Commentary: Migraine and the relationship to gynecologic conditions, May 2023

The theme of this month's round-up is women's health, specifically as it relates to migraine. Three recent studies have highlighted the connection between estrogen and migraine, in terms of the potential increase in risk for certain conditions, such as gestational hypertension and endometriosis, and the use of potential therapies, such as calcitonin gene-related peptide (CGRP) antagonist medications to treat menstrual migraine.

Although most practitioners know that there is a deep connection between vascular risk and migraine, most are unfamiliar with the specific interplay between these two conditions. Antihypertensive medications are common preventive treatments for migraine, and migraine itself has been associated with an increased risk for specific vascular issues in pregnancy, most notably venous sinus thrombosis. Crowe and colleagues specifically looked at whether women with migraine experience a higher risk for hypertensive disorders of pregnancy.

This was a UK-based prospective cohort study using a large longitudinal database called the Clinical Practice Research Datalink. Over 1 million live-born or stillborn deliveries were analyzed from 1993 through 2020. The data were linked to diagnosis and prescription codes for migraine that were filled or documented before 20 weeks of gestation and compared with diagnosis codes for hypertensive disorders that occurred from week 20 through the pregnancy and delivery. Regression models were then used to estimate risk ratios and CI. Only single pregnancies were counted because multiple pregnancies already are associated with a higher risk for most other vascular conditions.

Any history of migraine prior to pregnancy was associated with an increased risk for gestational hypertension, eclampsia, and preeclampsia (relative risk 1.17). The greatest risk was higher frequency. Migraine that persisted into the first trimester led to a relative risk of 1.84. The use of migraine medications, especially vasoconstrictive-type medications, was also associated with a higher risk compared with women without migraine.

Women with migraine frequently present before family planning to discuss the potential risks and options of migraine treatment during pregnancy. In addition to discussing the most appropriate preventive and acute medications, it would be appropriate also to discuss any potential red flag symptoms that may occur during pregnancy. This discussion should include hypertensive disorders of pregnancy as per this study.

Since the advent of CGRP antagonist treatments for migraine, many practitioners and patients have been curious to know whether specific features of migraine are better treated with this class of medication. There are now both acute and preventive CGRP antagonists, both as small molecule agents and monoclonal antibodies (mAb). Menstrual migraines specifically can be a more difficult-to-treat subtype, and often when other triggers are negated, hormonal fluctuation can still be a significant problem for many patients. Verhagen and colleagues set out to determine whether CGRP mAb are more or less effective for menstrually associated migraine.

This analysis was post hoc, using data from a single-arm study investigating the efficacy of two of the CGRP mAb medications: erenumab and fremanezumab. Patients were included if they had a history of migraine with > 8 monthly migraine days and at least one antihypertensive or antiepileptic preventive treatment for migraine had previously failed. Any other prophylactic medications were tapered before starting this trial; patients were given a validated electronic diary, and adherence to this diary had to be > 80%. Women were also excluded if they did not have regular menses (for instance, if they were on continuous hormonal contraception) or they were postmenopausal. Logistic regression was used to compare the preventive effect of these medications on perimenstrual and non-perimenstrual migraine attacks.

A total of 45 women were included in this observation. The relative reduction in total monthly migraine days was 31.4%; 28% were noted during and around menses, 32% were during other times of the menstrual cycle. Sensitivity analysis showed no significant difference between these two periods of time, and the ratio remained statistically similar as well.

It appears that the relative reduction in monthly migraine days did not fluctuate when the patient was treated with a CGRP antagonist mAb. Although other classes of preventive medication, specifically onabotulinumtoxinA (Botox), may affect menstrually associated migraine less potently, it appears that the CGRP antagonist class may be just as effective regardless of the underlying migraine trigger. It would definitely be worth considering a CGRP antagonist trial, or the addition of a CGRP mAb, if menstrual migraine remains significant despite otherwise effective preventive treatment.

Migraine is strongly affected by fluctuations in estrogen, and women with endometriosis often experience headaches associated with their severe attacks. Pasquini and colleagues specifically looked to see if the headache associated with endometriosis could be better diagnosed. Specifically, were these women experiencing migraine or another headache disorder?

