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CME / ABIM MOC / CE

What Does New Cluster Headache Research Show About Sex Differences?

  • Authors: News Author: Kelli Whitlock Burton; CME Author: Laurie Barclay, MD
  • CME / ABIM MOC / CE Released: 2/17/2023
  • Valid for credit through: 2/17/2024, 11:59 PM EST
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  • Credits Available

    Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 0.25 ABIM MOC points

    Nurses - 0.25 ANCC Contact Hour(s) (0 contact hours are in the area of pharmacology)

    Pharmacists - 0.25 ACPE Contact Hour(s) (0.025 CEUs)

    Physician Assistant - 0.25 AAPA hour(s) of Category I credit

    IPCE - 0.25 Interprofessional Continuing Education (IPCE) credit

    You Are Eligible For

    • Letter of Completion
    • ABIM MOC points

Target Audience and Goal Statement

This activity is intended for neurologists, family medicine/primary care clinicians, internists, obstetricians/gynecologists/women’s health clinicians, nurses/nurse practitioners, pharmacists, physician assistants, and other members of the health care team who treat and manage patients with cluster headaches.

The goal of this activity is for members of the health care team to be better able to describe sex differences in patient demographics, clinical phenotype, chronobiology, triggers, treatment, and lifestyle in a Swedish population with cluster headache, based on a survey study of patients identified from medical records from 2014 to 2020 from hospitals and neurology clinics in Sweden.

Upon completion of this activity, participants will:

  • Assess sex differences in patient demographics, clinical phenotype, chronobiology, triggers, treatment, and lifestyle in a Swedish population with cluster headache, based on a survey study
  • Evaluate the clinical implications of sex differences in patient demographics, clinical phenotype, chronobiology, triggers, treatment, and lifestyle in a Swedish population with cluster headache, based on a survey study
  • Outline implications for the healthcare team


Disclosures

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All relevant financial relationships for anyone with the ability to control the content of this educational activity are listed below and have been mitigated. Others involved in the planning of this activity have no relevant financial relationships.


News Author

  • Kelli Whitlock Burton

    Freelance writer, Medscape

    Disclosures

    Kelli Whitlock Burton has no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer, Medscape, LLC

    Disclosures

    Laurie Barclay, MD, has no relevant financial relationships.

Editor/Nurse Planner

  • Lisa Simani, APRN, MS, ACNP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Lisa Simani, APRN, MS, ACNP, has no relevant financial relationships.

Compliance Reviewer

  • Amanda Jett, PharmD, BCACP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Amanda Jett, PharmD, BCACP, has no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has no relevant financial relationships.


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Medscape

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In support of improving patient care, Medscape, LLC is jointly accredited with commendation by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

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This activity was planned by and for the healthcare team, and learners will receive 0.25 Interprofessional Continuing Education (IPCE) credit for learning and change.

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CME / ABIM MOC / CE

What Does New Cluster Headache Research Show About Sex Differences?

Authors: News Author: Kelli Whitlock Burton; CME Author: Laurie Barclay, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 2/17/2023

Valid for credit through: 2/17/2024, 11:59 PM EST

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Clinical Context

Cluster headache (CH) is a severely painful headache disorder characterized by unilateral, orbital head pain often accompanied by autonomic symptoms, such as lacrimation, ptosis, or restlessness. During an active bout, headache attacks lasting between 15 and 180 minutes occur up to 8 times daily. Although CH is considered male-predominant, the reported male-to-female ratio has shifted from approximately 6:1 before 1960 to 5.1-2.5:1 in 2018. This shift may result from lifestyle changes in both sexes and/or from increased CH recognition.

Study Synopsis and Perspective

Women with CH have more severe symptoms and longer headache bouts than men, and they are more likely to have a chronic subtype of the disorder, new research shows.

The study, which is the largest to date involving patients with CH, adds to a growing body of work that suggests that an illness that affects mostly men may actually have a much greater effect on women.

“The main thing from this study is to show clinicians that women can suffer from [CH] too,” senior investigator Andrea Carmine Belin, PhD, associate professor of neuroscience at the Karolinska Institutet, Stockholm, Sweden, told Medscape Medical News.

