How Oxytocin, CGRP, and Sex Hormones Work Together to Influence Migraine, Especially in Women | Research

The takeaway

A drop in oxytocin, estrogen, and progesterone levels may trigger migraine attacks, and new research reveals close molecular links between estrogen and the CGRP pathway that underlies current migraine treatments.

3x higher prevalence in women
Migraine affects women three times more than men, linked to fluctuations in estrogen, progesterone, and oxytocin levels that influence CGRP expression in the migraine pathway

What the researchers found

The review reveals that estrogen has a close transcriptional relationship with calcitonin gene-related peptide (CGRP) and its receptor component RAMP1, both central targets of current migraine therapies. Falling plasma levels of estrogen, progesterone, and hypothalamic oxytocin may trigger migraine attacks, while higher levels appear protective.

Oxytocin receptors have recently been found to be expressed in the trigeminovascular system (TGVS), the key neural pathway in migraine. Estrogen, acting through multiple receptor subtypes, influences expression levels of both oxytocin and its receptor, creating a hormonal-peptide axis that may explain the three-fold higher migraine prevalence in women.

Why it matters

Understanding why migraine disproportionately affects women has been a longstanding challenge. This review connects the dots between hormonal fluctuations and the molecular pathways targeted by modern migraine drugs, potentially opening new treatment approaches — including oxytocin-based therapies — and explaining why current CGRP-targeting treatments may work differently in men and women.

How the study worked

This is a narrative review synthesizing recent data on the expression and function of sex hormones, hypothalamic hormones (oxytocin, vasopressin), and migraine-related peptides (CGRP) in neural structures relevant to migraine, including both the central nervous system and the trigeminovascular system.

What this study cannot tell us

This is a narrative review, not a systematic review or meta-analysis. The underlying mechanisms linking hormone fluctuations to migraine are still not fully understood. Testosterone and vasopressin are noted as less extensively studied. The clinical applicability of oxytocin receptor findings in the trigeminovascular system has not yet been tested in therapeutic trials.

How to read the evidence

This is a narrative review synthesizing recent molecular and clinical data. While it draws on important new findings about receptor expression and transcriptional relationships, much of the mechanistic framework remains hypothesis-generating rather than definitively established through clinical trials.

When this study was published

Published in 2026 incorporating the latest molecular data, this review is highly current and reflects the most recent understanding of hormone-peptide interactions in migraine.

The bigger picture

This review bridges two active research fronts — hormonal migraine triggers and CGRP-targeted therapies — through the emerging role of oxytocin. As CGRP-blocking drugs (like erenumab and fremanezumab) become standard migraine treatments, understanding how sex hormones regulate CGRP expression could lead to more personalized treatment strategies and potentially new peptide-based therapies using oxytocin.

Questions still open

Could oxytocin-based therapies provide a new treatment approach for hormonal migraine in women?
Do CGRP-targeting migraine drugs work differently in women depending on their hormonal status or menstrual cycle phase?
What role does testosterone play in the lower migraine prevalence seen in men?

Common questions

Why are migraines more common in women than men?

Women experience migraine three times more often than men, largely due to fluctuations in sex hormones. Drops in estrogen and progesterone — during menstruation, after pregnancy, or around menopause — can trigger migraine attacks. New research shows that estrogen directly influences production of CGRP, a key molecule in migraine pain pathways, and also affects oxytocin levels, creating a complex hormonal-peptide link that makes women more susceptible.

What is the connection between oxytocin and migraine?

Oxytocin is a peptide hormone best known for its role in bonding and childbirth, but researchers have recently discovered that oxytocin receptors are present in the trigeminovascular system — the neural pathway responsible for migraine pain. Oxytocin levels drop at menstruation onset, which coincides with a common migraine trigger point. Estrogen influences oxytocin expression, suggesting a hormonal-peptide axis that may contribute to migraine susceptibility and could represent a new therapeutic target.

Read the original research

Hypothalamic and sex-related hormones in migraine.

The journal of headache and pain, 27(1)

View on PubMed ↗Publisher’s paper ↗

Citation

Warfvinge, Karin; Edvinsson, Jacob C A; Maddahi, Aida; Edvinsson, Lars. (2026). Hypothalamic and sex-related hormones in migraine.. The journal of headache and pain, 27(1). https://doi.org/10.1186/s10194-026-02289-z