Migraine and the Menstrual Cycle

1. Migraine and the Menstrual
Cycle

2. What is a migraine?
A migraine is a moderate to severe steady or throbbing
headache often on one side of the head that is commonly
associated with sensitivity to light and sound, nausea and
occasionally vomiting. It is a debilitating headache, usually
made worse by routine activity. A small number of people
may experience visual disturbances, called aura, just prior
to their headache. Diagnosis is typically based on clinical
evidence, including patient history and diary information.

3. What is a menstrual migraine?
People who experience migraines are called migraineurs…
(MM) includes menstrually related migraine (MRM) which
is a migraine headache that occurs regularly two days
before to three days after the onset of menstrual flow, as
well as pure menstrual migraine (PMM), which refers to
attacks occurring only during menstruation.1
1. MacGregor EA. “Menstural” migraine: Towards a definition. Cephalalgia 1996; 16:11-16.

4. How do hormones trigger a migraine?
Most female migraineurs report an increased frequency of
migraine attacks immediately before and during
menstruation. Understanding the hormonal fluctuations
that occur during the monthly menstrual cycle can be very
helpful in managing and preventing hormonally related
migraines.

5. How do hormones trigger a migraine?
The monthly menstrual cycle is regulated by hormones of
the pituitary gland and the ovaries, primarily estrogen and
progesterone. Menstrual migraine can be triggered by a
drop in serum estrogen levels, which has an effect on the
central nervous system, specifically the serotonin
receptors in the brain. When serum estrogen
concentrations decline, serotonin levels also fall. This may
provoke dilatation of blood vessels and activation of the
trigeminal nerve pathways, culminating in a migraine
attack.

6. The menstrual cycle and the migraineur
An average menstrual cycle is 28 days long, but can vary
widely from woman to woman. The menstrual cycle has
two phases: The follicular phase and the luteal phase.
Fluctuations in hormone levels, primarily in the luteal
phase, may trigger menstrual related migraines in
migraineurs.

7. The bar graph above depicts each phase of the menstrual cycle.

8. Follicular phase: The follicular phase is the first half of the menstrual cycle and gets its name from the
development of the new egg follicle in the ovary. “Day 1” of menstruation is marked by bleeding which is
caused by shedding of the endometrium. As the cycle begins serum estradiol and progesterone concentrations
are low, which cause the hypothalamus in the brain to increase gonadotropin-releasing hormone (GnRH). This
signals the pituitary gland in the brain to release the follicle-stimulating hormone (FSH) and luteinizing hormone
(LH). FSH and LH are carried to the ovaries. One dominant follicle will develop.
During this phase it is possible for a woman to experience a MM based on the drop in estrogen which occurred
during the second half of the last cycle preceding menstruation. This period of vulnerability may last several
days after the onset of menstruation, after which it is rare for a hormonally related migraine to occur. A
headache which occurs during the second half of the follicular phase is less likely due to hormonal triggers.

9. Ovulation phase: Mid-cycle, high levels of estrogen cause the pituitary gland to release a large amount of LH
(called the LH surge), which triggers ovulation. The dominant egg follicle bursts and releases the mature egg,
which travels to the fallopian tubes. This triggers a gradual increase in serum progesterone concentrations. A
small percentage of women experience migraine during this time.

10. Luteal phase: After ovulation the ruptured follicle becomes the corpus luteum, a mass of cells that produces
the hormone progesterone. If the egg is not fertilized, the corpus luteum deteriorates and progesterone
production halts. This causes the lining of the uterus to break down and once again triggers the onset of
menstruation.
A woman who is sensitive to hormonal fluctuations is most likely to experience a migraine during this phase
due to the drop in estrogen levels which, in turn, causes changes in the serotonergic system in the brain.

11. Intervention overview
The treatment approach for MM is the same as for
migraine occurring at any time. The primary goals of
treatment are to decrease attack frequency, duration,
accompanying symptoms, and disability. It is far preferable
to prevent a migraine attack than to treat one once it has
started, an all migraineurs should initiate preventive
healthy lifestyle strategies either alone or in addition to
pharmacological therapies.

12. Intervention overview
Patients may be advised to keep a headache diary for two to three
months to identify personal triggers such as hormonal, dietary,
weather, stress, and other issues. This will help physicians in
personalizing a treatment program to manage migraine.
Acute treatment approaches are employed first. For migraineurs who
do not obtain satisfactory relief with acute strategies and who regularly
experience MM, physicians may initiate preventive strategies. Many
health care providers will follow a stratified approach including
behavioral strategies, acute pharmacological treatments and if
necessary, non-hormonal or hormonal preventive treatments.

13. Non-Pharmacological Treatment:
Healthy Lifestyle Modification
All women who experience migraines should adopt a
healthy lifestyle and learn to avoid potential migraine
triggers. These habits can make a significant difference in
avoiding migraine attacks and reducing or managing pain
during attacks. These strategies should be combined with
any additional pharmacological treatments.

14. Non-Pharmacological Treatment:
Healthy Lifestyle Modification
These strategies include…
•Proper sleep and hygiene. Get regular and adequate
amounts of sleep (aim for eight hours for an adult and adjust
as necessary). Attempt to go to sleep and wake at the same
times every day including weekends and holidays. Avoid use
of sleep medication.
•Avoid Dietary Triggers, especially alcohol and caffeine.
Patients may keep a headache diary to identify other specific
triggers, although experts warn against excessive elimination
of foods. Eat regular, healthy meals and avoid skipping
meals.

