Cited by 457Hormonal and reproductive studiesMuscle Physiology and DisordersMuscle metabolism and nutrition

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Testosterone action on skeletal muscle

Herbst, Karen L, Bhasin, Shalender·2004·Current Opinion in Clinical Nutrition and Metabolic Care

DOI 10.1097/00075197-200405000-00006

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Abstract

PURPOSE OF REVIEW: To highlight recent data demonstrating direct anabolic effects of androgens on the mammalian skeletal muscle and review the mechanisms by which testosterone regulates body composition. RECENT FINDINGS: Testosterone increases lean body mass and decreases fat mass in young men; the magnitude of the changes induced by testosterone in lean and fat mass are correlated with testosterone dose and the prevalent testosterone concentrations. Older men are as responsive to the anabolic effects of testosterone on the muscle as young men, but have increased frequency of adverse events with higher testosterone doses. This reciprocal change in lean and fat mass induced by androgens is best explained by the hypothesis that androgens promote the commitment of mesenchymal pluripotent cells into myogenic lineage and inhibit adipogenesis through an androgen receptor mediated pathway. Resident muscle satellite cells increase in number with testosterone administration forming myoblasts leading to greater numbers of myonuclei in larger myofibers. Testosterone administration is associated with increased size of motor neurons. The roles of 5-alpha reduction and aromatization of testosterone into dihydrotestosterone and estradiol, respectively, in mediating testosterone effects on body composition are poorly understood. SUMMARY: Testosterone induces skeletal muscle hypertrophy by multiple mechanisms, including its effects in modulating the commitment of pluripotent mesenchymal cells. These changes in skeletal muscle lead to improved muscle strength and leg power; however, further studies are needed to determine the effects of testosterone on physical function and health-related outcomes in sarcopenia associated with aging and chronic illness.

