Safety of hormonal contraceptives among women with migraine: A systematic review

doi:10.1016/j.contraception.2016.04.016

Contraception

Volume 94, Issue 6, December 2016, Pages 630-640

https://doi.org/10.1016/j.contraception.2016.04.016 Get rights and content

Abstract

Background

Migraine is common among women of reproductive age and is associated with an increased risk of ischemic stroke. Combined oral contraceptives (COCs) are also associated with an increased risk of ischemic stroke. Use of hormonal contraception among women with migraine might further elevate the risk of stroke among women of reproductive age.

Objective

To identify evidence regarding the risk of arterial thromboembolism (stroke or myocardial infarction) among women with migraine who use hormonal contraceptives.

Methods

We searched the PubMed database for all articles published from database inception through January 2016. We included studies that examined women with migraine overall or separated by subtype (with or without aura). Hormonal contraceptives of interest included combined hormonal methods (COCs, patch and ring) and progestin-only methods (progestin-only pills, injectables, implants and progestin intrauterine devices).

Results

Seven articles met inclusion criteria. All were case–control studies of fair to poor quality reporting on use of COCs or oral contraceptives (OCs) not further described and all reported stroke outcomes. Four studies demonstrated that, among women with migraine (not separated by subtype), COC use was associated with approximately two to four times the risk of stroke compared with nonuse. The only study to examine specific migraine subtypes found an elevated risk of stroke among women with migraine with aura, and this risk was similar regardless of OC use, although these odds ratios were not reported. Two studies did not report risks among women with migraine and COC use combined, but both found increased risks of stroke with migraine and COC use independently. No evidence was found on other hormonal contraceptives or on risk of myocardial infarction.

Conclusion

Limited evidence suggests a two- to fourfold increased risk of stroke among women with migraine who use COCs compared with nonuse. Additional study is needed on the risks of hormonal contraceptives, including combined and progestin-only methods, among women with different migraine subtypes.

Introduction

Migraine is common among women, with a lifetime prevalence of 43% [1]. Migraine is divided into two major subtypes, those with or without aura [2]. Typical characteristics of migraine without aura include unilateral location, pulsating quality and moderate or severe intensity and may be associated with nausea, photophobia and phonophobia. Menstrual migraine is classified as migraine without aura [2]. Aura is a complex of neurological symptoms that occurs just before or at the onset of a migraine and includes symptoms such as visual changes, numbness or speech disturbance [2]. Migraine with aura occurs in about a third of people with migraine [3]. Although rare among women of reproductive age, stroke is a devastating event and is associated with migraine. Migraine with aura has been shown to be associated with an increased risk of stroke, particularly ischemic stroke [4]. Migraine without aura has not been consistently associated with an increased risk of stroke, although one study found an association [4].

The use of hormonal contraception, specifically use of combined oral contraceptives (COCs), has also been associated with an increased risk of stroke [5]. COCs are the most commonly used reversible method of contraception in the US and are even used as treatment of certain migraine subtypes responsive to hormonal manipulation, including menstrual migraine [6]. However, given the independent effects of migraine and COC use on stroke risk, there is theoretical concern that use of COCs among women with migraine headaches would further elevate the risk of stroke to an unacceptable level for contraceptive use. The US Centers for Disease Control and Prevention (CDC) publishes the US Medical Eligibility Criteria for Contraceptive Use (US MEC), which provides guidance for the safety of contraceptive methods among women with certain medical conditions including migraine [7]. This systematic review updates a previous review conducted for the World Health Organization (WHO) MEC, from which the US MEC is adapted [8]. The previous review concluded that among women with migraine, COC use was associated with a two- to fourfold higher risk of ischemic stroke compared with nonuse.

Section snippets

Materials and methods

We conducted this systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines [9].

Results

The search identified 287 articles, of which 7 met inclusion criteria (Fig. 1 and Table 1) [12], [13], [14], [15], [16], [17], [18]. One article was newly published since the previous systematic review [15]. All included articles were case–control studies describing stroke risk among women with migraine using COCs or oral contraceptives (OCs) not further specified. No studies were identified that included other hormonal methods of contraception or reported on myocardial infarctions.

