Treatment of Poor Sperm Quality and Erectile Dysfunction With Oral Pentoxifylline: A Systematic Review

Abstract

Background: Pentoxifylline (PTX) is a member of methylxanthine chemicals and a type of non-selective phosphodiesterase-5 inhibitors, which has been used in male infertility treatment to improve sperm quality and erectile dysfunction (ED) treatment. Mutually tight associations existed between ED and male infertility. Using PTX might kill two birds with one stone by improving sperm quality and erectile function in infertile men with ED.Methods: PubMed, Cochrane Library, EMBASE, and Web of Science were searched by October 2021. Based on available evidence from observational studies and randomized-controlled trials (RCTs), we conducted a systematic review to summarize the efficacy and safety of PTX in treating ED and male infertility. The protocol of the article was registered and updated in PROSPERO (CRD42021291396).Results: From 202 records, eight studies (7 RCTs) evaluating the role of PTX in ED and three studies (2 RCTs) assessing the efficacy of PTX in male infertility were included in the systematic review. Three studies (100.00%) and two studies (100.00%) reported the beneficial role of PTX in improving sperm progressive motility and normal sperm morphology rate, respectively. In contrast, only one study (33.33%) indicated the favorable role of PTX in enhancing sperm concentration. As for ED, three (60.00%) studies supported the treatment role of PTX alone in ED, and two studies (66.67%) favored the combination use of PTX and selective PDE5Is compared with selective PDE5Is alone. Safety analysis showed that PTX was a well-tolerated drug in ED and male infertility treatment.Conclusion: Given the association between ED and male infertility and satisfying findings from available evidence, PTX administration for the simultaneous treatment of poor sperm quality and mild ED in infertile men will highly enhance the treatment compliance. However, the finding should be treated carefully until validated by further studies.

Protective effects of pentoxifylline against chlorine-induced acute lung injury in rats

“…It increases the deformability of erythrocytes, reduce blood viscosity, and inhibit fibrotic progression [ 47 , 48 ]. Recent researches also demonstrated that PTX exerted beneficial effects in treating erectile dysfunction, hearing loss, Peyronie’s disease and osteoradionecrosis [ 49 – 52 ]. As well, in a prospective study, PTX inhibits COVID-19 severity by reduction of IL-6 and c-reactive protein (CRP) and improved prognosis of patients when combined with antioxidants [ 53 ].…”

Effect of antioxidants on semen parameters in men with oligo‐astheno‐teratozoospermia: a network meta‐analysis

“…76 Besides this "pharmacological" effect, pentoxifylline also exerts some pleiotropic "nutraceutical" anti-inflammatory and antioxidant activities. 77,78 As a methylxanthine derivative, it inhibits xanthine oxidase, 79 a key enzyme in purine metabolism that leads to the synthesis of oxidant radicals. Moreover, pentoxifylline exerts direct scavenger activity on ROS 79,80 and blocks their generation by neutrophils in response to proinflammatory cytokines.…”

“…Pentoxifylline has a specific action of inhibiting phosphodiesterases that degrade cyclic adenosine monophosphate (cAMP), involved, together with its downstream target enzyme, protein kinase A (PKA), in the regulation of sperm axoneme dynein dynamics 76 . Besides this “pharmacological” effect, pentoxifylline also exerts some pleiotropic “nutraceutical” anti‐inflammatory and antioxidant activities 77,78 . As a methylxanthine derivative, it inhibits xanthine oxidase, 79 a key enzyme in purine metabolism that leads to the synthesis of oxidant radicals.…”

Cyclic Adenosine Monophosphate: A Central Player in Gamete Development and Fertilization, and Possible Target for Infertility Therapies

“…Encouraging results were achieved with one particular analog, PTXm-1, which showed comparable beneficial effect on sperm motility as PTX, even at much lower concentrations, has less effect on sperm acrosome reaction, better sperm DNA integrity, extended sperm longevity and superior embryo quality [ 43 ]. In addition, other phosphodiesterase inhibitors, such as sildenafil, primarily a GMP-specific phosphodiesterase inhibitor, can increase cAMP levels in sperm cells [ 44 ]. A comparison of the usefulness of these different agents is a challenge for future research.…”