This was a consecutive case-control series of 131 women admitted to a specialty endometriosis clinic. They were given a validated headache questionnaire that was reviewed by a neurologist to determine a diagnosis of migraine vs a diagnosis of another headache disorder. The case group included women with a history of endometriosis who were previously diagnosed with migraine, while the control group consisted of women with endometriosis only who did not have a history of headache.

Diagnosis of migraine was made in 53.4% of all patients: 18.6% of those experienced pure menstrual migraine (defined as migraine only occurring perimenstrually), 46% had some menstrually associated migraine symptoms, and 36% had purely non-menstrual migraine. Painful periods and dysuria were more frequent in patients with endometriosis and migraine compared with those without migraine. Other menstrually related conditions, including the duration of endometriosis, the phenotype of endometriosis, the presence of other systemic comorbidities, or heavy menstrual bleeding did not seem to differ significantly between the migraine and non-migraine groups.

Women of reproductive age consistently are seen most often for migraine and other headache conditions. Much of this is related to menstrual migraine and the effect that hormonal fluctuation has on migraine frequency and severity. Most practitioners work closely with their patient's gynecologist to determine which hormonal treatments and migraine treatments are most appropriate and safe for each individual situation. This study in particular sheds light on the particular phenotypes of headache pain and the specific headache diagnosis that most women with endometriosis experience.

The theme of this month's round-up is women's health, specifically as it relates to migraine. Three recent studies have highlighted the connection between estrogen and migraine, in terms of the potential increase in risk for certain conditions, such as gestational hypertension and endometriosis, and the use of potential therapies, such as calcitonin gene-related peptide (CGRP) antagonist medications to treat menstrual migraine.

Although most practitioners know that there is a deep connection between vascular risk and migraine, most are unfamiliar with the specific interplay between these two conditions. Antihypertensive medications are common preventive treatments for migraine, and migraine itself has been associated with an increased risk for specific vascular issues in pregnancy, most notably venous sinus thrombosis. Crowe and colleagues specifically looked at whether women with migraine experience a higher risk for hypertensive disorders of pregnancy.

This was a UK-based prospective cohort study using a large longitudinal database called the Clinical Practice Research Datalink. Over 1 million live-born or stillborn deliveries were analyzed from 1993 through 2020. The data were linked to diagnosis and prescription codes for migraine that were filled or documented before 20 weeks of gestation and compared with diagnosis codes for hypertensive disorders that occurred from week 20 through the pregnancy and delivery. Regression models were then used to estimate risk ratios and CI. Only single pregnancies were counted because multiple pregnancies already are associated with a higher risk for most other vascular conditions.

Any history of migraine prior to pregnancy was associated with an increased risk for gestational hypertension, eclampsia, and preeclampsia (relative risk 1.17). The greatest risk was higher frequency. Migraine that persisted into the first trimester led to a relative risk of 1.84. The use of migraine medications, especially vasoconstrictive-type medications, was also associated with a higher risk compared with women without migraine.

Women with migraine frequently present before family planning to discuss the potential risks and options of migraine treatment during pregnancy. In addition to discussing the most appropriate preventive and acute medications, it would be appropriate also to discuss any potential red flag symptoms that may occur during pregnancy. This discussion should include hypertensive disorders of pregnancy as per this study.

Since the advent of CGRP antagonist treatments for migraine, many practitioners and patients have been curious to know whether specific features of migraine are better treated with this class of medication. There are now both acute and preventive CGRP antagonists, both as small molecule agents and monoclonal antibodies (mAb). Menstrual migraines specifically can be a more difficult-to-treat subtype, and often when other triggers are negated, hormonal fluctuation can still be a significant problem for many patients. Verhagen and colleagues set out to determine whether CGRP mAb are more or less effective for menstrually associated migraine.