The one

Discussion

This systematic review identified seven studies which reported associations between migraine headaches, OC use and ischemic or hemorrhagic stroke. Four studies demonstrated that the ORs for migraine and COC use were two to four times as high as ORs for migraine and no COC use [12], [13], [17], [18]. However, CIs were wide, and direct comparisons with statistical testing were not performed, as both groups were compared to women without migraine not using COCs. Two of these studies specifically

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Hormonal contraceptives (HCs) have been shown to be safe and effective when used correctly and consistently, however, as other classes of drugs, they are also associated with adverse health outcomes. In this study, we aim to explain the occurrence of common and unexpected HCs side effects (SEs) integrating drug-target, drug-SE and protein-protein interaction (PPI) public databases. We created a tripartite network that includes three types of vertices: SEs, drugs, and targets. The three layers are linked by means of the inter-layer associations drug-target and drug-SE, whereas only the target layer is characterized also by intra-layer links (PPIs). We exploited the drug-mediated association SE-target to identify the side effect modules defined as a network connected component composed of target proteins plus the proteins needed to connect them. We found that module proteins are associated with diseases/phenotypes and/or KEGG pathways related to the SEs. In particular, in many cases, targets are not enriched in SE features, whereas investigating their neighborhood (here defined as the proteins that allow the targets' connection) we found SE-related pathways. These results show that HCs action can perturb the targets’ neighborhood inducing unwanted reaction and that the proposed approach can help to understand how, and through which molecular mechanisms, side effects can occur. The approach is general in its nature: it can be applied to other drugs categories providing a support in identifying a subject-specific therapy that takes into account comorbidities and lifestyle to reduce or avoid the most undesired side effects.
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Women have the opportunity to meet personal contraceptive goals with convenient, highly reliable, and easily reversible methods. Long-acting reversible contraception represents an increasingly popular option for most women throughout the reproductive lifespan. Nonetheless, many women and their health care providers are challenged by coexisting medical issues. We aim to help clinicians individualize contraception and use shared decision-making to enhance patient satisfaction and continuation with their method.
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Nine studies focused on the complications faced by women who have migraines and use the combined contraceptive pill. These papers consisted of one case control study [26], two systematic reviews [7,25] one meta-analysis ([27]), two review articles [13,18], one society statement [28], and two cross sectional studies [20,24],). All these research papers confirmed the increased risk of vascular events in these women.
Migraines are the third most prevalent disorder, and seventh-highest specific cause of disability worldwide. Migraines have a multitude of underlying aetiologies; the pathology may come as a result of hormonal treatment or as a sole symptom during menstrual cycle or pregnancy, with variable intensity and duration. In addition, clinicians should be fully aware of the potential complications and well-versed in management options.
A systematic review of the incidence, symptoms, treatment options and complications among women suffering from migraines in gynaecology, as well as obstetrical cases has been performed. The significance of migraines as a marker in antenatal care and contraception treatment has also been investigated.
The incidence of migraines in gynaecological and obstetrical cases, and contraceptive users were 11.7–12.5 %, 9–38.5 %, and 16.7–54.7% respectively. There is an average six-fold increase in the risk of stroke in women who take combined hormonal contraception and suffer from migraines. Four papers with 1565 patients proposed the combination of triptans along with the progesterone only pill. Desogestrel 75mcg/day was found to reduce the intensity of migraines compared to the combined hormonal contraceptives. The risk of gestational hypertension, pre-eclampsia, low birth weight, and preterm birth was found to be increased in pregnant women suffering from migraines.
Migraines have a high incidence in gynaecology and obstetrics. Health care providers must include screening questions when history taking to identify women with migraines and effectively manage them. Proper follow-up and treatment is required for all women with migraines in order to minimize the risk of cerebrovascular events, and negative pregnancy outcomes. Women with migraines are advised to avoid combined hormonal contraception and use progesterone only pills.
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^☆: Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the US Centers for Disease Control and Prevention.

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ReviewSafety of hormonal contraceptives among women with migraine: A systematic review☆

Abstract

Background

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Materials and methods

Results

Discussion

Thromb Res

Contraception

Am J Prev Med

Am J Med

Contraception

Contraception

Migraine in women: the role of hormones and their impact on vascular diseases

J Headache Pain

The international classification of headache disorders, 3rd edition (beta version)

Cephalalgia

Migraine and stroke: a complex association with clinical implications

Lancet Neurol

The association of migraine with ischemic stroke

Curr Neurol Neurosci Rep

Migraine management during menstruation and menopause

Continuum

U.S. medical eligibility criteria for contraceptive use, 2010

MMWR Recomm Rep

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

Br Med J

Risk of acute thromboembolic events with oral contraceptive use: a systematic review and meta-analysis

Obstet Gynecol

Associated risk factors

J Am Med Assoc

Migraine and stroke in young women: case–control study. The World Health Organisation collaborative study of cardiovascular disease and steroid hormone contraception

Br Med J

Oral contraceptives, pregnancy and the risk of cerebral thromboembolism: the influence of diabetes, hypertension, migraine and previous thrombotic disease

Br J Obstet Gynaecol

Probable migraine with visual aura and risk of ischemic stroke: the stroke prevention in young women study

Stroke

Ischemic stroke in young women: a nested case–control study using the UK general practice research database

Stroke

Review
Safety of hormonal contraceptives among women with migraine: A systematic review☆