Pure menstrual migraine and menstrually-related migraine are very common forms of migraine, often referred to generically as hormonal headache. Overall, migraine is estimated to effect about 18% of women and 6% of men. That is a 3:1 ratio of women over men. Much of that uneven ratio is due to the hormonal influence of migraine in women, particularly estrogen. Thus, why these headaches are often referred to as hormonal headaches. Even more specifically, it is the drop in estrogen during the menstrual cycle which is the most common culprit for menstrually-related migraine (migraines during menses and outside of menses) and pure menstrual migraine (migraines during menses only). What is the best menstrual migraine treatment?
Let’s first talk about some basic oral contraceptive facts. Estrogen and progestin are the components in combination oral contraceptives (COC). In most COCs, the estrogen is ethinyl estradiol (some older ones use mestranol). Most COCs nowadays are low dose COCs (35 mcg (micrograms) or less of ethinyl estradiol), which has less risk of thromboembolic (blood clot) events.
Combined hormonal contraception (CHC) also come as patches (Ortho Evra) and vaginal rings (Nuvaring). Patch users may be exposed to 60% more estrogen than in a 35 mcg ethinyl estradiol oral contraceptive, levels may not remain steady and peak values may be lower. The vaginal ring delivers 15 mcg ethinyl estradiol and 120 mcg etonogestrel, and is replaced every 4 weeks.
Contraceptive doses of hormones suppress ovarian function, prevent ovulation and pregnancy, and often provide “supraphysiologic” doses of hormones.
Hormonal therapy (such as ethinyl estradiol 20 mcg): do not suppress ovarian function, do not prevent pregnancy, and are for more physiologic doses. They are meant as estrogen replacement. Endogenous ovarian hormonal production is typically still occurring.
So what is the connection with contraception, migraine, and stroke (and similar terms floating around such as migraine stroke, migraine with stroke, migraine with aura stroke, ocular migraine stroke, stroke migraine, and aura migraine stroke)? We will get to those answers and more a little further down.
CONTRACEPTION ADJUSTMENT HACKS TO LESSEN MENSTRUAL MIGRAINE
Most menstrual migraines occur in association with the drop in estrogen during the menstrual cycle. This occurs just prior to ovulation, at the end of the luteal phase if pregnancy does not occur, and during the placebo pill of oral contraceptives. It is recommended to use a monophasic pill containing 35 mcg or less of ethinyl estradiol (20-35 mcg of ethinyl estradiol is typical for most common formulations). Some data suggest 20 mcg pills may not sufficiently suppress ovulation. For women over 160 lbs, the 35 mcg ethinyl estradiol pills will be more protective than those with less than 35 mcg.
Here are a few options (certainly not an all-inclusive list) for the treatment for menstrual migraine to discuss with your doctor to treat menstrual migraine with combined hormonal contraception adjustments if you are using oral contraceptives:
1) Continuous extended release contraception:
-Cycle off to have withdrawal bleeding only as needed. Most commonly this is done every 3 months.
-Seasonale (levonorgestrel 150 mcg, ethinyl estradiol 30 mcg): 12 weeks of active contraceptive pill, followed by 1 week of placebo. This essentially results in 4 yearly menstrual cycles.
-Lybrel (levonorgestrel 90 mcg, ethinyl estradiol 20 mcg): active contraceptive pill taken continuously with no placebo intervals.
2) Add-back estrogen the week of placebo to minimize drop in estradiol:
-Mircette (desogestrel 150 mcg, ethinyl estradiol): 3 weeks of 20 mcg ethinyl estradiol; 2 days placebo; 5 days of 10 mcg ethinyl estradiol.
-Seasonique: Continuous extended-release oral contraceptive pill of 30 mcg ethinyl estradiol for 12 weeks followed by 1 week of low dose ethinyl estradiol 10 mcg.
-Ethinyl estradiol 10 mcg patch during placebo week.
3) Extended dosing regimens:
-Yaz (drospirenone 3000 mcg, ethinyl estradiol 20 mcg): 24 active oral contraceptive pills followed by 4 days placebo.
-Loestrin 24 (norethindrone 1000 mcg, ethinyl estradiol 20 mccg): 24 active oral contraceptive pills followed by 4 days placebo.
STROKE RISK AND RECOMMENDATIONS FOR ORAL CONTRACEPTION IN MIGRAINE
Women younger than age 45 who have migraine with aura, have a 2 fold increased risk of stroke, although this risk is still very low. This risk increases to 6 fold in the setting of oral contraceptive use containing estrogen, and rockets to more than 9 fold with combined smoking and oral contraceptive use. So, if you have migraine with aura, you can absolutely NOT be a smoker and use estrogen containing contraception, especially if you are under age 45!!! Women who are smokers and have migraine with aura should consider estrogen containing oral contraception a contraindication. You can read about migraine aura here. Notably, migraine without aura does not appear to have the same increased risk.
