What is Menstrual Migraine? 2024
“The Pill”
Migraine headache occurs in 12% of the World population. Twenty-five % of women and six % of men have migraine headache. Migraine headache is the 5th most common cause of disability and the 10th most common cause of a visit to the emergency room. The three most painful conditions known to man are migraine, a kidney stone, and childbirth.
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This is an article by Britt Talley Daniel MD, member of the American Academy of Neurology, the American Headache Society, migraine textbook author, podcaster, YouTube video producer, and blogger.
Menstrual Migraine refers to headaches that come with a decrease in estrogen after exposure to previous elevated levels of estrogen such as happens naturally in women monthly during their menstrual period or in women taking cycled estrogen/progesterone birth control pills. This used to be called catamenial Migraine.
“The curse”
Related questions.
What is Migraine?
Primary” in medicine means that the exact root cause of a medical problem is not understood. For instance, high blood pressure may be called “Primary hypertension” which is a very common medical problem, but the exact cause is not completely understood.
In the same frame of mind, the International Classification of Headache Disorders V 3, (ICHD3), lists 2 type of “primary” headache and these are migraine and tension type headache. 99% of all headache cases are either migraine (30%), or tension type headache (70%). Tension type headache is the most frequent type of headache but is rarely seen in a headache clinic.
What about Migraines during the normal menstrual cycle?
Migraine is 30% of headache cases and 50% of migraineurs have “Menstrually Related Migraine” (MRM) or migraine occurring in time related to the woman’s menstrual cycle and the implicit decrease in estrogen. ICHD3 defines menstrually related migraine as a migraine headache that occurs the day of onset of menstrual bleeding, 2 days before, or 2 days after.
Pure menstrual Migraine (PMM) consists of women who only have Migraine headaches during their menstrual cycle. PMM has a prevalence of 4-12% while MRM prevalence is 50%.
Estrogen and women’s menstrual cycle?
The exact understanding of this relationship is not clearly known, but Migraine is a genetic, inherited medical condition affecting a woman’s hormonal cycle. It is clear that a decreasing level of estrogen is an important factor in triggering migraine in women. This occurs during the normal menstrual cycle when estrogen production decreases and progesterone increases.
Similar estrogen withdrawal occurs with the use of “The Pill” during the fourth week of the cycle when the pills change from estrogen to progesterone. Other estrogen products such as the patch provide a steady does of estrogen daily so that there is no decrease.
A forgotten dose of estrogen therapy or women who use other drugs that reduce estrogen levels produces similar migraine headaches with decreased estrogen availability.
The migraine/estrogen relationship is likely why women have migraine 3 times more than men. The menstrual timed headache is usually the worse, most intense, longest lasting migraine a woman may have during a month.
Medication with estrogen may be delivered through oral, transdermal, injectable, and vaginal formulations. The transdermal delivery systems include patches, gels, sprays, and lotions, while vaginal products include suppositories, creams, and rings.
All estrogen delivery methods may aggravate migraine headache intensity, occurrence, or possibly produce worrisome neurologic symptoms of stroke risk. Women who take the birth control pill may be converted to migraine with aura type symptoms with the development of visual images, arm or facial numbness, or trouble talking. These women should stop estrogen treatment immediately for fear of imminent stroke risk.
Framingham data has found a 6% risk for stroke for patients with migraine with aura and this stroke risk is increased for women on the “pill.”
Read about “Migraine and Stroke” on my website, www.doctormigraine.com. Please click here to read.
How does estrogen affect the brain to cause migraine?
Although Liveing, the late nineteenth migraine savant and expert, described catamenial (menstrual related) migraine in his famous book On Megrim in 1873,[i] it took another century and a half to determine that the human brain, both male and female, has estrogen receptors.
In about 50 % of women with menstrually related migraine without aura there is a strong occurrence of headaches which come around the end of the third week of the menstrual cycle, at the time when estrogen has been found to fall.
There likely is a different gene sequence for menstrually related migraine without aura. Fifty percent of women with migraine without aura have no estrogen relationship at all. Exactly why falling estrogen levels trigger migraine is not clearly understood, but the relationship of falling estrogen as a trigger for migraine to occur is well known and factual.
