Effects of graded doses of testosterone on erythropoiesis in healthy young and older men

Abstract

Context: Erythrocytosis is a dose-limiting adverse effect of testosterone therapy, especially in older men.

Objective: Our objective was to compare the dose-related changes in hemoglobin and hematocrit in young and older men and determine whether age-related differences in erythropoietic response to testosterone can be explained by changes in erythropoietin and soluble transferrin receptor (sTfR) levels.

Design: We conducted a secondary analysis of data from a testosterone dose-response study in young and older men who received long-acting GnRH agonist monthly plus one of five weekly doses of testosterone enanthate (25, 50, 125, 300, or 600 mg im) for 20 wk.

Setting: The study took place at a General Clinical Research Center.

Participants: Participants included 60 older men aged 60-75 yr and 61 young men aged 19-35 yr.

Outcome measures: Outcome measures included hematocrit and hemoglobin and serum erythropoietin and sTfR levels.

Results: Hemoglobin and hematocrit increased significantly in a linear, dose-dependent fashion in both young and older men in response to graded doses of testosterone (P<0.0001). The increases in hemoglobin and hematocrit were significantly greater in older than young men. There was no significant difference in percent change from baseline in erythropoietin or sTfR levels across groups in either young or older men. Changes in erythropoietin or sTfR levels were not significantly correlated with changes in total or free testosterone levels.

Conclusions: Testosterone has a dose-dependent stimulatory effect on erythropoiesis in men that is more pronounced in older men. The testosterone-induced rise in hemoglobin and hematocrit and age-related differences in response to testosterone therapy may be mediated by factors other than erythropoietin and sTfR.

Figures

Figure 1

A, Hemoglobin in young (left panel) and older (right panel) men during the 20-wk treatment period. Data are mean ± sem. Hg, Hemoglobin. B, Hematocrit in young (left panel) and older (right panel) men during the 20-wk treatment period. Data are mean ± sem. Hct, Hematocrit. C, Mean ± sem percent changes in hemoglobin (Hg) in young (left panel) and older (right panel) men during testosterone treatment. D, Mean ± sem percent changes in hematocrit in young (left panel) and older (right panel) men during testosterone treatment. TE, Testosterone enanthate.

Figure 2

A, Serum erythropoietin (Epo) levels in young (left panel) and older (right panel) men during the 20-wk treatment period. Data are mean ± sem. Overall ANOVA did not reveal an age or dose effect. B, Serum sTfR levels in young (left panel) and older (right panel) men during the 20-wk treatment period. Data are mean ± sem. Overall ANOVA did not reveal an age or dose effect. C, Changes in serum erythropoietin levels in young (○ with dashed line) and older men (▪ with solid line) are plotted against serum total testosterone (left panel) and free testosterone (right panel) levels during testosterone treatment. There was no significant correlation between total or free testosterone and change in erythropoietin levels in either young or older men. There was no age effect on the relationship between percent change in erythropoietin levels and testosterone levels. D, Changes in serum sTfR levels in young (○ with dashed line) and older men (▪ with solid line) are plotted against serum total testosterone (left panel) and free testosterone (right panel) levels during testosterone treatment. There was no significant correlation between total or free testosterone during treatment and change in StFR levels in either young or older men. There was no age effect on the relationship between percent change in sFtR levels and testosterone levels. T, Testosterone; TE, testosterone enanthate.