SAT-150 Trends in Blood-Based Cardiometabolic Profiles During Testosterone Replacement Therapy: A Longitudinal Study of Over 4,000 Men

Abstract Disclosure: A.K. Clift: I am an employee of Manual (Menwell Ltd), a healthcare provider that provides testosterone replacement therapy. H. Johnson: I am an employee of Manual (Menwell Ltd), a healthcare provider that provides testosterone replacement therapy. V.N. Liu: I am an employee of Manual (Menwell Ltd), a healthcare provider that provides testosterone replacement therapy. D.R. Huang: I am an employee of Manual (Menwell Ltd), a healthcare provider that provides testosterone replacement therapy. M. Khera: consulting fees from Endo, Inc., serves as a consultant for Halozyme, Marius Pharmaceuticals, Petros Pharma, AbbVie, Inc., Tolmar, and Boston Scientific, and holds stocks of Sprout Pharmaceuticals. The bidirectional interplay between testosterone deficiency (TD) and cardiometabolic health in men is complex. Cross-sectional studies show associations between lower endogenous testosterone and poorer metabolic health, and trials report that testosterone replacement therapy (TRT) benefits metabolic health in men with metabolic syndrome or diabetes but without TD. However, the longitudinal impact of TRT on key cardiometabolic markers in men with TD is poorly understood. This retrospective cohort study utilized routinely collected data from men commencing TRT for TD with UK-based private healthcare providers. We examined trends over 12 months in the following markers: total cholesterol, HDL, LDL, HbA1c, triglycerides and the triglyceride: HDL ratio. Mixed effects methods were used to model marker trajectories during the course of TRT, and relative percentage changes were calculated from 0 to 12 months. Relative changes were estimated overall and in sub-groups (by age group, BMI group, and in men with elevated baseline marker results). The cohort comprised 4,307 men (median age 41 years; baseline BMI 28.4 kg/m²) starting TRT between Nov 2019 and Oct 2024. There were modest changes in total cholesterol (-7.20%, p<0.01), HDL (-11.38%, p<0.01), and HbA1c (-3.38%, p<0.01) over 12 months of TRT. No changes in LDL were observed (0%). Larger differences were observed for triglycerides and triglyceride:HDL ratios. The relative change in triglycerides at the cohort level was -28.37%; for men aged <50 this was -27.23%; for men aged 50+ this was -30.23% (all p<0.01). In men with baseline triglycerides >2.3mmol/L, the relative change at 12 months was -43.42% (p<0.01). The relative change in triglyceride:HDL ratio at 12months was -19.60%; in men aged <50 this was -19.50% and for men aged 50+ this was -25.64% (all p<0.01). Triglyceride:HDL changes across BMI categories ranged between -14.02% (up to 25) to -27.31% (30-39.9) (p<0.01). We observed that men with the highest baseline triglyceride:HDL ratios (>6) had a relative change of -66.49% at 12months (p=0.012). The cardiometabolic effects of TRT were most pronounced on triglyceride levels, with significant reductions observed over 12 months in both total triglycerides and the triglyceride:HDL ratio. The latter is a strong predictor of cardiometabolic risk. These reductions were of larger magnitude in men with elevated baseline values, suggesting potential of TRT to improve longer-term metabolic health in hypogonadal men. Further study is needed to quantify these potential benefits. Presentation: Saturday, July 12, 2025