Phase-specific sequential press-needle therapy for menstrual migraine: a randomized trial protocol.

BACKGROUND: Menstrual migraine (MM) is a neurological disorder affecting women of childbearing age. According to the definition in the International Classification of Headache Disorders, 3rd Edition (ICHD-3), it includes pure menstrual migraine (PMM) and menstrually-related migraine (MRM). The efficacy and safety of acupressure therapy for menstrual migraine have not yet been fully evaluated, particularly when administered sequentially according to specific phases of the menstrual cycle. Therefore, we designed this trial to preliminarily assess whether sequential acupressure therapy shows a favorable trend in efficacy compared with oral naproxen sodium, and to evaluate its feasibility, safety, and tolerability, thereby providing baseline data for future large-scale confirmatory trials. METHODS: This is a randomized, active-controlled, parallel-group trial. A total of 76 eligible women aged 18-45 years with migraine without aura and diagnosed with pure menstrual migraine or menstrually-related migraine will be recruited and randomly allocated to receive either sequential press-needle therapy or oral naproxen sodium therapy. In the press-needle group, treatment is delivered at designated acupoints across two phases (pre-menstrual and post-menstrual) per menstrual cycle. Each phase includes 2 sessions with a 2-day interval (4 sessions per cycle), repeated for 3 consecutive cycles. In the control group, oral naproxen sodium (550 mg twice daily after breakfast and dinner) is initiated 2-3 days before the expected onset of menstruation and continued until menstruation ends (5-7 consecutive days per cycle), also for 3 complete cycles. Compliance is monitored by a daily medication diary and telephone follow-up. The primary outcome is the change in the number of headache days with a peak pain intensity of ≥4 (moderate-to-severe) on a 0-10 Numeric Rating Scale (NRS, where 4-6 = moderate, 7-10 = severe) per menstrual cycle from baseline to the end of the 3-month intervention. Secondary outcomes include headache intensity, functional impact, quality of life, acute medication use, and heart rate variability indices. Exploratory outcomes include serum biomarkers and resting-state functional MRI. CONCLUSION: This trial will evaluate the preliminary efficacy and safety of sequential press-needle therapy compared with oral naproxen sodium for menstrual migraine. The results will be used to estimate effect sizes and inform the design of future adequately powered confirmatory trials. STUDY PROTOCOL REGISTRATION: https://itmctr.ccebtcm.org.cn/mgt/project/view/2049072453099061248, ITMCTR2025002153.