The findings were published online December 21, 2022, in Neurology.[1]

Severe and Debilitating

CH is rare, but it is among the most severe and debilitating types of headache. It causes intense pain behind the eyes. The pain has been described as being worse than the pain associated with childbirth or kidney stones.[2]

In addition, attacks can occur multiple times in a day and can last up to 3 hours.

As reported by Medscape Medical News, a recent study showed that participants with CH were significantly more likely to have comorbid conditions, including mental disorders and other neurologic diseases.[3]

In the current study,1,484 Swedish individuals were recruited for inclusion into a CH biobank, of whom 874 completed a survey that collected demographic data and information about symptoms, including severity and frequency. The patients included 575 male and 299 female participants with CH.

The study participants were identified between 2014 and 2020 by requesting medical records for International Classification of Diseases, 10th Revision (ICD-10), code G44.0 for CH from all major hospitals and neurology clinics over Sweden, as well as in conjunction with CH outpatient visits to neurology clinics. Study participants were diagnosed with CH and subtype by neurologists through structured interviews and clinical examination according to criteria of the International Classification of Headache Disorders, 3rd Edition.[1]

Each study participant completed a 3-part questionnaire that included a first part on personal, demographic and medical information. A second part was designed to assess different parts of the disease, and the third included lifestyle questions. For neurology outpatients, the questionnaire was completed in relation to the visit. All data were self-reported except CH diagnosis, which was verified using ICD-10 code G44.0. All participants were genotyped for their biological sex, and it matched their self-reported sex. The age at the time of completing the survey varied slightly between male and female participants (51.3±13.9 vs 49.0±15.0; P=.028)[1]

Gender Gap Closing?

Women were significantly more likely than men to have headache bouts lasting 4 months or longer and were more likely to have attacks that followed a circadian pattern, with early-morning onset.

Women were more likely than men to experience the onset of CH before age 20 years (23.0% vs 16.2%; odds ratio [OR], 0.64; 95% CI, 0.44-0.92; P=.020). However, there was no difference overall in the average age of disease onset.[1]

Chronic CH was nearly twice as common in women as men (18.4% vs 9.4%; OR, 0.46; 95% CI, 0.32-0.70; P=.0002). Women were also more likely to have a co-occurring migraine or tension-type headache and to have an immediate family member who had a history of CH (15.4% vs 7.1%; OR, 0.42; 95% CI, 0.27-0.66; P=.0002).[1]

CH triggered by sleep deprivation, stress, and changes in weather or temperature was also more common in women, whereas among men, attacks were more often triggered by alcohol consumption (56.5% vs 40.5%; OR, 1.91; 95% CI, 1.29-2.81; P=.001).Alcohol was the most common trigger by far (50.7%) for both men and women, and stress was the second most common trigger (26.7%), with more females being affected than males (20.5% vs 37.4%; OR, 0.43; 95% CI, 0.28-0.66; P=.0001). Most of the participants described food items or nonalcoholic beverages that may trigger an attack were chocolate, sweets or food/beverages with high sugar content, coffee/tea, (strong) cheese, food with high salt content, and spicy/pungent food.[1]

Women were more apt to use oxygen 36.5% vs 27.8%; OR, 0.67; 95% CI, 0.49-0.92; P=.013) for acute attacks and to use preventive medications. They also reported a higher incidence of ptosis (drooping eyelids; 60.5% vs 47.0%; OR, 0.58; 95% CI, 0.43-0.76; P=.0002) and restlessness (53.9 % vs 45.6%; OR, 0.72; 95% CI, 0.54-0.95; P=.024). Menstruation and other hormone-related factors were reported as triggers by 1.2% of women.[1]

Although CH remains more common in men than women, that gender gap is closing, Dr Belin said. That is in part because of better diagnosis, but also a result of a growing incidence of the disorder in women. Overall, the true number of female patients with CH is probably larger than reported, she added.

“I have patients in our cohort and our clinic who say they go to neurologists with all the symptoms of cluster headache, and the neurologists say that ‘you can’t have cluster headache because you’re a woman,’ “Dr Belin said.

The investigators have created a CH biobank and have DNA samples and clinical data on more than 900 patients with CH. That will make it easier to investigate the underlying cause of the disorder and the reasons for the differences in clinical presentation, they note.

