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Testosterone dose-response relationships in healthy young men
Abstract
Testosterone increases muscle mass and strength and regulates other physiological processes, but we do not know whether testosterone effects are dose dependent and whether dose requirements for maintaining various androgen-dependent processes are similar. To determine the effects of graded doses of testosterone on body composition, muscle size, strength, power, sexual and cognitive functions, prostate-specific antigen (PSA), plasma lipids, hemoglobin, and insulin-like growth factor I (IGF-I) levels, 61 eugonadal men, 18-35 yr, were randomized to one of five groups to receive 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 of testosterone enanthate for 20 wk. Energy and protein intakes were standardized. The administration of the GnRH agonist plus graded doses of testosterone resulted in mean nadir testosterone concentrations of 253, 306, 542, 1,345, and 2,370 ng/dl at the 25-, 50-, 125-, 300-, and 600-mg doses, respectively. Fat-free mass increased dose dependently in men receiving 125, 300, or 600 mg of testosterone weekly (change +3.4, 5.2, and 7.9 kg, respectively). The changes in fat-free mass were highly dependent on testosterone dose (P = 0.0001) and correlated with log testosterone concentrations (r = 0.73, P = 0.0001). Changes in leg press strength, leg power, thigh and quadriceps muscle volumes, hemoglobin, and IGF-I were positively correlated with testosterone concentrations, whereas changes in fat mass and plasma high-density lipoprotein (HDL) cholesterol were negatively correlated. Sexual function, visual-spatial cognition and mood, and PSA levels did not change significantly at any dose. We conclude that changes in circulating testosterone concentrations, induced by GnRH agonist and testosterone administration, are associated with testosterone dose- and concentration-dependent changes in fat-free mass, muscle size, strength and power, fat mass, hemoglobin, HDL cholesterol, and IGF-I levels, in conformity with a single linear dose-response relationship. However, different androgen-dependent processes have different testosterone dose-response relationships.
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“Dose-response studies show that in men whose endogenous testosterone is fully suppressed, add-back administration of increasing doses of testosterone that produce graded increases in circulating testosterone causes a dose-dependent (whether expressed according to testosterone dose or circulating levels) increase in muscle mass (measured as lean body mass) and strength (65, 111).”
From Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance (2018) · cites this paper as [111]
In the citing paper
“In the Bhasin et al. (111) studies, in both young and older men the highest testosterone dose produced a 12% increase in blood hemoglobin compared with the lowest dose, reflecting a strong dose-response relationship (Fig. 6) (131).”
From Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance (2018) · cites this paper as [111]
In the citing paper
“The basis for the sex difference in muscle mass and strength is the sex difference in circulating testosterone as clearly shown (for example) by (1) the enhanced athletic performance of men compared with prepubertal boys and women (8); (2) the close correspondence of muscle growth (muscle size) with muscle strength in ascending dose studies in men by Bhasin et al. (111, 117–119) and Finkelstein et”
From Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance (2018) · cites this paper as [111]
In the citing paper
“In a series of studies, Bhasin et al. (8) have demonstrated that upon testosterone administration, there is a positive correlation between blood testosterone concentrations and leg press strength, thigh, and quadriceps muscle volume, and, further, levels of hemoglobin and IGF1.”
From Onset of effects of testosterone treatment and time span until maximum effects are achieved (2011) · cites this paper as [8]
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Metadata
- Authors
- Bhasin, S., Woodhouse, L., Casaburi, R., Singh, A. B., Bhasin, D., Berman, N., Chen, X., Yarasheski, K. E., Magliano, L., Dzekov, C., Dzekov, J., Bross, R., Phillips, J., Sinha-Hikim, I., Shen, R., & Storer, T. W.
- Affiliations
- Charles R. Drew University of Medicine and Science (US)
- University of California, Los Angeles (US)
- Washington University in St. Louis (US)
- El Camino College (US)
- Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles 90059;
- ORCID
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2001-12-01
- Volume
- 281
- Issue
- 6
- Pages
- E1172-E1181
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2109494488
- Cited by
- 967
- References
- 52
- Citations by year
- 2026: 32 · 2025: 36 · 2024: 35 · 2023: 38 · 2022: 54 · 2021: 29 · 2020: 34 · 2019: 39 · 2018: 36 · 2017: 41 · 2016: 41 · 2015: 29 · 2014: 39 · 2013: 40 · 2012: 34
- FWCI
- 23.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p41rr000954-34, ODP 1397)
- U.S. Public Health Service (00954, MO-00425)
- National Institute on Aging (1RO1-AG-14369, R01AG014369)
- National Institute of Diabetes and Digestive and Kidney Diseases (1RO1 DK-49296, R01DK049296, 1RO1-DK-59297-01)
- National Center for Research Resources (P20 RR 11145-01, G12 RR 03026, P41-RR000954, G12RR003026, P20RR011145)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- testosterone, dose-response relationship, testosterone enanthate, GnRH agonist, testosterone replacement therapy, fat-free mass, muscle strength, muscle power, muscle volume, hemoglobin, HDL cholesterol, insulin-like growth factor I, prostate-specific antigen, sexual function, cognitive function, young men
- MeSH terms
- Adult, Androgen Antagonists, Body Composition, Body Water, Dose-Response Relationship, Drug, Double-Blind Method, Humans, Insulin-Like Growth Factor I, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Male, Nutritional Physiological Phenomena, Sexual Behavior, Testosterone, Exercise, Muscle, Skeletal
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