Welch, et al,[ii] writing in 2006 in Neurol Sci. on “Mismatch in how oestrogen modulates molecular and neuronal function may explain menstrual migraine,” offered the hypothesis of a “mismatch” between the timing of estrogen effects on gene regulation in the central nervous system, and its effects on cell membranes. Welch, et al, stated:
“On the basis of experimental studies and literature review, we propose that abnormalities in how estrogen modulates neuronal function in migraine are due to a mismatch between its gene-regulation and membrane effects. In the interictal phase when estrogen levels peak, increased neuronal excitability is balanced by homeostatic gene regulation in brain cortex, and nocioceptive systems.
When levels fall at menses, mismatch in homeostatic gene regulation by estrogen unmasks non-nuclear mitogen-activated hyperexcitability of cell membranes, sensitizing neurons to triggers that activate migraine attacks. At the trough of estrogen levels, the down-regulating effect on inflammatory genes is lost and peptide modulated central sensitization is increased as is pain and disability of the migraine attack.
Estrogen production
“Ice is nice.”
The early to mid-follicular phases of the menstrual cycle are characterized by rising levels of estrogen, produced by follicles in the ovary and under the influence of follicle stimulating hormone (FSH). Then luteinizing hormone (LH) causes the release of a follicle. Ovulation comes in 48-72 hours, with the luteal phase characterized by high levels of both estradiol and progesterone. If the ovum is not fertilized and implanted, the corpus luteum regresses resulting in declining levels of estrogen and progesterone. The drop in estrogen in the late luteal phase is thought to be the key factor in the pathogenesis of menstrual migraine.
What about estrogen withdrawal migraines?
Sommerville wrote extensively on the subject of estrogen-withdrawal migraine and the influence of progesterone and estradiol in the early 1970s. Using quasi-experimental observations in a small number of women with menstrually related migraine without aura, Sommerville posited that the late luteal phase decline in estrogen levels could trigger migraine. He gave supplemental estrogen to women who reliably experienced migraine attacks at the time of menstrual flow and found that the migraine was delayed until of the supplement wore off. He also found that progesterone did not prevent menstrual migraine attacks.[iii],[iv],[v],[vi],[vii]
Are we sure about the migraine/estrogen withdrawal theory?
Lichten, et al,[viii] writing in 1996 in Headache on “The confirmation of a biochemical marker for women’s hormonal migraine: The depo-estradiol challenge test,” performed a study which supported estrogen withdrawal as a migraine trigger in postmenopausal women. These researchers gave an intramuscular injection of estradiol in menopausal subjects and then recorded the occurrence of subsequent migraines.
Lichten, et al, studied 28 postmenopausal women volunteers made up of 16 women who had a history of severe, cyclic, menstrually related migraine attacks before becoming menopausal and 12 women (the control group) who had no history of migraine or headache. The results of this study were that:
“Menopausal complaints of vasomotor symptoms were relieved for at least the first 2 weeks of the study. No member of the control group reported a migraine during the month. However, a severe migraine was reported by all 16 women with a history of migraine. The average day of the migraine occurrence was 18.5 + 2.8.”
Lichten, et al, concluded:
“This study confirms two factors about menopausal hormonal migraine: (1) it can be precipitated by a drop in serum estrogen levels, and (2) a period of estrogen priming is a necessary prerequisite. This study also identifies that there are two biologically different populations of postmenopausal women: (1) those who developed migraine after a single depo-estradiol injection, and (2) those who did not. By understanding that in addition to the biological predisposition to migraine there exists the biochemical cofactor of falling estrogen levels, we may better understand this phenomenon and develop means to prevent its occurrence.
Is Estrogen withdrawal really a Migraine Trigger?
Loder, et al,[ix] writing in 2007 in Headache on “Hormonal Management of Migraine Associated With Menses and the Menopause: A Clinical Review,” stated:
“Cyclic ovarian sex steroid production may affect the clinical expression of migraine, as demonstrated by a wide variety of clinical, epidemiologic, and basic science observations.
