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STOWE, VT. – , said Susan Hutchinson, MD, director of the Orange County Migraine and Headache Center in Irvine, Calif. Compared with headaches associated with nonmenstrual migraine, headaches resulting from menstrual migraine last longer and are more difficult to treat. They tend to be associated with morning awakening and with nausea and vomiting. But in younger women with regular menses, menstrual migraine is predictable. The disorder offers “an incredible chance to be preemptive and think about short-term preventive strategies,” Dr. Hutchinson said at the annual meeting of the Headache Cooperative of New England.
What is menstrual migraine?
Menstrual migraine occurs during the perimenstrual window, which begins at 2 days before onset of bleeding and ends at 3 days of menses. Migraine that occurs during this window at least two-thirds of the time satisfies the criteria for menstrual migraine. A prospective headache diary is recommended, but not required, for making the diagnosis, said Dr. Hutchinson.
Most women with migraine have perimenstrual exacerbation of their headaches, as well as headaches at other times of the month. This phenotype is called menstrually related migraine. Pure menstrual migraine is migraine associated exclusively with menses. The International Classification of Headache Disorders-3 recognizes that menstrual migraine can be with or without aura. A headache diary can help distinguish between menstrual migraine and menstrually related migraine.
For pure menstrual migraine, it is appropriate to treat during the perimenstrual window. Preventive treatment may not be necessary throughout the month, said Dr. Hutchinson. Furthermore, hormonal treatment is the type of therapy most likely to be effective, she added. Menstrually related migraine requires a broader approach.
Gathering information during the visit
A 1972 study by Somerville and colleagues indicated that a decrease in estrogen is a powerful trigger of migraine. The investigators administered estrogen (i.e., intramuscular estradiol) or progesterone during the late luteal phase to women with menstrual migraine. Among women who received estrogen, migraine onset was postponed until the estrogen level decreased. The administration of progesterone postponed bleeding, but did not affect migraine. Progesterone treatment prevents migraine effectively on occasion, but estrogen treatment is much more likely to be a successful strategy, said Dr. Hutchinson.
Neurologists should ask certain questions of women with migraine, whether the patients are new or not, to gather information needed to make treatment decisions. For example, it is advisable to ask a woman whether she often has a headache with her period. “You may not want to use the word ‘migraine,’ because many women have been taught that headache is part of PMS,” said Dr. Hutchinson. Asking a woman how pregnancy, delivery, and breastfeeding affected her headaches can add further detail to her history and provide insight about the effects of hormonal changes. Asking what type of birth control the woman is taking can influence the choice of treatment, since some therapies are not appropriate during pregnancy.
Available treatments
NSAIDs are among the treatments that neurologists should consider for the short-term prevention of menstrually related migraine, said Dr. Hutchinson. A study of 35 patients by Sances et al. compared placebo with 550 mg of naproxen sodium given twice daily. Treatment began at 7 days before bleeding onset and continued until the 6th day of menses. Patients underwent treatment for three menstrual cycles. Naproxen sodium significantly reduced headache intensity, headache duration, and the number of headache days, compared with baseline. Treatment was superior to placebo at 3 months. Approximately 33% of patients in the active group were headache free, but no controls were.
Magnesium is another potentially effective option. Facchinetti et al. compared placebo with 360 mg/day of magnesium in a study of 20 patients. Treatment, which was given for two cycles, began at 15 days before menses and ended at the start of menses. Compared with placebo, magnesium reduced the number of headache days and the total pain index. Magnesium is inexpensive, but it causes diarrhea in some patients. “Some women choose to take magnesium all month long, other women start at around ovulation,” said Dr. Hutchinson.
Hormonal treatments are another possible option for the short-term prevention of menstrually related migraine. For women who do not plan to become pregnant, oral contraceptive pills can keep estrogen levels high enough to prevent menstrually related migraine. Gynecologists may suggest that a woman take the pill continuously, skipping the placebo, for an entire year, but Dr. Hutchinson recommends that a woman stop taking the pill for 4 days approximately every 3 months. This discontinuation allows for withdrawal bleeding, but is not likely to cause a prolonged enough decrease in estrogen to provoke migraine, she said. The continuous contraceptive ring, which is inserted vaginally, is an alternative to the pill.
