Effects of Hydrogen Sulfide on Erectile Function and Its Possible Mechanism(s) of Action

Abstract

The current pharmacotherapy for erectile dysfunction (ED) relies significantly on the use of phosphodiesterase type 5 (PDE5) inhibitors, but quite a proportion of ED patients are resistant to this therapy, necessitating a search for an alternative treatment. We reviewed available published data to analyze current evidence of hydrogen sulfide (H(2) S) as a novel pharmacotherapeutic agent with supportive role in sexual function. To discuss the role of H(2) S in erectile function, its possible mechanism of action, and how this knowledge may be exploited for therapeutic use. Pubmed and Medline search was conducted to identify original articles and reviews. Data from peer-reviewed publications. Animal studies using different species, including in vitro study done in humans, show evidence of H(2) S's pro-erectile effects. The mechanism behind is still unclear, but evidence in literature points out the involvement of K(+) (ATP) channel, modulation of protein with anti-erectile effects, as well as involvement of the nitrergic pathway through a complex cross-talk. A new drug called H(2) S-donating sildenafil (ACS6), which incorporated an H(2) S-donating moiety in sildenafil, has been developed. While more studies are still needed, this heralded a new pharmacotherapeutical approach, which is multipronged in nature. Given the mounting evidence of H(2) S's role in erectile function and how it appears to achieve its pro-erectile effects through different mechanisms, H(2) S represents a potentially important treatment alternative or adjunct to PDE5 inhibitors.