Abstract
BACKGROUND: Treatment of patients with erectile dysfunction (ED) was revolutionized by the development and approval of phosphodiesterase type 5 inhibitors (PDE5is), which have been repeatedly shown to be safe and effective in men with this condition. However, some patients do not respond to these agents and others may prefer an alternative therapy. AIM: The objective of this paper is to evaluate topical therapies for ED used in clinical studies, either as single agents or in combination with a PDE5i, and consequently determine which topical therapies meet the criteria of an 'ideal medication for ED.' METHODS: The PubMed database was searched to identify clinical studies of topical agents that have been evaluated in men with ED. This review was supplemented by a search of presentations at the 2024 annual meetings of the American Urological Association and Sexual Medicine Society of North America. RESULTS: The literature review and subsequent screening resulted in 39 clinical studies and 5 meeting abstracts for review. The studies demonstrated efficacy for intraurethral and topical alprostadil, topical prostaglandin E(1) ethyl ester, nitric oxide donors, testosterone (in selected patients), and a non-medicated hydro-alcoholic gel. The studies reviewed also demonstrated a significant benefit of adding topical alprostadil to therapy in patients with inadequate responses to PDE5is. An effective topical therapy delivered to its site of action with a rapid onset could improve patients' and partners' satisfaction with and acceptance of treatment. These actions have been demonstrated by a new over-the-counter agent, MED3000, authorized by the United States Food and Drug Administration, and for topical alprostadil, which is available with a prescription in the European Union. CLINICAL TRANSLATION: The availability of safe and effective topical ED therapy is an important addition to current treatment options for men with this condition. STRENGTHS AND LIMITATIONS: This study provides results from a comprehensive search strategy by including a wide range of search criteria. However, the heterogeneity of studies evaluated creates difficulties in directly comparing results from different studies. CONCLUSION: The results of this analysis show that current topical therapies can provide statistically and clinically significant improvements in erectile function in men with ED and may provide an effective alternative to PDE5i in men who require or prefer an alternative therapy.