Understanding Menstrual Migraine.

PREMISE: Menstrual-related migraine is very prevalent, very disabling, yet very easy to manage given a good understanding of its cause. POSSIBLE SOLUTION: This article is intended to help with that understanding and to enable headache specialists to prescribe or create effective hormonal preventives of menstrual-related migraine.

Cognitive-Behavioral Therapy for Insomnia to Reduce Chronic Migraine: A Sequential Bayesian Analysis.

BACKGROUND: Insomnia is frequently comorbid with chronic migraine, and small trials suggest that cognitive-behavioral treatment of insomnia (CBTi) may reduce migraine frequency. This study endeavored to provide a quantitative synthesis of existing CBTi trials for adults with chronic migraine using Bayesian statistical methods, given their utility in combining prior knowledge with sequentially gathered data. METHODS: Completer analyses of 2 randomized trials comparing CBTi to a sham control intervention (Calhoun and Ford, 2007; Smitherman et al, 2016) were used to quantify the effects of a brief course of treatment on headache frequency. Change in headache frequency from baseline to the primary endpoint (6-8 weeks posttreatment) was regressed on group status using a Gaussian linear model with each study specified in the order of completion. To estimate the combined effect, posterior distributions from the Calhoun and Ford study were used as informative priors for conditioning on the Smitherman et al data. RESULTS: In a combined analysis of these prior studies, monthly headache frequency of the treatment group decreased by 6.2 days (95%CrI: -9.7 to -2.7) more than the control group, supporting an interpretation that there is a 97.5% chance that the treatment intervention is at least 2.7 days better than the control intervention. The analysis supports the hypothesis that at least for those who complete treatment, there is high probability that individuals who receive CBTi experience greater headache reduction than those who receive a control intervention equated for therapist time and out-of-session skills practice. CONCLUSION: Cognitive-behavioral interventions for comorbid insomnia hold promise for reducing headache frequency among those with chronic migraine. These findings add to a small but growing body of literature that migraineurs with comorbid conditions often respond well to behavioral interventions, and that targeting comorbidities may improve migraine itself.

Hormonal Contraceptives and Migraine With Aura-Is There Still a Risk?

Unnecessary confusion still surrounds the use of combined hormonal contraceptives (CHCs) in the setting of migraine with aura (MwA). Clearing this confusion is a key issue for headache specialists, since most women with migraine have menstrual-related migraine (MRM), and some CHCs can prevent this particularly severe migraine. Their use, however, is still restricted by current guidelines due to concerns of increased stroke risk - concerns that originated over half a century ago in the era of high dose contraceptives. Yet studies consistently show that stroke risk is not increased with today's very low dose CHCs containing 20-25 µg ethinyl estradiol (EE), and continuous ultra low-dose formulations (10-15 µg EE) may even reduce aura frequency, thereby potentially decreasing stroke risk. This article clarifies the stroke risk of CHCs and examines their impact on migraine. It also examines how stroke risk is altered by the estrogen content of the CHC, by contributing factors such as smoking, age and hypertension, and by aura frequency. And finally, it puts these risks into a meaningful context with a risk/benefit assessment.

Presenting a New, Non-Hormonally Mediated Cyclic Headache in Women: End-Menstrual Migraine.

BACKGROUND: This retrospective observational study describes what appears to be a not-uncommon yet not previously typified headache disorder, "end-menstrual migraine" (EMM) named for its proximate occurrence with the terminal days of menstrual bleeding each month. METHODS: Our menstrual migraine (MM) clinic's database was queried for patients with migraine, regular menses, and the locally used diagnostic code of EMM, signifying the patient's assertion that she had migraine at the end of menses as well as calendar data confirming that association. Serum ferritin levels were available for all subjects with EMM. RESULTS: Among the most recently seen 119 women in the clinic, 85 had both regular menses and a diagnosis of migraine, and were thus appropriate for evaluation. In this selected population, 30 women (35.3%) were confirmed to have EMM. Twenty-eight of those 30 patients (93.3%) had ferritin levels that fell below the generally accepted lower desirable limit of 50 ng/mL (mean = 21.9 ng/mL) - half of whom fell below 18 ng/mL, the established minimum levels for women. CONCLUSIONS: EMM is a common complaint in women evaluated for menstrual-related migraine (MRM), yet these migraines occur many days after the estrogen withdrawal that precipitates MRM. The authors do not believe that EMM is hormonally mediated, but rather that it is causally related to menstrual blood loss, resulting in a brief relative anemia with consequent migraine. Further study is needed to substantiate this association, search for confounders, and evaluate response to iron therapy.

