Hormones and Migraine: A Case Study

[[{"type":"media","view_mode":"media_crop","fid":"63143","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_4929325944716","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"8053","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 375px; width: 435px; float: right;","title":"©ktsdesign/Shutterstock.com","typeof":"foaf:Image"}}]]Follow this case of a young woman seen in primary care with a complaint of headache that may sound familiar to you. There are some fine distinctions to be made among headaches that are associated with hormonal changes in women. Find out what you know about diagnosis, acute treatment, and successful management of hormone-related headache.

Haley, a 25-year-old woman, comes to your office for her annual examination. She complains of headaches that occur several days before menses. OTC analgesics like ibuprofen only help somewhat. If untreated, her headaches can last 48-72 hours. There is some relief several days into menses, but then a headache could occur at the end of menses as well. She is frustrated because she does not feel as sharp cognitively in her work as a legal secretary on her headache days.

1. The most likely diagnosis for her headaches is:

A. Premenstrual syndrome (PMS)

B. Tension headache

C. Migraine headache

D. Cluster headache

Please click here for answer, discussion, and next question.

The correct answer: C. Migraine headache

The most likely diagnosis is migraine given the association with menses, duration of the attacks, the cognitive dysfunction, and the lack of efficacy of OTC NSAIDs.

Although Haley may have PMS, the hallmark symptoms of this syndrome are breast tenderness, bloating, and fatigue. Tension headache is more likely to respond to an OTC NSAID and does not typically have the predictable association with menses. Cluster headache is quite rare in women, and is often referred to as the “suicide” headache, and is characterized by unilateral piercing pain in and around one eye with associated autonomic symptoms on same side as pain. It can include nasal congestion, watery eye, and drooping eyelid.

Migraine, including menstrual migraine, is quite common in the female population. Epidemiological studies in the US reveal an 18% annual migraine prevalence rate in women compared to a 6%-7% annual prevalence rate among men.¹ About 60% of women with migraine have menstrual migraine.² This translates into over 10 million women with menstrual migraine in any given year in the US. 

Cluster headache is quite rare in women, and is often referred to as the "suicide" headache.

Women like Haley are very common in the primary care setting. Correct diagnosis of headache type can be critical in helping women like her. Most can be managed in a primary care setting and do not need to be referred to a neurologist or headache specialist.

2. What additional symptoms of Haley’s headache attacks would support the diagnosis of migraine?

A. Bitemporal tightness feeling in her scalp muscles

B. Nausea

C. Agitation

D. Double vision

E. All of the above

Please click here for answer, discussion, and next question.

The correct answer is B. Nausea

The symptom most supportive of the migraine diagnosis is nausea. Epidemiological studies demonstrate that 73% of migraine sufferers experience nausea with some of their migraine attacks.³ Bi-temporal scalp tightness is suggestive of tension headache. Agitation is typical of cluster headache. Double vision is not typical for the visual aura symptoms reported by migraine sufferers and needs to be carefully evaluated.

3. To make the diagnosis of menstrual migraine, which of the following is true?

A. Migraine occurs with every menstrual period.

B. Migraine occurs in association with at least 50% of menses.

C. Migraine occurs in association with at least 75% of menses.

D. Migraine occurs in association with at least 66% of menses.

Please click here for answer, discussion, and next question.

The correct answer is D. Migraine occurs in association with at least 66% of menses.

The International Classification of Headache Disorders (ICHD) Criteria states that to make the diagnosis of menstrual migraine, a woman needs to have a migraine attack with at least 66% of her menstrual cycles.⁴ Furthermore, this migraine must occur within -2 to +3 of a woman’s cycle. Also, by ICHD definition, menstrual migraine is migraine without aura.⁴

To be classified as menstrual migraine, a migraine headache must occur within -2 to +3 of a woman’s cycle.

On further questioning, Haley admits to having other headache days outside of her menses and sometimes these non-menstrual headaches can be quite disabling with throbbing pain, nausea, and sensitivity to light. Triggers appear to be lack of sleep, stress, and changes in barometric pressure.

Menstrual migraine can be subdivided into pure menstrual migraine and menstrual-related migraine.

4. Haley’s menstrual migraine would fit the definition of:

A. Pure menstrual migraine

B. Menstrual-related migraine

C. Both of the above

D. None of the above

Please click here for answer, discussion, and next question.

The correct answer is B. Menstrual-related migraine

Haley has migraine attacks outside of the menstrual window of -2 to +3, thereby meeting the definition of menstrual-related migraine. This is more common than pure menstrual migraine, in which women only experience migraine headaches with menses and at no other time of the month. This distinction is important because the treatment approach differs. For pure menstrual migraine, acute and preventive treatment can be focused solely on the vulnerable time of a woman’s cycle around her menses. For women like Haley who have menstrual-related migraine, treatment needs to take into account all migraine triggers and typically involves preventive treatment throughout the month with a combination of pharmacologic and non-pharmacologic treatment approaches.