This analysis was post hoc, using data from a single-arm study investigating the efficacy of two of the CGRP mAb medications: erenumab and fremanezumab. Patients were included if they had a history of migraine with > 8 monthly migraine days and at least one antihypertensive or antiepileptic preventive treatment for migraine had previously failed. Any other prophylactic medications were tapered before starting this trial; patients were given a validated electronic diary, and adherence to this diary had to be > 80%. Women were also excluded if they did not have regular menses (for instance, if they were on continuous hormonal contraception) or they were postmenopausal. Logistic regression was used to compare the preventive effect of these medications on perimenstrual and non-perimenstrual migraine attacks.

A total of 45 women were included in this observation. The relative reduction in total monthly migraine days was 31.4%; 28% were noted during and around menses, 32% were during other times of the menstrual cycle. Sensitivity analysis showed no significant difference between these two periods of time, and the ratio remained statistically similar as well.

It appears that the relative reduction in monthly migraine days did not fluctuate when the patient was treated with a CGRP antagonist mAb. Although other classes of preventive medication, specifically onabotulinumtoxinA (Botox), may affect menstrually associated migraine less potently, it appears that the CGRP antagonist class may be just as effective regardless of the underlying migraine trigger. It would definitely be worth considering a CGRP antagonist trial, or the addition of a CGRP mAb, if menstrual migraine remains significant despite otherwise effective preventive treatment.

Migraine is strongly affected by fluctuations in estrogen, and women with endometriosis often experience headaches associated with their severe attacks. Pasquini and colleagues specifically looked to see if the headache associated with endometriosis could be better diagnosed. Specifically, were these women experiencing migraine or another headache disorder?

This was a consecutive case-control series of 131 women admitted to a specialty endometriosis clinic. They were given a validated headache questionnaire that was reviewed by a neurologist to determine a diagnosis of migraine vs a diagnosis of another headache disorder. The case group included women with a history of endometriosis who were previously diagnosed with migraine, while the control group consisted of women with endometriosis only who did not have a history of headache.

Diagnosis of migraine was made in 53.4% of all patients: 18.6% of those experienced pure menstrual migraine (defined as migraine only occurring perimenstrually), 46% had some menstrually associated migraine symptoms, and 36% had purely non-menstrual migraine. Painful periods and dysuria were more frequent in patients with endometriosis and migraine compared with those without migraine. Other menstrually related conditions, including the duration of endometriosis, the phenotype of endometriosis, the presence of other systemic comorbidities, or heavy menstrual bleeding did not seem to differ significantly between the migraine and non-migraine groups.

Women of reproductive age consistently are seen most often for migraine and other headache conditions. Much of this is related to menstrual migraine and the effect that hormonal fluctuation has on migraine frequency and severity. Most practitioners work closely with their patient's gynecologist to determine which hormonal treatments and migraine treatments are most appropriate and safe for each individual situation. This study in particular sheds light on the particular phenotypes of headache pain and the specific headache diagnosis that most women with endometriosis experience.

The theme of this month's round-up is women's health, specifically as it relates to migraine. Three recent studies have highlighted the connection between estrogen and migraine, in terms of the potential increase in risk for certain conditions, such as gestational hypertension and endometriosis, and the use of potential therapies, such as calcitonin gene-related peptide (CGRP) antagonist medications to treat menstrual migraine.

Although most practitioners know that there is a deep connection between vascular risk and migraine, most are unfamiliar with the specific interplay between these two conditions. Antihypertensive medications are common preventive treatments for migraine, and migraine itself has been associated with an increased risk for specific vascular issues in pregnancy, most notably venous sinus thrombosis. Crowe and colleagues specifically looked at whether women with migraine experience a higher risk for hypertensive disorders of pregnancy.

This was a UK-based prospective cohort study using a large longitudinal database called the Clinical Practice Research Datalink. Over 1 million live-born or stillborn deliveries were analyzed from 1993 through 2020. The data were linked to diagnosis and prescription codes for migraine that were filled or documented before 20 weeks of gestation and compared with diagnosis codes for hypertensive disorders that occurred from week 20 through the pregnancy and delivery. Regression models were then used to estimate risk ratios and CI. Only single pregnancies were counted because multiple pregnancies already are associated with a higher risk for most other vascular conditions.

