QUOTE
Hormonal Influences on Common Health Problems in Women
Peggy Keen, PhD, RNC
IntroductionWomen have experienced and described the surge and ebb of hormones related to puberty, fertility, childbirth, and menopause for eons. In the recent past, hormonal influences related to oral contraception (OC) use and hormone replacement therapy (HRT) have also become a part of many women's lives. However, there is now a growing body of evidence linking the female sex hormones estrogen and progesterone with common health problems experienced by women. These links -- specifically hormonal influences on migraine headache and rhinitis -- were described during 2 sessions presented at the 4th Annual Conference of the National Association of Nurse Practitioners in Women's Health. Margaret Moloney, RN-C, PhD, ANP,[1] Emory University School of Nursing, Atlanta, Georgia, provided an overview of the differential diagnosis and management for migraine headaches, with an emphasis on migraines related to menstruation, pregnancy, and menopause. Judith S. Lynch, MS, MA, ARNP, FAANP,[2] who works in a private allergy practice and is on faculty at Yale University School of Nursing, New Haven, Connecticut, described hormonal links to rhinitis, particularly rhinitis associated with pregnancy.
Migraine Headaches and HormonesMigraine headaches are a significant cause of morbidity, especially among women, in the United States. A population-based survey mailed to 20,000 households in the United States in 1999 found that 48% reported a physician diagnosis of migraine that met the International Headache Society case definition for migraine.[3] This incidence reflected a 10% increase from the findings of a methodologically identical survey conducted in 1989. Significant disability was reported; 57% of those with diagnosed migraine headaches reported at least a 50% reduction in work/school productivity (P < .001). Nearly 23% of households surveyed reported at least 1 member with diagnosed migraine headache.[4] In addition, a recent study conducted in an urgent care department showed that many individuals with migraine remain underdiagnosed and undertreated.[5]
There is no sex difference in rate of occurrence of migraine headaches in prepubertal children, but the ratio changes in adulthood when females are 3 times more likely than males to experience this condition.[6] The peak incidence of onset occurs during adolescence; prevalence is highest between the ages of 25 and 55 years.[1] In the 1999 population-based survey previously described, the prevalence of migraine was 18.2% among females, compared with 6.5% in males.[3] In addition, the effects of migraine are more severe in women.[1]
The essential mechanisms responsible for migraine are still unknown. Moloney described the current theory of pathophysiology that includes trigeminal nerve stimulation by unknown factors, neurotransmitters combining with blood vessel receptors, and inflammation and dilation of cranial blood vessels. There also seems to be an inherited susceptibility to migraine. It is also recognized that although migraine appears to occur randomly or be precipitated by known trigger factors for many women, in others there are predictable changes due to alterations in hormonal state.[7]
Menarche, pregnancy, OC use, menopause, and use of HRT are events or interventions that change the levels and cycling of sex hormones. In turn, estrogen and progestins, whether endogenous or exogenous, strongly affect central serotonergic and opioid neurons responsible for neuronal activity and receptor density.[6] Hormonal fluctuations and the subsequent cascade of events appear to potentially affect the occurrence or intensity of migraine. Other hormonal responses involving serotonin or melatonin could also be factors.[8]
Migraine Related to MenstruationThe incidence of migraine triggered by menstruation is unclear. Estimates found in the medical literature range from slightly less than half of women with migraine[9] to as high as 70%.[10] Moloney described the typical pattern as headache beginning several days premenstrually or during menses, but stated that women for whom menstruation is a primary trigger may also experience migraine at other times of their cycle.
It has been proposed that the term menstrual migraine be restricted to attacks occurring on day 1 +/- 2 days of the menstrual cycle, and only for women who do not have migraine at any other time.[11] However, while some clinicians use the term "true menstrual migraine" to make this distinction, the International Headache Society has not classified this type of headache and there currently is a lack of agreed terminology or definition of "menstrual migraine."[12] The term "menstrual cycle-related migraine" is also found in the medical literature.