The distinction between pure menstrual migraine and menstrual-related migraine is important becuase the treatment approach is different for each.

Haley now asks for treatment that could work better than OTC NSAIDs. Assume that Haley is in good overall health, has normal blood pressure and normal body weight, is a non-smoker, and is taking no prescription medications other than a combined ethinyl estradiol/progestin contraceptive pill.

5. What would be a reasonable first-line treatment option for her migraine attacks?

A. Naproxen 500 mg

B. Sumatriptan 100 mg

C. Butalbital/APAP/caffeine 50/325/40

D. Dihydroergotamine nasal spray

E. Acetaminophen with codeine

Please click here for answer, discussion, and next question.

The correct answer is B. Sumatriptan 100 mg

An oral generic triptan would be a prudent acute treatment choice. The triptans are migraine-specific and likely to be more effective than an OTC or prescription strength NSAID. Butalbital-containing preparations are not migraine-specific, can cause sedation, and often lead to medication overuse.

Dihydroergotamine nasal spray is Category X for pregnancy and not a good choice in women who may want to get pregnant or who forget to take their oral contraceptive and become pregnant accidentally. Acetaminophen with codeine can cause drowsiness, is not migraine-specific, and like butalbital-containing preparations, can lead to medication overuse.

Acetaminophen with codeine can cause drowsiness, is not migraine-specific, and like butalbital-containing preparations, can lead to medication overuse.

Haley is given a prescription for sumatriptan 100 mg oral tablets #9 for a 30-day supply. She is instructed to the drug take early in a migraine attack, and to repeat it in 2 hours if necessary. Maximum dose is 200 mg in a 24-hour period. She is given a refill on her monophasic low-dose (20 mcg ethinyl estradiol) contraceptive pills. Information on keeping a headache diary, electronic or paper, is offered and she is asked to return in 3 months.

Upon return, Haley states that sumatriptan 100 mg works well for her non-menstrual migraines but not as well for her menstrual migraines. The latter are more likely to be associated with more nausea and to last longer, and to awaken her with a severity of an “8-9” on a 10-point scale. At times, she delays taking the oral sumatriptan due to her nausea.

5. Reasonable treatment options now that Haley indicates migraine-induced nausea is a problem include all of the following except:

A. An anti-nausea medication like ondansetron, promethazine, or metoclopramide

B. An orally dissolving triptan like rizatriptan or zolmitriptan

C. A nasal delivery such as sumatriptan nasal spray or the breath-powered nasal delivery of sumatriptan (brand name Onzetra Xsail)

D. An injectable form of sumatriptan (3, 4, and 6 mg options)

E. An opioid such as hydrocodone

Please click here for answer, discussion, and next question.

The correct answer is E. An opioid such as hydrocodone (is not appropriate)

All treatment options are reasonable except for an opioid for this young woman who works as a legal secretary and who wants to stay alert and focused, and not have migraines interfere with her daily functioning. Opioids such as hydrocodone are not migraine-specific, can cause sedation, and may lead to medication overuse and drug dependency.

Looking at the other options, it is important to remember that the orally dissolving triptans are not sublingual and the small particles still need to get down into the GI system to be effective. A nasal or injectable form of sumatriptan could be quite helpful for Haley. She can use the oral sumatriptan for mild to moderate migraine attacks and go straight for the non-oral delivery options for her more severe migraines including menstrual migraines associated with significant nausea and disability.

She can use the oral sumatriptan for mild to moderate migraine attacks and ... the non-oral delivery options for her more severe migraines including menstrual migraines associated with significant nausea and disability.

A review of Haley’s headache diary shows an average of 8 to 9 headache days per month with 2 to 3 of the days occurring 1 to 2 days before menses, 1 to 2 at end of menses, and the remaining days scattered throughout the month. Common triggers include stress, lack of sleep, and changes in weather and barometric pressure.

She asks what she can do to better prevent her migraines. She has heard of Botox injections, herbal treatments, and prescription preventives but she is not sure she wants to take a daily preventive with possible side effects. Currently she takes no supplements except an occasional multivitamin when she feels tired.

6. Herbal preventives that show some efficacy for migraine prevention include all of the following except:

A. B₂ (Riboflavin)

B. Vitamin D

C. Butterbur

D. Magnesium

E. CoQ10

Please click here for answer, discussion, and next question.

