Migraine: Endometriosis Linked to More Than Double the Risk


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Researchers may have uncovered the surprising connection between endometriosis and migraine. South_agency/E+/Getty Images
  • Those with endometriosis had 2.3 times the odds of also having migraine, according to a new analysis of more than 13 million females.
  • The researchers said the two conditions may share a pain pathway.
  • A planned clinical trial will test whether migraine medication can relieve endometriosis pain.

In a new analysis, researchers found females with endometriosis were 2.3 times more likely to also have migraine, and they said the two conditions may share a pain pathway involving nerves and inflammation.

Recognizing that connection earlier could lead to coordinated care for both conditions, the researchers said.

The analysis, presented at the American Neurological Association (ANA) Annual Meeting in San Diego on October 20, included more than 13 million females. The research hasn’t yet been published in a peer-reviewed scientific journal.

Endometriosis occurs when tissue similar to what lines the uterus grows outside the uterus, Mallory Stuparich, MD, a gynecologic surgeon at MemorialCare Miller Children’s & Women’s Hospital in Long Beach, California, told Healthline. Stuparich was not involved in the study.

Yohannes Woubishet Woldeamanuel, MD, lead author of the study and assistant professor of neurology at Mayo Clinic Arizona, told Healthline that migraine also involves more than one part of the body.

“Migraine is more than a headache,” he said.

Headache is one symptom, Woldeamanuel said, but migraine can also cause sensory, motor, and balance symptoms.

“Migraine is a little complex. It’s a multiple-nervous system involving a condition,” he said.

Endometriosis pain and the nervous system

Stuparich said endometriosis pain typically develops in 2 ways. The first starts in the lesions themselves.

“There are inflammatory markers that are created by the endometriosis lesions themselves, and those inflammatory markers can irritate the nerves that live close by the lesions,” she said.

The second involves the nervous system, Stuparich said. Scar tissue can grow its own nerve supply, and years of chronic pain can change how the nervous system responds. That adaptation can “perpetuate pain or make people feel sensations that normally wouldn’t be painful,” she said.

Stuparich said the inflammatory and immune processes involved in endometriosis have “pretty significant overlap in the setting of migraines.”

CGRP’s role in endometriosis and migraine

One possible link between the two conditions is calcitonin gene-related peptide (CGRP), a chemical messenger that helps transmit pain signals, the researchers said.

CGRP plays a key role in migraine attacks, Woldeamanuel said, and blocking it reduces those attacks. CGRP medications work by blocking the sites where CGRP attaches or by binding to CGRP itself.

Researchers have also found CGRP in endometriosis tissue.

Research on genetics, inflammation, and hormones

Other studies point to shared biology between the two conditions:

Stuparich said she was “not surprised at all” by the finding because it matches what she sees in her own patients.

“We see this overlap of patients who have endometriosis also having migraines,” she said.

Stuparich said the science still has gaps. She noted that nothing has been proven conclusively in peer-reviewed research yet, but the way both diseases behave supports a connection.

“It makes sense that there would be overlap,” she said.

Endometriosis and migraine are treated by different specialists, so the overlap is easy to miss, Woldeamanuel said.

For the analysis, researchers at Mayo Clinic Arizona reviewed 35 studies published over 50 years, comparing migraine rates among 207,675 females with endometriosis and 12,963,120 females without the condition.

Short-term health records miss up to 90% of that overlap, according to the analysis. Migraine rates in females with endometriosis changed depending on how each study identified migraine.

“This data is hiding,” Woldeamanuel said.

  • 1 year of billing codes: fewer than 5%
  • longer-term insurance claims: 18% to 43%
  • doctors interviewing patients directly: 54% to 78%

“These two clinics are siloed. One clinic doesn’t ask about the other condition. They just focus on their own specialty,” Woldeamanuel said.

The findings of the analysis have not been published in a peer-reviewed journal.

Some treatments already overlap, Stuparich said. Hormonal birth control “can sometimes be used to treat menstrually associated migraines,” she said.

Stuparich said she has heard anecdotally of patients whose endometriosis symptoms improved after they started CGRP medications for migraine, though long-term data are still lacking.

The researchers said the findings support studying whether existing CGRP-blocking migraine medications could also relieve endometriosis pain, potentially offering one treatment for both conditions.

Woldeamanuel leads a planned Mayo Clinic trial testing one of those medications, rimegepant (Nurtec ODT), for endometriosis pain. The trial will also track migraine days in participants who have both conditions. It’s expected to finish in 2031, according to ClinicalTrials.gov.

People who suspect they have both conditions can take steps now to get them treated together, Stuparich said.

Patients can raise the connection themselves, Stuparich said. She suggested a starting point for each appointment:

  • At a gynecology visit: Mention that you’ve “come across some information that endometriosis and migraines could be associated,” then ask, “What can I do about that?”
  • At a neurology visit: Describe painful periods that “really disrupt my quality of life,” then ask, “What can we do about that?”

Patients can also ask for an early referral to the other specialist so both conditions get coordinated care, Woldeamanuel said. “The earlier it’s diagnosed, the better it’s managed,” he said.

Stuparich said doctors are moving away from viewing endometriosis as only a gynecologic disorder because it can affect the whole body.

“It is a whole body systemic neuroinflammatory neuroimmune disorder,” she said.



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