The onset of menses is associated with estrogen withdrawal, the most marked fluctuation during the cycle. The prostaglandin release that occurs around the time of menses may also be an important factor for some women suffering from menstrual migraine.[11] One theory is that abnormal central nervous system response to normal hormonal fluctuations may trigger the neurologic and vasospastic symptoms of migraine.[9] Thus, the high estrogen level during pregnancy, the fluctuating levels of estrogen in the perimenopause, and low estrogen levels at menopause can also affect the frequency and severity of headaches. Headaches related to OC or HRT use may also be partially related to the periodic use or discontinuation of these artificial sex hormone preparations.[13]
After describing the criteria for migraine with aura (MA) and migraine without aura (MO), Moloney stated that the majority of menstrual migraines are not accompanied by aura. An interesting study assessing the relationship between MA and MO in 268 women showed several hormonally related differences.[14] A significantly greater number of women who had migraine headaches during menses had MO (P < .03); the incidence of menstrual migraines was also increased in MO patients compared with those with MA (P < .01). The initial onset of headaches during pregnancy was significantly higher for patients with MA (P < .01). However, there were no differences between groups with respect to onset of migraine at menarche, during early cycles of oral contraceptive use, in the postpartum period, or after menopause. A similar migraine course during pregnancy, OC use, and menopause was also observed. An interesting observation was that 8 patients diagnosed with coexisting MA and MO first experienced the aura symptom in the early cycles of OC use. Based on these findings, the investigators suggested that gonadal hormone fluctuation may influence both types of migraine.
Treatment of Menstrual MigraineTreatment for migraine, especially headaches related to hormonal fluctuations, is challenging. Moloney emphasized that it make take many months of trying different medications to arrive at what works best for an individual patient. The treatment regimen may be a single drug or a compilation of prophylactic medications, acute medications, and nonpharmacologic measures.
Treatment of menstrual migraine may include an attempt to stabilize hormone levels via the administration of exogenous hormones. However, this approach remains somewhat controversial, and is supported by only scant efficacy data. If estrogen supplementation is prescribed, it is most often in the form of OCs. Use of OCs improves migraine for some women, but exacerbates the condition in others.[6,15] A case-control study showed that use of OCs increased headaches more frequently in women with MA, compared with those with MO; 56.4% vs 25.3%, respectively.[16]
If OCs are prescribed, Moloney recommended use of a low-dose combined preparation of estrogen (less than 35 mcg ethinyl estradiol) and progestin. Certain types of exogenous estrogen, such as estradiol, tend to be less likely to aggravate migraine. OCs are best taken without interruption for 3 months at a time to allow continuous estrogen delivery.
It is important to remember that general hormonal prescribing guidelines should always be followed when treating menstrual migraine. OCs should not be prescribed for individuals with absolute contraindications, or for those 40 years of age or older who have other risk factors for stroke. Because women with migraine are at increased risk for ischemic stroke compared with the general population, there is a potential synergistic effect with OC use, particularly if other risk factors such as smoking or history of hypertension are present.[6,17] The combined stroke risk is also considered to be higher for MA. Many clinicians will not prescribe estrogen preparations for women with MA who are older than 40 years of age.
If headaches worsen, it may be helpful to change the type of estrogen, further decrease the dose, or add an androgen.[6] If headaches have a marked increase in severity or frequency, are suddenly accompanied by an aura, or are accompanied by usual aura symptoms such as prolonged aura, oral hormone preparations may need to be discontinued.[6]
Another hormonal treatment possibility is use of a low-dose HRT patch applied premenstrually. The lowest dosage available should initially be used. Moloney recommended applying a patch 3 days before menses, replacing it on the day prior to menses, and replacing it again on day 2 of the menstrual cycle.
Over-the-counter (OTC) drugs may work well for treatment of mild to moderate menstrual migraines. If taken early in the course of a headache, acetylsalicylic acid and acetaminophen (with or without caffeine) can also be effective. Nonsteroidal anti-inflammatory drugs (NSAIDs) taken for several days prior to menses may also be helpful. In particular, naproxen in prescription dosages has successfully been used preventively.[8] Other medications that may be used for short-term perimenstrual prophylaxis include dihydroergotamine, methergine, propranolol (the only beta-blocker approved for migraine prophylaxis), anticonvulsants, calcium-channel blockers, antidepressants, and serotonin agonists (triptans).[6] According to Moloney, most drugs used for preventive treatment are only about 55% to 60% effective.
