SUN-140 - Multiorgan Clinical Outcomes of Testosterone Replacement Therapy in Adult Men with Hypogonadism: A Systematic Review

Background
Male hypogonadism is a prevalent endocrine disorder of low testosterone that significantly impairs quality of life, sexual function, and metabolic health. Testosterone replacement therapy (TRT) restores physiological hormone levels, though multi-organ effects remain incompletely defined and clinically debated, particularly regarding long-term safety. This review synthesizes evidence on TRT’s multi-organ clinical efficacy and safety in hypogonadal men across clinical settings.
Methods
This systematic review was conducted per PRISMA 2020 guidelines (PROSPERO: CRD420261334073). PubMed/MEDLINE, Embase, Scopus, and Cochrane CENTRAL were searched for English-language studies without date restrictions. Eligible studies included randomized controlled trials (RCTs), observational studies, and systematic and narrative reviews evaluating TRT in adult hypogonadal men with multi-organ outcomes; select preclinical studies were included for mechanistic insights. Animal studies without relevant outcomes, case reports, and studies not reporting multi-organ outcomes were excluded. Study selection and data extraction were performed independently by multiple reviewers, with discrepancies resolved by a third reviewer. Quality appraisal used Cochrane RoB-2, NIH Quality Assessment Tool, SANRA-2, AMSTAR-2, and Modified SYRCLE, including only studies scoring ≥70%.
Results
Forty-two studies met inclusion criteria: RCTs, observational studies, systematic and narrative reviews, and select preclinical studies. TRT consistently improved sexual desire, libido, and satisfaction, with variable effects on erectile function. Metabolic benefits included improved insulin sensitivity, glycemic control, and body composition. Musculoskeletal effects included increased lean mass and strength. Cardiovascular outcomes were largely neutral, without consistent increases in major adverse events, though isolated thromboembolic events were reported. Hematologic effects included increased hemoglobin and hematocrit. Psychiatric outcomes improved mood, energy, and depressive symptoms, with inconsistent effects on cognition and major depressive disorder. Endocrine effects included suppression of the hypothalamic–pituitary–gonadal axis and reduced spermatogenesis. TRT was well tolerated, with mild adverse effects such as gynecomastia, fluid retention, gastrointestinal symptoms, and occasional liver enzyme elevations; serious events were rare.
Conclusion
TRT provides consistent biochemical and symptomatic benefits across sexual, metabolic, and musculoskeletal domains in hypogonadal men, though hematologic and reproductive monitoring remains essential. These findings support individualized use while underscoring the need for long-term, high-quality studies to better define multi-organ risks, benefit durability, and patient selection.

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