Evaluating the impact of testosterone replacement therapy on carotid atherosclerosis: a systematic review and meta-analysis
Creators: name: Haider, Syed Hamza
name: Irfan, Areeka
name: Sheikh, Samir Mustafa
name: Abid, Muhammad Taha
name: Naz, Turba
name: Abbas, Mudassir
name: Raza, Alishba
Publisher: name: Taylor & Francis
Year: 2024
Subjects: Cell Biology
Biological Sciences not elsewhere classified
Science Policy

description: <b>Aim:</b> This meta-analysis investigates the association between testosterone replacement therapy [TRT] and carotid artery atherosclerosis. <b>Methods:</b> 3 databases were searched for studies up to June 2023 per the PRISMA guidelines. The eligibility criteria comprised RCTs and observational studies involving hypogonadal males receiving exogenous testosterone, in which CIMT was assessed. CAA was the primary outcome, whereas secondary outcomes included HDL, LDL, CRP, total cholesterol and total testosterone. The statistical analysis was performed using Review Manager. <b>Results:</b> Statistical analysis revealed no association between TRT and assessed outcomes. There was a significant increase in total testosterone levels, depicting indirect anti-atherosclerotic effects of TRT. <b>Conclusion:</b> Meta-analysis shows no relation between TRT and CIMT or other markers, allowing its safe usage for hypogonadal males. Cardiovascular diseases, including atherosclerosis, are major global health concerns, with carotid artery atherosclerosis (CAA) being a critical risk factor for ischemic stroke. Testosterone replacement therapy (TRT) is administered to individuals with low testosterone levels (hypogonadism), aiming to restore hormonal balance and potentially improve various aspects of health, including mood, energy levels and sexual function. TRT has been associated with both potential benefits, such as improved lipid profiles and reduced inflammatory markers and concerns, including adverse cardiovascular events. Conducting a comprehensive meta-analysis focusing on the relationship between TRT and CAA, particularly assessing carotid intima-media thickness (CIMT), is crucial for understanding TRT's impact on cardiovascular health and guiding clinical decision-making for individuals with hypogonadism. Meta-analysis was conducted adhering to PRISMA guidelines, utilizing PubMed, Cochrane and MEDLINE databases up to June 2023. Selection criteria included randomized control trials and observational studies with at least 16 weeks follow-up, focusing on males with hypogonadism comparing TRT with Placebo, assessing CIMT as a marker of carotid atherosclerosis. Statistical analysis was performed using Review Manager 5.3, employing a random-effects model, subgroup analysis and sensitivity analysis to evaluate heterogeneity and potential biases. The screening of 844 articles resulted in the selection of four studies comprising 184 participants, assessing the effects of testosterone replacement therapy (TRT) on atherosclerotic markers in hypogonadal males. No significant relationship was found between TRT and carotid intimal media thickness (CIMT), HDL, LDL, CRP, or total cholesterol. However, TRT significantly increased total testosterone levels. Subgroup analysis showed insignificant differences in outcomes between randomized controlled trials (RCTs) and observational studies, with overall minimal safety risks associated with TRT observed across atherosclerotic markers. Study involving 184 hypogonadal males found no significant association between CIMT and TRT, indicating safe usage of TRT without major side effects on carotid artery health. TRT showed no significant impact on HDL, LDL, CRP, or total cholesterol levels, but significantly increased total testosterone levels, potentially benefiting hypogonadal patients. Despite limitations such as small sample sizes and variations in TRT dosages and patient comorbidities, the study's comprehensive analysis enhances understanding of TRT's effects on atherosclerosis risk markers. TRT in hypogonadal males is not associated with progression of carotid artery atherosclerosis (CAA) but increases total testosterone levels, suggesting potential anti-atherosclerotic effects. This indicates its safety and potential benefits in hypogonadism management. Further research is required for a comprehensive risk-benefit assessment.