, cognitive, affective, functional, or quality-of-life outcomes. Studies focusing on patients with severe systemic diseases and hormone deficiencies related to specific diseases were excluded.
CLINICAL …, 2005
Objectives Ageing in men is associated with a gradual decline in serum testosterone levels and a concomitant loss of muscle mass, accumulation of central adiposity, impaired mobility and increased risk of bone fractures. Whether androgen treatment might be beneficial in these subjects is still under debate. We have carried out a systematic review of randomized controlled trials (RCTs) evaluating the effects of testosterone (T) administration to middle-aged and ageing men on body composition, muscle strength, bone density, markers of bone metabolism and serum lipid profile. Data source A comprehensive search of all published randomized clinical trials was performed using the MEDLINE, Cochrane Library, EMBASE and Current Contents databases. Review methods Guided by prespecified criteria, software-assisted data abstraction and quality assessed by two independent reviewers, 29 RCTs were found to be eligible. For each investigated variable, we reported the results of pooled estimates of testosterone treatment using the random effect model of meta-analysis. Heterogeneity, reproducibility and consistency of the findings across studies were explored using sensitivity and meta-regression analysis. Results Overall, 1083 subjects were evaluated, 625 randomized to T, 427 to placebo and 31 to observation (control group). Weighted mean age was 64·5 years (range 49·9 -77·6) and mean serum testosterone was 10·9 nmol / l (range 7·8 -19). Testosterone treatment produced: (i) a reduction of 1·6 kg (CI: 2·5 -0·6) of total body fat, corresponding to − 6·2% (CI: 9·2 -3·3) variation of initial body fat, (ii) an increase in fat free mass of 1·6 kg (CI: 0·6 -2·6), corresponding to +2·7% (CI: 1·1 -4·4) increase over baseline and (iii) no change in body weight. The effects of T on muscle strength were heterogeneous, showing a tendency towards improvement only at the leg/knee extension and handgrip of the dominant arm (pooled effect size = 0·3 standard mean difference (SMD), CI: − 0·0 to 0·6). Testosterone improved bone mineral density (BMD) at the lumbar spine by +3·7% (CI: 1·0 -6·4%) compared to placebo, but not at the femoral neck, and produced a consistent reduction in bone resorption markers (pooled effect size = − 0·6 SMD, CI: − 1·0 to − 0·2). Testosterone also reduced total cholesterol by 0·23 mmol / l (CI: − 0·37 to − 0·10), especially in men with lower baseline T concentrations, with no change in low density lipoprotein (LDL)-cholesterol. A significant reduction of high density lipoprotein (HDL)-cholesterol was found only in studies with higher mean T-values at baseline ( − 0·085 mmol/l, CI: − 0·017 to − 0·003). Sensitivity and meta-regression analysis revealed that the dose / type of T used, in particular the possibility of aromatization, explained the heterogeneity in findings observed on bone density and HDL-cholesterol among studies. Conclusion The present analysis provides an estimate of the average treatment effects of testosterone therapy in middle-aged men. Our findings are sufficiently strong to justify further interventional studies focused on alternative targets of androgenic treatment carrying more stringent clinical implications, in particular the cardiovascular, metabolic and neurological systems. studies linking androgen decline with the frailty of old age, and the ADAM syndrome has not been universally accepted as a true clinical entity. An alternative approach would be to evaluate whether increasing serum testosterone concentration of ageing men to the level found in young adults improves or reverses these symptoms. Despite much recent interest by physicians, the media and the general population, and the publication of several studies examining the effects of testosterone treatment on body composition, 7-25 strength, bone density and metabolism and lipid
Testosterone supplementation in older men: a rational idea whose time has not yet come
Journal of andrology
Forty years after the introduction of estrogens, the debate over the risks and benefits of estrogen replacement therapy in postmenopausal women is still not entirely settled. In contrast, the issues of testosterone replacement in older men are just beginning to be addressed. There is agreement that total, free, and bioavailable testosterone (ie, not bound by sex hormone-binding globulin) levels decline progressively with advancing age (
The Role of Testosterone in the Elderly: What Do We Know?
International Journal of Molecular Sciences, 2022
Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different ...
Testosterone for the aging male; current evidence and recommended practice
Clinical Interventions in Aging, 2008
An international consensus document was recently published and provides guidance on the diagnosis, treatment and monitoring of late-onset hypogonadism (LOH) in men. The diagnosis of LOH requires biochemical and clinical components. Controversy in defi ning the clinical syndrome continues due to the high prevalence of hypogonadal symptoms in the aging male population and the non-specifi c nature of these symptoms. Further controversy surrounds setting a lower limit of normal testosterone, the limitations of the commonly available total testosterone result in assessing some patients and the unavailability of reliable measures of bioavailable or free testosterone for general clinical use. As with any clinical intervention testosterone treatment should be judged on a balance of risk versus benefi t. The traditional benefi ts of testosterone on sexual function, mood, strength and quality of life remain the primary goals of treatment but possible benefi cial effects on other parameters such as bone density, obesity, insulin resistance and angina are emerging and will be reviewed. Potential concerns regarding the effects of testosterone on prostate disease, aggression and polycythaemia will also be addressed. The options available for treatment have increased in recent years with the availability of a number of testosterone preparations which can reliably produce physiological serum concentrations.