title: Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point.
abstract: BACKGROUND
  The mechanisms by which testosterone increases hemoglobin and hematocrit remain unclear.
  
  
  METHODS
  We assessed the hormonal and hematologic responses to testosterone administration in a clinical trial in which older men with mobility limitation were randomized to either placebo or testosterone gel daily for 6 months.
  
  
  RESULTS
  The 7%-10% increase in hemoglobin and hematocrit, respectively, with testosterone administration was associated with significantly increased erythropoietin (EPO) levels and decreased ferritin and hepcidin levels at 1 and 3 months. At 6 months, EPO and hepcidin levels returned toward baseline in spite of continued testosterone administration, but EPO levels remained nonsuppressed even though elevated hemoglobin and hematocrit higher than at baseline, suggesting a new set point. Consistent with increased iron utilization, soluble transferrin receptor (sTR) levels and ratio of sTR/log ferritin increased significantly in testosterone-treated men. Hormonal and hematologic responses were similar in anemic participants. The majority of testosterone-treated anemic participants increased their hemoglobin into normal range.
  
  
  CONCLUSIONS
  Testosterone-induced increase in hemoglobin and hematocrit is associated with stimulation of EPO and reduced ferritin and hepcidin concentrations. We propose that testosterone stimulates erythropoiesis by stimulating EPO and recalibrating the set point of EPO in relation to hemoglobin and by increasing iron utilization for erythropoiesis.
authors.affiliation: Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston Claude D. Pepper Older Americans Independence Center for Function Promoting Therapies, Boston Medical Center, Massachusetts. SBhasin@partners.org.
authors.forename: Eric
authors.initials: E
authors.lastname: Bachman
authors.affiliation: Section of Hematology/Oncology Sickle Cell Center, MC 712, University of Illinois at Chicago.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Travison
authors.affiliation: Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston Claude D. Pepper Older Americans Independence Center for Function Promoting Therapies, Boston Medical Center, Massachusetts.
authors.forename: Shehzad
authors.initials: S
authors.lastname: Basaria
authors.affiliation: Section of Hematology/Oncology Sickle Cell Center, MC 712, University of Illinois at Chicago.
authors.forename: Maithili N
authors.initials: MN
authors.lastname: Davda
authors.affiliation: Section of Hematology/Oncology Sickle Cell Center, MC 712, University of Illinois at Chicago.
authors.forename: Wen
authors.initials: W
authors.lastname: Guo
authors.affiliation: Section of Hematology/Oncology Sickle Cell Center, MC 712, University of Illinois at Chicago.
authors.forename: Michelle
authors.initials: M
authors.lastname: Li
authors.affiliation: Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston Claude D. Pepper Older Americans Independence Center for Function Promoting Therapies, Boston Medical Center, Massachusetts.
authors.forename: John
authors.initials: J
authors.lastname: Connor Westfall
authors.affiliation: Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston Claude D. Pepper Older Americans Independence Center for Function Promoting Therapies, Boston Medical Center, Massachusetts.
authors.forename: Harold
authors.initials: H
authors.lastname: Bae
authors.affiliation: Section of Hematology/Oncology Sickle Cell Center, MC 712, University of Illinois at Chicago.
authors.forename: Victor
authors.initials: V
authors.lastname: Gordeuk
authors.affiliation: Brigham and Women's Hospital, Department of Medicine, Section on Men's Health, Aging and Metabolism, Boston, Massachusetts.
authors.forename: Shalender
authors.initials: S
authors.lastname: Bhasin
mesh_terms: D000368:Aged; D000728:Androgens / Q000008:administration & dosage / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000097:blood*; D005500:Follow-Up Studies; D006454:Hemoglobins / Q000187:drug effects / Q000378:metabolism; D064451:Hepcidins / Q000037:antagonists & inhibitors* / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D051346:Mobility Limitation; D011086:Polycythemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D011863:Radioimmunoassay; D013739:Testosterone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D000728:Androgens; D006454:Hemoglobins; D064451:Hepcidins; D004921:Erythropoietin; D013739:Testosterone
keywords: Erythropoietin; Ferritin.; Hepcidin; Testosterone