1

How effective is prescription medication in reducing menstrual

migraine days in menstruating women?

Sarah Bergfelt, Biomedical Engineering

Nina Grimm, Pharmacy

Samantha Kern, Physician Assistant

Katrina Taliani, Nursing

HOW EFFECTIVE IS PRESCRIPTION MEDICATION IN MENSTRUAL MIGRAINES 2

Introduction

Approximately 2% of the world population suffers from chronic migraines. Out of that

population, roughly 6-9% of those who suffer are men dealing with severe migraines and

17-18% are women dealing with severe migraines as well (Young, 2019). While there are a

multitude of different migraine triggers, one of the way migraines can be triggered in women is

when there is a sufficient decline in estrogen concentration, like at the beginning of menstruation

(Calhoun, 2018). Even menstrual migraine attacks themselves can be triggered by a variety of

factors such as stress of menstruation or oral contraceptives, and like any other kind of

migraines, the symptoms will vary with each patient (Young, 2019). Treatment for this chronic

headache can include lifestyle changes, alternative medicine, and drug therapy. Less frequent

migraines may be suggest a lifestyle change, while severe migraines are more likely to be

prescribed drug therapy. All in all, each situation is unique and a health professional must

diagnose and treat migraines on a personal basis (Jasmin 2017). However, since migraine

treatment itself is so expensive, both the cause and the intervention method needed to be

narrowed down, resulting in the focused foreground question being, “How effective is

prescription medication in menstrual migraines?”

In order to treat migraines or certain types of migraines, such as the menstrual related

migraines (MRM) discussed here, patients must go through a process of many consultations to

find what works best for them. Since there is no cure for migraines, it is often a very frustrating

process, especially as not all treatments will work for everyone. This being said, it is quite

important for health professionals to effectively aid in providing the best treatment as possible. If
HOW EFFECTIVE IS PRESCRIPTION MEDICATION IN MENSTRUAL MIGRAINES 3

a patient were to seek medical attention for migraines, they would be greeted by a nurse who

would take basic measurements such as blood pressure and weight and proceed to ask questions

about symptoms that would assist the doctor. Most often in a doctor’s office, patients are seen by

physician assistants who would see the patient and then consult the primary physician to search

for the best treatment. If the physician would decide said patient needs a prescription medication,

a pharmacist would fill it and provide information needed about the drug. Some migraines are so

severe, they require a CT scan to effectively diagnose and treat them. These machines found in

hospitals are created and maintained by biomedical engineers in order to make sure they work

correctly, and to continue to develop newer models in order to advance them as much as

possible. So, while migraines may seem like a job for only a neurologist, several more health

professionals assist in the process in order to ensure the patient receives the best services. It is

important for each profession to try and think of unique and different ways to help treat this

incurable condition as each case varies, and like previously mentioned, not all treatment will

work with every patient. This means it is extra important to effectively diagnose each case so

time is not wasted on ineffective treatment if possible.

Annotated Bibliography

Allais, G., Bussone, G., Tullo, V., Cortelli, P., Valguarnera, F., Barbanti, P., Benedetto, C.

(2015). Frovatriptan 2.5 mg plus dexketoprofen (25 mg or 37.5 mg) in menstrually

related migraine. Subanalysis from a double-blind, randomized trial. ​Cephalalgia : an

international journal of headache​, ​35​(1), 45–50. doi:10.1177/0333102414542290

HOW EFFECTIVE IS PRESCRIPTION MEDICATION IN MENSTRUAL MIGRAINES 4

Annotation

This​ ​study analyzed the difference between Frovatriptan and Dexktoprofen versus just

Frovatriptan in treatment of menstrual migraines. Not only that, it was designed to show which

dose of Dexketoprofen, 25 mg or 37.5 mg, would be the most effective as well. While the whole

study had 248 women as test subjects, this article analyzed a subgroup of 78 that actually

suffered from MRM. For the trial, the primary endpoint was the amount of patients pain free

without any sort of rescue medicine at the end of two hours. There were three secondary end

points which were 1) the rate of headache relief within two hours, 2) sustained pain free at 48

hours rates of those pain free at the two hour mark, and 3) patients preference of the treatment.