For women who do not want or need contraception, an estrogen patch or gel may be appropriate. Two studies in the 1980s found that a gel containing 1.5 mg of estradiol per 2.5 g reduced migraine frequency, duration, and severity. These studies did not gather long-term safety data, however. A 2006 study by MacGregor et al. found that percutaneous estradiol was associated with a 22% reduction in the number of migraine days, as well as with decreases in headache severity and associated nausea. But the risk of migraine during the 5 days following treatment cessation was increased by 40%. This finding suggests that the treatment period should be extended, said Dr. Hutchinson.
In addition to the timing, the dose of treatment affects the outcome. Smite et al. found no benefit of a 50-mcg dose of estradiol, compared with placebo. Pradalier and colleagues found that a 100-mcg dose was associated with decreased use of rescue medication, compared with a 25-mcg dose. These studies did not gather long-term safety data.
Oral contraceptives and the risk of stroke
Combined oral contraceptives, however, are associated with increased risk of stroke in women with migraine with aura. The dose of estrogen in the contraceptive affects the level of risk, said Dr. Hutchinson. A systematic review by Sheikh et al. found that high-dose ethinyl estradiol (i.e., greater than 50 mcg) was associated with a higher risk of ischemic and hemorrhagic stroke than low-dose ethinyl estradiol (i.e., less than 50 mcg) was. A 20-mcg dose was associated with an odds ratio of stroke of 1.7. Furthermore, among women using combined hormonal contraception, the risk of stroke was higher in women with aura than in women without aura.
“I like to look at the big picture,” said Dr. Hutchinson. “There’s a big difference between a woman who has one or two auras a year that last for 10 minutes and a woman who has complicated aura. I’m going to approach [the latter] woman differently.”
No consensus guidelines for prescribing combined oral contraceptives to women with migraine and aura have been developed. The International Headache Society says that physicians may prescribe low-dose estrogen to women with simple visual aura. The American College of Obstetricians and Gynecologists recommends progestin-only intrauterine or barrier contraception for this population. The World Health Organization holds that estrogen-containing contraception is contraindicated in all women who have migraine with aura.
“If you have women who have migraine without aura, low–estrogen dose combined hormonal contraceptives can be quite appropriate,” said Dr. Hutchinson. “I would tend to go with a 10- or 20-mcg low dose. It could be an option for women with migraine with aura, but only if the benefits outweigh the risks.” In a study by Calhoun et al., the vaginal ring was associated with reduced aura frequency in women with migraine and aura.
Choosing preventive and rescue medications
Although no triptan has FDA approval for the short-term prevention of menstrual migraine, studies have suggested that they are effective. In a study by Sances and colleagues, a twice-daily 1-mg dose of naratriptan taken 6 days perimenstrually reduced the frequency of menstrual-related migraine. At least 50% of treated patients in the study had no menstrual-related migraine. Silberstein and colleagues found that 59% of women who took 2.5 mg of frovatriptan twice daily had no menstrual-related migraine during the 6-day perimenstrual period, compared with 33% of women who received placebo.
Patients with menstrual migraine sometimes need rescue medication. Sumatriptan, either as an injection or an inhaled therapy, is one option. Another injectable option is a 60-mg intramuscular dose of ketorolac. Finally, occipital or sphenopalatine nerve block may be effective as well.
Dr. Hutchinson reported consulting for or serving on the advisory board of Alder, Allergan, Amgen, Biohaven, electroCore, Lilly, Novartis, Supernus, Teva, Theranica, and Upsher-Smith. She has served on speakers bureaus for Allergan, Amgen, electroCore, Lilly, Novartis, Supernus, and Teva.
