MP35-02: Comparison of prevalence of polycythemia between nasal testosterone gel vs intramuscular testosterone cypionate: Evaluation of data from an ongoing Phase IV, Open-label, Randomized Clinical Trial

Parris Diaz*, Daniel C. Gonzalez, Miami, FL, Jesse Ory, Halifax, Canada, Navin C. Balaji, Rohit Reddy, Manuel Molina, Ranjith Ramasamy, Miami, FL

Introduction: Recent studies suggests that the method of delivery may affect the prevalence of potential side effects such as polycythemia and decreased spermatogenesis in men on testosterone therapy. We hypothesized that intranasal short-acting testosterone would have a lower rate of polycythemia than injectable long-acting testosterone because shorter-acting formulations can more closely mimic normal physiology. Therefore, we compared the effects of nasal testosterone (NT) and injectable Testosterone Cypionate (TC) on hematocrit and serum testosterone levels in testosterone deficient men over 4-months.

Methods: This Phase IV, randomized, open-label clinical trial was performed on 30 symptomatic, testosterone-deficient men with at least two serum testosterone levels below 300 ng/dL drawn before 10AM. Men were randomized (1:1) to receive either nasal testosterone three times per day (5.5mg per nostril) or intramuscular TC (200mg) once every two weeks. Hematocrit and serum testosterone were evaluated before and after four months. The primary outcome was changes in hematocrit. Secondary outcomes were E, DHT, PSA and 17-OHP.

Trial registration: NCT04439799. Registered June 19,2020.

Results: Median participant age was 45 years-old. At baseline, serum T of all participants was 239.6 ng/dL and hematocrit of 43.1. The 4-month change in hematocrit in NT group (-1.1 from baseline) was significantly less than the change in hematocrit seen in the TC group (+5.1 from baseline), (p < 0.001, t = -7.6). Prevalence of polycythemia (HCT > 52%) after 4 months was 0% in NT group and 5.5% in TC. Both groups increased testosterone levels above baseline at 1 and 4 months, with a larger increase seen in the TC group compared to Natesto (p=0.029, t = 1.71). In the NT group, secondary outcomes E, DHT, PSA, and 17-OHP changed -2.9 (p = 0.54), +4.3 (p = 0.64), +0.3 (p = 0.52), and -1.6 ( p = 0.88) from baseline, respectively. In the TC group, secondary outcomes E, DHT, PSA, and 17-OHP changed +21.2 (p = 0.019), +4.3 (p = 0.64), +0.3 (p = 0.52), and -42.9 (p > 0.001) from baseline, respectively.

Conclusions: Short-acting nasal testosterone does not appear to increase serum hematocrit when compared to intramuscular testosterone cypionate, while both modalities returned men to a eugonadal serum testosterone level (>300 ng/dL) in 83% of men. In men who are at risk of developing polycythemia (obstructive sleep apnea, high baseline hematocrit), nasal testosterone gel or other short acting formulations should be considered.

Source of Funding: Investigator Initiated Grant funded by Acerus Pharmaceuticals.