A critical analysis of the quality of testosterone therapy randomized controlled trials

In recent years, the utilization of testosterone (T)s testing and prescriptions has experienced a significant surge. As a result, the market for testosterone therapy (TTh) has increased dramatically with the surge of T products undergoing trials. Our aim was to undertake a critical analysis of randomized controlled trials (RCTs) that focused on TTh, specifically with an emphasis on the quality of the trials and their delineation of adverse events (AE).

A literature review of PubMed was conducted to identify RCTs using TTh, excluding non-English, animal, or female-based studies. Trials were assessed for sample size, duration, pre-, and post-treatment T levels, adverse event definitions. We also assessed the reported rates of polycythemia (PCT), gynecomastia (GYN), major adverse cardiovascular events (MACE), and obstructive sleep apnea (OSA).

Thirty RCTs met the inclusion criteria, with a median study sample size of 76 and median follow-up of 8 months. The present analysis reveals that TTh trials are highly heterogeneous in both reporting of definitions and rates of AEs, such as PCT, GYN, and MACE. Among the included trials, 83% measured hematocrit (HCT) levels, but only 23% reported baseline values, with a median baseline HCT of 43% and an on-treatment median of 45%. GYN was reported in 17% of the RCTs, though none detailed the grade of GYN. MACE were reported in only 20% of the trials, with varying definitions. OSA was mentioned as an AE in 33% of trials, but only three reported incidence rates.

This analysis highlights the suboptimal reporting of AE outcomes in TTh RCTs. These findings underscore the need for a greater level of standardization in such trials.