STOWE, VT. – , said Susan Hutchinson, MD, director of the Orange County Migraine and Headache Center in Irvine, Calif. Compared with headaches associated with nonmenstrual migraine, headaches resulting from menstrual migraine last longer and are more difficult to treat. They tend to be associated with morning awakening and with nausea and vomiting. But in younger women with regular menses, menstrual migraine is predictable. The disorder offers “an incredible chance to be preemptive and think about short-term preventive strategies,” Dr. Hutchinson said at the annual meeting of the Headache Cooperative of New England.
What is menstrual migraine?
Menstrual migraine occurs during the perimenstrual window, which begins at 2 days before onset of bleeding and ends at 3 days of menses. Migraine that occurs during this window at least two-thirds of the time satisfies the criteria for menstrual migraine. A prospective headache diary is recommended, but not required, for making the diagnosis, said Dr. Hutchinson.
Most women with migraine have perimenstrual exacerbation of their headaches, as well as headaches at other times of the month. This phenotype is called menstrually related migraine. Pure menstrual migraine is migraine associated exclusively with menses. The International Classification of Headache Disorders-3 recognizes that menstrual migraine can be with or without aura. A headache diary can help distinguish between menstrual migraine and menstrually related migraine.
For pure menstrual migraine, it is appropriate to treat during the perimenstrual window. Preventive treatment may not be necessary throughout the month, said Dr. Hutchinson. Furthermore, hormonal treatment is the type of therapy most likely to be effective, she added. Menstrually related migraine requires a broader approach.
Gathering information during the visit
A 1972 study by Somerville and colleagues indicated that a decrease in estrogen is a powerful trigger of migraine. The investigators administered estrogen (i.e., intramuscular estradiol) or progesterone during the late luteal phase to women with menstrual migraine. Among women who received estrogen, migraine onset was postponed until the estrogen level decreased. The administration of progesterone postponed bleeding, but did not affect migraine. Progesterone treatment prevents migraine effectively on occasion, but estrogen treatment is much more likely to be a successful strategy, said Dr. Hutchinson.
Neurologists should ask certain questions of women with migraine, whether the patients are new or not, to gather information needed to make treatment decisions. For example, it is advisable to ask a woman whether she often has a headache with her period. “You may not want to use the word ‘migraine,’ because many women have been taught that headache is part of PMS,” said Dr. Hutchinson. Asking a woman how pregnancy, delivery, and breastfeeding affected her headaches can add further detail to her history and provide insight about the effects of hormonal changes. Asking what type of birth control the woman is taking can influence the choice of treatment, since some therapies are not appropriate during pregnancy.
Available treatments
NSAIDs are among the treatments that neurologists should consider for the short-term prevention of menstrually related migraine, said Dr. Hutchinson. A study of 35 patients by Sances et al. compared placebo with 550 mg of naproxen sodium given twice daily. Treatment began at 7 days before bleeding onset and continued until the 6th day of menses. Patients underwent treatment for three menstrual cycles. Naproxen sodium significantly reduced headache intensity, headache duration, and the number of headache days, compared with baseline. Treatment was superior to placebo at 3 months. Approximately 33% of patients in the active group were headache free, but no controls were.
Magnesium is another potentially effective option. Facchinetti et al. compared placebo with 360 mg/day of magnesium in a study of 20 patients. Treatment, which was given for two cycles, began at 15 days before menses and ended at the start of menses. Compared with placebo, magnesium reduced the number of headache days and the total pain index. Magnesium is inexpensive, but it causes diarrhea in some patients. “Some women choose to take magnesium all month long, other women start at around ovulation,” said Dr. Hutchinson.
Hormonal treatments are another possible option for the short-term prevention of menstrually related migraine. For women who do not plan to become pregnant, oral contraceptive pills can keep estrogen levels high enough to prevent menstrually related migraine. Gynecologists may suggest that a woman take the pill continuously, skipping the placebo, for an entire year, but Dr. Hutchinson recommends that a woman stop taking the pill for 4 days approximately every 3 months. This discontinuation allows for withdrawal bleeding, but is not likely to cause a prolonged enough decrease in estrogen to provoke migraine, she said. The continuous contraceptive ring, which is inserted vaginally, is an alternative to the pill.