Magnesium (200-600 mg/day) taken before onset of menses, vitamin B2 (400 mg/day), vitamin B6 (50-100 mg/day), vitamin D, and calcium all have limited reports of effectiveness.[18-21] Although there are anecdotal reports of success with all of these substance, optimal dosages are not currently known. The approach taken by Moloney is to ensure that women with migraine use a daily multivitamin and are meeting their daily recommendation for calcium intake.
As previously mentioned, prostaglandin production may also play a role in the exacerbation of menstrually related migraine. An interesting study of mefenamic acid, a prostaglandin synthesis inhibitor, administered to patients at the beginning of MO symptoms, demonstrated significant pain relief with treatment.[22] Significant pain relief was experienced by 79.16% of treated women, compared with a 16.6% placebo response. All participants who initially responded to placebo suffered migraine recurrence, compared with a recurrence of 26.5% in those treated with mefenamic acid.
An overview of a number of migraine-specific medications was provided, including the newer serotonin agonists, commonly referred to as triptans. It is beyond the scope of this report to include information about all of the medications used for the prophylactic or acute treatment of migraine. However, a comprehensive compendium of these preparations, including dosages and prescribing comments, accompanies a recent article about caring for women with migraine written by Moloney and colleagues at Emory School of Nursing.[8]
Moloney emphasized that any medication used for treatment of migraine, particularly those used for preventive treatment, must be tried for a minimum of 2-3 months. The adage to "start low and go slow" with prescribing any medication is an important management principle. Migraine-specific drugs should be used to treat severe headaches; use of a nonoral route should be considered for patients with symptoms of gastrointestinal distress. If acute treatment is need more than 2 to 3 days per week, preventive medication should be considered. It is also important to watch for "rebound" with many of these medications, where overuse actually begins to cause headache.
Migraine During Perimenopause and MenopauseThe perimenopause is marked by even wider than usual fluctuations in estrogen, while in menopause, low estrogen predominates. Although migraine prevalence typically decreases with age, it may either worsen or improve in relation to perimenopause and menopause. However, an estimated two thirds of all women with migraine experience improvement following menopause.[1]
It may be particularly challenging to provide hormone replacement, either with estrogen alone (ERT), or with estrogen and progestin (HRT), to women with migraine when pharmacologic intervention is indicated for management of menopausal symptoms. As with OCs, artificial hormone supplementation at menopause or in the perimenopause may relieve or exacerbate migraine.[1] Two recent studies have demonstrated an association between worsening of migraine with previous OC use and worsening with HRT use during menopause.[16,26]
Recommended approaches to hormone replacement during menopause are similar to those for prescribing OCs: use of a low-dose preparation that contains synthetic ethinyl estradiol or a pure estrone, and continuous administration of the replacement preparation. It may also be helpful to add an androgen.[27] Use of a transdermal patch can also be tried. The patch initial dose should be low; ethinyl estradiol is the estrogen preparation of choice, and consistent absorption is preferable.[6,28]
Women with an intact uterus also need progesterone in association with estrogen replacement. This may also aggravate migraine. If this occurs, suggestions include use of a micronized progesterone[8] or use of a continuous low dose of megestrol.[29] Changing types of progestin may also provide some relief.[6] As with any medical treatment, the clinician must always consider the risks vs benefit when prescribing HRT.
Hormone-Associated RhinitisAs part of her comprehensive overview of allergies and rhinitis in women, Lynch discussed the known association between hormones, particularly estrogen and its effect on nasal mucosa.[2] Estrogen has a cholinergic action on mucosa, causing pooling of nasal vasculature resulting in mucosal engorgement and accompanied by edema of the nasal turbinates. These changes are also accompanied by hypersecretion of either very thin or very thick mucus, depending on what cells in the nose are specifically involved. Hormonal effects on nasal mucosa are frequently most prominent during pregnancy, a sustained high estrogen state. Progesterone also increases during pregnancy, but the effects of this hormone on nasal mucosa are less well understood.
