Hormones and Pain Sensitivity for Migraine

(IHS Trial)

Not currently recruiting at 1 trial location

Overseen By Alana McMichael, MA

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Must not be taking: Contraceptive pills

Disqualifiers: Pregnancy, Chronic pain, Neurological, others

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the link between sex hormones (such as estrogen, progesterone, and testosterone) and pain perception, particularly in individuals with migraines. Researchers aim to determine if hormone levels influence migraine intensity and pain sensitivity. The trial includes two groups: adolescents with migraines and healthy adolescents without migraines or a close family history of migraines. It seeks participants aged 11-15 who speak English and do not use medications that alter hormone levels. As an unphased study, this trial provides a unique opportunity to advance understanding of migraines and hormone interactions.

Will I have to stop taking my current medications?

If you are taking medications that affect sex hormone levels, like contraceptive pills, you will need to stop taking them to participate in this trial.

What prior data suggests that sex hormones are safe for adolescents?

Research has shown that sex hormones can affect migraines. Changes in hormone levels can influence the frequency and severity of migraines. Women often experience more migraine symptoms when their hormone levels fluctuate, such as during their period.

Regarding safety, many people generally tolerate sex hormones well. Doctors already prescribe them in treatments like hormone replacement therapy to help with menopause symptoms. However, side effects can occur. Some individuals might experience mood swings, headaches, or weight changes when undergoing hormone treatments.

Consulting a healthcare provider about any concerns or questions regarding treatment is always advisable, especially when considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using sex hormones to address migraine pain because this approach is quite different from traditional treatments. Unlike common migraine medications, which often include pain relievers or triptans, sex hormones aim to target the underlying hormonal fluctuations that can trigger migraines, especially in adolescents. This method could offer a more personalized treatment by addressing the root cause rather than just the symptoms. By potentially reducing the frequency and severity of migraines, this approach could provide significant relief for those whose migraines are linked to hormonal changes.

What evidence suggests that sex hormones might be effective for migraine?

This trial will compare adolescents with a migraine diagnosis to healthy controls to explore the role of sex hormones in migraine sensitivity. Research has shown that sex hormones connect to migraines. Women often experience more migraine symptoms when their hormone levels change. Studies indicate that both male and female hormones might affect headaches. Some reports found that testosterone, a male hormone, relieved migraines in over 80% of patients. However, not all studies found a clear link between hormone levels and migraine severity, especially in men. These findings suggest hormones might play an important role in treating migraines. ^{1 6 7 8 9}

Who Is on the Research Team?

Hadas Nahman-Averbuch, PhD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This study is for boys and girls aged 11-15 who speak English. It includes two groups: one with adolescents diagnosed with migraines, and a control group of healthy individuals without a family history of migraines. Pregnant or breastfeeding teens, those with chronic pain (other than migraines), neurological issues, psychiatric conditions, or on hormone-altering meds can't participate.

Inclusion Criteria

English speakers

I am between 11 and 15 years old.

I am either male or female.

Exclusion Criteria

Pregnancy or breastfeeding

I have chronic pain, but not migraines, or any neurological or psychiatric conditions.

I am taking medication that affects my hormone levels.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Initial assessment of sex hormone levels and pain sensitivity

1 week

1 visit (in-person)

Follow-up

Participants are monitored for changes in pain sensitivity and hormone levels

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sex Hormones

Trial Overview The trial examines how puberty hormones affect pain sensitivity and migraine severity in adolescents. Participants will undergo tests using thermal and pressure stimuli to measure pain response, complete a migraine disability assessment (PedMIDAS), have their hormonal levels checked, and assess pubertal status.

How Is the Trial Designed?

Group I: Migraine Active Control 8 Interventions

Adolescents with a migraine diagnosis

Group II: Healthy control Placebo Group 7 Interventions

Adolescents without a migraine diagnosis

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

International Headache Society

Collaborator

Trials

3

Recruited

370+

Published Research Related to This Trial

In a case-control study of 15 postmenopausal women with migraine, no significant differences in serum levels of androgens (androstenedione, total testosterone, and free testosterone) were found compared to matched controls, suggesting that normal androgen levels do not play a significant role in migraine development.

The study indicates that while female hormones are often linked to migraines, androgens may not be a contributing factor in postmenopausal women not taking estrogen, highlighting the need for further research into other potential causes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum levels of androgens and migraine in postmenopausal women. Mattsson, P.[2019]

In a study of 891 individuals, females with migraines and tension-type headaches (TTH) had lower 2D:4D ratios compared to healthy controls, suggesting a link between prenatal hormone exposure and the risk of developing these headaches.

The findings indicate that the balance of prenatal estrogen and testosterone may influence the likelihood of experiencing migraines and TTH in adulthood, highlighting the potential role of early hormonal factors in headache disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The second to fourth digit ratio (2D:4D): a risk factor of migraine and tension-type headache. Xie, W., He, M., Liu, R., et al.[2018]

Men with migraine had a lower testosterone to estradiol ratio compared to men without migraine, indicating a potential hormonal imbalance that may contribute to migraine susceptibility.

