Vaginal Sildenafil for Primary Dysmenorrhea: A Randomized, Double-Blind, Placebo-Controlled, Two-Period Crossover Mechanistic Study
Kevin Hellman
Summary
This phase 1 randomized, double-blind, placebo-controlled, two-period crossover trial will evaluate whether a single 100 mg vaginal sildenafil citrate suppository reduces uterine hypercontractility during menstruation in adults with moderate-to-severe dysmenorrhea. Uterine contractility will be measured using cine magnetic resonance imaging (MRI). Key secondary objectives are to evaluate acute menstrual pain reduction over 4 hours, characterize limited systemic exposure using a single 4-hour plasma sildenafil concentration, and assess short-term safety and tolerability.
Description
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, participa…
Eligibility
- Age range
- 18–35 years
- Sex
- Female
- Healthy volunteers
- No
Inclusion Criteria: * Female sex assigned at birth * Age 18 to 35 years * History of moderate-to-severe primary dysmenorrhea * Regular menstrual cycles of approximately 21 to 35 days * Willing and able to complete 2 menstrual treatment visits in separate menstrual cycles * Able to provide informed consent * Able to comply with study procedures, including MRI procedures and vaginal self-administration of study product Exclusion Criteria: * Known hypersensitivity to sildenafil or any formulation component * Current use of nitrates or nitric oxide donors * Current use of potent CYP3A4 inhibito…
Interventions
- DrugSildenafil citrate vaginal suppository
A single 100 mg vaginal sildenafil citrate suppository compounded in an emulsifying MBK base is administered during one treatment period of the crossover study.
- DrugPlacebo vaginal suppository
A single matched placebo vaginal suppository without active sildenafil is administered during one treatment period of the crossover study.
Location
- Evanston HospitalEvanston, Illinois