Testosterone Suppresses Hepcidin in Men: A Potential Mechanism for Testosterone-Induced Erythrocytosis
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CONTEXT: The mechanisms by which testosterone increases hemoglobin and hematocrit are unknown. OBJECTIVE: The aim was to test the hypothesis that testosterone-induced increase in hematocrit is associated with suppression of the iron regulatory peptide hepcidin. PARTICIPANTS: Healthy younger men (ages 19-35 yr; n = 53) and older men (ages 59-75 yr; n = 56) were studied. METHODS: Weekly doses of testosterone enanthate (25, 50, 125, 300, and 600 mg) were administered over 20 wk, whereas endogenous testosterone was suppressed by monthly GnRH agonist administration. Blood and serum parameters from each individual were measured at wk 0, 1, 2, 4, 8, and 20. Longitudinal analyses were performed to examine the relationship between hepcidin, hemoglobin, hematocrit, and testosterone while controlling for potential confounders. RESULTS: High levels of testosterone markedly suppressed serum hepcidin within 1 wk. Hepcidin suppression in response to testosterone administration was dose-dependent in older men and more pronounced than in young men, and this corresponded to a greater rise in hemoglobin in older men. Serum hepcidin levels at 4 and 8 wk were predictive of change in hematocrit from baseline to peak levels. CONCLUSION: Testosterone administration is associated with suppression of serum hepcidin. Greater increases in hematocrit in older men during testosterone therapy are related to greater suppression of hepcidin.
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Testosterone fails to directly activate EPO transcription in Hep3B cells.
“Furthermore, testosterone fails to directly activate EPO transcription in Hep3B cells, an EPO-secreting cell line that is highly sensitive to hypoxic induction (11)”
From Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point (2014) · cites this paper as [11]
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- Authors
- Bachman, E., Feng, R., Travison, T., Li, M., Olbina, G., Ostland, V., Ulloor, J., Zhang, A., Basaria, S., Ganz, T., Westerman, M., & Bhasin, S.
- Affiliations
- Boston University (US)
- University of Pennsylvania (US)
- Intrinsic LifeSciences (United States) (US)
- University of California, Los Angeles (US)
- Corresponding author
- Bachman, Eric
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2010-10
- Volume
- 95
- Issue
- 10
- Pages
- 4743-4747
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC3050108
- OpenAlex
- W2150542348
- Cited by
- 247
- References
- 19
- Citations by year
- 2026: 18 · 2025: 14 · 2024: 9 · 2023: 16 · 2022: 16 · 2021: 11 · 2020: 23 · 2019: 15 · 2018: 13 · 2017: 18 · 2016: 12 · 2015: 20 · 2014: 15 · 2013: 20 · 2012: 16
- FWCI
- 9.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- School of Medicine, Boston University
- Evans Medical Foundation
- National Institutes of Health (5p30ag031679-15)
- National Institute on Aging (U01AG014369, U01 AG14369, P30-AG031679)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Keywords
- testosterone, hepcidin, testosterone enanthate, hematocrit, hemoglobin, iron regulation, GnRH agonist suppression, dose-response relationship, age differences, men
- MeSH terms
- Adult, Aged, Aging, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Humans, Injections, Male, Middle Aged, Polycythemia, Testosterone, Down-Regulation, Leuprolide, Antimicrobial Cationic Peptides, Young Adult, Hepcidins
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