Preventing Episodic Migraine With Caloric Vestibular Stimulation: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the safety and efficacy of a novel solid-state, caloric vestibular stimulation (CVS) device to provide adjuvant therapy for the prevention of episodic migraine in adult migraineurs. BACKGROUND: Migraine causes significant disability in ∼12% of the world population. No current migraine preventive treatment provides full clinical relief, and many exhibit high rates of discontinuation due to adverse events. Thus, new therapeutic options are needed. CVS may be an effective and safe adjuvant-therapy for the prevention of episodic migraine. METHODS: In a multicenter, parallel-arm, block-randomized, placebo-controlled clinical trial (clinicaltrials.gov: NCT01899040), subjects completed a 3-month treatment with the TNM™ device for CVS (refer to Fig. 2 for patient enrollment and allocation). The primary endpoint was the change in monthly migraine days from baseline to the third treatment month. Secondary endpoints were 50% responder rates, change in prescription analgesic usage and difference in total subjective headache-related pain scores. Device safety assessments included evaluation of any impact on mood, cognition, or balance. RESULTS: Per-protocol, active-arm subjects showed immediate and continued steady declines in migraine frequency over the treatment period. After 3 months of treatment, active-arm subjects exhibited significantly fewer migraine days (-3.9 ± 0.6 from a baseline burden of 7.7 ± 0.5 migraine days). These improvements were significantly greater than those observed in control subjects (-1.1 ± 0.6 from a baseline burden = 6.9 ± 0.7 migraine days) and represented a therapeutic gain of -2.8 migraine days, CI = -0.9 to -4.7, P = .012. Active arm subjects also reported greater reductions in acute medication usage and monthly pain scores compared to controls. No adverse effects on mood, cognition, or balance were reported. Subjects completed the trial with an average rate of 90% treatment adherence. No serious or unexpected adverse events were recorded. The rate of expected adverse events was similar across the active and the placebo groups, and evaluation confirmed that subject blinding remained intact. CONCLUSION: The TNM™ device for CVS appears to provide a clinically efficacious and highly tolerable adjuvant therapy for the prevention of episodic migraine.

Migraine Treatment in Pregnancy and Lactation.

PURPOSE OF REVIEW: Since up to 40.9% of reproductive aged women have migraine-and reproductive-aged women often reproduce-it is essential that we have good information and guidelines regarding proper treatment of migraine during pregnancy and lactation. RECENT FINDINGS: A review of articles published in the last year on the treatment of migraine during pregnancy and lactation found dishearteningly little. Nevertheless, this article will review the risk/safety information related to migraine treatment in both pregnancy and lactation, citing both new and less recent publications. There is little if any formal research is being carried out on pharmacotherapy for migraine that occurs during pregnancy or lactation. This is likely due to two issues: (1) neurology offers little training in female sex hormones, while gynecology is a surgical field; (2) there is the ever-present concern of litigation if any bad outcome occurs, yet there is no designation of "legally safe" that can be applied to a drug's use in pregnancy and lactation.

Non-Invasive Vagus Nerve Stimulation for the ACute Treatment of Cluster Headache: Findings From the Randomized, Double-Blind, Sham-Controlled ACT1 Study.

OBJECTIVE: To evaluate non-invasive vagus nerve stimulation (nVNS) as an acute cluster headache (CH) treatment. BACKGROUND: Many patients with CH experience excruciating attacks at a frequency that is not sufficiently addressed by current symptomatic treatments. METHODS: One hundred fifty subjects were enrolled and randomized (1:1) to receive nVNS or sham treatment for ≤1 month during a double-blind phase; completers could enter a 3-month nVNS open-label phase. The primary end point was response rate, defined as the proportion of subjects who achieved pain relief (pain intensity of 0 or 1) at 15 minutes after treatment initiation for the first CH attack without rescue medication use through 60 minutes. Secondary end points included the sustained response rate (15-60 minutes). Subanalyses of episodic cluster headache (eCH) and chronic cluster headache (cCH) cohorts were prespecified. RESULTS: The intent-to-treat population comprised 133 subjects: 60 nVNS-treated (eCH, n = 38; cCH, n = 22) and 73 sham-treated (eCH, n = 47; cCH, n = 26). A response was achieved in 26.7% of nVNS-treated subjects and 15.1% of sham-treated subjects (P = .1). Response rates were significantly higher with nVNS than with sham for the eCH cohort (nVNS, 34.2%; sham, 10.6%; P = .008) but not the cCH cohort (nVNS, 13.6%; sham, 23.1%; P = .48). Sustained response rates were significantly higher with nVNS for the eCH cohort (P = .008) and total population (P = .04). Adverse device effects (ADEs) were reported by 35/150 (nVNS, 11; sham, 24) subjects in the double-blind phase and 18/128 subjects in the open-label phase. No serious ADEs occurred. CONCLUSIONS: In one of the largest randomized sham-controlled studies for acute CH treatment, the response rate was not significantly different (vs sham) for the total population; nVNS provided significant, clinically meaningful, rapid, and sustained benefits for eCH but not for cCH, which affected results in the total population. This safe and well-tolerated treatment represents a novel and promising option for eCH. ClinicalTrials.gov identifier: NCT01792817.