Pregnancy rhinitis has been defined as nasal congestion during pregnancy that lasts 6 or more weeks and is not associated with other signs of respiratory infection or known allergy.[30] Pregnancy rhinitis affects approximately 20% of pregnant women.[31] The onset of pregnancy-associated rhinitis typically begins by the second month of pregnancy, and may persist to term. The condition typically resolves 1 to 2 weeks following delivery. A recent study in Sweden showed that the incidence of rhinitis was markedly increased in smokers, but not in individuals with a history of hay fever or asthma.[32]
The exact pathophysiology of pregnancy rhinitis is not known, but it is thought to be multifactorial.[31] In addition to rising estrogen and progesterone levels, there is an increase in glandular secretions from goblet cells, the cells on the surface of nasal mucosa that normally secrete protective mucus. In addition to an increased amount, the viscosity of secretions is changed during pregnancy. The increased secretions from the goblet cells are also accompanied by vasodilation. The increased blood volume associated with pregnancy may also play a role.[2] Testing of the mucociliary function in pregnant women has also shown that transport speed was higher in women with pregnancy rhinitis, and reduced in women without this condition.[31]
Lynch noted that pregnant women are also at increased risk for allergic rhinitis and have a 6-fold increased risk for rhinosinusitis. Why this risk increases during pregnancy is uncertain, but may be related to the estrogen-associated vascular engorgement that causes retention of mucus. In turn, the retained mucus can increase the risk of infection.
Case Study: A Young Woman Taking Oral ContraceptivesThe patient was a 31-year-old white female, living with 3 children in a nonsmoking household. She presented with a chief complaint of chronic nasal congestion. She had a past history of "sinus" problems and had been prescribed 4 courses of antibiotics over the past 6 months, ranging from first generation to fourth generation antibiotics. These treatments were accompanied by 3 bouts of yeast vaginitis. She had a questionable allergy history, and was very frustrated by the healthcare system in general since she believed that she was not getting any better. Current medications included daily Claritin, Ortho-Tri-Cyclen for contraception, NSAIDs for relief of pain from nasal congestion, and Afrin nasal spray. She had a nasoseptal reconstruction several years previously following a motor vehicle accident, and a tonsillectomy in childhood. Allergy testing as teenager indicated that she was weakly positive for molds and dust, but she elected not to undertake immunotherapy. There were no known allergies to medication.
Symptoms included a chronic nasal congestion that got worse 4-5 days before menses, a moderate to severe postnasal drip without any nasal discharge, and diffuse frontal headaches. She denied facial or dental pain.
Mild allergic shiners (vascular pooling under the eyes that is indicative of allergy) were seen on physical exam. Other findings included a nondeviated septum, pale boggy nasal mucosa, and swollen turbinates. Clear discharge from the postnasal drip was noted in the posterior pharynx.
Skin and RAST testing were negative, as were sinus films and a screening computed tomography. Nasal cultures showed no bacterial growth.
Differential diagnoses included allergy, rebound from chronic use of nasal spray (rhinitis medicamentosa), and chronic rhinosinusitis.
The final diagnosis was an estrogen-induced rhinitis, related to use of OCs, with an overlay of perennial mild allergic rhinitis. As a general rule, Lynch recommended assessing any hormonal preparation patients are taking, and decreasing or eliminating estrogen content if possible. For this patient, it was also important to discontinue the chronic use of OTC nasal spray. This can be aided by use of a 5-day course of oral corticosteroids, and concurrent but decreasing use of an intranasal steroid spray.
With respect to this particular patient, Lynch noted that NSAIDs may also cause nasal congestion. Use of aspirin, beta-blockers, antidepressants, and anxiolytics (particularly alprazolam) has also been associated with increased nasal congestion.
SummaryMigraine is a difficult condition to treat successfully under the best of circumstances. Migraines associated with hormonal fluctuations may be even more challenging. Providing patients with education about their condition and treatments and enlisting them as a partner in what may be a lengthy process of trial and error to arrive at the optimal treatment approach can contribute to a positive outcome.
The association between hormonal changes and rhinitis is an important area for research. There is currently only 1 ongoing study assessing the effect of hormones on nasal reactivity in women. Hopefully, there will be more data in the next decade that will further define the etiology, and lead to successful intervention for hormonally related rhinitis.
