Efficacy and safety of oral pentoxifylline on semen parameters and reproductive hormones in idiopathic male infertility: a systematic review and meta-analysis

Background: Male infertility accounts for nearly half of infertility cases, with abnormal semen quality being a major cause. Pentoxifylline (PTX), a methylxanthine derivative with antioxidant and anti-inflammatory properties, has been proposed to improve semen parameters, but evidence remains inconsistent. This systematic review and meta-analysis aimed to assess the efficacy and safety of oral PTX supplementation compared with placebo in improving semen parameters and reproductive hormone profiles in infertile men.

Methods: PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from inception to July 2025. Randomized controlled trials (RCTs) comparing oral PTX with placebo in infertile men were included. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Primary outcomes included semen parameters (sperm concentration, total motility, morphology, semen volume). Secondary outcomes comprised serum hormones [testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH)]. Data were pooled calculating mean difference (MD) with 95% confidence intervals (CIs).

Results: Five RCTs involving 455 participants were included. PTX dosages ranged from 800 to 1,200 mg/day, with treatment durations of 3 to 6 months. PTX supplementation correlated with increased total sperm motility (MD =10.44, 95% CI: 3.57–17.30) and normal morphology (MD =3.86, 95% CI: 1.01–6.71). Sperm concentration transiently improved at 3 months but did not differ significantly from placebo at 6 months. No significant differences were observed in testosterone (MD =0.22, 95% CI: −0.23 to 0.67) or FSH (MD =−1.51, 95% CI: −4.16 to 1.14) levels, whereas LH decreased marginally (MD =−0.97, 95% CI: −1.45 to −0.49). Reported adverse events were predominantly mild and gastrointestinal.

Conclusions: PTX supplementation appears to enhance sperm motility and morphology in infertile men with a favorable safety profile. Its effects on sperm concentration and reproductive hormones are less consistent, and evidence on ultimate clinical effectiveness regarding pregnancy and live birth rates remains unproven. Larger, high-quality trials with reproductive endpoints are needed to clarify its clinical role.