Comparison of Hematocrit Change in Testosterone-deficient Men Treated with Intranasal Testosterone Gel Vs Intramuscular Testosterone Cypionate: A Randomized Clinical Trial.

PURPOSE:Our primary aim was to compare changes in hematocrit in testosterone-deficient men treated with intranasal testosterone gel vs intramuscular testosterone cypionate.MATERIALS AND METHODS:This 2-arm, open-label, randomized trial recruited men with testosterone deficiency at the University of Miami between August 2020 and October 2022. Men with 2 total testosterone levels <350 ng/dL and hypogonadal symptoms, aged 18-75 years were randomly assigned to receive either intranasal testosterone gel 11 mg 3 times daily or intramuscular testosterone cypionate 200 mg every 2 weeks. The primary outcome was change in hematocrit after 4 months of treatment. Secondary outcomes were changes in serum testosterone, estradiol, prostate-specific antigen, 17-hydroxyprogesterone, and the 6-item International Index of Erectile Function.RESULTS:Of the 81 men randomized, 54 completed treatment (intranasal n=23; intramuscular n=31). The mean age was 47.5 vs 49.5 years, with mean baseline testosterone of 244.6 vs 240.7 ng/dL and mean hematocrit of 44.4% vs 42.7% in intranasal vs intramuscular groups, respectively. Men who received intramuscular injections had a significant increase after 4 months of treatment in mean hematocrit from 42.7% to 46.6% (P < .0001), but there was no significant change in men who received intranasal gel (P = .233). Men in both groups experienced significantly increased serum testosterone levels throughout the study period, though a larger increase was seen in men treated with intramuscular injections (mean change 511 vs 283, P = .025). Men who received injections also experienced an increase in estradiol (mean change 22.9, P < .001), decrease in 17-hydroxyprogesterone (mean change -39.8, P < .0001), and increase in the 6-item International Index of Erectile Function score (mean change 4.8, P = .015); men treated with intranasal gel experienced no such changes. Prostate-specific antigen levels were stable in both groups.CONCLUSIONS:Intranasal testosterone gel does not appear to significantly affect hematocrit levels. Men who wish to avoid polycythemia or changes in estradiol or 17-hydroxyprogesterone levels may benefit from short-acting testosterone therapy formulations such as intranasal gel.