Symptomatic benefits of testosterone treatment in patient subgroups: a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis

• Published in: The Lancet. Healthy longevity 2023-10, Vol.4 (10), p.e561-e572
• Main Authors: Hudson, Jemma, Cruickshank, Moira, Quinton, Richard, Aucott, Lorna, Wu, Frederick, Grossmann, Mathis, Bhasin, Shalender, Snyder, Peter J, Ellenberg, Susan S, Travison, Thomas G, Brock, Gerald B, Gianatti, Emily J, van der Schouw, Yvonne T, Emmelot-Vonk, Marielle H, Giltay, Erik J, Hackett, Geoff, Ramachandran, Sudarshan, Svartberg, Johan, Hildreth, Kerry L, Antonic, Kristina Groti, Tenover, Joyce Lisa, Tan, Hui Meng, Ho Chee Kong, Christopher, Tan, Wei Shen, Marks, Leonard S, Ross, Richard J, Schwartz, Robert S, Manson, Paul, Roberts, Stephen A, Skovsager Andersen, Marianne, Velling Magnussen, Line, Aceves-Martins, Magaly, Gillies, Katie, Hernández, Rodolfo, Oliver, Nick, Dhillo, Waljit S, Bhattacharya, Siladitya, Brazzelli, Miriam, Jayasena, Channa N
• Format: Article
• Language: English
• Subjects: Erectile Dysfunction - drug therapy; Humans; Hypogonadism - drug therapy; Male; Obesity - drug therapy; Quality of Life; Testosterone - therapeutic use
• ISSN: 2666-7568; 2666-7568
• DOI: 10.1016/S2666-7568(23)00169-1

Testosterone replacement therapy is known to improve sexual function in men younger than 40 years with pathological hypogonadism. However, the extent to which testosterone alleviates sexual dysfunction in older men and men with obesity is unclear, despite the fact that testosterone is being increasingly prescribed to these patient populations. We aimed to evaluate whether subgroups of men with low testosterone derive any symptomatic benefit from testosterone treatment. We did a systematic review and meta-analysis to evaluate characteristics associated with symptomatic benefit of testosterone treatment versus placebo in men aged 18 years and older with a baseline serum total testosterone concentration of less than 12 nmol/L. We searched major electronic databases (MEDLINE, Embase, Science Citation Index, and the Cochrane Central Register of Controlled Trials) and clinical trial registries for reports published in English between Jan 1, 1992, and Aug 27, 2018. Anonymised individual participant data were requested from the investigators of all identified trials. Primary (cardiovascular) outcomes from this analysis have been published previously. In this report, we present the secondary outcomes of sexual function, quality of life, and psychological outcomes at 12 months. We did a one-stage individual participant data meta-analysis with a random-effects linear regression model, and a two-stage meta-analysis integrating individual participant data with aggregated data from studies that did not provide individual participant data. This study is registered with PROSPERO, CRD42018111005. 9871 citations were identified through database searches. After exclusion of duplicates and publications not meeting inclusion criteria, 225 full texts were assessed for inclusion, of which 109 publications reporting 35 primary studies (with a total 5601 participants) were included. Of these, 17 trials provided individual participant data (3431 participants; median age 67 years [IQR 60–72]; 3281 [97%] of 3380 aged ≥40 years) Compared with placebo, testosterone treatment increased 15-item International Index of Erectile Function (IIEF-15) total score (mean difference 5·52 [95% CI 3·95–7·10]; τ2=1·17; n=1412) and IIEF-15 erectile function subscore (2·14 [1·40–2·89]; τ2=0·64; n=1436), reaching the minimal clinically important difference for mild erectile dysfunction. These effects were not found to be dependent on participant age, obesity, presence of diabetes, or baseline serum tota