Menstruation is a recognized trigger for migraine in some women, but what happens during the menopause transition, when cycles begin to change, and hormone levels can fluctuate wildly for prolonged periods of time? Managing migraine through the perimenopausal and menopausal years was the subject of an expert interview during the Migraine Summit 2024 with Dr. Christine Lay, Professor of Neurology at the University of Toronto.
The intersection of perimenopause, menopause, and migraine
Perimenopause describes the time around the menopause transition when a woman is still experiencing menstrual cycles.1-3 This period can be quite prolonged in some women, beginning in their 30s when menstrual cycles become irregular and classic menopausal symptoms such as hot flashes can emerge, up until the menopause, which is defined as 12 months after the last menstrual period.3 Hormonal levels can continue to fluctuate and symptoms can persist for several years after the menopause in some women. In women with migraine, the menopausal transition can be even more tumultuous, with changes in migraine frequency, severity, duration, and response to treatment. Moreover, the interictal burden between migraine attacks may increase, with some women feeling generally more unwell between attacks compared to their premenopausal years.
Migraine worsening in a woman in her 40s can be one of the first signs of perimenopause
New insights into the pathophysiology of menstrual migraine and menopause
Although the pathophysiology of menstrual migraine is not fully understood, there is emerging evidence that it involves more than estrogen. It is widely accepted that the rapid decline in estrogen levels that occurs in the late luteal phase of the menstrual cycle can trigger menstrual migraine.1,3,4 However, the picture is more complex than estrogen alone, and other hormones and neuropeptides including oxytocin and calcitonin gene-related peptide (CGRP) likely play a role.1,2,4,5 Indeed, there are cycle-dependent changes in levels of CGRP in women, and levels of CGRP have also been shown to be higher in perimenopausal and menopausal women during hot flashes.5 One model posits that estrogen withdrawal triggers menstrual migraine via disruption of the balance between pro-migraine factors such as CGRP and anti-migraine factors such as oxytocin within the trigeminal ganglion, where receptors for all three molecules are found.4
Complex interplay between fluctuating estrogen levels and oxytocin and CGRP during the menopausal transition
Impact on migraine management during perimenopause and menopause
One of the key changes in women with menstrual migraine when their cycle frequency begins to change in the perimenopausal period is that the predictability of their migraine is lost, and migraine management may no longer be effective.2 For example, women with menstrual migraine may have been able to effectively prevent a menstrual migraine attack by taking triptans for two days prior to the start of menses as a “mini prophylaxis” regimen. But with unpredictable cycles, this may no longer be possible. According to Dr. Lay, the way migraine is managed may require re-thinking in women with menstrual migraine during the perimenopause. “Using different tools or using the same tools in different ways, we can generally help women pass through this time effectively managing their migraine.” Specifically, she advises women to pay attention to other migraine cues such as prodromal symptoms that might predict the onset of an imminent migraine attack.
Migraines can become less predictable during the perimenopause as cycles become irregular
Dr. Lay also recommends treating migraines more aggressively with acute medications to “put out the fire” before a full-blown attack sets in. For women who are not already on preventive migraine treatment, entering the perimenopause might be an opportune time to discuss preventive strategies with their healthcare provider. “For patients who did very well with older-school drugs and who haven’t touched base with their provider in the last 3 to 5 years, with so many terrific new targeted migraine medications that are available, we can do better.” Neuromodulation devices may also be effective options, particularly for women with comorbid conditions that may preclude the use of certain medications.
Perimenopause may be an opportune time for women to update their migraine protocol
In parallel, Dr. Lay advises women to track their migraines using a diary to document changes in their migraines and menstrual cycles, and to make healthy lifestyle changes that can ease the burden of perimenopause and menstrual migraine. This can include getting adequate sleep, regular exercise, and a healthy diet. Some medications that are used for the treatment of vasomotor symptoms (i.e., hot flashes) can also help manage migraine, such as some antidepressants, antiepileptics, and hormonal treatments.2 Oral contraceptives for perimenopausal women and hormone replacement therapy for menopausal women can help “flatten out” fluctuations in estrogen levels, but these treatments are associated with other risks that should be discussed in the context of benefit-risk and shared decision-making.2,3
Migraine beyond the menopause
Although some women with menstrual migraine experience a worsening during the perimenopausal years, many see an improvement once menopause is reached and hormonal fluctuations attenuate.3 However, Dr. Lay reiterated that the transition can be prolonged in some women and is “way too long to wait.” Instead, she advocated for healthcare providers to be “more forward-thinking and more aggressive in our treatment to help our patients” as they navigate this transformational life phase.
Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.
