PMID- 38224135 OWN - NLM STAT- MEDLINE DCOM- 20240116 LR - 20240405 IS - 1469-493X (Electronic) IS - 1361-6137 (Linking) VI - 1 IP - 1 DP - 2024 Jan 15 TI - Testosterone replacement in men with sexual dysfunction. PG - CD013071 LID - 10.1002/14651858.CD013071.pub2 [doi] LID - CD013071 AB - BACKGROUND: Clinical practice guidelines recommend testosterone replacement therapy (TRT) for men with sexual dysfunction and testosterone deficiency. However, TRT is commonly promoted in men without testosterone deficiency and existing trials often do not clearly report participants' testosterone levels or testosterone-related symptoms. This review assesses the potential benefits and harms of TRT in men presenting with complaints of sexual dysfunction. OBJECTIVES: To assess the effects of testosterone replacement therapy compared to placebo or other medical treatments in men with sexual dysfunction. SEARCH METHODS: We performed a comprehensive search of CENTRAL (the Cochrane Library), MEDLINE, EMBASE, and the trials registries ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform, with no restrictions on language of publication or publication status, up to 29 August 2023. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in men (40 years or over) with sexual dysfunction. We excluded men with primary or secondary hypogonadism. We compared testosterone or testosterone with phosphodiesterase-5 inhibitors (PDEI5I) to placebo or PDE5I alone. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the literature, assessed the risk of bias, extracted data, and rated the certainty of evidence (CoE) according to GRADE using a minimally contextualized approach. We performed statistical analyses using a random-effects model and interpreted them according to standard Cochrane methodology. Predefined primary outcomes were self-reported erectile dysfunction assessed by a validated instrument, sexual quality of life assessed by a validated instrument, and cardiovascular mortality. Secondary outcomes were treatment withdrawal due to adverse events, prostate-related events, and lower urinary tract symptoms (LUTS). We distinguished between short-term (up to 12 months) and long-term (> 12 months) outcomes. MAIN RESULTS: We identified 43 studies with 11,419 randomized participants across three comparisons: testosterone versus placebo, testosterone versus PDE5I, and testosterone with PDE5I versus PDE5I alone. This abstract focuses on the most relevant comparison of testosterone versus placebo. Testosterone versus placebo (up to 12 months) Based on a predefined sensitivity analysis of studies at low risk of bias, and an analysis combing data from the similar International Index of Erectile Function (IIEF-EF) and IIEF-5 instruments, TRT likely results in little to no difference in erectile function assessed with the IIEF-EF (mean difference (MD) 2.37, 95% confidence interval (CI) 1.67 to 3.08; I(2) = 0%; 6 RCTs, 2016 participants; moderate CoE) on a scale from 6 to 30 with larger values reflecting better erectile function. We assumed a minimal clinically important difference (MCID) of greater than or equal to 4. TRT likely results in little to no change in sexual quality of life assessed with the Aging Males' Symptoms scale (MD -2.31, 95% CI -3.63 to -1.00; I(2) = 0%; 5 RCTs, 1030 participants; moderate CoE) on a scale from 17 to 85 with larger values reflecting worse sexual quality of life. We assumed a MCID of greater than or equal to 10. TRT also likely results in little to no difference in cardiovascular mortality (risk ratio (RR) 0.83, 95% CI 0.21 to 3.26; I(2) = 0%; 10 RCTs, 3525 participants; moderate CoE). Based on two cardiovascular deaths in the placebo group and an assumed MCID of 3%, this would correspond to no additional deaths per 1000 men (95% CI 1 fewer to 4 more). TRT also likely results in little to no difference in treatment withdrawal due to adverse events, prostate-related events, or LUTS. Testosterone versus placebo (later than 12 months) We are very uncertain about the longer-term effects of TRT on erectile dysfunction assessed with the IIEF-EF (MD 4.20, 95% CI -2.03 to 10.43; 1 study, 42 participants; very low CoE). We did not find studies reporting on sexual quality of life or cardiovascular mortality. We are very uncertain about the effect of testosterone on treatment withdrawal due to adverse events. We found no studies reporting on prostate-related events or LUTS. AUTHORS' CONCLUSIONS: In the short term, TRT probably has little to no