Presentation Authors: Garrick M. Greear*, La Jolla, CA, Yash Khandwala, Stanford, CA, Brian Nguyen, Tung-Chin Hsieh, La Jolla, CA
Introduction: Testosterone supplementation is known to stimulate erythropoiesis and can lead to erythrocytosis, which may be associated with adverse cardiovascular events. The mechanism by which erythrocytosis occurs is multifactorial, but long-acting formulations are believed to be associated with a lower risk of erythrocytosis compared to short-acting injections. We evaluated the available long-acting formulations of testosterone, subcutaneous testosterone pellets (TP) and testosterone undecanoate (TU), and their comparative risk of erythrocytosis.
Methods: A retrospective review of 127 patients treated with TP or TU for hypogonadism (total testosterone < 300 ng/dL) over a 5-year period was conducted. Men with hematopoietic disorders were excluded. Testosterone (T), free testosterone (FT), estradiol (E2), PSA, hemoglobin (Hgb), and hematocrit (Hct) were evaluated. Descriptive statistics (Pearson chi-square and t-test) and multivariate logistic regression were performed to evaluate variables associated with erythrocytosis, defined by Hct > 50%.
Results: Of 127 men reviewed, 79 received TP and 48 received TU. Baseline characteristics were similar between the groups, including age, BMI, and proportion of patients with diabetes, hypertension, hyperlipidemia, or history of cardiovascular disease. Pre-treatment mean total T (TP 188 ng/dL, TU 214 ng/dL, p = 0.063), FT (TP 38 ng/dL, TU 36 ng/dL, p = 0.60), PSA (TP 1.54 ng/mL, TU 1.70 ng/mL, p = 0.59), Hgb (TP 14.8 g/dL, TU 14.9 g/dL, p = 0.80), and Hct (TP 43.6%, TU 42.5%, p = 0.23) were similar between groups. Post-treatment T levels were higher in the TP group (mean T: TP 658 ng/dL, TU 530 ng/dL, p = < 0.01; mean peak T: TP 1039 ng/dL, TU 665 ng/dL, p < 0.01). Mean peak E2 levels were higher in the TP group (TP 59.7 pg/mL, TU 36.8 pg/mL, p < 0.01). Men on TP had a higher Hct (TP 48.6%, TU 46.4%, p < 0.01) and rate of erythrocytosis (TP 36.7%, TU 18.8%, p = 0.03). Longer duration on therapy was observed in the TP group (TP 40.1 mo., TU 18.5 mo., p = < 0.01) but no significant difference in the time to erythrocytosis (TP 13.1 mo., TU 7.4 mo., p = 0.11) was observed. On multivariate analysis, only pre-treatment hemoglobin was independently associated with increased risk of erythrocytosis (OR 1.92, 95% CI 1.24 - 2.98, p < 0.01).
Conclusions: Erythrocytosis following long-acting testosterone supplementation was observed more often in men receiving TP with higher mean and peak T levels. The most important factor associated with erythrocytosis appears to be baseline hemoglobin concentration. Patients at risk for erythrocytosis may be more appropriate candidates for TU.