Phosphodiesterase Type 5 Inhibitor Tadalafil Reduces Resting Anal Opening Pressure in Healthy Women: a Randomized, Double-blind, Placebo-controlled Trial

Abstract Purpose Existing first-line treatments for chronic anal fissures aim to reduce internal anal sphincter pressure and increase healing rates. However, availability and side effects challenge the use of these treatment strategies. Phosphodiesterase inhibitors, known for their smooth muscle relaxant properties, have been proposed as alternative treatment candidates. This trial assessed the effect of the long-acting phosphodiesterase inhibitor, tadalafil, on anal opening pressure in healthy women. Methods Twenty-four healthy female volunteers participated in this randomized, placebo-controlled crossover trial. Participants were randomized to receive a single oral dose of 40 mg tadalafil or placebo at their first visit and the opposite treatment at their second visit. Two hours post-administration, coinciding with the time of peak plasma concentration for tadalafil, anal opening pressure was measured using anal acoustic reflectometry during rest and voluntary squeezes. Results Tadalafil reduced resting anal opening pressure with 12.9 (95% CI 5.0 to 20.9, p = 0.003) cmH₂O compared with placebo. A minor, statistically insignificant reduction in pressure was observed during squeeze (5.7 95% CI − 6.0 to 17.3 cmH₂O, p = 0.3). The most common adverse events were headaches, with 15 reports during tadalafil treatment and 3 with placebo. Conclusion Single-dose tadalafil moderately decreased resting anal opening pressure in healthy female volunteers, supporting its potential therapeutic role in managing chronic anal fissures. Further studies are needed to determine the dose-response relationship, therapeutic efficacy, and risk-benefit profile of tadalafil for this application.