Non-invasive Vagus Nerve Stimulation (nVNS) as mini-prophylaxis for menstrual/menstrually related migraine: an open-label study.

BACKGROUND: Menstrual migraine and menstrually related migraine attacks are typically longer, more disabling, and less responsive to medications than non-menstrual attacks. The aim of this study was to evaluate the efficacy, safety, and tolerability of non-invasive vagus nerve stimulation for the prophylactic treatment of menstrual migraine/menstrually related migraine. METHODS: Fifty-six enrolled subjects (menstrual migraine, 9 %; menstrually related migraine, 91 %), 33 (59 %) of whom were receiving other prophylactic therapies, entered a 12-week baseline period. Fifty-one subjects subsequently entered a 12-week treatment period to receive open-label prophylactic non-invasive vagus nerve stimulation adjunctively (31/51; 61 %) or as monotherapy (20/51; 39 %) on day -3 before estimated onset of menses through day +3 after the end of menses. RESULTS: The number of menstrual migraine/menstrually related migraine days per month was significantly reduced from baseline (mean ± standard error, 7.2 ± 0.7 days) to the end of treatment (mean ± standard error, 4.7 ± 0.5 days; P < 0.001) (primary end point). Of all subjects, 39 % (95 % confidence interval: 26 %, 54 %) (20/51) had a ≥ 50 % reduction (secondary end point). For the other secondary end points, clinically meaningful reductions in analgesic use (mean change ± standard error, -3.3 ± 0.6 times per month; P < 0.001), 6-item Headache Impact Test score (mean change ± standard error, -3.1 ± 0.7; P < 0.001), and Migraine Disability Assessment score (mean change ± standard error, -11.9 ± 3.4; P < 0.001) were observed, along with a modest reduction in pain intensity (mean change ± standard error, -0.5 ± 0.2; P = 0.002). There were no safety/tolerability concerns. CONCLUSIONS: These findings suggest that non-invasive vagus nerve stimulation is an effective treatment that reduces the number of menstrual migraine/menstrually related migraine days and analgesic use without safety/tolerability concerns in subjects with menstrual migraine/menstrually related migraine. Randomised controlled studies are warranted.

Migraine and estrogen.

PURPOSE OF REVIEW: The aim is to systematically and critically review the relationship between migraine and estrogen, the predominant female sex hormone, with a focus on studies published in the last 18 months. RECENT FINDINGS: Recent functional MRI (fMRI) studies of the brain support the existence of anatomical and functional differences between men and women, as well as between participants with migraine and healthy controls. In addition to the naturally occurring changes in endogenous sex hormones over the lifespan (e.g. puberty and menopause), exogenous sex hormones (e.g. hormonal contraception or hormone therapy) also may modulate migraine. Recent data support the historical view of an elevated risk of migraine with significant drops in estrogen levels. In addition, several lines of research support that reducing the magnitude of decline in estrogen concentrations prevents menstrually related migraine (MRM) and migraine aura frequency. SUMMARY: Current literature has consistently demonstrated that headache, in particular migraine, is more prevalent in women as compared with men, specifically during reproductive years. Recent studies have found differences in headache characteristics, central nervous system anatomy, as well as functional activation by fMRI between the sexes in migraine patients. Although the cause underlying these differences is likely multifactorial, considerable evidence supports an important role for sex hormones. Recent studies continue to support that MRM is precipitated by drops in estrogen concentrations, and minimizing this decline may prevent these headaches. Limited data also suggest that specific regimens of combined hormone contraceptive use in MRM and migraine with aura may decrease both headache frequency and aura.