Peggy Keen, PhD, RNC
IntroductionWomen have experienced and described the surge and ebb of hormones related to puberty, fertility, childbirth, and menopause for eons. In the recent past, hormonal influences related to oral contraception (OC) use and hormone replacement therapy (HRT) have also become a part of many women's lives. However, there is now a growing body of evidence linking the female sex hormones estrogen and progesterone with common health problems experienced by women. These links -- specifically hormonal influences on migraine headache and rhinitis -- were described during 2 sessions presented at the 4th Annual Conference of the National Association of Nurse Practitioners in Women's Health. Margaret Moloney, RN-C, PhD, ANP,[1] Emory University School of Nursing, Atlanta, Georgia, provided an overview of the differential diagnosis and management for migraine headaches, with an emphasis on migraines related to menstruation, pregnancy, and menopause. Judith S. Lynch, MS, MA, ARNP, FAANP,[2] who works in a private allergy practice and is on faculty at Yale University School of Nursing, New Haven, Connecticut, described hormonal links to rhinitis, particularly rhinitis associated with pregnancy.
Migraine Headaches and HormonesMigraine headaches are a significant cause of morbidity, especially among women, in the United States. A population-based survey mailed to 20,000 households in the United States in 1999 found that 48% reported a physician diagnosis of migraine that met the International Headache Society case definition for migraine.[3] This incidence reflected a 10% increase from the findings of a methodologically identical survey conducted in 1989. Significant disability was reported; 57% of those with diagnosed migraine headaches reported at least a 50% reduction in work/school productivity (P < .001). Nearly 23% of households surveyed reported at least 1 member with diagnosed migraine headache.[4] In addition, a recent study conducted in an urgent care department showed that many individuals with migraine remain underdiagnosed and undertreated.[5]
There is no sex difference in rate of occurrence of migraine headaches in prepubertal children, but the ratio changes in adulthood when females are 3 times more likely than males to experience this condition.[6] The peak incidence of onset occurs during adolescence; prevalence is highest between the ages of 25 and 55 years.[1] In the 1999 population-based survey previously described, the prevalence of migraine was 18.2% among females, compared with 6.5% in males.[3] In addition, the effects of migraine are more severe in women.[1]
The essential mechanisms responsible for migraine are still unknown. Moloney described the current theory of pathophysiology that includes trigeminal nerve stimulation by unknown factors, neurotransmitters combining with blood vessel receptors, and inflammation and dilation of cranial blood vessels. There also seems to be an inherited susceptibility to migraine. It is also recognized that although migraine appears to occur randomly or be precipitated by known trigger factors for many women, in others there are predictable changes due to alterations in hormonal state.[7]
Menarche, pregnancy, OC use, menopause, and use of HRT are events or interventions that change the levels and cycling of sex hormones. In turn, estrogen and progestins, whether endogenous or exogenous, strongly affect central serotonergic and opioid neurons responsible for neuronal activity and receptor density.[6] Hormonal fluctuations and the subsequent cascade of events appear to potentially affect the occurrence or intensity of migraine. Other hormonal responses involving serotonin or melatonin could also be factors.[8]
Migraine Related to MenstruationThe incidence of migraine triggered by menstruation is unclear. Estimates found in the medical literature range from slightly less than half of women with migraine[9] to as high as 70%.[10] Moloney described the typical pattern as headache beginning several days premenstrually or during menses, but stated that women for whom menstruation is a primary trigger may also experience migraine at other times of their cycle.
It has been proposed that the term menstrual migraine be restricted to attacks occurring on day 1 +/- 2 days of the menstrual cycle, and only for women who do not have migraine at any other time.[11] However, while some clinicians use the term "true menstrual migraine" to make this distinction, the International Headache Society has not classified this type of headache and there currently is a lack of agreed terminology or definition of "menstrual migraine."[12] The term "menstrual cycle-related migraine" is also found in the medical literature.
The onset of menses is associated with estrogen withdrawal, the most marked fluctuation during the cycle. The prostaglandin release that occurs around the time of menses may also be an important factor for some women suffering from menstrual migraine.[11] One theory is that abnormal central nervous system response to normal hormonal fluctuations may trigger the neurologic and vasospastic symptoms of migraine.[9] Thus, the high estrogen level during pregnancy, the fluctuating levels of estrogen in the perimenopause, and low estrogen levels at menopause can also affect the frequency and severity of headaches. Headaches related to OC or HRT use may also be partially related to the periodic use or discontinuation of these artificial sex hormone preparations.[13]
After describing the criteria for migraine with aura (MA) and migraine without aura (MO), Moloney stated that the majority of menstrual migraines are not accompanied by aura. An interesting study assessing the relationship between MA and MO in 268 women showed several hormonally related differences.[14] A significantly greater number of women who had migraine headaches during menses had MO (P < .03); the incidence of menstrual migraines was also increased in MO patients compared with those with MA (P < .01). The initial onset of headaches during pregnancy was significantly higher for patients with MA (P < .01). However, there were no differences between groups with respect to onset of migraine at menarche, during early cycles of oral contraceptive use, in the postpartum period, or after menopause. A similar migraine course during pregnancy, OC use, and menopause was also observed. An interesting observation was that 8 patients diagnosed with coexisting MA and MO first experienced the aura symptom in the early cycles of OC use. Based on these findings, the investigators suggested that gonadal hormone fluctuation may influence both types of migraine.
