Source: Medical Gas Research

PubMed ID: 42671404

DOI: 10.4103/mgr.MEDGASRES-D-25-00280

Benign prostatic hyperplasia is a common pathological condition in aging men. Although its pathophysiology is not yet fully understood, dysfunctions in the nitric oxide (NO) and hydrogen sulfide (H2S) signaling pathways may be critically involved. In the present review, we address the physiological roles of these gasotransmitters in the prostate and discuss how their modulation may be a valuable therapeutic strategy in benign prostatic hyperplasia. Reduced NO bioavailability, decreased expression of soluble guanylate cyclase, and increased oxidative stress are associated with prostatic smooth muscle hypercontractility, increased cell proliferation, and impaired prostatic blood flow, contributing to the development of benign prostatic hyperplasia. Similarly, reductions in H2S-synthesizing enzymes, including cystathionine γ-lyase, have been observed during the aging process, suggesting a link between impaired H2S signaling and benign prostatic hyperplasia progression. Considering the critical roles of both the NO and H2S pathways in benign prostatic hyperplasia pathogenesis, the pharmacological modulation of these signaling cascades has emerged as a key therapeutic approach. Phosphodiesterase 5 inhibitors and NO donors improved benign prostatic hyperplasia and benign prostatic hyperplasia-related symptoms in clinical and preclinical studies, mainly by reducing prostate smooth muscle tone and prostatic cell proliferation. On the other hand, the therapeutic role of H2S in benign prostatic hyperplasia is less explored, although recent data suggest a promising effect. Novel therapeutic strategies to treat benign prostatic hyperplasia experimentally have been emerging and include soluble guanylate cyclase stimulators/activators, the inhibition of multidrug resistance proteins or DNA methylation, and hybrid molecules that release both NO and H2S; however, more comprehensive clinical studies to assess their efficacy in humans are needed.