Erectile dysfunction (ED) is a common issue that affects older men and is often associated with various health conditions. Phosphodiesterase 5 inhibitors are commonly used to treat ED; however, their effectiveness may be limited, or the medication may be contraindicated. Therefore, topical gels are being developed as an alternative option for the pharmacologic treatment of ED. This review aimed to provide an overview of the efficacy and safety of topical agents for the treatment of ED. The PubMed, Cochrane, Embase, and Web of Science databases were searched. Articles were included that investigated ED and topical agents operating through the skin of the penis, evaluated the effectiveness of the treatment, and involved patients randomized into groups. Topical alprostadil, glyceryl trinitrate (MED2005), and an over-the-counter formulation (MED3000) were used as alternative treatments for ED in 7 articles, which included 3475 patients. Topical alprostadil induced an erection in 67% to 75% of patients. Adequate erections for vaginal penetration were reported in 38.7% of the alprostadil-treated patients vs 6.9% of the placebo-treated patients. Topical alprostadil significantly and dose dependently improved the total score change on the International Index of Erectile Function as compared with the placebo. MED2005 exhibited a rapid onset of action, with nearly 70% effectiveness within 10minutes. MED3000 met the minimal clinically important difference threshold of a 4-point increase on the erectile function domain of the International Index of Erectile Function, with an improvement of 5.73 points in 24weeks. Topical therapy for ED also had acceptable safety profiles. Topical agents via various mechanisms are effective and well-tolerated treatments for ED. A fast-acting drug that significantly reduces side effects as compared with other options has been discovered. However, its efficacy relative to current first-line therapies remains unclear. Topical agents present a viable therapeutic alternative for individuals who are unable or unwilling to take oral phosphodiesterase 5 inhibitors.
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