Rapid Decline in Urinary Estrogen Indicates Vulnerability in Female Migraineurs

woman headache
woman headache
The findings suggest a neuroendocrine vulnerability in women with migraine.

Women with a history of migraine headaches were found to have a more rapid decline in urinary conjugated estrogen during the late luteal phase, highlighting a possible biomarker of neuroendocrine susceptibility to migraine.

“These results suggest that a ‘two-hit’ process may link estrogen withdrawal to menstrual migraine, said study author Jelena Pavlović, MD, PhD, of Albert Einstein College of Medicine in New York, in a statement. “More rapid estrogen decline may make women vulnerable to common triggers for migraine attacks such as stress, lack of sleep, foods, and wine.”

Late luteal phase estrogen decline has previously been implicated in menstrual migraines that are observed in the 2 days prior to and the first 3 days of the menstrual cycle. However the data is limited in this area, with only a few small studies involving mean hormone levels.

To further explore this relationship between sex hormone levels and migraine, Dr Pavlović and colleagues analyzed data from the Study of Women’s Health Across the Nation (SWAN) Daily Hormone Study. Data was obtained through migraine history, daily headache diary, and peak, average, and day-to-day hormone levels.

The SWAN daily hormone study included 848 women aged 42 to 52 years who were not using hormone therapy. Participants provided a first morning urine sample daily for a menstrual cycle or 50 days. Participants from the control group were excluded if they reported a severe headache in the daily diary to avoid including a participant with undiagnosed migraine headaches.

Related Articles

In total, the study included 223 controls and 114 migraineurs. Participants tended to be in early perimenopause, and those with a migraine history were more likely to be black or white, have a higher mean BMI, and a history of smoking.

Participants with a history of migraine demonstrated a greater rate of decline in conjugated urinary estrogen in the 2 days after the luteal peak than controls by percent change (40% vs 30%, P<.001) and absolute change (33.8 pg/mgCr vs 23.1 pg/mgCr, P=.002). The differences continued to be significant after adjusting for demographics.

No differences were observed for daily or absolute peak conjugated urinary estrogen, luteinizing hormone, follicle-stimulating hormone, and pregnanediol-3-glucuronide.

Notably, the rate of decline in conjugated urinary estrogen was not different in migraineurs with or without headache occurrence during the studied menstrual cycle.

The authors suggest that the results imply that estrogen withdrawal does not directly trigger a migraine, but rather “the more rapid estrogen decline is an endogenous trait of women with migraine that confers neuroendocrine vulnerability that may facilitate initiation of migraine attack(s) by common triggers.”


Pavlovic JM, Allshouse AA, Santoro NF, et al. Sex hormones in women with and without migraine: Evidence of migraine-specific hormone profiles. Neurology. 2016;87:1–8.