effect on erectile function, sexual quality of life, or cardiovascular mortality compared to a placebo. It likely results in little to no difference in treatment withdrawals due to adverse events, prostate-related events, or LUTS. In the long term, we are very uncertain about the effects of TRT on erectile function when compared to placebo; we did not find data on its effects on sexual quality of life or cardiovascular mortality. The certainty of evidence ranged from moderate (signaling that we are confident that the reported effect size is likely to be close to the true effect) to very low (indicating that the true effect is likely to be substantially different). The findings of this review should help to inform future guidelines and clinical decision-making at the point of care. CI - Copyright (c) 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. FAU - Lee, Hunju AU - Lee H AD - Department of Preventive Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea, South. FAU - Hwang, Eu Chang AU - Hwang EC AD - Department of Urology, Chonnam National University Medical School, Chonnam National University Hwasun Hospital, Hwasun, Korea, South. AD - Center of Evidence-Based Medicine, Institute of Convergence Science, Yonsei University, Seoul, Korea, South. FAU - Oh, Cheol Kyu AU - Oh CK AD - Department of Urology, Heaundae Paik Hospital, Inje University, Busan, Korea, South. FAU - Lee, Solam AU - Lee S AD - Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea, South. FAU - Yu, Ho Song AU - Yu HS AD - Department of Urology, Chonnam National University, Gwangju, Korea, South. FAU - Lim, Jung Soo AU - Lim JS AD - Division of Endocrinology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea, South. FAU - Kim, Hong Wook AU - Kim HW AD - Department of Urology, Konyang University College of Medicine, Daejeon, Korea, South. FAU - Walsh, Thomas AU - Walsh T AD - Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD, USA. FAU - Kim, Myung Ha AU - Kim MH AD - Yonsei Wonju Medical Library, Yonsei University Wonju College of Medicine, Wonju, Korea, South. FAU - Jung, Jae Hung AU - Jung JH AD - Center of Evidence-Based Medicine, Institute of Convergence Science, Yonsei University, Seoul, Korea, South. AD - Department of Urology, Yonsei University Wonju College of Medicine, Wonju, Korea, South. AD - Department of Precision Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea, South. FAU - Dahm, Philipp AU - Dahm P AD - Department of Urology, University of Minnesota, Minneapolis, Minnesota, USA. AD - Urology Section, Minneapolis VA Health Care System, Minneapolis, Minnesota, USA. LA - eng SI - ClinicalTrials.gov/NCT01816295 SI - ClinicalTrials.gov/NCT00244023 SI - ClinicalTrials.gov/NCT00696748 SI - ClinicalTrials.gov/NCT01419236 SI - ClinicalTrials.gov/NCT00799617 SI - ClinicalTrials.gov/NCT00512707 SI - ClinicalTrials.gov/NCT00240981 PT - Journal Article PT - Review PT - Systematic Review DEP - 20240115 PL - England TA - Cochrane Database Syst Rev JT - The Cochrane database of systematic reviews JID - 100909747 RN - 3XMK78S47O (Testosterone) SB - IM UOF - doi: 10.1002/14651858.CD013071 MH - Male MH - Humans MH - *Erectile Dysfunction/drug therapy MH - *Prostatic Hyperplasia/complications MH - Testosterone/adverse effects MH - Prostate MH - *Lower Urinary Tract Symptoms/drug therapy MH - *Cardiovascular Diseases PMC - PMC10788910 COIS- Hunju Lee (HL): editor for the Korean Satellite of Cochrane Urology, but was excluded from the editorial processing of this review. Eu Chang Hwang (ECH): editor for Cochrane Urology, but was excluded from the editorial processing of this review. Cheol Kyu Oh (CKO): none known. Solam Lee (SL): none known. Ho Song Yu (HSY): none known. Jung Soo Lim (JSL): none known. Hong Wook Kim (HWK): none known. Thomas Walsh (TW): Biote (Independent Contractor - Consultant). Myung Ha Kim (MHK): none known. Jae Hung Jung (JHJ): editor for Cochrane Urology, but was excluded from the editorial processing of this review. Philipp Dahm (PD): editor for Cochrane Urology, but was excluded from the editorial processing of this review. EDAT- 2024/01/15 12:42 MHDA- 2024/01/16 06:41 PMCR- 2025/01/15 CRDT- 2024/01/15 08:17 PHST- 2025/01/15 00:00 [pmc-release] PHST- 2024/01/16 06:41 [medline] PHST- 2024/01/15 12:42 [pubmed] PHST- 2024/01/15 08:17 [entrez] AID - CD013071.pub2 [pii] AID - 10.1002/14651858.CD013071.pub2 [doi] PST - epublish SO - Cochrane Database Syst Rev. 2024 Jan 15;1(1):CD013071. doi: 10.1002/14651858.CD013071.pub2.