Treatment with sildenafil oral film improves orgasmic intensity: a secondary, exploratory post-hoc analysis of a...

Erectile dysfunction (ED) impairs sexual function beyond erection itself, yet its effect on orgasmic intensity, measurable by the validated psychometric tool Orgasmometer, remains largely unexplored. Sildenafil oral film (OF) is a novel formulation offering rapid dissolution and flexible dosing (25-100 mg, including an intermediate 75 mg dose).

To investigate the relationship between ED severity and orgasmic intensity, and to evaluate whether Sildenafil OF restores orgasmic intensity in men with ED.

This secondary, exploratory analysis of orgasmic intensity was not prespecified and was performed post-hoc on a Phase III, multicenter, randomized, double-blind, flexible-dose, placebo-controlled trial conducted across 17 US centers (January-December 2024; NCT05490680). Heterosexual men with a ≥6-month ED diagnosis were randomized 3:1 to Sildenafil OF or placebo for 12 weeks. Outcomes were assessed at baseline and at weeks 2, 4, 8, and 12.

Primary endpoints were the International Index of Erectile Function (IIEF) Erectile Function domain and Sexual Encounter Profile questions 2 and 3 (SEP2/SEP3). The secondary endpoint of interest was the Orgasmometer score, alongside the Erection Hardness Score (EHS) and all IIEF domains.

Of 488 randomized participants, 439 completed all visits (Sildenafil OF: n = 326; placebo: n = 113). Baseline Orgasmometer scores progressively declined with ED severity (P < .001). Sildenafil OF significantly improved Orgasmometer scores versus placebo at week 2 (+1.67, P < .001), with continued improvement through week 12. Linear mixed-effects models identified the composite erectile score (EHS, SEP2, SEP3) as the strongest predictor of orgasmic intensity (β = 1.05 ± 0.03, P < .001). A formal counterfactual mediation analysis showed that erectile improvement partially mediated the treatment effect (indirect effect 0.66, 95% CI, 0.26-1.18; proportion mediated ~43%, 95% CI, 21%-67%), with a significant direct effect persisting (0.86, 95% CI, 0.41-1.37).

Because erectile improvement explained ~43% of the effect on orgasmic intensity, erectile measures alone may not fully capture treatment response; a single-item assessment of orgasmic intensity may therefore complement erectile evaluation in men with ED. Sildenafil OF represents an effective, patient-friendly option addressing both domains.

Strengths include large sample size, rigorous randomized controlled trial design, and use of a validated measure. Limitations include restriction to heterosexual men, absence of a healthy control group, and post-hoc analysis.

In men with ED, orgasmic intensity was progressively lower with increasing ED severity, and treatment with Sildenafil OF improved it substantially, but not exclusively, through improvements in erectile rigidity and maintenance. Orgasmic intensity is a clinically relevant, low-burden measure that may complement erectile assessment in men with ED.