Injectable sumatriptan for cyclic vomiting syndrome in adults: a case series.

OBJECTIVE: To better familiarize the reader with a migraine-related disorder, cyclic vomiting syndrome (CVS) in adults, and to discuss its diagnosis and treatment. BACKGROUND: CVS is a profoundly disabling disorder characterized by recurrent, stereotypic episodes of incapacitating nausea and vomiting, separated by completely asymptomatic intervals. CVS episodes tend to start at the same time of day, persist for the same duration, and present with the same intensity and associated symptoms. Most patients experience prodromal symptoms and can identify triggers that precipitate attacks, such as menstruation, lack of sleep, certain foods, physical exertion, and stress. The prevalence of CVS in adults is unknown, but since its occurrence in this age group has been little recognized, patients typically experience lengthy delay in diagnosis or misdiagnosis. METHOD: Literature review, case reports, and discussion. RESULTS: Given genetic links of CVS to migraine, as well as its comorbidity, typical migraine triggers, and response to similar acute and preventive medications, CVS likely represents a disorder on the migraine spectrum. CONCLUSION: Adult CVS is not only highly comorbid with migraine, but it responds to migraine preventives, and in some cases to injectable sumatriptan even in the absence of headache.

Current topics and controversies in menstrual migraine.

As menstrual-related migraine (MRM) has been reported to be longer, more disabling, less responsive to acute therapy, and more prone to recurrence than nonmenstrual migraine attacks, effective preventive strategies are key to their management. Some combined hormonal contraceptives have been suggested as specific preventives for MRM. This article takes a closer look at some of these products, including concerns surrounding them, non-contraceptive benefits, and their potential role as preventive agents for MRM.

Menstrual migraine: update on pathophysiology and approach to therapy and management.

OPINION STATEMENT: Menstrual migraine (MM) is often reported to be more severe and more resistant to treatment than other migraines. Nevertheless, initial treatment should be the same as for any migraine. When results of acute therapy are incomplete or unsatisfactory, preventive strategies are warranted, including both pharmacologic preventives and careful adherence to lifestyle modifications. Where MM differs from other attacks is in its predictable timing and discrete precipitants. These differences allow for unique preventive strategies that target either the timing of the attacks or their hormonal precipitants. Nonspecific MM strategies-those that do not address the hormonal mechanism-include scheduled dosing of nonsteroidal anti-inflammatory drugs (NSAIDs) or triptans throughout the menstrual window. NSAIDs are a good choice when there is comorbid dysmenorrhea and allow for treatment of breakthrough headaches with triptans. Both strategies require that the timing of MM is highly predictable. Specific strategies for MM are those that reduce or eliminate the premenstrual decline in estradiol that predictably precipitates attacks. These include continuous or extended-cycle dosing of combined hormonal contraceptives (CHCs). A number of common gynecologic comorbidities argue for early adoption of these treatments, as CHCs effectively treat dysmenorrhea, menorrhagia, ovarian cysts, endometriosis, and irregular cycles. In the author's experience, hormonal preventives are the best approach for most women whose menstrual attacks are resistant to acute therapy. They afford the greatest therapeutic benefit in prevention while treating common comorbidities and allowing for acute treatment with triptans when needed.

The point prevalence of dizziness or vertigo in migraine--and factors that influence presentation.

