Testosterone supplementation therapy for older men : potential benefits and risks / David A. Gruenewald, Alvin M. Matsumoto. - (Journal of the American Geriatrics Society 51 (2003) 1 (January); p. 101-115)

• PMID: 12534854
• DOI: 10.1034/j.1601-5215.2002.51018.x

Abstract

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.

In healthy older men with low-normal to mildly decreased testosterone levels, testosterone supplementation increased lean body mass and decreased fat mass. Upper and lower body strength, functional performance, sexual functioning, and mood were improved or unchanged with testosterone replacement. Variable effects on cognitive function were reported, with improvements in some cognitive domains (e.g., spatial, working, and verbal memory). Testosterone supplementation improved exercise-induced coronary ischemia in men with coronary heart disease, whereas angina pectoris was improved or unchanged. In a few studies, men with low testosterone levels were more likely to experience improvements in lumbar bone mineral density, self-perceived functional status, libido, erectile function, and exercise-induced coronary ischemia with testosterone replacement than men with less marked testosterone deficiency. No major unfavorable effects on lipids were reported, but hematocrit and prostate specific antigen levels often increased.

Based on these results, testosterone supplementation cannot be recommended at this time for older men with normal or low-normal testosterone levels and no clinical manifestations of hypogonadism. However, testosterone replacement may be warranted in older men with markedly decreased testosterone levels, regardless of symptoms, and in men with mildly decreased testosterone levels and symptoms or signs suggesting hypogonadism. The long-term safety and efficacy of testosterone supplementation remain uncertain. Establishment of evidence-based indications will depend on further demonstrations of favorable clinical outcomes and symptomatic, functional, and quality-of-life benefits in carefully performed, long-term, randomized, placebo-controlled clinical trials.

Treatment with oxandrolone and the durability of effects in older men / E. Todd Schroeder, Ling Zheng, Kevin E. Yarasheski, Dajun Qian, Yolanda Stewart, Carla Flores, Carmen Martinez, Michael Terk, Fred R. Sattler. - (Journal of Applied Physiology 96 (2004) 3 (March); p. 1055-1062)

• PMID: 14578370
• DOI: 10.1152/japplphysiol.00808.2003

Abstract

We investigated the effects of the anabolic androgen, oxandrolone, on lean body mass (LBM), muscle size, fat, and maximum voluntary muscle strength, and we determined the durability of effects after treatment was stopped. Thirty-two healthy 60- to 87-yr-old men were randomized to receive 20 mg oxandrolone/day (n = 20) or placebo (n = 12) for 12 wk. Body composition [dual-energy X-ray absorptiometry (DEXA), magnetic resonance imaging, and (2)H(2)O dilution] and muscle strength [1 repetition maximum (1 RM)] were evaluated at baseline and after 12 wk of treatment; body composition (DEXA) and 1-RM strength were then assessed 12 wk after treatment was discontinued (week 24). At week 12, oxandrolone increased LBM by 3.0 +/- 1.5 kg (P < 0.001), total body water by 2.9 +/- 3.7 kg (P = 0.002), and proximal thigh muscle area by 12.4 +/- 8.4 cm(2) (P < 0.001); these increases were greater (P < 0.003) than in the placebo group. Oxandrolone increased 1-RM strength for leg press by 6.7 +/- 6.4% (P < 0.001), leg flexion by 7.0 +/- 7.8% (P < 0.001), chest press by 9.3 +/- 6.7% (P < 0.001), and latissimus pull-down exercises by 5.1 +/- 9.1% (P = 0.02); these increases were greater than placebo. Oxandrolone reduced total (-1.9 +/- 1.0 kg) and trunk fat (-1.3 +/- 0.6 kg; P < 0.001), and these decreases were greater (P < 0.001) than placebo. Twelve weeks after oxandrolone was discontinued (week 24), the increments in LBM and muscle strength were no longer different from baseline (P > 0.15). However, the decreases in total and trunk fat were sustained (-1.5 +/- 1.8, P = 0.001 and -1.0 +/- 1.1 kg, P < 0.001, respectively). Thus oxandrolone induced short-term improvements in LBM, muscle area, and strength, while reducing whole body and trunk adiposity. Anabolic improvements were lost 12 wk after discontinuing oxandrolone, whereas improvements in fat mass were largely sustained.

Nandrolone decanoate administration does not attenuate muscle atrophy during a short period of disuse / Astrid M.H. Horstman, Evelien M.P. Backx, Joey S.J. Smeets, Gabriel N. Marzuca-Nassr, Janneau van Kranenburg, Douwe de Boer, John Dolmans, Tim Snijders, Lex B. Verdijk, Lisette C.P.G.M. de Groot, Luc J.C. van Loon. - (PLos One 14 (2019) 1 (28 January); p. 1-15)

• PMID: 30689637
• PMCID: PMC6349315
• DOI: 10.1371/journal.pone.0210823

Abstract

Background: A few days of bed rest or immobilization following injury, disease, or surgery can lead to considerable loss of skeletal muscle mass and strength. It has been speculated that such short, successive periods of muscle disuse may be largely responsible for the age-related loss of muscle mass throughout the lifespan.

