Ms. M, a 36-year-old (G0P0) Black woman seeks contraceptive counseling. She has a history of migraine headache without aura, ulcerative colitis, major depressive disorder, and obesity (body mass index [BMI], 49 kg/m2). She has recently become sexually active with a man and has had one lifetime partner. Ms. M is not using any form of contraception, and her notable medications include topiramate 50 mg twice daily for migraine prophylaxis.
Ms. M's gynecologic history includes menarche at 11 years, and her menstrual cycles are irregular, occurring every few months. The patient's levels of thyrotropin, follicle-stimulating hormone, and prolactin are normal; findings on pelvic ultrasonography are also normal. Ms. M's Papanicolaou testing is up-to-date and negative for intraepithelial lesion or cancer. The patient's physical exam is notable for acne and hirsutism, and her vitals are as follows: temperature 98.4° F (36.9° C), pulse 76 beats per minute, respiratory rate 20, and BP 118/75 mm Hg.
Ms. M's goals for contraception are high effectiveness for pregnancy prevention, long acting and reversible characteristics, prevention of weight gain, and avoidance of injections.
Migraine headache: Definition and prevalence
Four out of 10 women will have a migraine headache in their lifetime.1 Migraine is the third leading cause of disability worldwide for both women and men.2,3 Migraine symptoms include unilateral or bilateral head pain that is usually characterized as pressure with throbbing and pounding. The pain is typically associated with sensitivity to light, sound, or movement, and is associated with nausea with or without vomiting. If left untreated, the pain continues for 4 or more hours.4
Approximately 20% of patients with migraine experience aura; the majority do not. Migraine with aura involves transient focal neurologic symptoms that usually occur before the onset of headache.5 Transient symptoms can include visual changes often involving both visual fields, unilateral paresthesia of the face or body, language impairment, and rarely, motor impairment.4,6
A migraine headache starts with an environmental stimulus that triggers depolarization across the cerebral cortex.7-9 Common stimuli include stress, lights, changes in weather patterns, and sleep disturbances. A decrease in estrogen during the luteal phase of the menstrual cycle is another stimulus.10 A migraine headache occurs when the internal and environmental triggers reach a threshold and cause changes to the brain's chemistry.11
The stimulus begins a cycle of neuropeptide release and persistent inflammation and excitability of the cortex as well as intracranial arterial dilation.7,12 Pain impulses are transmitted by the trigeminal nerve to the rest of the brain.11 A prodrome or postdrome of fatigue, nausea, vision changes, and poor concentration may occur up to 2 days before or after the migraine headache. Migraine treatments typically reduce the excitability of the brain cortex via medications (such as antiepileptic drugs) or promote vasoconstriction via other agents (including caffeine and triptans).
Migraine and stroke risk
It is important to distinguish between migraine with aura and migraine without aura to offer the optimal contraceptive counseling advice. Professional groups consider the risk of stroke when making contraceptive recommendations. The absolute risk of ischemic stroke varies greatly among women depending on risk factors. The absolute risk of an ischemic stroke among young women without migraine who do not use combined hormonal contraception (CHC) is small (2.5/100,000 per year).13 In contrast, the absolute stroke risk in women who have migraine without aura is 4/100,000 per year and increases to 10/100,000 in this group of women who take CHCs. The risk is even higher for women who have migraine with aura. In comparison to women without migraine, women who have migraine with aura have double the risk of stroke (5.9/100,000 per year) and this increases to a nearly 6-fold greater risk of stroke (14.5/100,000 per year) with CHC use.13 (See Absolute stroke risk in women based on CHC use and headache history.) Various other contributors to stroke risk add to the complexity of contraception management for this population.
Small variations in contraceptive estrogen doses may also influence a woman's risk of stroke. Ethinyl estradiol doses greater than 50 mcg have clear associations with ischemic stroke risk; however, more research is needed to determine whether lower doses of ethinyl estradiol pose lower risks.10,14 Similarly, data on the safety of combined hormonal transdermal patch and vaginal ring use are limited, but their presumed stroke risk is similar to that of oral CHC.13
Although no professional organizations recommend oral CHC for women experiencing migraine with aura, some academic discussions have contradicted current guidelines. Calhoun supports the use of low-dose, estrogen-containing contraceptives therapeutically—even for women who have auras—and recommends perhaps not considering aura an absolute contraindication to their use.15 The use of low-dose estrogen in women with migraine aura has been considered if the benefits are greater than the risks; CHC's potential benefits include decreased risk of colorectal, endometrial, and ovarian cancers.16 CHCs prevent pregnancy by suppressing ovulation, blunting endometrial development, and thickening cervical mucus. Continuous CHC treatment avoids or minimizes the luteal phase decrease in estrogen, which is a known trigger for migraine and may decrease migraine frequency. The potential risk of stroke or other thrombotic complications is increased in the presence of hypertension, obesity, tobacco use, and in women 35 years of age and older.