Subsequently, multiple lines of evidence have confirmed the validity of estrogen withdrawal, after periods of sustained high levels, as a migraine trigger in premenstrual women.”
Do rising levels of Estrogen protect against Migraine occurrence?
MacGregor, et al,[x] writing in Neurology in 2006 studied “the association between urinary hormone levels and migraine with particular reference to rising and falling levels of estrogen across the menstrual cycle in women with menstrual and menstrually related migraine.”
They found a significantly higher number of migraine attacks during the late luteal/early follicular phase of falling estrogen and lower number of attacks during rising phases of estrogen. MacGregor, et al, stated:
“These findings confirm a relationship between migraine and changing levels of estrogen, supporting the hypothesis of perimenstrual but not postovulatory estrogen "withdrawal" migraine. In addition, rising levels of estrogen appear to offer some protection against migraine.”
The worry of taking estrogen based birth control.
Another common estrogen related problem occurs when these women take a birth control pill which delivers estrogen for three weeks and then progesterone for another week--the typical “Pill.” These women may find that taking the pill aggravates their migraine experience by increasing the number of headaches or by worsening the severity of the headaches.
Also taking the pill may bring on migraine aura symptoms such as visual images, numbness on one side of the body, or trouble talking. Rarely the pill may produce a stroke with permanent neurological deficit.
Does migraine stop after menstruation stops?
The old wives’ tale is that migraine goes away after menstruation stops. This doesn’t happen in 30% of migraine without aura women who have never had estrogen related headaches. Their migraines aren’t going to stop after menopause. However, estrogen reactive women usually have a pretty rocky time during the irregular pulse and varying amount of estrogen their bodies make during perimenopause when their migraines, which were once at least predictable, are now severe and irregular.
Problem with exogenous estrogen
Then sometimes to treat estrogen lack symptoms-- vasomotor hot flashes, emotional nervous symptoms, vaginal dryness, and to belay the soft bone situation of osteoporosis-- a gynecologist, internist, or general medical doctor may prescribe exogenous estrogen. This may help the estrogen lack symptoms, such as vaginal dryness or hot flashes, but it may very well aggravate the occurrence and severity of their migraine experience.
This analysis leads to the following dictum regarding estrogen and migraine:
Circulating estrogen may aggravate migraine:
1. if it is pulsed or cycled, such as happens with the normal menstrual cycle with estrogen withdrawal.
2. Elevated levels of estrogen may aggravate migraine.
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“Just my time of the month.”
Bibliography
[i] Pearce JMS. Fragments of Neurological History. Imperial College Press. Nervous System Diseases. 2003:148.
[ii] Welch KM, Brandes JL, Berman NE. Mismatch in how oestrogen modulates molecular and neuronal function may explain menstrual migraine. Neurol Sci. 2006;27(suppl2):S190-S192.
[iii] Somerville BW. Estrogen-withdrawal migraine. 1. Duration of exposure required and attempted prophylaxis by premenstrual estrogen administration. Neurology. 1975;25:239-244.
[iv] Somerville BW. Estrogen-withdrawal migraine. II. Attempted prophylaxis by continuous estradiol administration. Neurology. 1975;25;245-250.
[v] Somerville BW. The influence of progesterone and estradiol upon migraine. Headache. 1972;12:93-102.
[vi] Somerville BW. The role of estradiol withdrawal in the etiology of menstrual migraine. Neurology. 1972;22:355-365.
[vii] Somerville BW. The role of progesterone in menstrual migraine. Neurology. 1971;21:853-859.
[viii] Lichten EM, Lichten JB, Whitty A, Pieper D. The confirmation of a biochemical marker for women’s hormonal migraine: The depo-estradiol challenge test. Headache. 1996;36:367-371.
[ix] Loder E, Rizzoli P, Golub, J. Hormonal Management of Migraine Associated With Menses and the Menopause: A Clinical Review: CME. Headache. The Journal of Head and Face Pain 2007;47(20)329-340.
[x] MacGregor EA, Frith A, Ellis J, Aspinall L, Hackshaw A. Incidence of migraine relative to menstrual cycle phases of rising and falling estrogen. Neurology. 2006;67:2154-2158.
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