Migraine Headache in Menopause - How Sleep Deprivation and Hormonal Change Play Havoc with the Menopausal Woman

Jerome Goldstein, MD

General Considerations of Migraine Headache

Headache, the most common symptom in medical practice, and specifically migraine headache represent personal and public health issues of great importance. It is currently estimated that there are well over 20,000,00 migraine headache sufferers in the United States. This is a conservative estimate and does not include other related headache diagnoses. Exacting the correct headache diagnosis is of paramount importance in having a successful treatment plan as well as having an appropriate health care provider/patient relationship. Seventy five percent of migraine headache sufferers are women with headache beginning at the time of menarche, modified by menses, birth control pills, fertility drugs, pregnancy and menopause as well as perimenopause.

Although male children predominate in the diagnosis of migraine headache, it is a known fact that with the onset of menses women are in the great preponderance with the diagnosis of migraine headache. Use of birth control pills can make migraine headache more prominent and fertility drugs can increase the frequency of debilitating migraine headache dramatically. Migraine headache is very frequently absent during the second and third trimesters of pregnancy and post partum breast feeding. With perimenopause there can be dramatic fluctuations in the frequency and severity of migraine headache but a majority of lifelong migraineurs enjoy cessation of symptoms during menopause. This is, of course, notwithstanding hormonal manipulation.

The characteristics of migraine headache are well known to the headache scientific community as outlined by the diagnostic guidelines of the International Headache Society. A migraine headache diagnosis is comprised of the following:

1. At least four episodes of headache.
2. Each episode lasting four to 72 hours.
3. Each episode either preceded or not preceded by an aura.
4. Throbbing or nonthrobbing headache that is usually lateralized but can be bilateral.
5. Each episode accompanied by nausea and/or vomiting and/or photopbobia and photophobia.
6. Each episode made worse by exercise.

Although there has been some controversy regarding the exact characteristics of migraine headache, the convention of having some element of nausea and/or vomiting and/or photophobia and phonophobia have become very firmly entrenched in the diagnosis of migraine headache, as well as defining migraine headache for clinical trials for headache research.

Thus a firm diagnosis of migraine headache can facilitate use of the newer medications used to treat on both an acute and prophylactic basis.

There has been considerable interest in the origin of migraine headache. Presently the scientific community agrees that the generator of migraine headache is in the trigeminal-vascular area of the brainstem and is based on alteration of the 1B and 1D receptors. It is also felt to be based in the modification of serotonin metabolism. This basic generator of migraine headache is modified by almost every element of the central nervous system and it comes as no surprise to any medical practitioner that hormonal changes occurring throughout a woman's life, as well as disturbances in sleep patterns, can affect migraine headache.

In consideration of the hormonal changes noted throughout a woman's life, multiple studies confirm that a menstrual-related-migraine headache accompanies the drop in estrogen prior to and in the first day or two of the menstrual flow. Despite this known fact, most attempts at changing or regulating the estrogen level through birth control pills or other methods have had only marginal success in the treatment of menstrual-related migraine headache.

Women in menopause and perimenopause experience a symptom complex that most often includes hot flushes, insomnia, nocturnal sweating, dizziness, headache and palpitations. Falling estrodial levels in menopause can result in increased headache and fluctuating headache patterns as menopause proceeds. The relationship of neurochemicals in menopause such as gamma-aminobutyric acid and enkephalins to hormonal changes is verified by the fact that most menopausal symptoms do respond to hormone replacement therapy with the exception of tension-type headache, which may respond equally to placebo and hormone replacement therapy. Also women who were former migraine sufferers with a history of worsening headache during menses, worsening headache with use of birth control pills, improvement with pregnancy, and worsening with hormone replacement therapy tend to have worsening of migraine headache during the menopause. A history of hormonal symptomatology related to hormonal change is a true warning sign for the perimenopausal or menopausal woman.

In contrast to the migraine hormonal pattern leading to increased headache in menopause, those women who exhibit a long history of tension type headache with migraine characteristics have a more even pattern of headache distribution with menopause.

We often think of the above menopausal symptoms as a phenomenon more emphasized in western society and the industrialized world. However, studies carried out in many third world and less industrialized countries, confirm the constellation of menopausal symptoms similar to the generally accepted complex including headache and disorders of sleep. Specifically a study in done in Ghana confirmed the worldwide presence of the menopausal symptom complex.