There is also risk associated with unintended pregnancy if a contraceptive is not used. Stroke risk in pregnancy is about 30 (95% CI, 18.8 to 47.9) per 100,000 pregnancies.17 The risk of ischemic stroke among those with migraine increases with pregnancy because pregnancy increases the incidence of thromboembolism. Although CHC may increase the risk of stroke, there is a “competing risk of pregnancy,” which the contraceptive method should prevent.14
Disagreement about contraceptive eligibility criteria
Many professional organizations have published contraceptive eligibility criteria for women with migraine headaches. The eligibility for women with or without migraine aura is further determined by their age and whether the method will be initiated or continued upon the migraine's diagnosis (see Contraceptive eligibility for patients with migraine with and without aura).18-20 All professional groups recommend that women with migraine aura use progesterone-only pills, injection, implant, levonorgestrel (LNG)-containing intrauterine device (IUD), or copper IUD. Although most groups acknowledge the advantages of using CHC for women who have migraine without aura over the perceived risks, the World Health Organization (WHO) states that risks outweigh benefits in these women if they are older than 35.20
Progesterone-only methods of contraception are generally recognized as safe in women experiencing migraines with or without aura. Progesterones prevent pregnancy by thinning the uterine lining and thickening cervical mucus. Stroke risk does not seem to vary among different generations of progesterones.13,21 Some evidence indicates that progesterones can help in the treatment of migraine, but this has not been extensively studied. A progesterone-only pill containing 75 mcg/day of desogestrel has been linked to a small but statistically significant decrease in the number of migraine episodes and headache days.22 No significant headache benefit was found in a study consisting of etonogestrel implant and LNG-IUD users.23,24
Therapeutic interventions: Making the best suggestion in this case
Although a diagnosis of migraine without aura in an otherwise low-risk patient (tobacco-free, normotensive, normal BMI, and no history of coronary artery disease, deep vein thrombosis, or pulmonary embolism) is not an absolute contraindication to CHC, it must be weighed against other options that are safer and better suited to a patient's preferences.13
The authors considered safer progesterone-only options, but many had drawbacks. Medroxyprogesterone acetate, which prevents pregnancy through endometrial suppression, requires an office visit every 12 weeks for an injection. Etonogestrel subdermal contraceptive implant use was also not an ideal choice, as it requires piercing the skin for placement and may not be optimally effective in obese women. The etonogestrel implant was not studied in women whose weight was more than 130% of their ideal body weight; therefore, its effectiveness is unknown.25 A third progesterone-only option, the norethindrone tablet, interacts with topiramate and did not meet the patient's needs for a long-acting method.
Ms. M's use of topiramate further affected contraceptive decision-making in several ways. Topiramate is an antiepileptic drug that is used commonly for migraine prophylaxis at a total daily dose of 25 to 100 mg. Topiramate is known to interact with CHCs and subdermal contraceptive implants by increasing their metabolism and rendering them less effective. Due to teratogenic risk, topiramate should only be prescribed with effective forms of contraception that do not have a drug-drug interaction, such as IUDs or injections.18 Ms. M was not offered CHC because of her increased ischemic stroke risk, use of topiramate, and desire for a long-acting contraceptive method.
Follow-up and outcomes
After Ms. M's initial visit for contraceptive counseling, the NP sought expert advice regarding the choice of contraception and communicated the recommendations to the patient. In this case, intrauterine contraception, either a copper IUD or LNG-IUD, was recommended. An LNG 52-mg device was the preferred IUD because it offered an advantage of endometrial cancer protection considering Ms. M's obesity, which is a known risk factor for development of endometrial cancer.23,26 She chose to schedule LNG-IUD placement 2 months later.
After a human chorionic gonadotropin urine test was completed with negative results, an endometrial biopsy was performed immediately before 52-mg LNG-IUD insertion. The biopsy obtained due to Ms. M's age, obesity, and irregular menstrual pattern was benign. By the time of the LNG-IUD placement, she was no longer sexually active but had the LNG-IUD in place for endometrial protection. The 52-mg LNG-IUD provided Ms. M with reliable contraception for 5 years without concerns for medication adherence.
This case illustrates one of the daily challenges of primary care—how to balance a patient's preferences, needs, and risk factors to provide an evidence-based plan of care. Ms. M was taking a teratogenic medication, had irregular uterine bleeding, and experienced migraine headache without aura. The clinician considered Ms. M's preference for a highly effective, noninjectable form of contraception, her risk of stroke, and her additional need for endometrial cancer protection.
