Update on late-onset hypogonadism: current concepts, controversies, clinical diagnosis, pathogenesis, and treatment approaches

Abstract Introduction Since its proposal in 2002, late-onset hypogonadism (LOH) has been a subject of considerable controversy. Although its status as a pathophysiological entity is undisputed, the underlying mechanisms remain contentious and are not fully understood. Objectives To evaluate current therapies for LOH, such as testosterone replacement therapy (TRT) and weight loss interventions, and to explore innovative anti-aging strategies aimed at counteracting age-related factors contributing to LOH. Methods A comprehensive literature review was conducted to explore the ongoing controversies and challenges in the clinical diagnosis of LOH. Additionally, the efficacy and limitations of current therapeutic approaches, including novel anti-aging strategies and combination therapies were critically examined. Results Current therapies address specific aspects of LOH, such as TRT for low testosterone levels and weight loss interventions for obesity, which is the strongest risk factor. However, these therapies have shortcomings, including potential health hazards associated with TRT and disputed efficacy of weight loss interventions. Recent discoveries have led to the development of innovative anti-aging strategies, which show promise in overcoming the limitations of existing methods. Several clinical trials have substantiated the efficacy of these novel approaches, particularly when used in combination therapies. Conclusions While further clinical trials are necessary, novel anti-aging strategies hold promise for enhancing the efficacy of existing LOH treatments and overcoming their limitations. These innovative approaches could potentially offer more effective solutions for managing LOH.