Midlife migraines ‘treatable,’ but team-based approach needed
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The cause of midlife migraines in women is likely multifactorial, though research suggests that fluctuating hormone levels may play a role, according to a speaker at the North American Menopause Society annual meeting.
Migraines are the second leading cause of disability globally, and 1 in 4 women experience migraine during the reproductive life cycle, Kevin Weber, MD, MHA, assistant professor of neurology at The Ohio State University, said during a presentation. Among women, migraine prevalence is highest at menarche and after, during menstruation, during ovulation, postpartum and during perimenopause. Prevalence is lowest during the second and third trimesters of pregnancy and after menopause, when circulating estrogen levels are lower, he said.
“It is suspected that sustained, high levels of estradiol, followed by precipitous drop, explains why the increase in migraine attacks is typically greater at menstruation than at ovulation,” Weber said.
A “vascular hypothesis” — migraines attributed to dilating blood vessels in the brain — has fallen out of favor, Weber said; migraine is now thought to be a neural process with many contributing factors. Estradiol crosses the blood-brain barrier and can be synthesized in the brain, Weber said. Its rise and fall can lead to intra- and extracellular effects in brain structures, increased neural excitability and increased neurotransmitter release in the pain signaling pathways.
“Estradiol effects a large number of neurotransmitter pathways, particularly involving the pain system,” Weber said.
Weber highlighted migraine types related to different stages of the reproductive life cycle:
- Menstrual migraine — Women who have migraine attacks only during their menstrual cycle are rare, Weber said. Menstrual-related migraine, however, is far more common, with migraine attacks reported during and around menses. “Estrogen withdrawal” headache is also commonly seen among some women during the placebo period of oral contraceptive therapy, Weber said.
- Perimenopause/menopause transition migraine — During perimenopause and the menopause transition, an orderly pattern of estrogen and progesterone fluctuation disappears, and fluctuations in sex hormones “undoubtedly” lead to an increase in migraine incidence, Weber said. “We know migraine prevalence ranges from 10% to 29% during the menopausal period, and 8% to 13% of women develop new-onset migraine during menopause,” Weber said. “That is always concerning for people who develop new-onset migraine at age 50 years.”
- Menopause — After menopause, migraine incidence and prevalence drop dramatically, although prevalence never falls below that of men at the same age, Weber said. “We think that is due to stabilizing estradiol levels,” Weber said. “Interestingly, women who experienced menstrual migraines tend to experience a better prognosis postmenopause. We do not know why this is yet.”
- Surgical menopause — There is evidence that surgical menopause worsens migraine, even if ovaries are not removed. “As neurologists, we are asked about this a lot,” Weber said. “We know surgical menopause seems to worsen migraine.” A hysterectomy, however, may not alleviate migraine pain and may even worsen migraine symptoms, he said.
No cure, but ‘treatable’
There is no cure for migraine, but the condition is treatable, according to Carolyn Bernstein, MD, FAHS, assistant professor of neurology at Harvard Medical School and associate neurologist at Brigham and Women’s Hospital. For menopausal women, clinicians should try to use migraine treatments that may help with more than one condition, such as climacteric symptoms. She suggested a “migraine diary” as a great first approach for women, who should record migraine frequency, characteristics, potential triggers, duration and any attempted treatments.
Lifestyle counseling and simple mindfulness techniques may be helpful for some women, though many often need more intensive therapy.
Calcitonin gene-related peptide (CGRP), a highly potent vasoactive peptide released from sensory nerves in the brain, is a target for newer migraine therapies, with six CGRP treatments approved during the last 3 years, Bernstein said. These treatments tend to be well tolerated, have few interactions and can be very effective — though currently there is no biomarker to determine optimal candidates for such treatments, she said. CGRP biologics are also expensive, often come with hurdles for insurance approval and require patient monitoring.
“There is a lot of direct-to-patient marketing, and women will ask you about these treatments,” Bernstein said. “They are often a good choice for many people and can be effective, and it is probably in everyone’s best interest to refer to a neurology colleague.”
Weber said it is important that the OB/GYN, primary care physician or other providers managing hormonal treatments for menopause build a relationship with a neurologist to address migraine.
“[Migraine treatment] is very individualized, and it is very important that clinicians communicate and work together to manage a woman throughout her migraine life cycle, because some of these patients really suffer,” Weber said.
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Weber K. Presented at: North American Menopause Society Annual Meeting; Sept. 22-25, 2021 (hybrid meeting).
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