Treatment of Menstrual MigraineTreatment for migraine, especially headaches related to hormonal fluctuations, is challenging. Moloney emphasized that it make take many months of trying different medications to arrive at what works best for an individual patient. The treatment regimen may be a single drug or a compilation of prophylactic medications, acute medications, and nonpharmacologic measures.
Treatment of menstrual migraine may include an attempt to stabilize hormone levels via the administration of exogenous hormones. However, this approach remains somewhat controversial, and is supported by only scant efficacy data. If estrogen supplementation is prescribed, it is most often in the form of OCs. Use of OCs improves migraine for some women, but exacerbates the condition in others.[6,15] A case-control study showed that use of OCs increased headaches more frequently in women with MA, compared with those with MO; 56.4% vs 25.3%, respectively.[16]
If OCs are prescribed, Moloney recommended use of a low-dose combined preparation of estrogen (less than 35 mcg ethinyl estradiol) and progestin. Certain types of exogenous estrogen, such as estradiol, tend to be less likely to aggravate migraine. OCs are best taken without interruption for 3 months at a time to allow continuous estrogen delivery.
It is important to remember that general hormonal prescribing guidelines should always be followed when treating menstrual migraine. OCs should not be prescribed for individuals with absolute contraindications, or for those 40 years of age or older who have other risk factors for stroke. Because women with migraine are at increased risk for ischemic stroke compared with the general population, there is a potential synergistic effect with OC use, particularly if other risk factors such as smoking or history of hypertension are present.[6,17] The combined stroke risk is also considered to be higher for MA. Many clinicians will not prescribe estrogen preparations for women with MA who are older than 40 years of age.
If headaches worsen, it may be helpful to change the type of estrogen, further decrease the dose, or add an androgen.[6] If headaches have a marked increase in severity or frequency, are suddenly accompanied by an aura, or are accompanied by usual aura symptoms such as prolonged aura, oral hormone preparations may need to be discontinued.[6]
Another hormonal treatment possibility is use of a low-dose HRT patch applied premenstrually. The lowest dosage available should initially be used. Moloney recommended applying a patch 3 days before menses, replacing it on the day prior to menses, and replacing it again on day 2 of the menstrual cycle.
Over-the-counter (OTC) drugs may work well for treatment of mild to moderate menstrual migraines. If taken early in the course of a headache, acetylsalicylic acid and acetaminophen (with or without caffeine) can also be effective. Nonsteroidal anti-inflammatory drugs (NSAIDs) taken for several days prior to menses may also be helpful. In particular, naproxen in prescription dosages has successfully been used preventively.[8] Other medications that may be used for short-term perimenstrual prophylaxis include dihydroergotamine, methergine, propranolol (the only beta-blocker approved for migraine prophylaxis), anticonvulsants, calcium-channel blockers, antidepressants, and serotonin agonists (triptans).[6] According to Moloney, most drugs used for preventive treatment are only about 55% to 60% effective.
Magnesium (200-600 mg/day) taken before onset of menses, vitamin B2 (400 mg/day), vitamin B6 (50-100 mg/day), vitamin D, and calcium all have limited reports of effectiveness.[18-21] Although there are anecdotal reports of success with all of these substance, optimal dosages are not currently known. The approach taken by Moloney is to ensure that women with migraine use a daily multivitamin and are meeting their daily recommendation for calcium intake.