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Withania somnifera and Trigonella foenum-graecum as ingredients of testosterone-boosting supplements: Possible clinical implications
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Testosterone is lower in men with non-alcoholic fatty liver disease and alcohol-related cirrhosis and is associated with adverse clinical outcomes
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“This may relate to the action of testosterone on muscle [25], with a known association between sarcopenia and adverse outcomes in cirrhosis [26], and potentially other actions such as its impact on insulin resistance and haemato-poiesis [22].”
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The Effects of Whey Protein Supplementation on Performance and Hormonal Adaptations Following Resistance Training in Novice Men
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“Testosterone also increases protein synthesis by binding to the androgen receptor for the complex to become a transcription factor and thirdly by possibly activating muscle satellite cells, which is important because gene transcription is an initial target for the modulation of protein synthesis [45,46].”
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Protein Energy Metabolism in Chronic Kidney Disease
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Hypogonadism is frequent in very old men with multimorbidity and is associated with anemia and sarcopenia
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Regulatory Mechanisms of Muscle Mass: The Critical Role of Resistance Training in Children and Adolescent
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“The known anabolic eﬀect of TES on skeletal muscle growth suggests that a positive relationship exists between FFM and TES (Bhasin et al., 1997; Bhasin et al., 2003; Herbst and Bhasin, 2004; Araujo et al., 2008).”
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Endogenous testosterone reduces hepatic lipid accumulation in protein-restricted male rats
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Cardiovascular Disease Risk Among Transgender People with HIV
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Growth, pectoralis muscle performance, and testis of pelung cockerels (Gallus gallus gallus [Linnaeus, 1758]) supplemented with blood clam shell powder (Anadara granosa [Linnaeus, 1758])
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The effects of glutamine supplementation on performance and hormonal responses in non-athlete male students during eight week resistance training
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Mechanisms of Anabolic Steroid Action in Bovine Skeletal Muscle
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Effect of Rehabilitation Program on Endocrinological Parameters in Patients with COPD and in Healthy Subjects
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“between systemic infl ammation (IL-6 levels, an important infl ammatory cytokine) and decreased concentrations of testosterone known as a stimulator of protein anabolism (37).”
Background
Human sex hormone-binding globulin does not provide metabolic protection against diet-induced obesity and dysglycemia in mice
Sofer, Y., Nevo, N., Vechoropoulos, M., Shefer, G., Osher, E., Landis, N., Tordjman, K., Hammond, G. L., & Stern, N. (2018) · Endocrine Connections · doi:10.1530/ec-17-0240 · Cited by 6
Serum branched-chain amino acids are mainly associated with body mass index and waist circumference
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Testosterone-mediated activation of androgenic signalling sustains in vitro the transformed and radioresistant phenotype of rhabdomyosarcoma cell lines
Giannattasio, S., Megiorni, F., Nisio, V. D., Fattore, A. D., Fontanella, R. A., Camero, S., Antinozzi, C., Festuccia, C., Gravina, G. L., Cecconi, S., et al. (2018) · Journal of Endocrinological Investigation · doi:10.1007/s40618-018-0900-6 · Cited by 6
Protein Energy Metabolism in Chronic Kidney Disease
Velasquez, M. T., Andrews, S. C., & Raj, D. S. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-815876-0.00016-4 · Cited by 7
The Eurycoma Longifolia Freeze-Dried Water Extract-Physta Does not Change Normal Ratios of Testosterone to Epitestosterone in Healthy Males
George, A. A. (2013) · Journal of Sports Medicine & Doping Studies · doi:10.4172/2161-0673.1000127 · Cited by 6
“While the role of testosterone is known to affect muscles [20], the role of E.”
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Update on therapies for sarcopenia: novel approaches for age-related muscle wasting and weakness
Lynch, G. S. (2004) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.14.9.1329 · Cited by 6
Should hormone replacement therapy (any route of administration) be considered in all postmenopausal women with lower urinary tract symptoms? Report from the ICI‐RS 2023
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“17 Low serum total testosterone has been associated with an increased likelihood of SUI (odds ratio [OR: 1.45, 95% CI: 1.03 – 2.12] and MUI [OR: 1.68, 95% CI: 1.23 – 2.22).”
BackgroundInfluential
Andropause: A Neglected Disease Entity
Ajayi, A. F., David, O. T., Ayodele, A. A., Oluwatoyin, A. L., Obukohwo, O. M., Oyedokun, P. A., Akanbi, G. B., Nene, D. S., & Magret, A. A. (2024) · OBM Geriatrics · doi:10.21926/obm.geriatr.2402276 · Cited by 7
Levels of Sex Hormones and Abdominal Muscle Composition in Men from The Multi-Ethnic Study of Atherosclerosis
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“Gonadal hormone effects are commonly described to act through a direct action on the muscle fiber (Herbst and Bhasin, 2004); however, recently evidence has been presented for an indirect action on the neuromuscular complex which includes the neuromuscular junction dimensions and activity…”
Background
Iron status, catabolic/anabolic balance, and skeletal muscle performance in men with heart failure with reduced ejection fraction
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“target tissues for circulating steroid hormones, in which they exert their direct anabolic properties [27, 28].”
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Sex-Based Differences in Muscle Stem Cell Regulation Following Exercise
Beaudry, K. M., & Lisio, M. D. (2024) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000337 · Cited by 5
“Testosterone is an anabolic hormone, and is associated with an increase in lean body mass and a reduction in whole-body and regional fat mass (3).”
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Effects of testosterone and vitamin D on fall risk in pre-frail hypogonadal men: a factorial design RCT
Bischoff-Ferrari, H. A., Kistler-Fischbacher, M., Gaengler, S., Münzer, T., Dawson‐Hughes, B., Lang, W., Theiler, R., Egli, A., Orav, E. J., & Freystaetter, G. (2024) · The journal of nutrition health & aging · doi:10.1016/j.jnha.2024.100217 · Cited by 5
Perceived physical strength in men is attractive to women but may come at a cost to ejaculate quality
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Weber, C. F., Schallner, J., & von der Hagen, M. (2022) · Brain and Development · doi:10.1016/j.braindev.2022.09.005 · Cited by 6
Muscle diseases and aging
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“…mass and a reduction in fat mass in young as well as old men, it has been suggested that it may be promoting differentiation of mesenchymal pluripotent cells into the OGLU SE myogenic lineage rather than the adipogenic lineage through an androgen receptor mediated pathway (Herbst and Bhasin, 2004).”
Background
A single dose of dihydrotestosterone induced a myogenic transcriptional program in female intra-abdominal adipose tissue
Giorgio, M. R. D., Yoshioka, M., & St‐Amand, J. (2010) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2010.02.023 · Cited by 5
“It should be noted that both adipocytes and muscular cells derive from the same precursors, the mesenchymal pluripotent cells [45].”
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Molecular Regulation and Rejuvenation of Muscle Stem (Satellite) Cell Aging
Meiliana, A., Dewi, N. M., & Wijaya, A. (2015) · The Indonesian Biomedical Journal · doi:10.18585/inabj.v7i2.73 · Cited by 4
“(165) During aging, systemic levels of androgens decline, which is concomitant with a loss in muscle mass and a gain in fat mass.(166,167) Ectopic adipocyte deposition in the skeletal muscle characterizes various disorders, including obesity/type-2 diabetes, sarcopenia, and muscular dystrophies.”
Background
Depression and stress
Pollard, T. M. (2001) · Cambridge University Press eBooks · doi:10.1017/cbo9780511841118.009 · Cited by 5
Endocrine function during exercise and response to training
van der Kolk, J. H. (2013) · Elsevier eBooks · doi:10.1016/b978-0-7020-4771-8.00034-x · Cited by 5

Authors: Herbst, K. L., & Bhasin, S.
Affiliations: University of California, Los Angeles (US)
Corresponding author: Bhasin, Shalender
ORCID: Herbst, Karen L
Bhasin, Shalender
Venue: Current Opinion in Clinical Nutrition and Metabolic Care
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2004-05
Volume: 7
Issue: 3
Pages: 271-277
ISSN: 1363-1950 (ISSN-L)
DOI: 10.1097/00075197-200405000-00006
OpenAlex: W2095240081
Cited by: 457
References: 46
Citations by year: 2026: 7 · 2025: 13 · 2024: 27 · 2023: 38 · 2022: 32 · 2021: 27 · 2020: 22 · 2019: 22 · 2018: 21 · 2017: 22 · 2016: 15 · 2015: 13 · 2014: 12 · 2013: 24 · 2012: 18
FWCI: 2.51
Type: journal article
Language: en
Open access: closed
Locations: Current Opinion in Clinical Nutrition & Metabolic Care (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
Keywords: testosterone, skeletal muscle hypertrophy, androgen action, body composition, lean body mass, fat mass, androgen receptor, mesenchymal differentiation, myogenesis, adipogenesis, satellite cells, myonuclei, motor neurons, dihydrotestosterone, estradiol, aging, sarcopenia, muscle strength, leg power
MeSH terms: Aging, Animals, Body Composition, Female, Humans, Male, Testosterone, Muscle, Skeletal, Muscle Development, Pluripotent Stem Cells

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