Positive univariate associations between polycythemia (hematocrit >0.50) and log(testosterone) (odds ratio (OR) 24.7, 95% confidence interval (CI): 4.3, 141.2, P <0.01) and age (OR 1.1, 95% CI: 1.0, 1.1, P =0.03) and a borderline relationship with current smoking (OR 4.2, 95% CI: 0.9, 20.0, P =0.08) were unveiled. A sensitivity analysis using alternate definitions of polycythemia was performed to capture all potential covariants. Multivariate regression analysis incorporating all potential covariants disclosed the independent OR of developing polycythemia (after adjusting for smoking and age) for log(testosterone) to be 15.0 (95% CI: 2.5, 90.8). Duration of testosterone therapy did not alter the risk of polycythemia. A direct relationship between testosterone and erythropoietin was observed ( P =0.05).
Higher trough serum testosterone concentrations but not duration of treatment predict the development of polycythemia in men receiving long-acting depot testosterone treatment.
Short acting injectable testosterone is associated with greater risk of erythrocytosis when compared with other formulations. The mechanism of the pathophysiology and its role on thromboembolic events remains unclear, though few data support an increased risk of CV events resulting from testosterone-induced erythrocytosis.
sTfR levels were not significantly different between young and older men at baseline. The changes in sTfR levels did not differ among the five dose groups either in young or in older men (ANOVA, young men P = 0.08, older men P = 0.054, Fig. 2B[2B).]). The percent change in sTfR levels during treatment was not significantly different between the young and older men. There was no significant difference in percent change from baseline in serum sTfR levels across testosterone dose groups in either younger or older men (Fig. 2B[2B]).
Testosterone dose or serum total and free testosterone levels were not significantly correlated with changes in sTfR levels (Fig. 2D[2D]).
Despite the strong association of testosterone dose and erythrocytosis, we found no dose-dependent effect of testosterone enanthate on erythropoietin or sTfR levels. Testosterone-associated increase in hemoglobin was not accompanied by a significant increase in erythropoietin or sTfR levels. Thus, the greater increase in hematocrit and hemoglobin observed in older men during testosterone therapy is not explained by the changes in erythropoietin and sTfR levels.