Endocrine-metabolic crosstalk in erectile dysfunction: mechanistic insights and therapeutic implications

Erectile dysfunction (ED) is a prevalent male sexual disorder frequently coexisting with cardiometabolic diseases. Although phosphodiesterase type 5 inhibitors remain the first-line therapy, limited efficacy or safety concerns in some patients highlight the need for alternative approaches. Emerging evidence demonstrates that endocrine abnormalities-including dysregulation of testosterone, estradiol, prolactin, and thyroid hormones-play crucial roles in the pathogenesis of ED. These hormones influence erectile capacity through central neuroendocrine and peripheral vascular mechanisms, while their interaction with metabolic disorders such as obesity and diabetes further exacerbates disease severity. We searched PubMed, Web of Science, and Embase up to August 2025 for studies examining hormonal mechanisms, clinical manifestations, and therapeutic interventions in ED. Current findings indicate that androgen deficiency impairs erection via a threshold mechanism; estradiol exerts bidirectional effects on libido and endothelial function; both hyper- and hypoprolactinemia disrupt sexual performance; and thyroid dysfunction is associated with ED, with restoration of euthyroidism being linked to improvement in erectile function in selected patients. Therapeutic options include testosterone replacement, selective estrogen receptor modulators, aromatase inhibitors, dopamine agonists, and thyroid hormone therapy, often combined with metabolic or lifestyle interventions. Integrating multi-hormonal regulation with metabolic health may shift ED management from symptomatic control toward precision, individualized medicine.