Objective: To assess whether a single intramuscular injection of nandrolone decanoate prior to immobilization can attenuate the loss of muscle mass and strength in vivo in humans.

Design, setting and participants: Thirty healthy (22 ± 1 years) men were subjected to 7 days of one-legged knee immobilization by means of a full leg cast with (NAD, n = 15) or without (CON, n = 15) prior intramuscular nandrolone decanoate injection (200 mg).

Measures: Before and immediately after immobilization, quadriceps muscle cross-sectional area (CSA) (by means of single-slice computed tomography (CT) scans of the upper leg) and one-legged knee extension strength (one-repetition maximum [1-RM]) were assessed for both legs. Furthermore, muscle biopsies from the immobilized leg were taken before and after immobilization to assess type I and type II muscle fiber cross-sectional area.

Results: Quadriceps muscle CSA decreased during immobilization in both CON and NAD (-6 ± 1% and -6 ± 1%, respectively; main effect of time P<0.01), with no differences between the groups (time × treatment interaction, P = 0.59). Leg muscle strength declined following immobilization (-6 ± 2% in CON and -7 ± 3% in NAD; main effect of time, P<0.05), with no differences between groups (time × treatment interaction, P = 0.55).

Conclusions: This is the first study to report that nandrolone decanoate administration does not preserve skeletal muscle mass and strength during a short period of leg immobilization in vivo in humans.

The benefits and risks of testosterone replacement therapy: a review / Nazem Bassil, Saad Alkaade, John E. Morley. - (Therapeutics and clinical risk management 5 (2009) 3 (11 June); p. 427-448)

• PMID: 19707253
• PMCID: PMC2701485
• DOI: 10.2147/tcrm.s3025

Abstract

Increased longevity and population aging will increase the number of men with late onset hypogonadism. It is a common condition, but often underdiagnosed and undertreated. The indication of testosterone-replacement therapy (TRT) treatment requires the presence of low testosterone level, and symptoms and signs of hypogonadism. Although controversy remains regarding indications for testosterone supplementation in aging men due to lack of large-scale, long-term studies assessing the benefits and risks of testosterone-replacement therapy in men, reports indicate that TRT may produce a wide range of benefits for men with hypogonadism that include improvement in libido and sexual function, bone density, muscle mass, body composition, mood, erythropoiesis, cognition, quality of life and cardiovascular disease. Perhaps the most controversial area is the issue of risk, especially possible stimulation of prostate cancer by testosterone, even though no evidence to support this risk exists. Other possible risks include worsening symptoms of benign prostatic hypertrophy, liver toxicity, hyperviscosity, erythrocytosis, worsening untreated sleep apnea or severe heart failure. Despite this controversy, testosterone supplementation in the United States has increased substantially over the past several years. The physician should discuss with the patient the potential benefits and risks of TRT. The purpose of this review is to discuss what is known and not known regarding the benefits and risks of TRT.

Testosterone threshold levels and lean tissue mass targets needed to enhance skeletal muscle strength and function: the HORMA trial / Fred Sattler, Shalender Bhasin, Jiaxiu He, Chih-Ping Chou, Carmen Castaneda-Sceppa, Kevin Yarasheski, Ellen Binder, E. Todd Schroeder, Miwa Kawakubo, Anqi Zhang, Ronenn Roubenoff, Stanley Azen. - (Journals of Gerontology: Series A 66A (2011) 1 (January); p. 122-129)

• PMID: 21059836
• PMCID: PMC3032430
• DOI: 10.1093/gerona/glq183

Abstract

Background: In the HORMA (Hormonal Regulators of Muscle and Metabolism in Aging) Trial, supplemental testosterone and recombinant human growth hormone (rhGH) enhanced lean body mass, appendicular skeletal muscle mass, muscle performance, and physical function, but there was substantial interindividual variability in outcomes.

Methods: One hundred and twelve men aged 65-90 years received testosterone gel (5 g/d vs 10 g/d via Leydig cell clamp) and rhGH (0 vs 3 vs 5 μg/kg/d) in a double-masked 2 × 3 factorial design for 16 weeks. Outcomes included lean tissue mass by dual energy x-ray absorptiometry, one-repetition maximum strength, Margaria stair power, and activity questionnaires. We used pathway analysis to determine the relationship between changes in hormone levels, muscle mass, strength, and function.

Results: Increases in total testosterone of 1046 ng/dL (95% confidence interval = 1040-1051) and 898 ng/dL (95% confidence interval = 892-904) were necessary to achieve median increases in lean body mass of 1.5 kg and appendicular skeletal muscle mass of 0.8 kg, respectively, which were required to significantly enhance one-repetition maximum strength (≥ 30%). Co-treatment with rhGH lowered the testosterone levels (quantified using liquid chromatography-tandem mass spectrometry) necessary to reach these lean mass thresholds. Changes in one-repetition maximum strength were associated with increases in stair climbing power (r = .26, p = .01). Pathway analysis supported the model that changes in testosterone and insulin-like growth factor 1 levels are related to changes in lean body mass needed to enhance muscle performance and physical function. Testosterone's effects on physical activity were mediated through a different pathway because testosterone directly affected Physical Activity Score of the Elderly.