The primary end result did show a significant difference between the trial types. With

only Frovatriptan 29% were pain free. Add in Dexketoprofen to the treatment plan and that

percentage rises to 48% under the 25 mg dose, and 61% under the 37.5 mg dose. This gap

between just Frovatriptan versus the combination was prevalent in all of the end points as well.

52% of those on Frovatriptan felt pain relief after 2 hours, but with 25 mg and 37.5 mg doses of

Dexktoprofen, those percentages raised to 81% and 88% respectively. Those still pain free at 48

hours was just 18% for Frovatriptan alone, 30% with the 25 mg dose of Dexketoprofen, and 44%

with the 37.5 mg dose. The patients’ opinion on the treatment followed suit, with 47% of those

given just Frovatriptan rating it either excellent or good, 61% of the 25 mg Dexketoprofen group,

and 80% of the 37.5 mg group. Together, the results for all four of the end points show that the

combination approach provides much better treatment, and that higher doses of Dexketoprofen

provide even stronger relief.

HOW EFFECTIVE IS PRESCRIPTION MEDICATION IN MENSTRUAL MIGRAINES 5

Overall, the study seemed to fit the research question extremely well. It was a good study

type for the kind of research topic as it was a double blind case study which makes sure to

eliminate bias. All of the endpoint results were calculated for just the 78 women who actually

suffered from MRM which backed up the population we were trying to study. Not only that, but

as the Deketoprofen was administered in different amounts, it showed not only the effectiveness

of one versus two prescription medications, it showed that a higher dose may also be beneficial.

Allais, G., Tullo, V., Omboni, S., Pezzola, D., Zava, D., Benedetto, C., & Bussone, G.

(2013). Frovatriptan vs. other triptans for the acute treatment of oral

contraceptive-induced menstrual migraine: pooled analysis of three double-blind,

randomized, crossover, multicenter studies. ​Neurological Sciences,​ ​34,​ 83–86.

https://doi-org.authenticate.library.duq.edu/10.1007/s10072-013-1393-x

Annotation:

This article was a summination of three different studies comparing the effects of

Frovatriptan versus three other different triptans on treating specifically oral

contraceptive-induced menstrual migraines or OCMM. A total of 280 women were studied

across three trials, with the 35 actively taking oral contraceptives included in the analysis. The

first trial focused on 2.5mg Frovatriptan versus 10.0 mg Rizatriptan, the second on 2.5mg

Frovatriptan versus 2.5 Zolmatriptan, and the third on 2.5 mg Frovatriptan versus 12.5 mg

Almotriptan. The goal was to overall figure out what would treat OCMM the best. In order to do

this, subjects in each sub group would treat anywhere from 1-3 migraine attacks with

Frovatriptan over the course of three months. After that, patients would switch to the other
HOW EFFECTIVE IS PRESCRIPTION MEDICATION IN MENSTRUAL MIGRAINES 6

triptan for another three months. Additionally, the women were studied during the withdrawal

period in order to see how each affected ongoing migraines when the triptans weren’t being used.

While evaluating the trial results, three endpoints were considered. The first two

included pain free episodes and pain relief episodes after 2 and 24 hours. The third included

withdrawal symptoms within 24-48 hours. At the two hour mark, the efficiency of Frovatriptan

and the other three triptans were quite similar. Frovatriptan had a pain free and pain relief

proportion of 25% and 51% while the other triptans clocked in at 28% and 48%. However,

Frovatriptan did seem to have a more sustained affect so this lead to higher pain free and pain

relief values as 24 hours with Frovatriptan showing 71% and 83% respectively while the other

triptans were reading at 60% and 76%. It also showed a lower percentage of headache relapse at

24 hours and even more at 48 hours with Frovatriptan at 17% and 21% compared to the 27% and

31% with the other triptans. Overall, if treating an acute attack, Frovatriptan and other triptans

seem to share a similar efficient. However, based on the long lasting effects of Frovatriptan, it

would seem more worthwhile to use a dose of 2.5 mg to treat OCMM than the other triptans.

