Diagnostic and Therapeutic Potential of Substance P/NK1 Receptor in Primary Dysmenorrhea: A Pilot Study

ABSTRACT Background and Aims Primary dysmenorrhea is a prevalent condition that causes significant menstrual pain and discomfort, impacting many women′s daily activities. The Substance P/NK1 receptor (SP/NK1R) pathway has been linked to the pain mechanisms underlying dysmenorrhea, yet its potential as a therapeutic target remains inadequately explored. This study aimed to evaluate the therapeutic potential of NK1R antagonists, specifically dexamethasone and aprepitant, in alleviating the symptoms of primary dysmenorrhea. Methods A randomized controlled trial was conducted from March 2024 to December 2024 using a convenience sampling technique. Forty female participants were divided into three phases: Phase 1 (pre‐medication), Phase 2 (NSAIDs), and Phase 3 (dexamethasone + aprepitant). Ten control females without dysmenorrhea were also recruited. The study lasted for three menstrual cycles, with assessments of SP/NK1R levels, visual analogue scores (VAS), and pictorial blood loss. Data were analyzed using Two‐way ANOVA with repeated measures. Results The mean age of participants was 25.1 ± 7.6 years, and BMI was 20.47 ± 3.61 kg/m². SP/NK1R levels were significantly elevated in Phase 1 compared to controls. NK1R levels decreased significantly from 15.4 ng/mL in Phase 1 to 8.42 ng/mL in Phase 3. VAS scores decreased by 4.79 units. A linear mixed‐effects model revealed significant reductions in NK1R levels in Phase 2 versus Phase 1 ( p < 0.001) and Phase 3 versus Phase 1 ( p = 0.006). VAS scores improved significantly in Phase 3 compared to Phase 2 ( p = 0.0001 for SP and p = 0.0028 for NK1R). Heavy period patients had higher SP levels. Both SP and NK1R levels decreased across phases for normal and heavy period patients. Conclusion This pilot study suggests that NK1R antagonists (dexamethasone and aprepitant) may reduce discomfort in dysmenorrhea. Further research with a larger sample size and control for intra‐individual hormone levels is needed.