Any history of migraine prior to pregnancy was associated with an increased risk for gestational hypertension, eclampsia, and preeclampsia (relative risk 1.17). The greatest risk was higher frequency. Migraine that persisted into the first trimester led to a relative risk of 1.84. The use of migraine medications, especially vasoconstrictive-type medications, was also associated with a higher risk compared with women without migraine.

Women with migraine frequently present before family planning to discuss the potential risks and options of migraine treatment during pregnancy. In addition to discussing the most appropriate preventive and acute medications, it would be appropriate also to discuss any potential red flag symptoms that may occur during pregnancy. This discussion should include hypertensive disorders of pregnancy as per this study.

Since the advent of CGRP antagonist treatments for migraine, many practitioners and patients have been curious to know whether specific features of migraine are better treated with this class of medication. There are now both acute and preventive CGRP antagonists, both as small molecule agents and monoclonal antibodies (mAb). Menstrual migraines specifically can be a more difficult-to-treat subtype, and often when other triggers are negated, hormonal fluctuation can still be a significant problem for many patients. Verhagen and colleagues set out to determine whether CGRP mAb are more or less effective for menstrually associated migraine.

This analysis was post hoc, using data from a single-arm study investigating the efficacy of two of the CGRP mAb medications: erenumab and fremanezumab. Patients were included if they had a history of migraine with > 8 monthly migraine days and at least one antihypertensive or antiepileptic preventive treatment for migraine had previously failed. Any other prophylactic medications were tapered before starting this trial; patients were given a validated electronic diary, and adherence to this diary had to be > 80%. Women were also excluded if they did not have regular menses (for instance, if they were on continuous hormonal contraception) or they were postmenopausal. Logistic regression was used to compare the preventive effect of these medications on perimenstrual and non-perimenstrual migraine attacks.

A total of 45 women were included in this observation. The relative reduction in total monthly migraine days was 31.4%; 28% were noted during and around menses, 32% were during other times of the menstrual cycle. Sensitivity analysis showed no significant difference between these two periods of time, and the ratio remained statistically similar as well.

It appears that the relative reduction in monthly migraine days did not fluctuate when the patient was treated with a CGRP antagonist mAb. Although other classes of preventive medication, specifically onabotulinumtoxinA (Botox), may affect menstrually associated migraine less potently, it appears that the CGRP antagonist class may be just as effective regardless of the underlying migraine trigger. It would definitely be worth considering a CGRP antagonist trial, or the addition of a CGRP mAb, if menstrual migraine remains significant despite otherwise effective preventive treatment.

Migraine is strongly affected by fluctuations in estrogen, and women with endometriosis often experience headaches associated with their severe attacks. Pasquini and colleagues specifically looked to see if the headache associated with endometriosis could be better diagnosed. Specifically, were these women experiencing migraine or another headache disorder?

This was a consecutive case-control series of 131 women admitted to a specialty endometriosis clinic. They were given a validated headache questionnaire that was reviewed by a neurologist to determine a diagnosis of migraine vs a diagnosis of another headache disorder. The case group included women with a history of endometriosis who were previously diagnosed with migraine, while the control group consisted of women with endometriosis only who did not have a history of headache.

Diagnosis of migraine was made in 53.4% of all patients: 18.6% of those experienced pure menstrual migraine (defined as migraine only occurring perimenstrually), 46% had some menstrually associated migraine symptoms, and 36% had purely non-menstrual migraine. Painful periods and dysuria were more frequent in patients with endometriosis and migraine compared with those without migraine. Other menstrually related conditions, including the duration of endometriosis, the phenotype of endometriosis, the presence of other systemic comorbidities, or heavy menstrual bleeding did not seem to differ significantly between the migraine and non-migraine groups.

Women of reproductive age consistently are seen most often for migraine and other headache conditions. Much of this is related to menstrual migraine and the effect that hormonal fluctuation has on migraine frequency and severity. Most practitioners work closely with their patient's gynecologist to determine which hormonal treatments and migraine treatments are most appropriate and safe for each individual situation. This study in particular sheds light on the particular phenotypes of headache pain and the specific headache diagnosis that most women with endometriosis experience.