Erectile dysfunction (ED) is a prevalent condition affecting male sexual health, characterized by the inability to achieve or maintain satisfactory erections. ED has a multifactorial pathogenesis in which psychological, hormonal, neurologic, cardiovascular, and lifestyle factors all contribute to a progressive decline of erectile function. A critical underlying mechanism involves oxidative stress (OS), an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, which disrupts endothelial function, reduces nitric oxide (NO) bioavailability, and contributes to vascular dysfunction. This narrative review explores the interplay between OS and ED, focusing on the roles of ROS sources such as NADPH oxidase, xanthine oxidase, uncoupled nitric oxide synthase, and mitochondrial dysfunction. It examines the impact of OS on chronic conditions like hypertension, diabetes mellitus, hyperlipidemia, hypogonadism, and lifestyle factors like smoking and obesity, which exacerbate ED through endothelial and systemic effects. Emerging research underscores the potential of antioxidant therapies and lifestyle interventions to restore redox balance, improve endothelial function, and mitigate ED's progression. This review also highlights gaps in understanding the molecular pathways linking ROS to ED, emphasizing the need for further research to develop targeted therapeutic strategies.
International journal of molecular sciences. 2025 Mar 27*** epublish ***
Dake Zhu, Quan Minh Pham, Chunlin Wang, Elena Colonnello, Dimitri Yannas, Bac Hoai Nguyen, Yan Zhang, Emmanuele A Jannini, Andrea Sansone
Chair of Endocrinology and Medical Sexology (ENDOSEX), Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy., Department of Andrology and Sexual Medicine, Hanoi Medical University Hospital, Hanoi 100000, Vietnam., Department of Infertility and Sexual Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.