A Publication of the East Bay Headache Support Group
A Member of the American Council for Headache Education
(ACHE) Support Group Network

VOLUME 7, ISSUE 2
MARCH 2002

March 12th Meeting:  The Role of Hormones as Headache Trigger

The female sex has long been linked to migraine, and it’s well-known that women in their reproductive years, age 15-50 years, experience many more migraine headaches than men of similar age. Dr. Sondra Altman spoke to the support group on this topic six months ago, but since the meeting was scheduled for that infamous Tuesday, September 11, very few were able to attend. We have decided to bring back the very hot topic of hormones, and are pleased to welcome Dr. Angelyn Thomas, an Oakland gynecologist, as our speaker on March 12.

Dr. Thomas graduated from UC Berkeley and then received her M.D. from Harvard University. She is in private practice in Oakland with Dr. Yvette Gentry, where her clinical interests include incontinence procedures, medical and surgical management of abnormal uterine bleeding, and perimenopausal/postmenopausal hormone management. Dr. Thomas is Board-Certified and a Fellow of the American College of Obstetrics and Gynecology.

Dr. Thomas will address the role hormones play in the etiology of migraine headaches, including a discussion of hormone related issues as they pertain to headaches premenstrually; during pregnancy, lactation and postpartum; and during the perimenopausal and menopausal years. The pros and cons of hormone treatment will also be presented, as well as nonpharmacologic options for treatment of headaches.

Migraine affects three times more women than men, and approximately 60% of these women associate some of their migraines with their menstrual cycles. These migraines are referred to as menstrual migraines or menstrually related migraines. Symptomatic medications that treat the individual attack and non-drug strategies have been the traditional methods in dealing with menstrual migraine pain.

However, for some women symptomatic treatments prove ineffective in dealing with the severity of their menstrual migraine pain. Others become frustrated with the number of doses required due to the long duration of their menstrual migraines. Because the timing of menses and menstrual migraine is often predictable, new preventive treatments that are taken before the migraines begin are a viable alternative. These preventive treatments are usually started 1 to 2 days before the expected menstrual migraine and continued for 5 to 10 days.

Nonsteroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen (Motrin and Advil) and naproxen (Anaprox and Aleve) have shown benefit in reducing the frequency and intensity of menstrual migraine when taken before and during the menstrual period. These drugs block the production of prostaglandins that cause inflammation and that are produced by the uterus and released into the bloodstream during menstrual bleeding. A recent study with rofecoxib (Vioxx), a new anti-inflammatory drug with reduced gastrointestinal side effects, has demonstrated a significant reduction in menstrually related migraine frequency, starting 5 days before the menstrual period and continuing for 10 consecutive days at 25 mg or 50 mg daily. If the first NSAID is ineffective, others can be tried.

Magnesium supplementation has proven a benefit for some women with menstrual migraine. Reduced magnesium levels in migraine patients have been documented and possibly lead to menstrual migraine. A study with magnesium pyrrolidone carboxylic acid demonstrated decreased duration and intensity of menstrual migraine. Some headache experts recommend magnesium oxide 400 mg twice daily a few days before and during the menstrual cycle.

Migraine drugs normally taken during a migraine attack can also be used for prevention, beginning 2 days before the expected onset of headache and given for 5 consecutive days. There is no increased risk of drug rebound headache or other safety issues, provided these medications are used very infrequently or not at all at other times of the month. Ergotamines have been used; DHE nasal spray (Migranal) 2 mg every 8 hours was studied and shown to reduce menstrually related migraine pain severity. Sumatriptan (Imitrex) 25 mg 3 times daily has shown a reduction in the frequency and severity of menstrual migraine. Based upon the sumatriptan study results, naratriptan (Amerge) 1 mg twice daily was studied and was both effective and well tolerated. Other triptans, including zolmitriptan (Zomig), rizatriptan (Maxalt), and almotriptan (Axert), are also probably effective for menstrual migraine prevention.

