Study Results Show Possible Link Between Hormone Levels Before Birth and Migraine Risk

Analysis assessing data from the world’s largest twin registry also finds evidence that genetic factors for strong headaches may differ between men and women.

Hormone levels in the womb before birth could be linked to developing migraines in adulthood, the results of a study published in Frontiers in Pain Research showed.

The findings also suggested that the genetic factors related to migraine risk may differ for men and women.

“We are the first to show that females with a male co-twin have a higher risk of migraine compared to females with a female co-twin, suggesting that prenatal factors, possibly relating to in utero hormone levels, may contribute to migraine risk,” lead study author Morgan Fitzgerald, a senior research associate from the University of California’s San Diego School of Medicine, said in a statement. “We are also the first to present evidence that genetic factors related to migraine risk may be different between females and males.”.

Migraines are a debilitating and severe neurological disease that affects more than 12% of the world’s population, according to the statement.

Additionally, females are more likely to suffer from migraines than males by nearly 7 to 1, and migraines are the leading cause of disability in women.

Investigators used data from the Swedish Twin Registry, the largest twin registry in the world. Using these data, the investigators isolated factors contributing to female-male differences in migraines.

In the study, investigators included 51,872 individuals who had participated in prior Swedish Twin Registry studies. They identified individuals who experience migraines without auras, based on criteria set by the international Headache Society Classification of Headache Disorders.

“We found that the prenatal environment may contribute to migraine risk and that some of the genetic factors that contribute to migraine risk may be different between females and males,” Fitzgerald said.

Investigators used analytic methods to test different genes in females and males to determine if the migraine risk was greater for either, she said.

They also tested the presence of an opposite-sex twin in utero, which is thought to affect the prenatal hormone levels.

“The findings of our study are important because the more we understand the factors that contribute to migraine, and especially the differences between males and females, the more opportunity there is to improve clinical care, diagnostic abilities, and therapeutic interventions for both men and women,” Matthew Panizzon, PhD, also based at the UC San Diego School of Medicine, said in the statement.

Future studies will be needed to better understand some unanswered questions, including at what age and stage in life do migraines begin and which factors dictate the absence or presence of auras, investigators said.

Age at onset of migraines was not available in the data, so it is important for further studies to determine if the migraine onset typically coincides with the timing of critical hormonal events, such as puberty, Fitzgerald said.

The investigators said they hope that their findings will enable more effective and targeted treatment options for migraines.


Hormone exposure in the womb potentially linked to migraine risk in later life. EurekAlert. News release. December 15, 2021. March 10, 2022.

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