15. Non-Pharmacological Treatment:
Healthy Lifestyle Modification
• Regular Aerobic Exercise or Walking. Establish an exercise
routine for at least 30 minutes, five days per week.
• Avoid Stress. Use relaxation and coping strategies, such as
relaxation audio tapes and exercises, yoga, tai chi, and/or
learning relaxation and biofeedback skills from a qualified
psychologist or mental health professional.
• Do not smoke.
• Avoid Rebound Headaches. Do not use acute medications
(such as anti-inflammatory medications, acetaminophen, or
opioids) more than twice per week or more than 24 acute
medications per month to avoid triggering “rebound headaches”
and other stressful effects on the body.

16. Acute treatment
Acute treatment of MM is similar to therapies for migraine occurring at
any time. Medications that have been proven effective or that are
commonly used for the acute treatment are described below. Patients
often self-medicate on their own with the over-the-counter
medications; however, this may not be effective. Either a non-steroidal
anti-inflammatory drug (NSAID) alone, or in combination with a rapid-
onset triptan medication, is often prescribed first. Many patients
eventually require a triptan. If severe attacks cannot be controlled with
these medications then other analgesics, corticosteroids, and
dihydroergotamine (DHE) may be considered. If acute management is
inadequate, prevention therapy is indicated.

17. Acute treatment
• Nonsteroidal anti-inflammatory drugs (NSAIDs) are
medications which may reduce the severity, and duration of
migraine attacks and may also be useful to manage other
bothersome premenstrual symptoms. They work by
interfering in the formation of prostaglandins, which play a
role in migraine as well as other types of pain such as
dysmenorrhea. NSAIDs should not be used on a daily basis
or for extended periods of time without medical supervision
as there is a risk of developing a daily “drug rebound”
headache (i.e., a headache that returns as each dose
wears off) and potential gastrointestinal side effects.

18. Acute treatment
• Triptan medications are serotonin agonists. They can
eliminate or reduce pain associated with migraine as well
as reducing her migraine symptoms including nausea
and sensitivity to light and sound. Early intervention
(within the first half hour of migraine onset) is
recommended for maximum efficacy. Patients should
take the medication at the onset of pain, even if the pain
is only mild at that time. Use of triptans requires ongoing
medical supervision.

19. Preventive: Non-Hormonal Therapy
Preventive, or prophylactic, medications are prescribed to prevent or
reduce the number of attacks for migraineurs who experience frequent
migraines (2-3 or more per month.) A list of the classes of medications
used in migraine prevention is presented below. These therapies
require medical supervision. Each class of medications works
differently and may have other adverse affects or benefits. Preventive
medications typically take several weeks to reach maximum efficacy
and are dosed on a daily or cyclical basis. Successful therapy is
considered to be a 50% reduction in the frequency, duration, and
intensity of attacks. The majority of these medications are not FDA
approved as migraine prophylactic agents.

20. Standard Prophylactic Agents
• Anti-Epileptic Medications were originally used for the treatment of
epilepsy but have been shown to be effective in reducing the frequency and
severity of migraine attacks. Two medications, valproic acid and topiramate,
are FDA approved as migraine prevention agents.
• Calcium Channel Blockers and Beta Blockers are commonly prescribed
prophylactic agents for migraine. Traditionally used for management of high
blood pressure and coronary heart disease, these medications may relax
blood vessels and increase the supply of blood and oxygen to the heart
while reducing its stress. The improvement in blood flow may help prevent
migraine attacks.
• Antidepressants originally developed to treat depression are often
prescribed with a good degree of success in reducing both frequency and
severity of migraine, perhaps by regulating serotonin and adrenaline levels
in the brain.

21. Mini-Prophylactic Agents
• NSAIDs are often used on a daily basis to prevent the
onset of MM. They are typically initiated 2 days before
the expected onset of the MM and continued for 5-7
days.
• Long acting triptans, such as naratriptan and
frovatriptan, are increasingly being used for prophylaxis
of MM. Therapy begins two days before the anticipated
onset of the MM and is continued on a twice-daily basis
for 5-6 days.

22. Preventive: Hormonal Therapy
Hormonal prophylaxis may be appropriate and effective for
migraineurs
1.In whom MM does not respond to acute or non-hormonal preventive
approaches
2.Who are interested in contraception, or
3.Who may benefit from other effects of hormonal therapies (i.e.
women with endometriosis, menorrhagia, dysmenorrhea, and irregular
cycles.)
Since MM is precipitated by a decline in serum estrogen levels,
hormonal preventive therapies aim to reduce or eliminate this decline.
This may involve the use of a supplemental estrogen taken
perimenstrually either by mouth or in a transdermal patch.

23. Preventive: Hormonal Therapy
Another approach is for women to use an extended or continuous
regimen of oral contraceptives (OC). This can be achieved by (a) not
taking the placebo pills provided in traditional 21-day regimens,
although women will need to get extra packs in the course of a year, or
(b) with the newer FDA approved, extended 84-day oral contraceptive
formula. The best OCs in migraineurs are felt to be the low-dose,
monophasic formulations, as opposed to the bi- or tri-phasic pills,
especially those above 20mcg.
All of these strategies require medical supervision. For adolescent girls
with MM, a medical professional who is experienced in treating this
young population should be involved in the treatment planning.