Overall, the study seemed like a solid choice for the research question as it hit all of the

parts of the question (prescription medicine, effectiveness, menstruating women). Not only that,

it is fairly recent (within the last six years) and nothing seems currently out of date. The

population, method, and analysis sections are very detailed so it is obvious that time was actually

taken for this study and nothing was rushed. They also provide limitations for the study which

shows a realistic view of the study. This is also shown through the lengths they went through to

have unbiased trials as all three studies were double blind and randomized.
HOW EFFECTIVE IS PRESCRIPTION MEDICATION IN MENSTRUAL MIGRAINES 7

Bhambri, Rahul; Martin, Vincent T.; Abdulsattar, Younos; Silberstein, Stephen; Almas, Mary;

Chatterjee, Anjan; Ramos, Elodie. (October 2013). ​Comparing the Efficacy of Eletriptan

for Migraine in Women During Menstrual and Non-Menstrual Time Periods: A Pooled

Analysis of Randomized Controlled Trials. ​Headache: The Journal of Head & Face Pain

(HEADACHE), Feb2014; 54(2): 343-354. (12p)

Annotation

This article goes on to explain the efficiency of eletriptan in treating migraine attacks

either one day before menstruation or four days after menstruation. It also tests the attacks that

occur during non-menstrual time periods. Data was taken from five similar double-blind

randomized control trials in which the women would receive a placebo or eletriptan in

20mg/40mg/80mg. With the five studies a total of 3217 women were apart of this trial, 2216

women were in group 1 which would receive treatment during menstruation and the others

would be in group 2 which would receive medication during non-menstruation. The large size of

the testing pool makes this trial more credible.

The results were compared after 2 hours in both groups, and within 22 hours for both

groups to test headache recurrence. After 2 hours both groups seemed to have similar headache

response ratios, but in both the response was drastically higher for the eletriptan dose than the

placebo. However after 22 hours headache recurrence was higher in group 1 (during

menstruation) than group 2, and recurrence rates were much lower in the women who received

eletriptan in group 2. Logistic Regression was used to depict the differences between groups 1

and 2, this analytical approach also reinforces the dependability of this trial. Overall eletriptan
HOW EFFECTIVE IS PRESCRIPTION MEDICATION IN MENSTRUAL MIGRAINES 8

was found to be more efficient at assisting in headache recurrence during non-menstruating

times, but still helped during menstruation too.

Coffee, A. L, Sulak, P.J., Hill, A.J., Hansen, D.J., Kuehl, T.J., & Clark, J. W. (2014). Extended

Cycle Combined Oral Contraceptives and Prophylactic Frovatriptan During the

Hormone-Free Interval in Women with Menstrual-Related Migraines. ​Journal of

Women’s Health (15409996),23(4), 310-317.

​https://www.liebertpub.com/doi/10.1089/jwh.2013.4485

Annotation

The article used a randomized control study to try and determine whether Levonorgestrel

and Ethinyl Estradiol reduced migraines during menstrual cycles. The study had a total of

twenty-one females that were split into two groups, one group with eleven females, and the other

group had the remaining ten females in it. The women were all on oral contraceptives for their

menstrual cycle; However, the study was to test whether using Levonorgestrel and Ethinyl

Estradiol during the hormone free interval of their cycle.

The members of group one received the extended oral contraceptives during their

hormone free interval, and the members of group two received a placebo during their hormone

free interval. The study ended after 168 days when they could determine and compare the results

from both groups.

Overall, daily headaches subsided with the use of the extended oral contraceptives. The

study compared the pre-study cycle scores of ​ ​1.29±0.10, to the scores taken at the end of the

study, which were 1.10±0.14. When looking at just the numbers, the number of headaches did
HOW EFFECTIVE IS PRESCRIPTION MEDICATION IN MENSTRUAL MIGRAINES 9

decrease; However there was a concerning side effect when the members of the study were going

through withdrawal. During the withdrawal from the extended oral contraceptives, the members

scores of headaches increased (p>0.01). In conclusion, the overall study did lessen headache

days; However, during the withdrawal phase, headache days increased.

