Hormones and Pain Sensitivity for Migraine

(IHS Trial)

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

100 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to investigate the relationships between sex hormone levels and experimental pain sensitivity and migraine severity will be examined.

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 data supports the effectiveness of the hormone treatment for migraine?

Research suggests that changes in sex hormones like estrogen and testosterone can influence migraine headaches. A study found that continuous testosterone treatment significantly reduced migraine severity in women, with 92% of participants reporting improvement. ^{1 2 3 4 5}

Is hormone therapy generally safe for humans?

Research shows that hormone therapies, including testosterone implants, have been used safely in humans for conditions like migraines, with many patients experiencing improvements without significant safety concerns. ^{2 4 5 6 7}

How does this hormone-based treatment for migraine differ from other treatments?

This treatment is unique because it focuses on the role of sex hormones like estrogen, progesterone, and testosterone in managing migraine, particularly in women and transgender individuals. Unlike standard migraine treatments, it considers hormonal fluctuations and their impact on pain sensitivity, offering a personalized approach based on hormonal influences. ^{2 3 6 8 9}

Research Team

Hadas Nahman-Averbuch, PhD

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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

I am between 11 and 15 years old.

English speakers

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

References

1. Spain pubmed.ncbi.nlm.nih.gov

[Migraine in females]. [2013]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Molecular mechanisms of hormones implicated in migraine and the translational implication for transgender patients. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Ovarian hormones and migraine headache: understanding mechanisms and pathogenesis--part I. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

Testosterone pellet implants and migraine headaches: a pilot study. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Female sex hormones in men with migraine. [2019]

6. England pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

The second to fourth digit ratio (2D:4D): a risk factor of migraine and tension-type headache. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Migraine and estrogen. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

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