Is the haematopoietic effect of testosterone mediated by erythropoietin? The results of a clinical trial in older men

Abstract

SUMMARYThe stimulatory effects of testosterone on erythropoiesis are very well known, but the mechanisms underlying the erythropoietic action of testosterone are still poorly understood, although erythropoietin has long been considered a potential mediator. A total of 108 healthy men >65 years old with serum testosterone concentration <475 ng/dL were recruited by direct mailings to alumni of the University of Pennsylvania and Temple University, and randomized to receive a 60-cm 2 testosterone or placebo patch for 36 months.Ninety-six subjects completed the trial. We used information and stored serum specimens from this trial to test the hypothesis that increasing testosterone increases haemoglobin by stimulating erythropoietin production. We used information of 67 men, 43 in the testosterone group and 24 in the placebo group who had banked specimens available for assays of testosterone, haemoglobin and erythropoietin at baseline and after 36 months. The original randomized clinical study was primarily designed to verify the effects of testosterone on bone mineral density. The primary outcome of this report was to investigate whether or not transdermal testosterone increases haemoglobin by increasing erythropoietin levels. The mean age ± SD of the 67 subjects at baseline was 71.8 ± 4.9 years. Testosterone replacement therapy for 36 months, as compared with placebo, induced a significant increase in haemoglobin (0.86 ± 0.31 g/dL, p = 0.01), but no change in erythropoietin levels (À0.24 ± 2.16 mIU/mL, p = 0.91). Included time-varying measure of erythropoietin did not significantly account for the effect of testosterone on haemoglobin (Treatment-by-time: b = 0.93, SE = 0.33, p = 0.01). No serious adverse effect was observed. Transdermal testosterone treatment of older men for 36 months significantly increased haemoglobin, but not erythropoietin levels. The haematopoietic effect of testosterone does not appear to be mediated by stimulation of erythropoietin production.

Hematopoietic Stem/Progenitor Cells Express Several Functional Sex Hormone Receptors—Novel Evidence for a Potential Developmental Link Between Hematopoiesis and Primordial Germ Cells

“…It has been also reported that they respond by clonogenic growth in vitro to certain sex hormones (SexHs), such as prolactin (PRL), androgens, and estrogens [1][2][3]. In further support of this notion, androgens (eg, danazol) are currently employed to treat aplastic anemia patients [4].…”

Adverse effects of testosterone replacement therapy: an update on the evidence and controversy

“…There were no 'serious' patient-centered adverse events (e.g. cerebrovascular accident, vascular occlusive events, venous thromboembolisms) reported during the study period of 36 months [Maggio et al 2013]. …”

Testosterone replacement therapy (TRT) and its effect on bone marrow. How serious is it and is there a true polyglobulia?

“…Snyder et al (1999) noticed that erythrocytosis occurred in 5.5 % of scrotal transdermal users, and the majority of changes took place over the fi rst three months of treatment (24). The frequency of polycythemia (hematocrit over 51 %) was related mainly to supra-physiological serum TST levels.…”

“…In another study, within the period of 36 months, Maggio et al (2013) reported, that there were no 'serious' patient-centered adverse events (e.g. cerebrovascular accident, vascular occlusive events, venous thromboembolisms).…”