Effects of graded doses of testosterone on erythropoiesis in healthy young and older men
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CONTEXT: Erythrocytosis is a dose-limiting adverse effect of testosterone therapy, especially in older men. OBJECTIVE: Our objective was to compare the dose-related changes in hemoglobin and hematocrit in young and older men and determine whether age-related differences in erythropoietic response to testosterone can be explained by changes in erythropoietin and soluble transferrin receptor (sTfR) levels. DESIGN: We conducted a secondary analysis of data from a testosterone dose-response study in young and older men who received long-acting GnRH agonist monthly plus one of five weekly doses of testosterone enanthate (25, 50, 125, 300, or 600 mg im) for 20 wk. SETTING: The study took place at a General Clinical Research Center. PARTICIPANTS: Participants included 60 older men aged 60-75 yr and 61 young men aged 19-35 yr. OUTCOME MEASURES: Outcome measures included hematocrit and hemoglobin and serum erythropoietin and sTfR levels. RESULTS: Hemoglobin and hematocrit increased significantly in a linear, dose-dependent fashion in both young and older men in response to graded doses of testosterone (P<0.0001). The increases in hemoglobin and hematocrit were significantly greater in older than young men. There was no significant difference in percent change from baseline in erythropoietin or sTfR levels across groups in either young or older men. Changes in erythropoietin or sTfR levels were not significantly correlated with changes in total or free testosterone levels. CONCLUSIONS: Testosterone has a dose-dependent stimulatory effect on erythropoiesis in men that is more pronounced in older men. The testosterone-induced rise in hemoglobin and hematocrit and age-related differences in response to testosterone therapy may be mediated by factors other than erythropoietin and sTfR.
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Testosterone exerts erythrogenic effects that result in increases in both haematocrit and haemoglobin.
“Testosterone exerts erythrogenic effects that results in increases in both HCT and Hgb.23”
Circulating hemoglobin levels are androgen-dependent and typically reported as 12% higher in males compared with females.
“Circulating hemoglobin levels are androgen-dependent [82] and typically reported as 12% higher in males compared with females [4].”
From Transgender Women in the Female Category of Sport: Perspectives on Testosterone Suppression and Performance Advantage (2021) · cites this paper as [82]
In Bhasin et al. 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.
“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 [131]
Increased red blood cell mass (erythrocytosis) is the most common adverse event associated with testosterone therapy in clinical practice and in testosterone trials.
“Increased red blood cell mass (erythrocytosis) is the most common adverse event associated with testosterone therapy in clinical practice and in testosterone trials (2,3).”
From Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point (2014) · cites this paper as [3]
Meta-analyses of randomized testosterone trials have reported very low frequency of neuro-occlusive events.
“The meta-analyses of randomized testosterone trials have, however, reported very low frequency of neuro-occlusive events (2,3,20).”
From Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point (2014) · cites this paper as [3]
Effects of testosterone on red blood cell formation (hemoglobin and hematocrit) are dose dependent.
“The effects of testosterone on red blood cell formation (hemoglobin and hematocrit) are dose dependent (14, 82, 83) while higher age is also a factor (44).”
From Onset of effects of testosterone treatment and time span until maximum effects are achieved (2011) · cites this paper as [83]
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- Authors
- Coviello, A. D., Kaplan, B., Lakshman, K. M., Chen, T., Singh, A. B., & Bhasin, S.
- Affiliations
- Boston University (US)
- Charles R. Drew University of Medicine and Science (US)
- Corresponding author
- Coviello, Andrea D.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2008-03-01
- Volume
- 93
- Issue
- 3
- Pages
- 914-919
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC2266950
- OpenAlex
- W2102205904
- Cited by
- 404
- References
- 38
- Citations by year
- 2026: 12 · 2025: 27 · 2024: 25 · 2023: 34 · 2022: 34 · 2021: 21 · 2020: 30 · 2019: 18 · 2018: 18 · 2017: 24 · 2016: 20 · 2015: 23 · 2014: 19 · 2013: 23 · 2012: 24
- FWCI
- 8.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- School of Medicine, Boston University
- National Institutes of Health
- National Institute on Aging (1R01 AG-14369-01, R01AG014369)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK049296, 2R01 DK49296-08, R01DK070534, R01DK059627)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD0434)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Keywords
- testosterone replacement therapy, erythropoiesis, erythrocytosis, testosterone enanthate, dose-response relationship, hemoglobin, hematocrit, erythropoietin, soluble transferrin receptor, age differences, older men, GnRH agonist
- MeSH terms
- Adolescent, Adult, Age Factors, Aged, Dose-Response Relationship, Drug, Erythropoiesis, Erythropoietin, Hematocrit, Hemoglobins, Humans, Male, Middle Aged, Receptors, Transferrin, Testosterone
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