An APRN in clinical practice must be aware of how a history of migraine headache affects contraceptive choice. Migraine headache without aura is not an absolute contraindication to CHC. Although current guidelines consider migraine with aura to be an absolute contraindication to the use of estrogen, there are academic discussions surrounding the therapeutic use of low-dose estrogen-containing contraceptives in these patients. The authors suggest further research to quantify the benefit of CHC use in women with migraine because the risk has already been established, and to further explore differences in therapeutic effect among the various progestins that are available. It would be helpful to develop a contraception risk calculator to quantify the risk versus benefit of a particular contraceptive for a particular individual.
Such a tool could greatly benefit clinical practice. At this time, APRNs rely on clinical practice guidelines based on aggregate risk data when engaging patients in shared decision-making. It continues to be important to consider key patient factors, such as age, comorbid conditions, and personal preferences when offering contraceptive advice to women with migraine headache.
1. Sacco S, Ricci S, Degan D, Carolei A. Migraine in women: the role of hormones and their impact on vascular diseases. J Headache Pain
2. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd Edition. Cephalalgia
3. G. B. D. Headache Collaborators. Global, regional, and national burden of migraine and tension-type headache, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol
4. Headache Classification Committee of the International Headache Society. The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia
5. Hipolito Rodrigues MA, Maitrot-Mantelet L, Plu-Bureau G, Gompel A. Migraine, hormones and the menopausal transition. Climacteric
6. Todd C, Lagman-Bartolome AM, Lay C. Women and migraine: the role of hormones. Curr Neurol Neurosci Rep
7. Goadsby PJ. Pathophysiology of migraine. Ann Indian Acad. Neurol
. 2012;15(Suppl 1):S15–22.
8. Lauritzen M, Dreier JP, Fabricius M, Hartings JA, Graf R, Strong AJ. Clinical relevance of cortical spreading depression in neurological disorders: migraine, malignant stroke, subarachnoid and intracranial hemorrhage, and traumatic brain injury. J Cereb Blood Flow Metab
9. Leão AAP. Spreading depression of activity in the cerebral cortex. J Neurophysiol
10. Faubion SS, Casey PM, Shuster LT. Hormonal contraception and migraine: clinical considerations. Curr Pain Headache Rep
11. MacGregor EA. Diagnosing migraine. J Fam Plann Reprod Health Care
12. Malhotra R. Understanding migraine: potential role of neurogenic inflammation. Ann Indian Acad Neurol
13. Sacco S, Merki-Feld GS, Ægidius KL, et al. Hormonal contraceptives and risk of ischemic stroke in women with migraine: a consensus statement from the European Headache Federation (EHF) and the European Society of Contraception and Reproductive Health (ESC). J Headache Pain
. 2017;18(1): 108. (Published correction appears in J Headache Pain
14. Sheikh HU, Pavlovic J, Loder E, Burch R. Risk of stroke associated with use of estrogen containing contraceptives in women with migraine: a systematic review. Headache
15. Calhoun AH. Hormonal contraceptives and migraine with aura-is there still a risk. Headache
16. Iversen L, Sivasubramaniam S, Lee AJ, Fielding S, Hannaford PC. Lifetime cancer risk and combined oral contraceptives: the Royal College of General Practitioners'Oral Contraception Study. Am J Obstet Gynecol
17. Swartz RH, Cayley ML, Foley NNN, et al. The incidence of pregnancy-related stroke: a systematic review and meta-analysis. Int J Stroke
18. Curtis KM, Tepper NK, Jatlaoui TC, et al. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm. Rep
19. Faculty of Sexual and Reproductive Healthcare. UKMEC summary table hormonal and intrauterine contraception. 2016. www.fsrh.org/standards-and-guidance/documents/ukmec-2016-summary-sheets
20. World Health Organization. Medical eligibility criteria for contraceptive use. 2015. https://www.who.int/reproductivehealth/publications/family_planning/Ex-Summ-MEC-5/en/
21. Calhoun AH, Batur P. Combined hormonal contraceptives and migraine: an update on the evidence. Cleve Clin J Med
22. Warhurst S, Rofe CJ, Brew BJ, et al. Effectiveness of the progestin-only pill for migraine treatment in women: a systematic review and meta-analysis. Cephalalgia
23. Bahamondes L, Valeria Bahamondes M, Shulman LP. Non-contraceptive benefits of hormonal and intrauterine reversible contraceptive methods. Hum Reprod Update
24. Bahamondes L, Brache V, Meirik O, et al. A 3-year multicentre randomized controlled trial of etonogestrel- and levonorgestrel-releasing contraceptive implants, with non-randomized matched copper-intrauterine device controls. Hum Reprod
25. NEXPLANON (etonogestrel implant). Highlights of prescribing information. 2019. www.merck.com/product/usa/pi_circulars/n/nexplanon/nexplanon_pi.pdf
26. Dottino JA, Hasselblad V, Secord AA, Myers ER, Chino J, Havrilesky LJ. . Levonorgestrel intrauterine device as an endometrial cancer prevention strategy in obese women. Obstet Gynecol