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

INTRODUCTION: 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). METHODS: 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). RESULTS: 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. DISCUSSION: 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.