As previously mentioned, prostaglandin production may also play a role in the exacerbation of menstrually related migraine. An interesting study of mefenamic acid, a prostaglandin synthesis inhibitor, administered to patients at the beginning of MO symptoms, demonstrated significant pain relief with treatment.[22] Significant pain relief was experienced by 79.16% of treated women, compared with a 16.6% placebo response. All participants who initially responded to placebo suffered migraine recurrence, compared with a recurrence of 26.5% in those treated with mefenamic acid.
An overview of a number of migraine-specific medications was provided, including the newer serotonin agonists, commonly referred to as triptans. It is beyond the scope of this report to include information about all of the medications used for the prophylactic or acute treatment of migraine. However, a comprehensive compendium of these preparations, including dosages and prescribing comments, accompanies a recent article about caring for women with migraine written by Moloney and colleagues at Emory School of Nursing.[8]
Moloney emphasized that any medication used for treatment of migraine, particularly those used for preventive treatment, must be tried for a minimum of 2-3 months. The adage to "start low and go slow" with prescribing any medication is an important management principle. Migraine-specific drugs should be used to treat severe headaches; use of a nonoral route should be considered for patients with symptoms of gastrointestinal distress. If acute treatment is need more than 2 to 3 days per week, preventive medication should be considered. It is also important to watch for "rebound" with many of these medications, where overuse actually begins to cause headache.
Migraine During Perimenopause and MenopauseThe perimenopause is marked by even wider than usual fluctuations in estrogen, while in menopause, low estrogen predominates. Although migraine prevalence typically decreases with age, it may either worsen or improve in relation to perimenopause and menopause. However, an estimated two thirds of all women with migraine experience improvement following menopause.[1]
It may be particularly challenging to provide hormone replacement, either with estrogen alone (ERT), or with estrogen and progestin (HRT), to women with migraine when pharmacologic intervention is indicated for management of menopausal symptoms. As with OCs, artificial hormone supplementation at menopause or in the perimenopause may relieve or exacerbate migraine.[1] Two recent studies have demonstrated an association between worsening of migraine with previous OC use and worsening with HRT use during menopause.[16,26]
Recommended approaches to hormone replacement during menopause are similar to those for prescribing OCs: use of a low-dose preparation that contains synthetic ethinyl estradiol or a pure estrone, and continuous administration of the replacement preparation. It may also be helpful to add an androgen.[27] Use of a transdermal patch can also be tried. The patch initial dose should be low; ethinyl estradiol is the estrogen preparation of choice, and consistent absorption is preferable.[6,28]
Women with an intact uterus also need progesterone in association with estrogen replacement. This may also aggravate migraine. If this occurs, suggestions include use of a micronized progesterone[8] or use of a continuous low dose of megestrol.[29] Changing types of progestin may also provide some relief.[6] As with any medical treatment, the clinician must always consider the risks vs benefit when prescribing HRT.
Hormone-Associated RhinitisAs part of her comprehensive overview of allergies and rhinitis in women, Lynch discussed the known association between hormones, particularly estrogen and its effect on nasal mucosa.[2] Estrogen has a cholinergic action on mucosa, causing pooling of nasal vasculature resulting in mucosal engorgement and accompanied by edema of the nasal turbinates. These changes are also accompanied by hypersecretion of either very thin or very thick mucus, depending on what cells in the nose are specifically involved. Hormonal effects on nasal mucosa are frequently most prominent during pregnancy, a sustained high estrogen state. Progesterone also increases during pregnancy, but the effects of this hormone on nasal mucosa are less well understood.
Pregnancy rhinitis has been defined as nasal congestion during pregnancy that lasts 6 or more weeks and is not associated with other signs of respiratory infection or known allergy.[30] Pregnancy rhinitis affects approximately 20% of pregnant women.[31] The onset of pregnancy-associated rhinitis typically begins by the second month of pregnancy, and may persist to term. The condition typically resolves 1 to 2 weeks following delivery. A recent study in Sweden showed that the incidence of rhinitis was markedly increased in smokers, but not in individuals with a history of hay fever or asthma.[32]
The exact pathophysiology of pregnancy rhinitis is not known, but it is thought to be multifactorial.[31] In addition to rising estrogen and progesterone levels, there is an increase in glandular secretions from goblet cells, the cells on the surface of nasal mucosa that normally secrete protective mucus. In addition to an increased amount, the viscosity of secretions is changed during pregnancy. The increased secretions from the goblet cells are also accompanied by vasodilation. The increased blood volume associated with pregnancy may also play a role.[2] Testing of the mucociliary function in pregnant women has also shown that transport speed was higher in women with pregnancy rhinitis, and reduced in women without this condition.[31]
Lynch noted that pregnant women are also at increased risk for allergic rhinitis and have a 6-fold increased risk for rhinosinusitis. Why this risk increases during pregnancy is uncertain, but may be related to the estrogen-associated vascular engorgement that causes retention of mucus. In turn, the retained mucus can increase the risk of infection.