Conclusions: To enhance muscle strength and physical function, threshold improvements in lean body mass and appendicular skeletal muscle mass are necessary and these can be achieved by targeting changes in testosterone levels. rhGH augments the effects of testosterone. To maximize functional improvements, the doses of anabolic hormones should be titrated to achieve target blood levels.

The aging population - is there a role for endocrine interventions? / Ralf Nass, Gudmundur Johannsson, Jens S. Christiansen, John J. Kopchick, Michael O. Thorner. - (Growth Hormone & IGF Research 19 (2009) 2 (April); p. 89-100)

• PMID: 18977675
• DOI: 10.1016/j.ghir.2008.09.002

Abstract

The expected increase in the aging population will have a significant impact on society and the health system in the coming years and decades. Enhancing healthspan, "healthy aging", and thus extending the time that the elderly are able to function independently is a significant task and is imperative. Age-dependent changes such as weight loss, sarcopenia and anorexia, which contribute to the development of frailty in the elderly are discussed. The role of the age-dependent decrease in growth hormone secretion in this process and the potential benefits and risks of hormonal interventions to delay, prevent or reverse frailty in the elderly are reviewed.

Diagnosis and Management of Anabolic Androgenic Steroid Use / Bradley D. Anawalt. -  (Journal of Clinical Endocrinology & Metabolism 104 (2019) 7 (July); p. 2490-2500)

• PMID: 30753550
• PMCID: PMC6517163
• DOI: 10.1210/jc.2018-01882

Abstract

Context: The lifetime prevalence of anabolic androgenic steroid (AAS) use is estimated at 1% to 5% worldwide. AAS use occurs primarily male elite athletes and men who want a muscular appearance. The evidence for effective, safe management of AAS cessation and withdrawal is weak.

Design: Key studies were extracted from PubMed (1990-2018) and Google Scholar with reference searches from relevant retrieved articles.

Results: The proven adverse effects of AASs include suppression of the gonadal axis and infertility, hirsutism and defeminization in women, and erythrocytosis. Alkylated AASs that are taken orally may cause hepatopathy. There is an association between high-dosage AAS use and increased risk of cardiovascular disease. Clues for AAS use include very low serum high-density cholesterol and sex hormone-binding globulin concentrations and unexplained erythrocytosis. For elite athletes, the biological passport (monitoring of blood or urinary androgen and androgen precursor concentrations after determining the athlete's baseline) is useful for detecting AAS use. For nonelite athletes, the best method to confirm AAS use is to inquire in a nonjudgmental manner. Cessation of chronic AAS use is associated with a withdrawal syndrome of anxiety and depression.

Conclusions: Men who use AASs <1 year typically recover normal hypothalamic-pituitary-testicular axis function within 1 year after cessation. Men who have infertility due to high-dosage AAS use ≥1 year might benefit from short-term treatment with clomiphene or human chorionic gonadotropin.

A case of affective disorder associated with the misuse of 'anabolic steroids' / H.M. Perry, G.W. Hughes. - (British Journal of Sports Medicine 26 (1992) 4 (December); p. 219-220)

• PMID: 1362688
• PMCID: PMC1478994
• DOI: 10.1136/bjsm.26.4.219

Abstract

In the pursuit of gains in muscle size and strength, body-builders may mistakenly use illicit drugs believing them to be anabolic steroids. The case described illustrates the physical and psychological dangers of such behaviour.

Anabolic steroid abuse : psychiatric and physical costs / Farid Talih, Omar Fattal, Donald Malone Jr. - (Cleveland Clinic Journal of Medicine 74 (2007) 5 (May); p. 341-352)

• PMID: 17506239
• DOI: 10.3949/ccjm.74.5.341

Abstract

The psychiatric effects of anabolic-androgenic steroids (i.e., testosterone and its derivatives) have been less well studied than their physical effects but are reported to include depression, mania, psychosis, and aggression. Dependence can also occur, with withdrawal involving psychiatric and physical symptoms. Adverse effects of steroid abuse should be managed by discontinuing the drugs-by tapering if necessary-and by treating the symptoms.

Muscle dysmorphia : a critical review of the proposed criteria / Bryan Chung. - (Perspectives in Biology and Medicine 44 (2001) 4 (Autumn); p. 565-574)

• PMID: 11600802
• DOI: 10.1353/pbm.2001.0062

Abstract

While body-image related disorders such as anorexia nervosa have focused on thinness, only recently have clinical criteria for a disorder that centers around muscularity--muscle dysmorphia--been proposed. An individual affected by muscle dysmorphia is overly concerned with his or her degree of muscularity. This preoccupation is manifested in the individual's behavior (excessive weight lifting, excessive attention to diet, social impairment). This article examines the historical aspects and proposed criteria for muscle dysmorphia and contrasts them with those of anorexia nervosa. While the authors of the proposed criteria have suggested that muscle dysmorphia be classified as a subcategory of body dysmorphic disorder, both the historical and clinical aspects of this syndrome are more consistent with its classification as an obsessive-compulsive disorder.