The effects and safety of testosterone replacement therapy for men with hypogonadism: the TestES evidence synthesis and economic evaluation

• Published in: Health technology assessment (Winchester, England) England), 2024-08, Vol.28 (43), p.1-210
• Main Authors: Cruickshank, Moira, Hudson, Jemma, Hernández, Rodolfo, Aceves-Martins, Magaly, Quinton, Richard, Gillies, Katie, Aucott, Lorna S, Kennedy, Charlotte, Manson, Paul, Oliver, Nicholas, Wu, Frederick, Bhattacharya, Siladitya, Dhillo, Waljit S, Jayasena, Channa N, Brazzelli, Miriam
• Format: Article
• Language: English
• Subjects: Adult; Aged; cardiovascular diseases; Cardiovascular Diseases - mortality; Cost-Benefit Analysis; economic evaluation; Hormone Replacement Therapy; Humans; hypogonadism; Hypogonadism - drug therapy; individual participant data meta-analysis; Male; Middle Aged; Quality of Life; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; sexual function; Technology Assessment, Biomedical; testosterone; Testosterone - adverse effects; Testosterone - therapeutic use
• ISSN: 2046-4924; 1366-5278; 2046-4924
• DOI: 10.3310/JRYT3981

Low levels of testosterone cause male hypogonadism, which is associated with sexual dysfunction, tiredness and reduced muscle strength and quality of life. Testosterone replacement therapy is commonly used for ameliorating symptoms of male hypogonadism, but there is uncertainty about the magnitude of its effects and its cardiovascular and cerebrovascular safety. The primary aim was to evaluate the safety of testosterone replacement therapy. We also assessed the clinical and cost-effectiveness of testosterone replacement therapy for men with male hypogonadism, and the existing qualitative evidence on men's experience and acceptability of testosterone replacement therapy. Evidence synthesis and individual participant data meta-analysis of effectiveness and safety, qualitative evidence synthesis and model-based cost-utility analysis. Major electronic databases were searched from 1992 to February 2021 and were restricted to English-language publications. We conducted a systematic review with meta-analysis of individual participant data according to current methodological standards. Evidence was considered from placebo-controlled randomised controlled trials assessing the effects of any formulation of testosterone replacement therapy in men with male hypogonadism. Primary outcomes were mortality and cardiovascular and cerebrovascular events. Data were extracted by one reviewer and cross-checked by a second reviewer. The risk of bias was assessed using the Cochrane Risk of Bias tool. We performed one-stage meta-analyses using the acquired individual participant data and two-stage meta-analyses to integrate the individual participant data with data extracted from eligible studies that did not provide individual participant data. A decision-analytic Markov model was developed to evaluate the cost per quality-adjusted life-years of the use of testosterone replacement therapy in cohorts of patients of different starting ages. We identified 35 trials (5601 randomised participants). Of these, 17 trials (3431 participants) provided individual participant data. There were too few deaths to assess mortality. There was no difference between the testosterone replacement therapy group (120/1601, 7.5%) and placebo group (110/1519, 7.2%) in the incidence of cardiovascular and/or cerebrovascular events (13 studies, odds ratio 1.07, 95% confidence interval 0.81 to 1.42;  = 0.62). Testosterone replacement therapy improved quality of life and sexual function in almost all patient