“We’re very interested in learning more about the treatment response in men and women and why chronic cluster headache seems to be more common in women,” Dr Belin said.

Greater Awareness

In an accompanying editorial, Mark Burish, MD, PhD, from UT Health, Houston, Texas, and Richard Lipton, MD, from Albert Einstein College of Medicine, New York City, note that this is one of the most comprehensive CH studies to date.[4]

The investigators “confirm previous epidemiologic suspicions, provide new insights, and raise important questions into sex hormones and the influence of genetic factors,” Dr Burish and Dr Lipton write.

“This large study of rigorously diagnosed cluster headache patients mandates an elevated index of suspicion for cluster headache in women, and an awareness of possibly more burdensome disease in women,” the editorialists add.

The study was funded by the Swedish Brain Foundation, the Mellby Gård Foundation, the Swedish Research Council, Region Stockholm, and Karolinska Institutet Research Funds. Dr Belin has disclosed no relevant financial relationships. Dr Burish is an unpaid member of the medical advisory board of Clusterbusters. Dr Lipton serves in unpaid positions on the editorial board of Neurology and Cephalalgia and as senior advisor to Headache. Full disclosures are included in the original articles.

Neurology. Published online December 21, 2022.

Study Highlights

  • Study participants were identified by screening medical records from 2014 to 2020, requested from hospitals and neurology clinics in Sweden for International Classification of Disease, 10th Revision, code for CH.
  • Participants (n=874; 66% male) answered a detailed questionnaire on clinical information and lifestyle, and all had CH diagnosis validated by the researchers.
  • Compared with males, females were more often diagnosed with chronic CH subtype (18.4% vs 9.4%; OR, 0.46; 95% CI, 0.31-0.70; P=.0002), reported longer bouts (≥4 months; P=.003), and used prophylactic treatment more often (47.7% vs 60.2%; OR, 0.60; 95% CI, 0.45-0.80; P=.0005), particularly oxygen (36.5% vs 27.8%; OR, 0.67; 95% CI, 0.49-0.92; P=.013).
  • Men and women had similar attack frequency and duration and high pain intensity.
  • Although average age of onset did not differ overall, CH onset before age 20 years was more likely in women than men (23.0% vs 16.2%; OR,64; 95% CI, 0.44-0.92; P=.020).
  • Compared with the general population, mean body mass index was higher for this sample with CH, but this difference was only significant for males (P=.009).
  • Females were more likely to experience ptosis (61% vs 47%; P=.0002) and restlessness (54% vs 46%; P=.02) and to have a positive family history for CH (15.4% vs 7.1%; OR, 0.42; 95% CI, 0.27-0.66; P=.0002).
  • More females than males reported diurnal rhythmicity of their attacks, with early-morning onset (74% vs 63%; P=.002) and co-occurring migraine (29.4% vs 12.5%; OR, 0.34; 95% CI, 0.24-0.49; P<.0001) or tension-type headache (57.6% vs 44.3%; OR, 0.58; 95% CI, 0.44-0.78; P=.0002).
  • Triggers more frequent in males than females included alcohol (56.5% vs 40.5%; P=.001), whereas those more frequent in females were insufficient sleep (31% vs 20%; P=.001), stress, and changes in weather or temperature.
  • The investigators concluded that their in-depth analysis of a well-characterized CH population showed significant differences between males and females with CH, which should be considered at time of diagnosis and when choosing treatment.
  • The findings also suggest that females generally may be more severely affected by CH than males.
  • Study limitations include self-reported data with potential for recall bias, sex bias in diagnosis potentially contributing to observed differences in severity, and observational design precluding causal inferences.
  • An accompanying editorial noted that this is one of the most comprehensive CH studies to date and used rigorously diagnosed patients.

Clinical Implications

  • There are significant differences between males and females with CH, which should be considered at time of diagnosis and when choosing treatment.
  • CH is still often misdiagnosed in females, perhaps because certain features of the disease in females resemble a migraine-like phenotype.
  • Implications for the Health Care Team: Clinicians should have a greater index of suspicion for CH in women and be aware that women may have more burdensome disease.
 

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