Martin, Vincent T.; Ballard, Jeanne; Diamond, Michael P.; Mannix, Lisa K.; Derosier, Frederick

J.; Lener, Shelly E.; Krishen, Alok; McDonald, Susan A. (May, 2014). Relief of

Menstrual Symptoms and Migraine with a Single-Tablet Formulation of Sumatriptan and

Naproxen Sodium. ​Journal of Women’s Health, 23(5) 3890-396 DOI: 10.1089

Annotation

This article discusses the results that were pooled from two replicate randomized control

trial containing sumatriptan-naproxen or a placebo. In this trial 621 adult menstruating women

would treat their menstrual migraine within one hour after the migraine began with either a

single dose of sumatriptan-naproxen or the placebo. The treatment-allocation ratio for this trial

was 1:1 with 319 women taking the placebo and 302 taking the sumatriptan-naproxen. This

specific treatment was chosen to try and see if menstrual migraine and dysmenorrhea share a

common pathway. So, a medication that contained a non-steroidal anti-inflammatory drug

combined with the triptan would be effective in eliminating both if the two were related.

Women would provide the pain with each symptom including migraines after 1, 2, 4, and

24 hours after taking their dosage. Relief of each symptom was compared using the

Cochran-Mantel-Haenszel test making this article strong using an analytical approach.

HOW EFFECTIVE IS PRESCRIPTION MEDICATION IN MENSTRUAL MIGRAINES 10

With several menstrual symptoms sumatriptan-naproxen surpassed the placebo in every trial.

With migraines the severity was tested between 2 and 24 hours after dosage. The results proved

that there was a relationship between menstrual symptoms and migraines. Women migraineurs

with greater number of dysmenorrhea had lower pain within 2 hours and they were able to

sustain the low pain rates over 24 hours. All in all, the sumatriptan-naproxen may aide in

menstrual migraines, but it depends on the other symptoms associated with menstruation too.

Silberstein, S. D., Armellino, J. J., Hoffman, H. D., Battikha, J. P., Hamelsky, S. W., Stewart, W.

F., & Lipton, R. B. (1999, March). Treatment of menstruation-associated migraine with

the nonprescription combination of acetaminophen, aspirin, and caffeine: results from

three randomized, placebo-controlled studies. Retrieved from

https://www.ncbi.nlm.nih.gov/pubmed/10321417

Annotation

This study examined the effects of a combination of acetaminophen, aspirin, and caffeine

(AAC) in helping relieve migraines related to menstrual cycle. The experiment, which was

randomized and placebo-controlled, included 185 women with menstrual migraine, 781 with

non-menstrual related migraines, and 1 woman who provided no information on her migraines.

The menstrual migraine population’s results were compared to the non-menstrual related

migraines in order to determine if there is a difference in the way each patient is affected.

The participants were asked to rate 5 aspects of their migraines on a scale at .5, 1, 2, 3, 4,

and 6 hours after they received their dose of AAC. The aspects tested were headache pain,

nausea, photophobia, phonophobia, and functional disability. Participants rated all these aspects
HOW EFFECTIVE IS PRESCRIPTION MEDICATION IN MENSTRUAL MIGRAINES 11

on a 4 point scale (0-3), with 3 being the worst, except functional disability was rated on a 4

point scale (0-4), with 4 being incapacitating.

When compared to the participants who randomly received the placebo, both menstrual

related and non-menstrual related migraine sufferers reported their pain intensity lowered to

either mild or none through the course of the 6 hours. It was evident to the researchers that AAC

proved to be effective in treating both types of migraines.

Silberstein, S. D., Massiou, H., Le Jeunne, C., Johnson-Pratt, L., McCarroll, K. A., & Lines, C.

R. (2000). Rizatriptan in the treatment of menstrual migraine. Obstetrics & Gynecology,

237–242. Retrieved from

https://www.sciencedirect.com/science/article/pii/S0029784400008802

Annotation

This article discusses the “randomized, double-masked, placebo-controlled” study that

investigated the effects of rizatriptan when used to relieve migraines related to the menstrual

cycle. All together, 335 women with menstrual migraines participated in the experiment,

however, 139 women received rizatriptan 10 mg, 115 women received rizatriptan 5 mg, and 81

women received the placebo. The authors, who display credibility and professional excellence

through advanced degrees and specialties in neuroscience, used statistical evidence gathered

from the experiment to present their results.