These migraine-specific drugs used for preventive menstrual migraine treatment are expensive, but when used appropriately for women who are dissatisfied with their symptomatic treatments, they can reduce the pain and suffering associated with migraine headache and enable women with menstrual migraine to continue their active lifestyles. To gain approval from insurance companies, we write specific directions, for example, “Amerge 1 mg twice daily for 5 days monthly for menstrual migraine prevention.”

Hormone manipulation can be beneficial for menstrual migraine prevention. Most experts agree that the rapid decline in estrogen levels around menses is the trigger for menstrual migraine, and various hormone therapy options have been studied and recommended. Adding estrogen in the form of a patch or a pill (beginning 2 or 3 days before the menstrual period) to smooth out the natural drop in estrogen can be beneficial. Women on birth control pills can discuss with the prescribing physician the option of taking continuous birth control pills for 3 to 4 months to avoid their periods and possibly their menstrual migraines.

Daily medication used for preventing frequent migraine attacks that are not triggered by hormones and the menstrual cycle can be beneficial for menstrual migraine prevention. Women who are already using these medications for non-menstrual migraine, but experience more severe headaches around menses, may discuss with their doctor whether they might benefit from increasing the dose of medication prior to their menses.

Other therapies for prevention of menstrual migraine, including diuretics, melatonin, and feverfew, are supported only by case reports and have not been properly studied. Preventive treatment of menstrual migraine is a challenging trial-and-error process, but persistence and good patient-physician communication can yield worthwhile improvements in migraine control.

There has been little written on estrogen and its role in menopausal migraine. In 1975 Dr. L. Kudrow, a neurologist, noted that menopausal migraine sufferers typically reported their migraines occurred the week off oral estrogen replacement therapy. Therefore, he suggested the use of continuous estrogen. In his study, this continuous course of therapy was associated with fewer migraines. In 1977 Dr. J. Stryker, a gynecologist, in an analysis of menopausal women followed for several years, noted that the addition of oral estrogen effectively decreased migraine complaints in two-thirds of her 49 patients who recorded this complaint. Dr. R. W. Greenblatt, another gynecologist, attested to the relief estradiol pellets had for some of his menopausal migraine patients. Finally, Dr. Lichten found that the use of continuous oral or transdermal estrogen replacement was effective in alleviating menopausal migraine in 19 of 24 subjects.

Studies done in the 1970s by Kudrow, Stryker and Greenblatt all concluded that there was a positive clinical effect on migraine when estrogen was given continuously. Lichten's study showed that some menopausal migraines can be seen as a result of estrogen withdrawal after a period of estrogen priming. Once priming occurs, withdrawal will result in migraine in a select population of women. Not every woman develops migraine in the menopause, but there seems to exist a genetically unique population who have a noted history of migraine in the reproductive years and who experience migraine under certain conditions of estradiol withdrawal [i.e. depo-estradiol injections]. In Lichten’s study, 14 of 26 women experienced a severe attack of migraine 14 to 23 days after a 5 mg estradiol cyprionate injection was given. The 12 who had no complaints of migraine had no personal or family history of headache.

The physician must first recognize that menopausal estrogen replacement can both alleviate and contribute to migraine occurrence. Secondly, the physician must know that there exists two populations of menopausal women, one that will not usually develop migraine no matter how the estrogen is given, and a second that will be sensitive to conditions that produce estrogen withdrawal.

Estrogen Replacement in the Menopause

There are three basic estrogen preparations: estrogen oral tablets, estradiol transdermal systems (the patch), and estradiol injections. Estradiol is available in all three forms, yet the absorption and half-life of estradiol varies by individual, by dose, and by route of administration.

Estradiol given orally is rapidly metabolized by the liver. Typical dosage is 1 to 2 mg daily. After oral ingestion the peak estradiol level is usually noted at 4-8 hours with a fall back to near baseline levels by 12-16 hours. Therefore, to maintain adequate estradiol levels in the headache patient, oral estradiol probably needs to be given every twelve hours. Even then it is more difficult to maintain a stable estradiol milieu with oral estradiol than with either the patch or injections.

