Blood pressure responses to testosterone therapy are amplified by hematocrit levels in opioid-induced androgen deficiency: a double-blind, randomized, placebo-controlled trial

Our study aimed to examine the effect of testosterone replacement therapy (TRT) on blood pressure in opioid-treated men with relative hypogonadism, and whether the effect of TRT on blood pressure was modified by body composition, red blood cell levels, or carotid intima media thickness. Men (over 18 years old) receiving opioid treatment and total testosterone less than 12 nmol were randomly assigned to receive either TRT or placebo. Baseline and 6-month measurements included anthropometric measurements, office blood pressure (OBPM), 24-h ambulatory blood pressure, blood samples, and carotid ultrasound. The mean systolic OBPM increased by 6.2 mmHg (0.2-12.1) in the TRT group and decreased by 7.0 mmHg (1.0-15.1) in the placebo group, with a mean difference of 13.2 mmHg (3.4-23.1), P = 0.01. In the TRT group, a 10 mmHg increase in systolic OBPM was associated with an increase in hematocrit of 0.3% points (0.1-0.5) (P = 0.01), whereas no association was observed in the placebo group (P = 0.266). Daytime SBP showed a nonsignificant increase of 5.2 mmHg (-1.7, 12.1) (P = 0.134) in the TRT group compared to that in the placebo group. However, the impact of TRT on the increase in daytime ambulatory blood pressure was significantly accentuated by baseline values of BMI, hematocrit, and hemoglobin. In conclusion, TRT was associated with higher OBPM compared to placebo, and the increase in blood pressure was linked to higher hematocrit during TRT. Our data suggest that men with opioid-induced androgen deficiency, particularly those with obesity or red blood cell levels in the upper normal range, are more susceptible to increased daytime SBP during TRT.