Melatonin as a Potential Prophylactic Therapy for Menstrual-Related Migraine Headache: A Randomized Clinical Trial

Background: Migraine is a common disabling and chronic neurological disorder a ecting women aged 25 - 55 with a considerably higher frequency. It has been shown that migraine attack rates change according to the hormonal changes during the menstrual cycle. A study showed that reduced progesterone levels, especially during the end days of the luteal phase and menstruation, are associated with increased episodes of attacks in more than half of the migraine patients. Moreover, another study suggested that the melatonin level changes are positively correlated with the progesterone blood level. Previous studies indicated that the level of nocturnal urinary melatonin is lower in patients with menstrual-related migraine than in healthy subjects. Objectives: Considering the potential role of melatonin in the circadian system and its relationship with gonadal steroid blood level changes in patients, we aimed to investigate the therapeutic eÿcacy of melatonin in patients with menstrual-related migraines. Methods: An open-label randomized clinical trial was conducted (IR code: IRCT20121110011424N4). Patients with menstrual-related migraine referring to the Neurology Clinic of Imam Khomeini Hospital were evaluated and randomly assigned to either naproxen (250 mg every 12 hours) or melatonin (3 mg, half an hour before sleep) treatment groups. At the end of the first and third menstrual bleeding phases, the patients were assessed by a migraine diary, Visual Analog scale (VAS) for pain, and the Berlin questionnaire. Results: The study evaluated 56 patients (26 in the melatonin arm and 30 in the naproxen arm). Attack days (P < 0.001) and the headache severity (P < 0.001) improved in both groups compared to baseline. A significant di erence was found between the mela-tonin and naproxen treatment groups in sedative and analgesic drug use (P < 0.05). Also, melatonin significantly changed the snor-ing rate and post-sleep tiredness compared to baseline (P < 0.05 and P < 0.05, respectively) whereas no improvement was observed in the naproxen treatment group concerning the sleep quality. Conclusions: We showed the beneficial role of melatonin in reducing the attack frequency and severity in migraine patients with menstrual-related headaches. Preventive therapy with melatonin also showed a significant reduction in the number of sedative drug use during attacks and improved the patients’ sleep quality when compared to naproxen.