Estradiol Transdermal System (patch) contains either .05 mg % or .10 mg % estradiol for absorption through the skin. The serum estradiol level reaches a peak within 4 hours of application, and serum levels are maintained for approximately 3-4 days. In many cases, Dr. Lichten has found that the .05 mg % patch is unable to maintain adequate estradiol levels to prevent migraine, so he usually prescribes the .10 mg % patch. Also, many patients seem to need to change the estradiol patch more often, after 2-1/2 or 3 days, to prevent a migraine attack. Since no estrogen preparation is perfect for all women, the clinician must recognize the limits of each preparation and treat accordingly.

In 1999, Dr. Lichten announced that a new formulation of the estradiol subcutaneous pellet would maintain estradiol levels for 6-8 weeks. In a study of 50 women between the ages of 31 and 57, there was an 85% reduction in the use of Imitrex injections and oral tablets. Dr. Lichten explained that the pellet prevented the normal drop in estradiol near menstruation. The patients were elated at this simple method for migraine prevention. For women in their 40s and 50s, many elected to have testosterone pellets inserted at the same time. They had renewed energy, sex drive, and a positive attitude as a direct result of the action of testosterone.

The physician must first realize that the old standard of estrogen replacement with conjugated estrogen for 21-25 days per month is absolutely wrong for the menopausal migraine patient. If a menopausal patient has hormonal migraine, Dr. Lichten suggests the following treatment courses:

Continuous estrogen. First try estrogen orally every day.  Next, try the estradiol .10% patch every 3 days.  Then try the 5mg estradiol injections every 7-10 days.  If this fails, then change to estradiol tablets taken orally every 12 hours.  If all fails, Dr. Lichten suggests the patient try the new subcutaneous estradiol pellets.  If headaches continue, stop all estrogen.

Progesterone Replacement in the Menopause

If a woman has had a hysterectomy, there may be no real need for progesterone replacement. But to protect against endo-metrial cancer in women who still have a uterus, it is generally recommended that estrogen supplements are opposed with either synthetic progestin or natural progesterone. Progestin and progesterone prevent the build up of the endometrial lining that can be associated with heavy bleeding and both pre- and malignant endometrial change. However, a rarely appreciated fact is that progesterone and progestin alone can cause migraine!

For example, in the typical estrogen/progestin replacement regimen, the meno-pausal woman takes estrogen for 21-25 days and progesterone for 10 to 14, or 25 days. Most women will report their severe headaches occur either 1) the days off both estrogen and progestin or, 2) the days on progestin. In a number of patients, daily headaches are noted on progestin therapy.

Dr. Lichten suggests the following steps to determine if the headache condition is caused by progestin therapy:

Stop all progestin for two months. If headaches continue, they are not related to progestin therapy.

Change from synthetic progestin to a natural progesterone. Shift to the lowest dose of progestin and limit it to 10 days.

If headaches continue, discontinue progestin therapy. But be monitored by a gynecologist experienced in vaginal ultrasound and endometrial sampling.t

Found on the Internet at www.usdoctor.com

East Bay Headache Support Group

The East Bay Headache Support Group is a nonprofit organization dedicated to providing a forum for headache sufferers.  The support group meets the second Tuesday every other month at John Muir Medical Center from 7:30 to 9:00 p.m.  It is open to all headache sufferers and their families; the meetings are free (however, donations to cover printing, postage, and Web site expenses are appreciated!). The support group meetings include lectures by guest speakers, question and answer sessions, and informational materials. 

Directions to John Muir Medical Center: Take Highway 680 to the Ygnacio Valley Road exit in Walnut Creek; go East approximately 1-1/2 miles, and turn right onto La Casa Via.  Turn left into the medical center parking lot, and enter at the Main Lobby. Take stairs or elevator to the lower level and follow signs to the meeting room.

We value your input! Call, fax, write, or e-mail us if you have any comments or suggestions, or would like to help. The planning committee meets the third Tuesday evening every other month and welcomes new members. Michael Stein, MD, Advisor; Leslie Davis, Editor; Dana Giese, Webmaster; Donna Johnson, Treasurer.  Also, Carol Bartlett, Reg Fong, Joan Kelley. 

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