title: Testosterone alters iron metabolism and stimulates red blood cell production independently of dihydrotestosterone.
abstract: Testosterone (T) stimulates erythropoiesis and regulates iron homeostasis. However, it remains unknown whether the (type II) 5α-reduction of T to dihydrotestosterone (DHT) mediates these androgenic effects, as it does in some other tissues. Our purpose was to determine whether inhibition of type II 5α-reductase (via finasteride) alters red blood cell (RBC) production and serum markers of iron homeostasis subsequent to testosterone-enanthate (TE) administration in older hypogonadal men. Sixty men aged ≥60 yr with serum T <300 ng/dl or bioavailable T <70 ng/dl received treatment with TE (125 mg/wk) vs. vehicle paired with finasteride (5 mg/day) vs. placebo using a 2 × 2 factorial design. Over the course of 12 mo, TE increased RBC count 9%, hematocrit 4%, and hemoglobin 8% while suppressing serum hepcidin 57% (P < 0.001 for all measurements). Most of the aforementioned changes occurred in the first 3 mo of treatment, and finasteride coadministration did not significantly alter any of these effects. TE also reduced serum ferritin 32% (P = 0.002) within 3 mo of treatment initiation without altering iron, transferrin, or transferrin saturation. We conclude that TE stimulates erythropoiesis and alters iron homeostasis independently of the type II 5α-reductase enzyme. These results demonstrate that elevated DHT is not required for androgen-mediated erythropoiesis or for alterations in iron homeostasis that would appear to support iron incorporation into RBCs.
authors: Research Service, Departments of Applied Physiology and Kinesiology.
authors: Luke A
authors: LA
authors: Beggs
authors: Research Service, Departments of Applied Physiology and Kinesiology.
authors: Joshua F
authors: JF
authors: Yarrow
authors: Research Service.
authors: Christine F
authors: CF
authors: Conover
authors: Geriatric Research, Education, and Clinical Center, and.
authors: John R
authors: JR
authors: Meuleman
authors: Department of Kinesiology, University of Rhode Island, Kingston, Rhode Island.
authors: Darren T
authors: DT
authors: Beck
authors: Research Pharmacy, Malcom Randall Veterans Affairs Medical Center, University of Florida, Gainesville, Florida;
authors: Matthew
authors: M
authors: Morrow
authors: Biostatistics, and.
authors: Baiming
authors: B
authors: Zou
authors: Health Outcomes and Policy, University of Florida, Gainesville, Florida; and.
authors: Jonathan J
authors: JJ
authors: Shuster
authors: Geriatric Research, Education, and Clinical Center, and Departments of Applied Physiology and Kinesiology, seborst@ufl.edu.
authors: Stephen E
authors: SE
authors: Borst
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D013196:Dihydrotestosterone / Q000378:metabolism*; D004311:Double-Blind Method; D004347:Drug Interactions; D004906:Erythrocyte Count; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism*; D005293:Ferritins / Q000097:blood; D018120:Finasteride / Q000494:pharmacology; D006801:Humans; D007501:Iron / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D013739:Testosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D014168:Transferrin / Q000032:analysis
chemical_list: D010919:Placebos; D014168:Transferrin; D013196:Dihydrotestosterone; D013739:Testosterone; D018120:Finasteride; C004648:testosterone enanthate; D005293:Ferritins; D007501:Iron
keywords: androgen; finasteride; hematocrit; hepcidin; hypogonadal; testosterone