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.

Distinctive Analysis of Macular Superficial Capillaries and Large Vessels Using Optical Coherence Tomographic Angiography in Healthy and Diabetic Eyes

“…And this might be explained by the androgen levels, which has been suggested to be associated with increased production of red blood cells. 22 There are several limitations for this study. First, the SS was not comparable among disease groups and healthy group, which could also contribute to the decrease of vessel density in the disease group.…”

Effect of testosterone on hepcidin, ferroportin, ferritin and iron binding capacity in patients with hypogonadotropic hypogonadism and type 2 diabetes

“…The effect of testosterone on hemoglobin is dose-dependent and evident within a month of starting testosterone replacement and generally plateaus by the fourth month (33). Prior studies have shown that testosterone increases the mobilization of iron from stores by suppressing hepcidin (20, 22). In the presence of erythropoietin, this translates into increased iron incorporation into red blood cells and erythropoiesis (34, 35).…”

“…In the presence of erythropoietin, this translates into increased iron incorporation into red blood cells and erythropoiesis (34, 35). This is accompanied by an increase in red blood cell mass, decrease in serum ferritin concentrations, and transient increases in serum erythropoietin and soluble transferrin receptor concentrations after testosterone replacement in elderly men (20-22, 33). Testosterone also suppresses the expression of hepcidin in hepatocytes in mice (34).…”

“…Since ferroportin is responsible for the transport of absorbed iron from the intestinal cell and then from the macrophage into the circulation, the inhibition and suppression of ferroportin is likely to reduce the bioavailability of iron. Testosterone replacement has recently been shown to suppress hepcidin concentrations in men (20-22). However, it is not known whether this results in increased cellular expression of ferroportin and other relevant mechanisms in humans.…”

Iron and Advanced Glycation End Products: Emerging Role of Iron in Androgen Deficiency in Obesity

“…Low T levels are associated with the development of anemia in the elderly [9] and men with type 2 diabetes [10]. Recent clinical studies showed that T administration increase iron absorption and red blood cells (RBCs) synthesis through the suppression of the master iron regulator hepcidin hormone [11][12][13]. Hepcidin is a liver-synthesized hormone that regulates iron absorption and mobilization.…”