Treating erectile dysfunction when PDE5 inhibitors fail

New oral drugs, especially phosphodiesterase type 5 (PDE5) inhibitors, have revolutionalised the treatment of erectile dysfunction by decreasing reliance on more invasive options. These inhibitors compete with cyclic GMP (guanosine monophosphate) for the PDE5 receptor site. Sexual arousal activates the nitric oxide-cyclic GMP pathway, leading to relaxation of cavernosal smooth muscle cells, engorgement of lacunar spaces, and erection. PDE5 hydrolyses cyclic GMP to 5-GMP, which terminates the pathway and produces detumescence, so that PDE5 inhibitors result in increased intracellular concentrations of cyclic GMP and erection. Three potent selective PDE5 inhibitors (sildenafil (Viagra; Pfizer), tadalafil (Cialis; Lilly), and vardenafil (Levitra; Bayer)) are currently available. Although large multicentre clinical trials have shown the efficacy and tolerability of these drugs in erectile dysfunction with various aetiologies and a broad range of severity, 30-35% of patients fail to respond. The reported 62% prescription renewal rate at three to four months of follow-up, which dropped to around 30% by 6-12 months, suggests that patients stop taking the drug for reasons other than failure of treatment.1 The reasons for acute or delayed failure include severe erectile dysfunction at presentation, worsening of endothelial dysfunction and progression of penile atherosclerosis, erectile dysfunction after radical prostatectomy, unrecognised hypogonadism, inadequate patient education and incorrect drug usage, the development of tachyphylaxis (drug tolerance), and psychosocial factors. Alternative treatment methods, education on the use of the drug, androgen replacement, lifestyle changes, correction of risk factors, and relationship or psychosexual counselling have been reported. We searched PubMed and Medline for papers published from January 1980 to May 2005, using the term “erectile dysfunction”. We selected papers (published in English) on the management of erectile dysfunction and erectile dysfunction that does not respond to oral drugs. We review the treatment options available to primary care doctors and specialists who treat sexual dysfunction and …