Testosterone Replacement in Older Hypogonadal Men: A 12-Month Randomized Controlled Trial

Division of Geriatric Medicine, St. Louis University Health Sciences Center, Missouri 63104, USA.
Journal of Clinical Endocrinology & Metabolism (Impact Factor: 6.21). 06/1997; 82(6):1661-7. DOI: 10.1210/jcem.82.6.3988
Source: PubMed


A decline in testicular function is recognized as a common occurrence in older men. However data are sparse regarding the effects of hypogonadism on age-associated physical and cognitive declines. This study was undertaken to examine the year-long effects of testosterone administration in this patient population. Fifteen hypogonadal men (mean age 68 +/- 6 yr) were randomly assigned to receive a placebo, and 17 hypogonadal men (mean age 65 +/- 7 yr) were randomly assigned to receive testosterone. Hypogonadism was defined as a bioavailable testosterone <60 ng/dL. The men received injections of placebo or 200 mg testosterone cypionate biweekly for 12 months. The main outcomes measured included grip strength, hemoglobin, prostate-specific antigen, leptin, and memory. Testosterone improved bilateral grip strength (P < 0.05 by ANOVA) and increased hemoglobin (P < 0.001 by ANOVA). The men assigned to testosterone had greater decreases in leptin than those assigned to the control group (mean +/- SEM: -2.0 +/- 0.9 ng/dL vs. 0.8 +/- 0.7 ng/dL; P < 0.02). There were no significant changes in prostate-specific antigen or memory. Three subjects receiving placebo and seven subjects receiving testosterone withdrew from the study. Three of those seven withdrew because of an abnormal elevation in hematocrit. Testosterone supplementation improved strength, increased hemoglobin, and lowered leptin levels in older hypogonadal men. Testosterone may have a role in the treatment of frailty in males with hypogonadism; however, older men receiving testosterone must be carefully monitored because of its potential risks.

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    • "TRT is not recommended for patients with breast or prostate cancer, a palpable prostate nodule, induration , or a prostate-specific antigen (PSA) estimate higher than 4 ng/ml for most men or 3 ng/ml in high-risk men (e.g., African-American men, or men with a family history of prostate cancer or cardiac conditions; Bhasin et al., 2010; Saad, 2009; Twiddy, Leon, & Wasan, 2011; Wang et al., 2009). On the other hand, TRT is recommended for many men showing symptoms of androgen deficiency, with the objectives to maintain secondary sex characteristic, improve sexual function (Isidori, Giannetta, Gianfrilli, et al., 2005; Wang et al., 2000), increase a sense of well-being, bone mineral density and free-fat mass (Benito et al., 2005; Isidori, Giannetta, Greco, et al., 2005), improve lipid profiles and insulin resistance ( Jones et al., 2011; Marin, 1995), increase muscle strength (Sih et al., 1997), and treat depression (Amore et al., 2012). Although TRT can reverse symptoms associated with low T, there are disadvantages and side effects to its use. "
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    ABSTRACT: Reduced serum testosterone (T), or hypogonadism, is estimated to affect about 5 million American men, including both aging and young men. Low serum T has been linked to mood changes, worsening cognition, fatigue, depression, decreased lean body mass and bone mineral density, increased visceral fat, metabolic syndrome, decreased libido, and sexual dysfunction. Administering exogenous T, known as T-replacement therapy (TRT), reverses many of the symptoms of low T levels. However, this treatment can result in luteinizing hormone suppression which, in turn, can lead to reduced sperm numbers and infertility, making TRT inappropriate for men who wish to father children. Additionally, TRT may result in supraphysiologic T levels, skin irritation, and T transfer to others upon contact; and there may be increased risk of prostate cancer and cardiovascular disease, particularly in aging men. Therefore, the development of alternate therapies for treating hypogonadism would be highly desirable. To do so requires greater understanding of the series of steps leading to T formation and how they are regulated, and the identification of key steps that are amenable to pharmacological modulation so as to induce T production. We review herein our current understanding of mechanisms underlying the pharmacological induction of T formation in hypogonadal testis.
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    • "Due to the wider range of strength assessments available, most studies in older men have focused on this parameter, with varying improvements seen. Grip strength, the most widely used strength assessment, has been found to increase in some trials,62111125126 but not others.106113114115116117120 Similarly, some studies have reported improvements in lower limb strength,18114127128 while others have failed to show any effect of treatment.107109111113117 "
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    ABSTRACT: Androgens have potent anabolic effects on skeletal muscle and decline with age in parallel to losses in muscle mass and strength. This loss of muscle mass and function, known as sarcopenia, is the central event in development of frailty, the vulnerable health status that presages adverse outcomes and rapid functional decline in older adults. The potential role of falling androgen levels in the development of frailty and their utility as function promoting therapies in older men has therefore attracted considerable attention. This review summarizes current concepts and definitions in muscle ageing, sarcopenia and frailty, and evaluates recent developments in the study of androgens and frailty. Current evidence from observational and interventional studies strongly supports an effect of androgens on muscle mass in ageing men, but effects on muscle strength and particularly physical function have been less clear. Androgen treatment has been generally well-tolerated in studies of older men, but concerns remain over higher dose treatments and use in populations with high cardiovascular risk. The first trials of selective androgen receptor modulators (SARMs) suggest similar effects on muscle mass and function to traditional androgen therapies in older adults. Important future directions include the use of these agents in combination with exercise training to promote functional ability across different populations of older adults, as well as more focus on the relationships between concurrent changes in hormone levels, body composition and physical function in observational studies.
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    • "While RCTs consistently show that testosterone treatment reduces total body fat mass, effects of testosterone treatment on regional adipose tissue distribution have been less well-studied (Table 3).858687888990919293949596979899100101102103104 RCTs assessing effects of testosterone therapy on VAT have shown inconsistent results with one showing a reduction89 and others no change.809093 "
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    ABSTRACT: With increasing modernization and urbanization of Asia, much of the future focus of the obesity epidemic will be in the Asian region. Low testosterone levels are frequently encountered in obese men who do not otherwise have a recognizable hypothalamic-pituitary-testicular (HPT) axis pathology. Moderate obesity predominantly decreases total testosterone due to insulin resistance-associated reductions in sex hormone binding globulin. More severe obesity is additionally associated with reductions in free testosterone levels due to suppression of the HPT axis. Low testosterone by itself leads to increasing adiposity, creating a self-perpetuating cycle of metabolic complications. Obesity-associated hypotestosteronemia is a functional, non-permanent state, which can be reversible, but this requires substantial weight loss. While testosterone treatment can lead to moderate reductions in fat mass, obesity by itself, in the absence of symptomatic androgen defi ciency, is not an established indication for testosterone therapy. Testosterone therapy may lead to a worsening of untreated sleep apnea and compromise fertility. Whether testosterone therapy augments diet- and exercise-induced weight loss requires evaluation in adequately designed randomized controlled clinical trials.
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