The correct answer is B. Vitamin D (has not shown efficacy for migraine prevention)

Efficacy for B₂, butterbur, magnesium, and CoQ10 for prevention of migraine has been demonstrated in clinical trials. The strongest level of evidence is for butterbur, which is now listed as Category A evidence in published guidelines for migraine prevention.⁵ Vitamin D is not known to be helpful for migraine prevention.

Haley decides to try herbal preventives and work on her health habits before taking a prescription preventive. She asks what dosages of the herbals to take to best prevent her migraines and how long they will take to work.

Herbal preventives can take 8-12 weeks to be efficacious and the following dosages are advised for migraine prevention:

  ^► Riboflavin 200 mg twice a day

  ^► Butterbur 75 mg twice a day for adults

  ^► Magnesium 200-300 mg twice a day (side-effects include diarrhea)

  ^► CoQ10 150 mg twice a day

Numerous OTC migraine preparations contain 2 or more of these herbals, so patients like Haley do not need to take them as 4 separate pills. Options include Migrant, MigreLief, and MigraHealth.

7. Additional treatment options for Haley may include all of the following except:

A. Continuous oral contraceptive use, skipping the placebo pills

B. Short-term prevention of menstrual migraine with an NSAID like naproxen

C. Short-term prevention with a long-acting triptan like naratriptan

D. Short-term prevention with sertraline or other SSRI

E.  Short-term prevention with magnesium during luteal phase

Please click here for answer, discussion, and next question.

The correct answer is D. Short-term prevention with sertraline or other SSRI (is not recommended as an option for this patient)

All of the options can be useful except for short-term prevention during the luteal phase with an SSRI. SSRIs, including fluoxetine and sertraline, have been shown to help prevent premenstrual dysphoric disorder (PMDD) but there are no evidence-based studies to support their use as a short-term preventive treatment during the luteal phase. In addition, using sertraline, citalopram and, in particular paroxetine, for a short time and then stopping could cause serotonin withdrawal symptoms. Therefore, this treatment approach is not recommended. If, on the other hand, a patient like Haley has PMDD or a major depressive disorder or a generalized anxiety disorder, then an SSRI may be prescribed but should be taken daily.

In addition, using sertraline, citalopram and, in particular paroxetine, for a short time and then stopping could cause serotonin withdrawal symptoms.

The drop in estradiol just before menses is a strong trigger for menstrual migraine. In a study by Somerville,⁶ estrogen injected in a group of women with menstrual migraine delayed the occurrence of migraine until the level of estrogen from the injection dropped. Giving those same women a progesterone injection delayed the bleeding but not migraine. For Haley, the drop in estrogen that occurs when she takes the placebo pills in her pill pack can be a trigger for her menstrual migraines. Eliminating the placebo pills could help and/or lessen the severity of her menstrual migraines.

8. When should Haley return to the office for a follow-up?

A. In 3 months

B. In 6 months

C. In 9 months

D. In 12 months

E. None of the above

Please click here for answer, discussion, and next question.

The correct answer is A. In 3 months (Haley should return)

Haley is experiencing 8 to 9 headache days per month and meets the definition of frequent episodic migraine. She is at risk of transforming into chronic migraine and medication overuse. Therefore, a 3-month follow-up visit is advisable if she is responding to the treatment plan. If her headache pattern begins to worsen or if she develops new onset aura symptoms, she should return before 3 months.

Fortunately, a primary health care provider can treat most women like Haley with menstrual migraine. Feeling comfortable making the diagnosis is critical. Development of a treatment plan in a collaborative approach with patients like Haley can help them live productive lives despite the burden of migraine.

Please clck here for the next topic in the Patient Care "What's New In Migraine" Special Report for PCPs:

Monoclonals and Migraine: What the Primary Care Physician Neesds to Know

For previous articles:

Pediatric and Adolescent Migraine: Update on Treatment Options

Introduction and Pre-test

References:

1. Victor TW, Hu X, Campbell JC, et al. Migraine prevalence by age and sex in the United States: as life-span study. Cephalalgia. 2010;30:1065-1072.

2. Mannix LK, Calhoun AH. Menstrual Migraine. Curr Treat Options Neurol. 2004;6:489-498.

3. Lipton RB, Stewart WF. Headache. 2001;41:646-657.

4. International Headache Society. The international classification of headache disorders 3rd edition (beta version) Cephalalgia. 2013;33:692-808.

https://www.ichd-3.org/appendix/

5. Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: NSAIDs and other complementary treatment for episodic migraine in adults. Neurology. 2012;78:1346-1353.

6. Sommerville BW. The role of estradiol withdrawal in the etiology of menstrual migraine. Neurology. 1972;22:355-365.