For women who do not want or need contraception, an estrogen patch or gel may be appropriate. Two studies in the 1980s found that a gel containing 1.5 mg of estradiol per 2.5 g reduced migraine frequency, duration, and severity. These studies did not gather long-term safety data, however. A 2006 study by MacGregor et al. found that percutaneous estradiol was associated with a 22% reduction in the number of migraine days, as well as with decreases in headache severity and associated nausea. But the risk of migraine during the 5 days following treatment cessation was increased by 40%. This finding suggests that the treatment period should be extended, said Dr. Hutchinson.
In addition to the timing, the dose of treatment affects the outcome. Smite et al. found no benefit of a 50-mcg dose of estradiol, compared with placebo. Pradalier and colleagues found that a 100-mcg dose was associated with decreased use of rescue medication, compared with a 25-mcg dose. These studies did not gather long-term safety data.
Oral contraceptives and the risk of stroke
Combined oral contraceptives, however, are associated with increased risk of stroke in women with migraine with aura. The dose of estrogen in the contraceptive affects the level of risk, said Dr. Hutchinson. A systematic review by Sheikh et al. found that high-dose ethinyl estradiol (i.e., greater than 50 mcg) was associated with a higher risk of ischemic and hemorrhagic stroke than low-dose ethinyl estradiol (i.e., less than 50 mcg) was. A 20-mcg dose was associated with an odds ratio of stroke of 1.7. Furthermore, among women using combined hormonal contraception, the risk of stroke was higher in women with aura than in women without aura.
“I like to look at the big picture,” said Dr. Hutchinson. “There’s a big difference between a woman who has one or two auras a year that last for 10 minutes and a woman who has complicated aura. I’m going to approach [the latter] woman differently.”
No consensus guidelines for prescribing combined oral contraceptives to women with migraine and aura have been developed. The International Headache Society says that physicians may prescribe low-dose estrogen to women with simple visual aura. The American College of Obstetricians and Gynecologists recommends progestin-only intrauterine or barrier contraception for this population. The World Health Organization holds that estrogen-containing contraception is contraindicated in all women who have migraine with aura.
“If you have women who have migraine without aura, low–estrogen dose combined hormonal contraceptives can be quite appropriate,” said Dr. Hutchinson. “I would tend to go with a 10- or 20-mcg low dose. It could be an option for women with migraine with aura, but only if the benefits outweigh the risks.” In a study by Calhoun et al., the vaginal ring was associated with reduced aura frequency in women with migraine and aura.
Choosing preventive and rescue medications
Although no triptan has FDA approval for the short-term prevention of menstrual migraine, studies have suggested that they are effective. In a study by Sances and colleagues, a twice-daily 1-mg dose of naratriptan taken 6 days perimenstrually reduced the frequency of menstrual-related migraine. At least 50% of treated patients in the study had no menstrual-related migraine. Silberstein and colleagues found that 59% of women who took 2.5 mg of frovatriptan twice daily had no menstrual-related migraine during the 6-day perimenstrual period, compared with 33% of women who received placebo.
Patients with menstrual migraine sometimes need rescue medication. Sumatriptan, either as an injection or an inhaled therapy, is one option. Another injectable option is a 60-mg intramuscular dose of ketorolac. Finally, occipital or sphenopalatine nerve block may be effective as well.
Dr. Hutchinson reported consulting for or serving on the advisory board of Alder, Allergan, Amgen, Biohaven, electroCore, Lilly, Novartis, Supernus, Teva, Theranica, and Upsher-Smith. She has served on speakers bureaus for Allergan, Amgen, electroCore, Lilly, Novartis, Supernus, and Teva.