Case Study: A Young Woman Taking Oral ContraceptivesThe patient was a 31-year-old white female, living with 3 children in a nonsmoking household. She presented with a chief complaint of chronic nasal congestion. She had a past history of "sinus" problems and had been prescribed 4 courses of antibiotics over the past 6 months, ranging from first generation to fourth generation antibiotics. These treatments were accompanied by 3 bouts of yeast vaginitis. She had a questionable allergy history, and was very frustrated by the healthcare system in general since she believed that she was not getting any better. Current medications included daily Claritin, Ortho-Tri-Cyclen for contraception, NSAIDs for relief of pain from nasal congestion, and Afrin nasal spray. She had a nasoseptal reconstruction several years previously following a motor vehicle accident, and a tonsillectomy in childhood. Allergy testing as teenager indicated that she was weakly positive for molds and dust, but she elected not to undertake immunotherapy. There were no known allergies to medication.
Symptoms included a chronic nasal congestion that got worse 4-5 days before menses, a moderate to severe postnasal drip without any nasal discharge, and diffuse frontal headaches. She denied facial or dental pain.
Mild allergic shiners (vascular pooling under the eyes that is indicative of allergy) were seen on physical exam. Other findings included a nondeviated septum, pale boggy nasal mucosa, and swollen turbinates. Clear discharge from the postnasal drip was noted in the posterior pharynx.
Skin and RAST testing were negative, as were sinus films and a screening computed tomography. Nasal cultures showed no bacterial growth.
Differential diagnoses included allergy, rebound from chronic use of nasal spray (rhinitis medicamentosa), and chronic rhinosinusitis.
The final diagnosis was an estrogen-induced rhinitis, related to use of OCs, with an overlay of perennial mild allergic rhinitis. As a general rule, Lynch recommended assessing any hormonal preparation patients are taking, and decreasing or eliminating estrogen content if possible. For this patient, it was also important to discontinue the chronic use of OTC nasal spray. This can be aided by use of a 5-day course of oral corticosteroids, and concurrent but decreasing use of an intranasal steroid spray.
With respect to this particular patient, Lynch noted that NSAIDs may also cause nasal congestion. Use of aspirin, beta-blockers, antidepressants, and anxiolytics (particularly alprazolam) has also been associated with increased nasal congestion.
SummaryMigraine is a difficult condition to treat successfully under the best of circumstances. Migraines associated with hormonal fluctuations may be even more challenging. Providing patients with education about their condition and treatments and enlisting them as a partner in what may be a lengthy process of trial and error to arrive at the optimal treatment approach can contribute to a positive outcome.
The association between hormonal changes and rhinitis is an important area for research. There is currently only 1 ongoing study assessing the effect of hormones on nasal reactivity in women. Hopefully, there will be more data in the next decade that will further define the etiology, and lead to successful intervention for hormonally related rhinitis.
http://www.medscape.com/viewarticle/420181
And yes, I have MAJOR post nasal drip - I am even taking allergy shots (immunotherapy)! I thought I had allergy problems so I started immunotherapy several months ago, only to learn that the allergies are really menopause induced. Now I don't know if I should stay with the immunotherapy or bail on it! I've already got so much invested - I've received 2 shots a week for 6 months, and 1 shot a week for a few months and still continue one a week. 
So, I too, cut all kinds of food from my diet - I was even checking ALL labels on my food when grocery shopping to make sure I didn't have any of the MSG derivatives in the food. This made grocery shopping, cooking, etc a MAJOR chore. I did this for 6 months - on a super strict migraine diet. But of course, the migraines didn't stop coming. Why, oh why, didn't the doctor just simply say, "Migraines which occur later in life in women are most likely the result of hormonal fluctuations due to perimenopause." 