Vaginal Sildenafil for Primary Dysmenorrhea

Dysmenorrhea is believed to be driven in part by excessive uterine contractility. Sildenafil, a phosphodiesterase-5 inhibitor, may reduce myometrial hypercontractility through enhanced nitric oxide-cGMP signaling. Prior vaginal sildenafil data suggested acute pain relief, but mechanism and systemic exposure were not well characterized. This mechanistic target-engagement study uses a randomized, double-blind, placebo-controlled, two-period crossover design. Participants will complete a screening visit and two menstrual treatment visits during separate cycles. At each treatment visit, participants with active menstrual pain will undergo baseline MRI, self-administer either vaginal sildenafil citrate 100 mg or matching placebo, and then complete repeat MRI assessments approximately 2 and 4 hours after dosing. Pain ratings, vital signs, adverse event assessments, pregnancy testing, and a single 4-hour blood draw for plasma sildenafil concentration will be obtained. Menstrual effluent samples will also be collected. The primary objective is to determine whether vaginal sildenafil produces measurable reductions in uterine hypercontractility during menstruation. Secondary objectives are to evaluate the effect of treatment on menstrual pain intensity over the 4-hour observation window, assess systemic exposure after vaginal administration, and characterize short-term hemodynamic and clinical tolerability.