OBJECTIVE: To ascertain and characterize the point prevalence of dizziness or vertigo in migraineurs presenting for routine appointments at a specialty headache clinic. BACKGROUND: Migraine, dizziness, and vertigo are all common in the general population, affecting 13%, 20-30%, and 5-10% respectively. Thereby, chance concurrence of migraine with either dizziness or vertigo would be expected in roughly 4% of the general population. It is the authors' clinical impression that severe attacks of migraine are far more commonly associated with these complaints than chance would predict. METHODS: This is a prospective, cross-sectional study of 462 consecutive patients who presented for consultation at a specialty headache clinic over a 4-month period of time. During routine check-in procedures, patients were asked to report their headache pain on a 1-10 Likert scale. Patients were also asked to report if they were currently experiencing dizziness or vertigo. Responses to these questions were recorded along with vital signs. Diagnosis of migraine with or without aura was made by headache medicine specialists in accordance with International Classification of Headache Disorders--second edition criteria. Chi-square analysis was used to examine the prevalence of vertigo or dizziness in subjects with varying intensity of headache, and by history of aura. RESULTS: Of the 425 evaluable subjects, 28% experienced aura. Subjects' average age was 43.8 years (range 15 to 76 years); 89.5% were female. At the time of evaluation, 72.4% of subjects reported some degree of ongoing headache pain and 15.7% reported concurrent dizziness or vertigo. The prevalence of dizziness or vertigo was twice as high (24.5% vs 12.1%) in migraine with aura compared to migraine without aura (P < .01), and prevalence increased with age (P < .05). There was a strong correlation between migraine pain and subjective complaint of vertigo (P < .001). When migraine pain was present at an intensity of 7 or greater (on a scale of 1-10), almost half of the subjects (47.5%) reported concomitant dizziness or vertigo. CONCLUSIONS: Subjective complaints of dizziness or vertigo appear to be relatively common accompaniments of migraine, particularly migraine with aura, and prevalence increases with age. Disequilibrium symptoms have a strong and positive association with the severity of migraine pain. With co-occurrence higher than expected by chance, the relationship either reflects comorbidity or these symptoms may be part of the migraine presentation. With a point prevalence of 15.7%, and factors that link expression both to the intensity of migraine pain and to migraine aura, the authors believe that the true relationship may prove to be the latter.

The prevalence of neck pain in migraine.

OBJECTIVE: To determine the prevalence of neck pain at the time of migraine treatment relative to the prevalence of nausea, a defining associated symptom of migraine. METHODS: This is a prospective, observational cross-sectional study of 113 migraineurs, ranging in attack frequency from episodic to chronic migraine. Subjects were examined by headache medicine specialists to confirm the diagnosis of migraine and exclude both cervicogenic headache and fibromyalgia. Details of all migraines were recorded over the course of at least 1 month and until 6 qualifying migraines had been treated. For each attack, subjects recorded the presence or absence of nausea as well as the intensity of headache and neck pain (graded as none, mild, moderate, or severe). RESULTS: Subjects recorded 2411 headache days, 786 of which were migraines. The majority of migraines were treated in the moderate pain stage. Regardless of the intensity of headache pain at time of treatment, neck pain was a more frequent accompaniment of migraine than was nausea (P< .0001). Prevalence of neck pain correlated with chronicity of headache as attacks moved from episodic to chronic daily headache. CONCLUSIONS: In this representative cross-section of migraineurs, neck pain was more commonly associated with migraine than was nausea, a defining characteristic of the disorder. Awareness of neck pain as a common associated feature of migraine may improve diagnostic accuracy and have a beneficial impact on time to treatment.

Treatment of cluster headache in pregnancy and lactation.

Cluster headache (CH) is a neurovascular headache syndrome characterized by headache attacks that occur with a circadian and circannual periodicity. The calculated prevalence of CH in reproductive-aged women is 7.5 of 100,000 women. Although data suggest that CH during pregnancy is a relatively rare condition, when it does occur, attacks remain unchanged in character and severity in the majority of patients. Thus, treatment of CH in pregnant and lactating women may remain a significant therapeutic challenge. This manuscript briefly reviews the epidemiology of CH in women, and then focuses on treatment options for both acute and preventative management of CH in pregnant and lactating women.

Hormonal therapies for menstrual migraine.

Menstrual-related migraine (MRM) affects the majority of female migraineurs, with menstrual-associated attacks reported to be more disabling, longer lasting, and less responsive to traditional treatments than nonmenstrual attacks. Emerging evidence suggests that minimizing or eliminating monthly declines in estrogen concentration may be effective in preventing MRM. This article gives a practical overview of current hormonal options, both contraceptive and noncontraceptive. Our intent is to help the reader better understand the differences in currently available formulations and how some of these agents may be utilized as hormonal preventives of MRM.

The associations between migraine, unipolar psychiatric comorbidities, and stress-related disorders and the role of estrogen.

Migraine is a common and often disabling neurovascular disorder. It has been linked with several psychiatric disorders, such as depression and anxiety, and to stress-related disorders, such as abuse and posttraumatic stress disorder (PTSD). Epidemiological data have consistently shown a higher prevalence of migraine, depression, anxiety, abuse, and PTSD in women as compared with men. The increased vulnerability of women to migraine and psychiatric disorders often occurs during periods of marked hormonal fluctuations of ovarian hormones. One consequence of these associations is the hypothesis that estrogens have a role in the pathophysiology of both disorders. This article offers an in-depth review of several studies linking psychiatric disorders and stress-related disorders with migraine. We also discuss the role of estrogen in the pathophysiologic overlap between these disorders. Finally, we briefly touch on where future research may be headed, in light of these data.