STOWE, VT. – , said Susan Hutchinson, MD, director of the Orange County Migraine and Headache Center in Irvine, Calif. Compared with headaches associated with nonmenstrual migraine, headaches resulting from menstrual migraine last longer and are more difficult to treat. They tend to be associated with morning awakening and with nausea and vomiting. But in younger women with regular menses, menstrual migraine is predictable. The disorder offers “an incredible chance to be preemptive and think about short-term preventive strategies,” Dr. Hutchinson said at the annual meeting of the Headache Cooperative of New England.
What is menstrual migraine?
Menstrual migraine occurs during the perimenstrual window, which begins at 2 days before onset of bleeding and ends at 3 days of menses. Migraine that occurs during this window at least two-thirds of the time satisfies the criteria for menstrual migraine. A prospective headache diary is recommended, but not required, for making the diagnosis, said Dr. Hutchinson.
Most women with migraine have perimenstrual exacerbation of their headaches, as well as headaches at other times of the month. This phenotype is called menstrually related migraine. Pure menstrual migraine is migraine associated exclusively with menses. The International Classification of Headache Disorders-3 recognizes that menstrual migraine can be with or without aura. A headache diary can help distinguish between menstrual migraine and menstrually related migraine.
For pure menstrual migraine, it is appropriate to treat during the perimenstrual window. Preventive treatment may not be necessary throughout the month, said Dr. Hutchinson. Furthermore, hormonal treatment is the type of therapy most likely to be effective, she added. Menstrually related migraine requires a broader approach.
Gathering information during the visit
A 1972 study by Somerville and colleagues indicated that a decrease in estrogen is a powerful trigger of migraine. The investigators administered estrogen (i.e., intramuscular estradiol) or progesterone during the late luteal phase to women with menstrual migraine. Among women who received estrogen, migraine onset was postponed until the estrogen level decreased. The administration of progesterone postponed bleeding, but did not affect migraine. Progesterone treatment prevents migraine effectively on occasion, but estrogen treatment is much more likely to be a successful strategy, said Dr. Hutchinson.
Neurologists should ask certain questions of women with migraine, whether the patients are new or not, to gather information needed to make treatment decisions. For example, it is advisable to ask a woman whether she often has a headache with her period. “You may not want to use the word ‘migraine,’ because many women have been taught that headache is part of PMS,” said Dr. Hutchinson. Asking a woman how pregnancy, delivery, and breastfeeding affected her headaches can add further detail to her history and provide insight about the effects of hormonal changes. Asking what type of birth control the woman is taking can influence the choice of treatment, since some therapies are not appropriate during pregnancy.
Available treatments
NSAIDs are among the treatments that neurologists should consider for the short-term prevention of menstrually related migraine, said Dr. Hutchinson. A study of 35 patients by Sances et al. compared placebo with 550 mg of naproxen sodium given twice daily. Treatment began at 7 days before bleeding onset and continued until the 6th day of menses. Patients underwent treatment for three menstrual cycles. Naproxen sodium significantly reduced headache intensity, headache duration, and the number of headache days, compared with baseline. Treatment was superior to placebo at 3 months. Approximately 33% of patients in the active group were headache free, but no controls were.
Magnesium is another potentially effective option. Facchinetti et al. compared placebo with 360 mg/day of magnesium in a study of 20 patients. Treatment, which was given for two cycles, began at 15 days before menses and ended at the start of menses. Compared with placebo, magnesium reduced the number of headache days and the total pain index. Magnesium is inexpensive, but it causes diarrhea in some patients. “Some women choose to take magnesium all month long, other women start at around ovulation,” said Dr. Hutchinson.
Hormonal treatments are another possible option for the short-term prevention of menstrually related migraine. For women who do not plan to become pregnant, oral contraceptive pills can keep estrogen levels high enough to prevent menstrually related migraine. Gynecologists may suggest that a woman take the pill continuously, skipping the placebo, for an entire year, but Dr. Hutchinson recommends that a woman stop taking the pill for 4 days approximately every 3 months. This discontinuation allows for withdrawal bleeding, but is not likely to cause a prolonged enough decrease in estrogen to provoke migraine, she said. The continuous contraceptive ring, which is inserted vaginally, is an alternative to the pill.
