Does testosterone supplementation increase PDE5-inhibitor responses in difficult-to-treat erectile dysfunction patients?

Introduction: Men with erectile dysfunction (ED) considered challenging-to-treat with PDE-5 inhibitors (PDE5i) include patients with severe neurological damage (e.g., due to radical prostatectomy), diabetes and severe vascular disease. Another factor that may limit PDE5i efficacy is the age-related decline of testosterone (T), occurring in 3 - 35% of older men depending on different cut-offs chosen. T regulation of PDE5 expression has been accepted as one of the major mechanisms controlling vasodilator mechanisms in penile tissue. Areas covered: We reviewed data regarding the use of T as a salvage therapy in PDE5i nonresponders. Expert opinion: Guidelines recommend that hypogonadal men with ED should commence therapy with PDE5i due to time course effects of T on erection that needs 6 - 12 weeks to occur. The possibility to 'salvage' some patients with low T not responding to PDE5i alone by adding T therapy should consider correct cut-off values, plasma T levels attained and androgen receptor (AR) polymorphism. Meta-analyses suggest that T treatment plus PDE5i yielded more effective results in noncontrolled versus controlled studies. We recommend T assay in all men with ED not responsive to PDE5i. Before commencing T treatment, side effects and consequent higher mortality in older frail men have to be avoided.