Safety and efficacy of sphenopalatine ganglion stimulation for chronic cluster headache: a double-blind, randomised controlled trial.

BACKGROUND: Chronic cluster headache is the most disabling form of cluster headache. The mainstay of treatment is attack prevention, but the available management options have little efficacy and are associated with substantial side-effects. In this study, we aimed to assess the safety and efficacy of sphenopalatine ganglion stimulation for treatment of chronic cluster headache. METHODS: We did a randomised, sham-controlled, parallel group, double-blind, safety and efficacy study at 21 headache centres in the USA. We recruited patients aged 22 years or older with chronic cluster headache, who reported a minimum of four cluster headache attacks per week that were unsuccessfully controlled by preventive treatments. Participants were randomly assigned (1:1) via an online adaptive randomisation procedure to either stimulation of the sphenopalatine ganglion or a sham control that delivered a cutaneous electrical stimulation. Patients and the clinical evaluator and surgeon were masked to group assignment. The primary efficacy endpoint, which was analysed with weighted generalised estimated equation logistic regression models, was the difference between groups in the proportion of stimulation-treated ipsilateral cluster attacks for which relief from pain was achieved 15 min after the start of stimulation without the use of acute drugs before that timepoint. Efficacy analyses were done in all patients who were implanted with a device and provided data for at least one treated attack during the 4-week experimental phase. Safety was assessed in all patients undergoing an implantation procedure up to the end of the open-label phase of the study, which followed the experimental phase. This trial is registered with ClinicalTrials.gov, number NCT02168764. FINDINGS: Between July 9, 2014, and Feb 14, 2017, 93 patients were enrolled and randomly assigned, 45 to the sphenopalatine ganglion stimulation group and 48 to the control group. 36 patients in the sphenopalatine ganglion stimulation group and 40 in the control group had at least one attack during the experimental phase and were included in efficacy analyses. The proportion of attacks for which pain relief was experienced at 15 min was 62·46% (95% CI 49·15-74·12) in the sphenopalatine ganglion stimulation group versus 38·87% (28·60-50·25) in the control group (odds ratio 2·62 [95% CI 1·28-5·34]; p=0·008). Nine serious adverse events were reported by the end of the open-label phase. Three of these serious adverse events were related to the implantation procedure (aspiration during intubation, nausea and vomiting, and venous injury or compromise). A fourth serious adverse event was an infection that was attributed to both the stimulation device and the implantation procedure. The other five serious adverse events were unrelated. There were no unanticipated serious adverse events. INTERPRETATION: Sphenopalatine ganglion stimulation seems efficacious and is well tolerated, and potentially offers an alternative approach to the treatment of chronic cluster headache. Further research is need to clarify its place in clinical practice. FUNDING: Autonomic Technologies.

Rational combination therapy in refractory migraine.

Refractory migraine (RM) headaches pose important treatment challenges to the patients who live with them and the clinicians who try to treat them. Defined based on the lack of response to acute, preventive, and nonpharmacologic treatment, RM is often treated with a combination of treatments. Although combination therapy for RM has not been systematically studied in randomized trials, clinical experience suggests that a rational approach to RM treatment, utilizing a combination of treatments, may be effective where monotherapy has failed. In this article we briefly identify patient populations appropriate for more aggressive migraine prevention with combination therapy. We then discuss modifiable risk factors and comorbidities in migraine and then focus on the use of rational combination therapy, as well as the duration migraine preventatives should be considered for use. Future research is needed to evaluate the full potential of rational combination treatment as a strategy for treating and ultimately preventing RM.

Migraine Throughout the Female Reproductive Life Cycle.

By the end of their reproductive life cycle, roughly 40% of women have experienced migraine. Women have certain times of vulnerability for migraine that relate to abrupt declines in estrogen levels. Specifically, the prevalence of migraine is higher after menarche, during menstruation, during the postpartum period, and during perimenopause, but it is commonly lower during the second and third trimesters of pregnancy and the postmenopausal years. Therapeutic strategies for migraine management include hormonal manipulation aimed at eliminating or minimizing the decreases in estrogen that trigger the especially severe menstrual-related attacks. This article reviews special considerations for triptan use in pregnant and lactating women and in women with high risk for cardiovascular disease. Health care professionals caring for women throughout their life span should be aware of these important sex-based differences in migraine and migraine management.