Introduction: Laboratory experiments indicate that the nitric oxide erectile pathway is testosterone-dependent. Castration induces erectile dysfunction (ED) and reduction in nitric oxide synthase and in phosphodiesterase type 5 (PDE5) in the erectile tissue. Furthermore, castration causes apoptosis adversely affecting smooth muscle content and penile hemodynamics leading to veno-occlusive dysfunction. Testosterone therapy reverses these structural, biochemical, and physiological changes. In humans, testosterone therapy improves erectile function in men with hypogonadism. However, the efficacy of testosterone monotherapy may not be adequate because of the multifactorial nature of the pathophysiology of ED.
Methods: Preliminary data from a number of studies have been reviewed.
Results: There are emerging evidence-based benefits to using the combination of testoterone and PDE5 inhibitors. A recently published multicenter, randomized, placebo-controlled study evaluated the safety and efficacy of testosterone gel 1% plus sildenafil vs. placebo gel plus sildenafil, in producing an erectile response in hypogonadal men who had failed prior sildenafil alone for ED. Screening yielded a prevalence of hypogonadism in ED patients who failed prior sildenafil. Following randomization, the double-blinded treatment phase was 12 weeks. Testosterone therapy with testosterone gel significantly improved erectile function in response to sildenafil. In addition, it significantly improved orgasmic function and patient satisfaction.
Conclusion: It is important to screen all men with ED for hypogonadism, especially those with a history of inadequate response to prior PDE5 inhibitors. The combination of testosterone plus PDE5 inhibitors may be considered for the treatment of ED in men with low to low-normal testosterone levels, who had inadequate response to prior treatment with PDE5 inhibitors alone.