Cited by 464Hormonal and reproductive studiesMuscle Physiology and DisordersMuscle metabolism and nutrition

The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.

Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy

Sinha-Hikim, Indrani, Artaza, Jorge, Woodhouse, Linda, Gonzalez-Cadavid, Nestor, Singh, Atam B., Lee, Martin I., Storer, Thomas W., Casaburi, Richard, Shen, Ruoquing, Bhasin, Shalender·2002·American Journal of Physiology-Endocrinology and Metabolism

DOI 10.1152/ajpendo.00502.2001

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Abstract

Administration of replacement doses of testosterone to healthy hypogonadal men and supraphysiological doses to eugonadal men increases muscle size. To determine whether testosterone-induced increase in muscle size is due to muscle fiber hypertrophy, 61 healthy men, 18–35 yr of age, received monthly injections of a long-acting gonadotropin-releasing hormone (GnRH) agonist to suppress endogenous testosterone secretion and weekly injections of 25, 50, 125, 300, or 600 mg testosterone enanthate (TE) for 20 wk. Thigh muscle volume was measured by magnetic resonance imaging (MRI) scan, and muscle biopsies were obtained from vastus lateralis muscle in 39 men before and after 20 wk of combined treatment with GnRH agonist and testosterone. Administration of GnRH agonist plus TE resulted in mean nadir testosterone concentrations of 234, 289, 695, 1,344, and 2,435 ng/dl at the 25-, 50-, 125-, 300-, and 600-mg doses, respectively. Graded doses of testosterone administration were associated with testosterone dose and concentration-dependent increase in muscle volume measured by MRI (changes in vastus lateralis volume, −4, +7, +15, +32, and +48 ml at 25-, 50-, 125-, 300-, and 600-mg doses, respectively). Changes in cross-sectional areas of both type I and II fibers were dependent on testosterone dose and significantly correlated with total ( r = 0.35, and 0.44, P < 0.0001 for type I and II fibers, respectively) and free ( r = 0.34 and 0.35, P < 0.005) testosterone concentrations during treatment. The men receiving 300 and 600 mg of TE weekly experienced significant increases from baseline in areas of type I (baseline vs. 20 wk, 3,176 ± 186 vs. 4,201 ± 252 μm 2, P < 0.05 at 300-mg dose, and 3,347 ± 253 vs. 4,984 ± 374 μm 2, P = 0.006 at 600-mg dose) muscle fibers; the men in the 600-mg group also had significant increments in cross-sectional area of type II (4,060 ± 401 vs. 5,526 ± 544 μm 2, P = 0.03) fibers. The relative proportions of type I and type II fibers did not change significantly after treatment in any group. The myonuclear number per fiber increased significantly in men receiving the 300- and 600-mg doses of TE and was significantly correlated with testosterone concentration and muscle fiber cross-sectional area. In conclusion, the increases in muscle volume in healthy eugonadal men treated with graded doses of testosterone are associated with concentration-dependent increases in cross-sectional areas of both type I and type II muscle fibers and myonuclear number. We conclude that the testosterone induced increase in muscle volume is due to muscle fiber hypertrophy.

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Authors: Sinha-Hikim, I., Artaza, J., Woodhouse, L., Gonzalez-Cadavid, N., Singh, A. B., Lee, M. I., Storer, T. W., Casaburi, R., Shen, R., & Bhasin, S.
Affiliations: Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, 90059; and
Charles R. Drew University of Medicine and Science (US)
University of California, Los Angeles (US)
ORCID: Woodhouse, Linda
Storer, Thomas W.
Casaburi, Richard
Bhasin, Shalender
Venue: American Journal of Physiology-Endocrinology and Metabolism
Publisher: American Physiological Society
Published: 2002-07-01
Volume: 283
Issue: 1
Pages: E154-E164
ISSN: 0193-1849 (ISSN-L)
1522-1555
DOI: 10.1152/ajpendo.00502.2001
OpenAlex: W2103672262
Cited by: 464
References: 47
Citations by year: 2026: 14 · 2025: 20 · 2024: 21 · 2023: 16 · 2022: 30 · 2021: 22 · 2020: 20 · 2019: 18 · 2018: 20 · 2017: 21 · 2016: 17 · 2015: 14 · 2014: 20 · 2013: 28 · 2012: 17
FWCI: 7.14
Type: journal article
Language: en
Open access: closed
Locations: American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5u01dk054047-06)
National Institute on Aging (1R01 AG-14369-01, R01AG014369)
National Institute of Diabetes and Digestive and Kidney Diseases (1R01 DK 59627-01, U01-DK-54047, R01DK059627)
National Center for Research Resources (U54 RR-00425, G12RR003026, P20RR011145)
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 enanthate, testosterone replacement therapy, muscle hypertrophy, muscle fiber cross-sectional area, vastus lateralis, thigh muscle volume, GnRH agonist, hypogonadism, dose-response relationship, free testosterone, healthy young men, muscle biopsy
MeSH terms: Adolescent, Adult, Body Composition, Dose-Response Relationship, Drug, Double-Blind Method, Humans, Hypertrophy, Gonadotropin-Releasing Hormone, Magnetic Resonance Imaging, Male, Reference Values, Testosterone, Muscle, Skeletal, Muscle Fibers, Skeletal, Muscle Fibers, Fast-Twitch, Muscle Fibers, Slow-Twitch, Anatomy, Cross-Sectional

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Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy

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