Through their experiment, researchers discovered that 68% of the 10 mg patients and

70% of the 5 mg patients felt pain relief just 2 hours after receiving their rizatriptan doses. Of the
HOW EFFECTIVE IS PRESCRIPTION MEDICATION IN MENSTRUAL MIGRAINES 12

placebo-receiving patients, 44% felt pain relief after their doses. The researchers also tested 393

participants who suffered from migraines not associated with menstrual cycles. In all, 69% of the

non-menstrual related migraine patients experienced pain relief 2 hours post-dose. It is clear that

rizatriptan had a generally positive impact on both patients suffering from menstrual-related

migraines and patients suffering from migraines not associated with menstrual cycle.

The results of the experiment helped determine the researchers original objective which

was to determine the effects of rizatriptan in relieving menstrual migraines, however the article

lacks specific detail in how the patients’ pain relief was measured. Because pain is subjective,

there should have been an explanation as to what measures were taken to determine what “pain

relief” represented for each participant. This information could be useful when comparing this

study to other studies with similar objectives.

Warhurst, S., Rofe, C. J., Brew, B. J., Bateson, D., McGeechan, K., Merki-Feld, G. S., …

Tomlinson, S. E. (2018). Effectiveness of the progestin-only pill for migraine

treatment in women: A systematic review and meta-analysis. ​Cephalalgia​, ​38​(4),

754–764.

​https://doi.org/10.1177/0333102417710636

Annotation

This article compared a various number of studies to try and determine the outcome when

using Progestin-only pills. The article states that migraines are very common in women during

their most productive years because this is also their peak fertility years. The authors used
HOW EFFECTIVE IS PRESCRIPTION MEDICATION IN MENSTRUAL MIGRAINES 13

systematic reviews and meta-analysis studies to help evaluate the effect that POP, or

Progestin-only pills, would have on women who suffer from menstrual migraines. They used

MEDLINE, EMBASE, and Cochrane Libraries to find numerous studies involving women who

were non-menopausal and who were in between the ages of 18 and 50.

The article includes results from a total of four studies that used Progestin-only pills to

test their theory on the reduction of migraine days. The pooled analysis studies used 75 mcg of

Desogestrel per day for a total of 180 days. At the end of the 180 days, they reviewed that the

Desogestrel had a large improvement when reducing the amount of migraine days the women

had; However, less than 10% of the women had adverse effects from the Desogestrel treatment.

Overall, the use of Progestin-only pills exhibits promise in lessening menstrual migraine days

Contributions of Group Members

For the paper, Sam and Sarah worked on the introduction together. Katrina worked on the title

page. Everyone altogether worked on the works cited and annotations with about two each. For

the poster, Nina created it, and everyone worked on editing the descriptions and filling out the

chart with their respective studies.

Additional Works Cited

Calhoun, A. H. (December 2018). Estrogen Associated Migraine. ​UpToDate. ​Retrieved from

https://www.uptodate.com/contents/estrogen-associated-migraine
HOW EFFECTIVE IS PRESCRIPTION MEDICATION IN MENSTRUAL MIGRAINES 14

Jasmin, L. (November 2018). Migraine. ​MedlinePlus.​ Retrieved from

https://medlineplus.gov/ency/article/000709.htm

​ etrieved from
(May 2019). Migraine Symptoms and Causes. ​Mayo Clinic. R

https://www.mayoclinic.org/diseases-conditions/migraine-headache/symptoms-causes/sy

c-20360201

​ etrieved from
Menstrual Migraine. ​The Migraine Trust. R

https://www.migrainetrust.org/about-migraine/types-of-migraine/menstrual-migraine/

Young, W. B. (October 2019). Migraine Pathology. ​Britannica.​ Retrieved from

https://www.britannica.com/science/migraine-pathology