The Role of Sleep Disorders in Migraine and Menopause

Sleep has often been known to be curative in migraine headache, especially when use of the newer triptan medications and analgesia fail to relieve headache. Even with the more selective and potent migraine specific medications patients may require analgesia and sedation to "break" a severe migraine attack. Alterations in the circadian rhythms change prolactin levels, growth hormone levels, and cortisol levels. Together with the changes that occur hormonally in menopause, most women do expect a somewhat mercurial course during early menopause. Circadian changes in endocrine function such as cortisol and PRL and vegetative phenomena such as temperature and blood pressure, have been found in all types of headache including migraine headache, cluster headache and mixed headache. Sleep deprivation and hormonal changes related to menopause and perimenopause increase susceptibility to increased migraine headache.

Male and Female Sex Differences in Headache

Sex differences in headache types is important in evaluation and treatment of all headache types but usually emphasized in cluster headache. While over 80 percent of cluster headache sufferers are male, multiple studies have confirmed that cluster headache in women does improve with pregnancy, once again confirming the neurobiological nature of most headache types.

We thus conclude that tension headache, migraine headache and cluster headache have variable but definite neurobiological hormonal patterns with migraine headache having the most prominent association, tension headache somewhat less prominent, and cluster headache although occurring most frequently in men, has hormonal associations in women.

Treating Menopausal Migraine Headache and Accompanying Sleep Disorders

Treatment of menopausal migraine headache is based on attempting even hormonal levels. Many forms of hormonal replacement therapy will approach that goal but do not always result in amelioration of the headache problem. Added regulation of sleep is very helpful especially with the use of bicyclic and tricyclic antidepressants. Use of the triptans is a tremendous added advantage in managing headache associated with the menopause and with the ability to choose between seven such agents at the present time (sumatriptan, zolmitriptan, rizatriptan, naratriptan, almotriptan, eletriptan, and frovatriptan) matching the duration of action, speed of action, side effect profile, and consistency of the various triptans to the patient, frequently leads to better control of the headache.

Since headache is a multifactorial, medical condition medications are only a part of the treatment plan of an astute health care provider. Regular sleep patterns, aerobic exercise and other measures such as biofeedback therapy, massage, acupuncture, etc., can be useful. Understanding the placement and utility of alternative therapies in the treatment of headache will yield the best results. For example Biofeedback therapy is best performed in the anxious patient with some psychotherapeutic intervention by the therapist. Massage, acupuncture, acupressure, rolfing, chiropractic and spinal adjustments are best suited to those patients with muscle spasm and contraction. Psychotherapy is most productive in headache and menopausal patients with a defined psychiatric diagnosis. A mere statement of depression is not sufficient in this setting since most patients with headache and other pain conditions will experience situational depression. Since all antidepressants of all categories have significant side effects that include weight gain, lethargy, diminished libido and increased agitation in varying degrees, the appropriateness of an antidepressant in the treatment of headache and menopausal symptoms and disorders of sleep requires careful consideration. Antidepressants that induce sleep have a definite added advantage in patients with insomnia. Antidepressants that address anxiety and possible mania are most helpful in patients with those diagnoses. Antipsychotic agents, although useful in patients with severe headache diagnoses, should be used with extreme caution.

The Placebo Effect in Headache Management

There is a definite placebo effect in all headache clinical trials which is significant. The placebo effect should be applied to all clinical settings in the headache patient. Considerable attention must be paid to merely addressing the headache problem together with the consequences of menopause and a possible dysfunction of sleep. Reassurance regarding possible intracranial pathology and the suggestions accompanying a new headache treatment plan can reduce the headache pain and severity up to thirty to forty40 percent. This placebo effect noted to be true in most conditions of pain is added to the medications and other non-medical treatments for any headache condition.

Evaluation - A Major Pitfall of Menopausal Headache

Menopausal patients with disorders of sleep mandating changes in hormonal and headache therapy have often had extensive medical evaluations. Along with these evaluations CT and MRI scans have been done in abundance. In such patients the statement of having had a negative CT or MRI scan could imply that the study is over twenty years old. There are significant warning signs of a new pathological process:

1. A headache disorder that is changing in character.
2. A headache disorder that is increasing in frequency and severity.
3. A headache disorder that is accompanied by new neurological signs and symptoms.

Migraine headache, menopause and disorders of sleep present a challenge both diagnostically and therapeutically.

Dr. Goldstein is the director of the San Francisco Clinical Research Center, San Francisco Headache Clinic and San Francisco Alzheimer's and Dementia Clinic and ahs been in the private practice of neurology since 1970. He is also a fellow in the American Academy of Neurology and assistant clinical professor of neurology at UCSF. He is also certified by the American Board of Psychiatry and Neurology and a member of the American Headache Society and was in the first group of fellows elected to this organization. He is also a member of the SFMS.