Oral contraceptive use in non-smoking women with migraine with aura is more controversial. The World Health Organization (WHO) and American College of Obstetrics and Gynecology (ACOG) suggest that in non-smoking women under age 35 with migraine with aura, there is an acceptable low risk of oral contraceptive use. However, in women over age 35, the risk is unacceptably higher and oral contraceptive use is contraindicated. According to the International Headache Society (IHS), in non-smoking women with migraine with aura who are either younger or older than age 35, taking into account other cardiovascular (heart disease) and cerebrovascular (stroke) risk factors should individualize the decision for oral contraceptives with weighing the risks vs. benefits. These risks would include ischemic heart disease, family history of early heart disease at a young age of less than 45 years old, heart disease with concern for emboli such as atrial fibrillation, uncontrolled hypertension, hyperlipidemia, diabetes, obesity, systemic disease associated with increased stroke (connective tissue disease, sickle cell, hypercoagulability (blood clots)), etc. In women with an increased risk of stroke, and especially with multiple vascular risk factors, non-estrogen methods of birth control such as progesterone-only forms of contraception are recommended.
It is also suggested to avoid in women (and men) with prolonged migraine aura (greater than 60 minutes), migraine with focal neurologic symptoms (such as hemiplegic migraine), and basilar migraine (now known as migraine with brainstem aura).
The bottom line is if you have typical migraine with aura without any atypical features (for example, aura does not extend more than 60 minutes), are not a smoker, and do not have cardiovascular or cerebrovascular risk factors as mentioned above, estrogen containing contraceptives are not an absolute contraindication. However, you and your doctor should ultimately decide whether the benefits outweigh the risks. If these medications are used, the recommendation is to use the lowest dose possible, 35 mcg or less. Higher doses of estrogen have quite clearly been associated with increased stroke risk (many earlier studies showing this connection were done with higher doses such as 50 mcg or more). Migraine associated stroke (migrainous infarction) is also discussed here. On the other hand, if you have migraine with aura, are under age 45, and are a smoker, the recommendation would be to avoid any estrogen containing contraception. Lastly, there doesn’t seem to be an increased risk with a progesterone-based pill. So, this is an alternative option to consider if you cannot use estrogen-based contraception, along with the many other non-estrogen options you can discuss with your gynecologist.
“MINI-PROPHYLAXIS” HACKS DURING THE MENSTRUAL CYCLE
Lastly, here are a few tricks (but certainly not an all-inclusive list) often used only during the menstrual cycle (after discussing with your doctor) to try to decrease migraine frequency. These are called “mini-prophylaxis” strategies since these medications are used daily, but only around the menstrual cycle, as opposed to a daily continuous preventive medication taken for months at a time (which is always a good option too). The goals of these strategies is use medications that have a longer duration of action (last longer) in hopes of preventing migraine recurrence/return within 24 hours, typical of menstrual migraine, and to target the long duration (often multiple days) commonly seen with menstrual migraines:
Naratriptan (Amerge) 1.25 mg twice daily (half of a 2.5 mg tablet) beginning 1-2 days before expected onset of menstrual migraine, and maintained for several days through period. In addition, you may use Naratriptan 2.5 mg for breakthrough migraines, but no more than once daily (2 total doses per 24 hours).
Frovatriptan (Frova) 1.25 mg twice daily (half of a 2.5 mg tablet) beginning 1-2 days before expected onset of menstrual migraine, and maintained for several days through period. In addition, you may use Frovatriptan 2.5 mg for breakthrough migraines, but no more than once daily (2 total doses per 24 hours).
Naproxen Sodium (Anaprox) 550 mg twice daily beginning 2 days before expected onset of menstrual migraine, and maintained through period. Take with food. In addition, you may use your triptan at earliest sign of breakthrough migraines and may repeat once in 2 hours if needed.
Methergine (Methylergonovine) 0.2 mg three to four times daily beginning 2 days before expected onset of menstrual migraine and continuing through cycle.
DHE Nasal Spray (Trudhesa, Migranal): 1 spray in each nostril by pointing away from face and not sniffing. Then, repeat one spray in each nostril in 15 minutes for a total of 4 sprays per dose. Repeat this dosing twice daily beginning 2 days before expected onset of menstrual migraine, and continue through period. Self injectable DHE is also an option and can be repeated every 8 hours as needed for several days.
Cafergot (Ergotamine 1 mg/Caffeine 100 mg): 2 tablets at migraine onset, followed by 1 tablet every half hour until relief occurs. Do not take more than 6 tablets per headache attack or 10 tablets in a 7-day period.
Ergomar (Ergotamine): 2 mg sublingually followed by 1-2 mg every half hour until relief occurs. Do not exceed 6 mg per day and no more than 10 mg per week.
Rizatriptan (Maxalt) 10 mg + Dexamethasone 4 mg at menstrual migraine onset.
Nurtec ODT (Rimegepant) 75 mg starting 1-2 days before start of menstrual migraine and continue once daily for a few days during menses. There is no evidence for this currently and it is not commonly done, but given that Nurtec ODT seems to provide relief for 48 hours with a single dose, it could be worth trying given the long duration and high 24 hour recurrence typically seen in menstrual migraine. Ubrelvy (Ubrogepant) could be another consideration.
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