Objective: To compare daily sex hormone levels and rates of change between women with history of migraine and controls.Methods: History of migraine, daily headache diaries, and daily hormone data were collected in ovulatory cycles of pre-and early perimenopausal women in the Study of Women's Health Across the Nation. Peak hormone levels, average daily levels, and within-woman day-to-day rates of decline over the 5 days following each hormone peak were calculated in ovulatory cycles for conjugated urinary estrogens (E1c), pregnanediol-3-glucuronide, luteinizing hormone, and follicle-stimulating hormone. Comparisons were made between migraineurs and controls using 2-sample t tests on the log scale with results reported as geometric means.Results: The sample included 114 women with history of migraine and 223 controls. Analyses of within-woman rates of decline showed that E1c decline over the 2 days following the luteal peak was greater in migraineurs for both absolute rate of decline (33.8 [95% confidence interval 28.0-40.8] pg/mgCr vs 23.1 [95% confidence interval 20.1-26.6] pg/mgCr, p 5 0.002) and percent change (40% vs 30%, p , 0.001). There was no significant difference between migraineurs and controls in absolute peak or daily E1c, pregnanediol-3-glucuronide, luteinizing hormone, and follicle-stimulating hormone levels. Secondary analyses demonstrated that, among migraineurs, the rate of E1c decline did not differ according to whether a headache occurred during the cycle studied.Conclusions: Migraineurs are characterized by faster late luteal phase E1c decline compared to controls. The timing and rate of estrogen withdrawal before menses may be a marker of neuroendocrine vulnerability in women with migraine. Neurology ® 2016;87:49-56 GLOSSARY BMI 5 body mass index; DHS 5 Daily Hormone Study; E1c 5 conjugated urinary estrogens; ELA 5 evidence of luteal activity; FSH 5 follicle-stimulating hormone; ICHD 5 International Classification of Headache Disorders; LH 5 luteinizing hormone; MHx 5 women with history of migraine; Pdg 5 pregnanediol-3-glucuronide; SWAN 5 Study of Women's Health Across the Nation.