Adjunct pentoxifylline offers limp promise for ED

The addition of the oral phosphodiesterase-5 (PDE-5) inhibitor pentoxifylline to sildenafil failed to show benefit in men with erectile dysfunction (ED) with suboptimal response to sildenafil, a Singapore study shows.

Despite evidence reflecting the efficacy of PDE-5 inhibitors in ED, about a third of patients still fail to respond. [Urology 2000;56:635-640; Urology 2001;57:1141-1144] “[Such cases might] require invasive second- or third-line treatments (ie, intracavernosal injection of vasodilators and surgical implantation of penile prostheses),” said the researchers, hence the need to establish other noninvasive alternatives.

The effect of pentoxifylline 400 mg was compared against placebo in 50 men with ED (mean age 59.7 years) from the National University Hospital, Singapore. Men were randomized 1:1 to receive thrice-daily doses of either drug on top of on-demand sildenafil 100 mg for 8 weeks. All participants were cautioned against any herbal remedies or other medications for ED. [Sex Med 2019;doi:10.1016/j.esxm.2019.08.012]

At 8 weeks, IIEF*-5 scores were similar between the pentoxifylline and the placebo arms (mean, 14.11 and 14.87; unadjusted mean difference, -0.76, 95 percent confidence interval [CI], -4.01 to 2.49; p=0.641), which were maintained even after adjusting for baseline scores (adjusted mean difference, -0.35, 95 percent CI, -2.00 to 1.31; p=0.673).

Of note was the improvement in ‘overall satisfaction’ in the IIEF score favouring pentoxifylline over placebo (unadjusted mean difference, 0.12, 95 percent CI, -1.49 to 1.25), which became significant after adjusting for baseline scores (adjusted mean difference, 1.11, 95 percent CI, 0.10–2.12; p=0.032).

“This … may suggest other possible aspects of sexual function not clearly evaluated in the IIEF, thus suggesting [that] pentoxifylline improves aspects of ED not fully evaluated by the IIEF,” said the researchers.

Fifteen adverse events were reported, the most common being gastrointestinal (eg, abdominal discomfort, distention, or bloating; bleeding from piles; change in bowel habits; and nausea) and neurologic (eg, fatigue, giddiness, headache, and lethargy) in nature.

There was a relatively high rate of noncompliance observed overall (33 percent) which, according to the researchers, could be due to the frequency of drug dosing. Nonetheless, given the 8-week treatment period as opposed to the 4-week treatment span in another trial, [Int Urol Nephrol 2008;40:133-136] the high noncompliance rate could not have contributed to the study drug’s lack of efficacy, the researchers pointed out.

“[Although] pentoxifylline is … used for chronic occlusive arterial disease, it improves capillary blood flow,” explained the researchers, citing evidence asserting the impact of pentoxifylline in increasing the penile brachial pressure index in men with ED. [Cochrane Database Syst Rev 2015;9:CD005262; Br J Urol 1996;77:563-565]

“[As such], we postulated that daily … pentoxifylline, based on the dosage used to treat peripheral vascular disease, would have a positive effect on erectile function and penile blood flow … [However, our trial showed otherwise,] suggesting that there is no role for pharmacologic augmentation using pentoxifylline in patients who fail PDE-5 inhibitors,” said the researchers.

It would be worth looking into the effect of pentoxifylline in combination with other PDE-5 inhibitors, the researchers suggested, given evidence showing its efficacy when added to tadalafil, with significant improvement in erectile function. [Pol Przegl Chir 2015;87:377-383] “[This could] be due to tadalafil’s longer half-life compared with sildenafil (17.5 vs 4–5 hours) … [M]ore randomized studies will be required to [ascertain] this.”