The study found that men with migraine reported more symptoms of androgen deficiency, suggesting that hormonal factors, particularly elevated estradiol levels, could play a role in the development and severity of migraines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Female sex hormones in men with migraine. van Oosterhout, WPJ., Schoonman, GG., van Zwet, EW., et al.[2019]

In a pilot study involving 27 women with a history of migraines, 92% reported a significant reduction in headache severity after receiving continuous testosterone implants for 3 months, with an average improvement of 3.3 on a 5-point scale.

The treatment was effective for both pre- and post-menopausal women, with 74% of participants experiencing no headaches at all during the treatment period, indicating a strong therapeutic effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone pellet implants and migraine headaches: a pilot study. Glaser, R., Dimitrakakis, C., Trimble, N., et al.[2013]

Chronic pain disorders, including migraines, are more commonly diagnosed in cisgender women, suggesting that female sex hormones like estrogens and progesterone may influence migraine pathophysiology.

The review highlights the need to consider both major and minor sex hormones in understanding migraines, especially for transgender and gender non-conforming individuals who may require hormone replacement therapy, indicating a gap in research for this underserved population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular mechanisms of hormones implicated in migraine and the translational implication for transgender patients. Martinez, CI., Liktor-Busa, E., Largent-Milnes, TM.[2023]

Migraine incidence in females significantly increases after puberty, with about 25% of reproductive-age women affected compared to only 8% of men, highlighting the influence of female sex hormones on migraine prevalence.

The characteristics of migraines in women change throughout different life stages—such as menstruation, pregnancy, and menopause—often correlating with estrogen levels, which suggests that hormonal treatments like contraceptives and hormone replacement therapy can impact migraine frequency and intensity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Migraine in females]. Raña-Martínez, N.[2013]

Ovarian hormones, particularly estrogen and progesterone, significantly influence the central nervous system and are linked to the occurrence and severity of migraine headaches in women, especially during reproductive milestones like menstruation, pregnancy, and menopause.

The review will explore how these hormones affect neurotransmitter systems and pain processing networks, providing insights into the biological mechanisms behind migraine headaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ovarian hormones and migraine headache: understanding mechanisms and pathogenesis--part I. Martin, VT., Behbehani, M.[2022]

Recent studies using functional MRI have shown that there are significant anatomical and functional differences in the brains of men and women, as well as between migraine sufferers and healthy individuals, highlighting the role of sex hormones in migraine prevalence and characteristics.

Evidence suggests that drops in estrogen levels are linked to an increased risk of menstrually related migraines, and strategies to minimize these declines, such as specific hormonal contraceptive regimens, may help reduce headache frequency and aura in affected individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Migraine and estrogen. Chai, NC., Peterlin, BL., Calhoun, AH.[2022]

Women experience migraines more frequently than men, particularly during their reproductive years, due to factors like hormonal fluctuations throughout the menstrual cycle.

Research shows that female hormones significantly impact the development and course of migraines, as seen in conditions like menstrual migraine and changes during menarche, pregnancy, and menopause.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Migraine and hormones: what can we be certain of?]. Bingel, U.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10889915/

How Sex Hormones Affect Migraine - PubMed Central - NIH Sex hormones and migraine are closely interlinked. Women report higher levels of migraine symptoms during periods of sex hormone fluctuation.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3444543/

Impact of sex hormonal changes on tension-type headache ... Our results revealed that sex hormonal changes affected migraineurs more frequently than TTH sufferers as expected [19, 26–29].

3. thejournalofheadacheandpain.biomedcentral.com thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-018-0922-7

Male and female sex hormones in primary headaches These gender differences suggest that both male and female sex hormones could have an influence on the course of primary headaches.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2452073X24000229

The role of androgens in migraine pathophysiology In these observational publications, it was reported that daily methyl testosterone in various doses led to migraine relief in >80 % of patients (Moehlig and ...

5. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1648017/pdf

Sex hormone profiles in men with migraine Furthermore, no significant correlations were found between sex hormones or their ratios, and clinical outcomes such as migraine days, pain ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6755575/

Male and female sex hormones in primary headaches - PMC The three primary headaches, tension-type headache, migraine and cluster headache, occur in both genders, but all seem to have a sex-specific prevalence.

7. link.springer.com link.springer.com/article/10.1007/s40120-025-00720-2

Menopause, Perimenopause, and Migraine One study showed that lower estradiol and higher FSH levels were associated with lower migraine prevalence in women with premenstrual syndrome ...

8. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/202685

The Influence of Estrogen on Migraine: A Systematic Review Epidemiological, pathophysiological, and clinical evidence link estrogen to migraine headaches. Triptans appear to provide acute relief and also may be useful ...

9. tandfonline.com tandfonline.com/doi/full/10.1080/14737175.2023.2296610

Considerations for hormonal therapy in migraine patients This review aims to present an overview on the relationship between migraine and sex hormones and to provide a summary of current evidence concerning efficacy ...