For women who do not want or need contraception, an estrogen patch or gel may be appropriate. Two studies in the 1980s found that a gel containing 1.5 mg of estradiol per 2.5 g reduced migraine frequency, duration, and severity. These studies did not gather long-term safety data, however. A 2006 study by MacGregor et al. found that percutaneous estradiol was associated with a 22% reduction in the number of migraine days, as well as with decreases in headache severity and associated nausea. But the risk of migraine during the 5 days following treatment cessation was increased by 40%. This finding suggests that the treatment period should be extended, said Dr. Hutchinson.
In addition to the timing, the dose of treatment affects the outcome. Smite et al. found no benefit of a 50-mcg dose of estradiol, compared with placebo. Pradalier and colleagues found that a 100-mcg dose was associated with decreased use of rescue medication, compared with a 25-mcg dose. These studies did not gather long-term safety data.
Oral contraceptives and the risk of stroke
Combined oral contraceptives, however, are associated with increased risk of stroke in women with migraine with aura. The dose of estrogen in the contraceptive affects the level of risk, said Dr. Hutchinson. A systematic review by Sheikh et al. found that high-dose ethinyl estradiol (i.e., greater than 50 mcg) was associated with a higher risk of ischemic and hemorrhagic stroke than low-dose ethinyl estradiol (i.e., less than 50 mcg) was. A 20-mcg dose was associated with an odds ratio of stroke of 1.7. Furthermore, among women using combined hormonal contraception, the risk of stroke was higher in women with aura than in women without aura.
“I like to look at the big picture,” said Dr. Hutchinson. “There’s a big difference between a woman who has one or two auras a year that last for 10 minutes and a woman who has complicated aura. I’m going to approach [the latter] woman differently.”
No consensus guidelines for prescribing combined oral contraceptives to women with migraine and aura have been developed. The International Headache Society says that physicians may prescribe low-dose estrogen to women with simple visual aura. The American College of Obstetricians and Gynecologists recommends progestin-only intrauterine or barrier contraception for this population. The World Health Organization holds that estrogen-containing contraception is contraindicated in all women who have migraine with aura.
“If you have women who have migraine without aura, low–estrogen dose combined hormonal contraceptives can be quite appropriate,” said Dr. Hutchinson. “I would tend to go with a 10- or 20-mcg low dose. It could be an option for women with migraine with aura, but only if the benefits outweigh the risks.” In a study by Calhoun et al., the vaginal ring was associated with reduced aura frequency in women with migraine and aura.
Choosing preventive and rescue medications
Although no triptan has FDA approval for the short-term prevention of menstrual migraine, studies have suggested that they are effective. In a study by Sances and colleagues, a twice-daily 1-mg dose of naratriptan taken 6 days perimenstrually reduced the frequency of menstrual-related migraine. At least 50% of treated patients in the study had no menstrual-related migraine. Silberstein and colleagues found that 59% of women who took 2.5 mg of frovatriptan twice daily had no menstrual-related migraine during the 6-day perimenstrual period, compared with 33% of women who received placebo.
Patients with menstrual migraine sometimes need rescue medication. Sumatriptan, either as an injection or an inhaled therapy, is one option. Another injectable option is a 60-mg intramuscular dose of ketorolac. Finally, occipital or sphenopalatine nerve block may be effective as well.
Dr. Hutchinson reported consulting for or serving on the advisory board of Alder, Allergan, Amgen, Biohaven, electroCore, Lilly, Novartis, Supernus, Teva, Theranica, and Upsher-Smith. She has served on speakers bureaus for Allergan, Amgen, electroCore, Lilly, Novartis, Supernus, and Teva.
REPORTING FROM HCNE Stowe 2020