Exploring testosterone’s influence on cardiovascular, metabolic, reproductive, and mental health

For decades, testosterone has been recognized as the primary driver of male reproductive development and secondary sex characteristics. Yet its influence extends beyond fertility and sexual function, touching nearly every system in the body. Declines in testosterone, particularly in aging men, are associated with osteoporosis, metabolic syndrome, cardiovascular disease, and depression. At the same time, excessive levels carry risks, including infertility or aggressive cancers. Traditional treatment approaches, such as testosterone replacement therapy (TRT), often struggled with balancing benefits against potential harms. Due to these challenges, there is a growing need for in-depth research on testosterone’s multifaceted mechanisms, associated disease risks, and personalized therapeutic strategies.

A new comprehensive review (DOI: 10.1002/uro2.115), published February 18, 2025, in UroPrecision, examines the complex relationship between testosterone and men’s health. Conducted by researchers from institutions in Germany, Qatar, Jordan, and Hungary, the study explores testosterone’s influence on cardiovascular, metabolic, reproductive, and mental health. It also evaluates how precision medicine and artificial intelligence are reshaping diagnosis and therapy for testosterone-related disorders. By integrating clinical evidence with biomarker advances, the paper provides a roadmap for more personalized and effective treatment strategies, particularly for conditions such as hypogonadism, infertility, and age-related decline.

The review details how testosterone production is tightly regulated through the hypothalamic-pituitary-gonadal axis, influencing libido, muscle growth, fat distribution, bone density, and mood. Imbalances manifest as hypogonadism, with symptoms ranging from erectile dysfunction to osteoporosis, or hypergonadism, characterized by excess hair growth, mood changes, and infertility. Treatments include TRT via injections, gels, or implants, alongside emerging alternatives like clomiphene citrate or gonadotropin therapy. However, concerns remain about cardiovascular safety, prostate health, and long-term outcomes.

Biomarker research is revolutionizing testosterone management. Traditional measures such as free testosterone and sex hormone-binding globulin are now complemented by advanced tools like liquid chromatography-mass spectrometry and novel indicators such as insulin-like factor 3. Genomic and proteomic profiling further identify patient-specific variations in testosterone metabolism and androgen receptor sensitivity. Artificial intelligence is emerging as a powerful aid, integrating clinical and genetic data to optimize TRT dosing, predict outcomes, and minimize risks. The authors emphasize that combining biomarkers, precision medicine, and AI may finally resolve long-standing debates over testosterone therapy’s safety and efficacy.

Testosterone is not merely a hormone of reproduction—it is a hormone of life. Our review shows how precision medicine and advanced diagnostics can move treatment beyond the ‘one-size-fits-all’ model. By considering genetic, hormonal, and lifestyle factors, we can tailor testosterone therapies that maximize benefits while minimizing risks. This personalized approach is especially critical for aging men, who face rising risks of cardiovascular disease, metabolic disorders, and cognitive decline. The future of men’s health lies in individualized, data-driven strategies.”

Dr. Aksam Yassin, lead author 

The findings hold broad clinical significance. Personalized testosterone therapy could transform care for millions of men worldwide, offering safer management of hypogonadism, improved fertility support, and enhanced protection against age-related conditions such as osteoporosis, heart disease, and Alzheimer’s disease. In reproductive health, testosterone is even being investigated as a potential male contraceptive. Integration of biomarkers, genetic testing, and AI will allow clinicians to better predict who will benefit most from therapy and who may face adverse effects. These innovations highlight a future where testosterone treatment is not only about restoring levels but about optimizing lifelong health outcomes.