A combination of phosphodiesterase type 5 inhibitor and tamoxifen for acute Peyronie’s disease: the first clinical signals

ObjectivesTo investigate which phosphodiesterase (PDE) isoforms are expressed in fibroblasts isolated from the tunica albuginea (TA) of patients with Peyronie's disease (PD), and to measure the potency of PDE inhibitors in preventing transformation of these fibroblasts to profibrotic myofibroblasts.Materials and MethodsFibroblasts isolated from the TA of men undergoing surgery for correction of PD curvature were transformed to myofibroblasts using transforming growth factor beta‐1. The expression of 21 PDE isoforms was investigated using quantitative reverse transcriptase‐polymerase chain reaction and protein analysis, as were the effects of various PDE inhibitors on prevention of myofibroblast transformation. Intracellular cAMP and cGMP in the presence of PDE inhibitors were quantified using cGMP/cAMP enzyme‐linked immunosorbant assay assays.ResultsWe found that PDE1A, 1C, 4, 5A, 7B and 8B were expressed at mRNA and protein levels. Selective inhibitors of these enzymes prevented myofibroblast transformation in a concentration‐dependent manner, with PDE1 inhibitor ITI‐214 and PDE4 inhibitors roflumilast and roflumilast N‐oxide showing greatest potency. ITI‐214 and roflumilast N‐oxide increased intracellular cAMP, but not cGMP, in a concentration‐dependent manner.ConclusionsThis is the first demonstration of the expression of PDE1, 7 and 8 isoforms, and the function of PDE1 and PDE4 in human TA fibroblasts. The ability of inhibitors of these enzymes to prevent myofibroblast transformation suggests that such inhibitors can be developed to treat acute PD.

show abstract

Acute Phase Peyronie’s Disease: Where Do We Stand?

Douroumis,

Kotrotsios,

Katsikatsos

et al. 2024

Cureus

View full text Add to dashboard Cite

Peyronie’s disease (PD) is a common benign condition characterized by superficial fibrosis and scar formation at the tunica albuginea of the penis, eventually leading to penile curvature. It is believed that penile micro-traumas during intercourse and subsequent activation of inflammatory processes constitute the pathogenetic basis of the disease. Routinely, PD is divided into acute and chronic phases, with pain during erection or flaccid state being the hallmark of the former. Surgical intervention should be avoided during the acute phase, as the risk of recurrence or progression of penile deformity during this stage might affect the optimal outcomes of the procedure. During this stage, many conservative treatment options have been suggested, including oral, topical, and intralesional therapies, extracorporeal shock wave therapy (ESWT), and penile traction therapy (PTT). Currently, the optimal treatment consists of a combined treatment strategy with phosphodiesterase type 5 inhibitors (PDE5Is), ESWT for pain management, PTT, and intralesional therapies. Large, well-designed randomized controlled trials (RCTs) are necessary to further elucidate the most efficient treatment option for acute phase PD.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

A combination of phosphodiesterase type 5 inhibitor and tamoxifen for acute Peyronie’s disease: the first clinical signals

Cited by 3 publications

References 25 publications

Commentary on “Phosphodiesterase type 5 inhibitors do not prevent curvature progression but shorten pain duration in the active phase of Peyronie’s disease: a retrospective cohort study”

Commentary on “Phosphodiesterase type 5 inhibitors do not prevent curvature progression but shorten pain duration in the active phase of Peyronie’s disease: a retrospective cohort study”

Inhibition of phosphodiesterases 1 and 4 prevents myofibroblast transformation in Peyronie's disease

Acute Phase Peyronie’s Disease: Where Do We Stand?

Contact Info

Product

Resources

About