Real-World Outcomes and Safety of Testosterone Therapy: A Longitudinal, Retrospective Cohort Study of Over 9,000 Men

Abstract

Purpose: Trials of testosterone therapy (TTh) focus on transdermal or intramuscular preparations. In clinical practice, a range of administrations are utilised, often with adjunct therapies, but evidence is limited. This study characterised the safety and effectiveness of TTh over 12 months in a real-world setting. Materials and Methods: A retrospective cohort study of adults treated by a men's health provider in the United Kingdom for testosterone deficiency between 2019 and 2024. Mixed effects models and Kaplan-Meier methodology were used. Changes in total testosterone, free testosterone, haematocrit, and quality of life (QoL; Likert scales of 1-5) domains over 12 months were evaluated overall and by baseline testosterone-defined groups. Results: The cohort comprised 9,537 men (median age 42 years). Mean follow-up was 8.47 months. 8,517 were treated with sub-cutaneous testosterone injections (89.20%), 366 were prescribed transdermal testosterone (3.84%), 7,079 were prescribed human chorionic gonadotropin (75.23%), 675 (7.08%) were prescribed clomiphene citrate, and 1,308 (13.72%) were prescribed tadalafil (men may have received >1 treatment). Significant increases were observed in all 8 QoL domains, e.g., +1.26 points (95% confidence interval [CI]: 1.01 to 1.43) for libido. The mean increase in haematocrit by month 12 was 0.03 L/L (95% CI: 0.03 to 0.03). Trends and magnitude of increases in total and free testosterone and QoL did not differ between biochemical categories, with no difference in the rate of haematocrit exceeding 0.54 (p=0.18). Conclusions: TTh in a 'real-world setting' had a favourable safety profile and was associated with significant increases in men's sexual function, energy levels, life enjoyment, and performance in both work and sport. Future studies should support development of nuanced algorithms considering age, symptom severity and testosterone profiles to identify men likely to benefit from TTh.