Approximately 30% of women afflicted with migraine have menstrually associated attacks. These migraines are often refractory to treatment. Evidence suggests estrogen and progestin fluctuations may influence menstrual migraine. Phytoestrogens have demonstrated estrogenic effects in some tissues, but are without stimulation of the endometrium, suggesting decreased risk with long-term use. This study was undertaken to assess the efficacy of a phytoestrogen combination in the prophylactic treatment of menstrual migraine. Forty-nine patients were randomized to receive either placebo, or a daily combination of 60 mg soy isoflavones, 100 mg dong quai, and 50 mg black cohosh, with each component standardized to its primary alkaloid. Patients received study medication for 24 weeks. Average frequency of menstrually associated migraine attacks during weeks 9-24 was reduced from 10.3 +/- 2.4 (mean +/- s.e.m.) in placebo treated patients to 4.7 +/- 1.8 (P < 0.01) in patients treated with the phytoestrogen preparation.