As the body is unable to eliminate excess iron, a negative feedback mechanism allowing iron to inhibit testosterone production to maintain body iron homeostasis is proposed. Testosterone directly regulates body iron levels through inhibition of the master regulator of iron metabolism, hepcidin. The stimulatory effects of testosterone on erythropoiesis appear to be attenuated by iron deficiency. In other studies, testosterone treatment had mixed effects on erythropoietin. This tendency occurred despite increased hemoglobin, which normally suppresses erythropoietin, suggesting a reset of the hemoglobin-erythropoietin relationship. Herein, we report that 125 mg/wk TE (a supraphysiological TRT dose that is within the FDA-approved range) increases RBC production in older hypogonadal men, which supports meta-analysis data indicating an average HCT increase of 3.2% in men receiving a range of doses and various forms of TRT (13). However, the role of the type II 5α-reductase enzyme in mediating androgen-induced erythropoiesis has received little attention in the literature. In contrast, prostate enlargement (2, 8–10, 26, 36) and other putative side effects resulting from androgen administration (e.g., male-pattern baldness or acne) (18) are mediated primarily by type II 5α-reductase. As such, determining the mechanism(s) through which administered T produces tissue- and/or cell-specific effects remains biologically significant and clinically important. A small study of men with transfusion-dependentβ-thalassemia, however, reported elevated seminal plasma iron concentrationsin five of six men, with concentrations approximately 5–10 times higher thanthe reference range . Seminal plasma iron concentrations are reportedly between 1.0 and 3.7μg/ml in healthy, normozoospermic men . Thus, some of the side effects of supplemental testosteroneuse may be directly related to iron overload. Thus, testosterone’s abilityto override the regulatory mechanisms to maximize iron absorption would beneficiallyincrease iron stores needed for rapid growth. Ferroportin was expressed in MNC but we could find no significant expression of hepcidin in these cells. Hemoglobin concentrations and the hematocrit were lower in men with HH (table 1). Data are presented as means±SD (or means±SE where indicated) for normally distributed data and median 25th, 75th percentile for non-normal data. Intrinsic Life Sciences, La Jolla, CA, assayed serum hepcidin using an enzyme-linked immunosorbent assay (CV 7%-9%; Hepcidin IDX assay) (25). We measured markers of erythropoiesis in the 116 of the 126 anemic men who had serum samples available from baseline, 1 month, and 3 months. We defined anemia as a hemoglobin level ≤12.7 g/dL, irrespective of race (24). Briefly, TE administration (i.e., the combined effects of groups 3 and 4) elevated nadir T and BioT 1.8- and 2.2-fold, respectively, over baseline. The primary outcomes from this RCT, including musculoskeletal and prostate findings, sex hormone concentrations, and clinical laboratory values, have been reported previously (10). Uij is the cluster effect due to subject j under treatment i and assumed to follow N(0,∑), with ∑ being the covariance matrix of 4 × 4 dimension. The bioactive 25-amino acid residue form of hepcidin was evaluated using a commercially available high-sensitivity ELISA (Bachem, UK) with a reported range of 0–25 ng/ml. One subject in the Vehicle-Finasteride group and one in the T group were removed for elevated PSA, one subject in the T-placebo group was removed for sleep apnea, and one subject in the T-finasteride group was removed for urinary symptoms. Proscar and matching placebo were donated by Merck, Delatestryl was donated by Novartis, and matching vehicle was prepared by WestLab Pharmacy (Gainesville, FL). Treatment lasted for 12 mo and consisted of Proscar (5 mg/day po finasteride), placebo and Delatestryl (125 mg/wk im TE), or vehicle. Our editors independently research, test, and recommend the best products; we may receive commissions on purchases made from our chosen links. Provided by the Springer Nature SharedIt content-sharing initiative Joseph S. Gabrielsen has declared no potential conflicts of interest.
