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Risk of high frequency migraine increases by 40-60% during perimenopause and menopause - "Are you ready for the ride of your life?" -What you need to know 

"Do not become alarmed when you experience yourself in totally new ways," sighs Grandmother Growth, tenderly. "You are changing, getting ready to be initiated into the third stage of your life. Are you ready for the ride of your life? -Susan Weed, Menopausal Years the Wise Woman Way

Menopause marks a major life transition for women, an end to our reproductive years and the cessation of menses. While the end to menstruation and the fear of an unwanted pregnancy may be welcomed by some, others may experience a sense of loss as their last opportunity for conception disappears. Many women may have concerns about cognition and memory, mood disorders, weight gain, increased signs of aging like wrinkles, curtailed sexuality, and decreased libido.

For those of us with migraine, "the ride of our lives" may come with additional challenges. A new study reported at the 56th Annual Scientific Meeting of the American Headache Society found the risk of high frequency migraine attacks increases by 40-60% during perimenopause and menopause for some women.

Data from the 2006 American Migraine Prevalence and Prevention (AMPP) Study survey was used for the analysis (Poster Presentation, Martin et al, 56th Annual Scientific Meeting of the AHS, 2014):

  • Women between ages 35-65 years who met the modified ICHD-3 beta criteria for migraine were included.
  • Women who had never menstruated, were pregnant, breast feeding or using exogenous sex hormones were excluded. Other exclusions included polycystic ovarian syndrome, hysterectomy, or oophorectomy.
  • Women with migraine were classified into a high frequency group if they experienced 10 or more headache days per month and into a low or moderate frequency migraine group if they had less than 10 headache days per month based on responses to the Migraine Disability Assessment Scale (MIDAS).
  • Women were classified as premenopausal (regular menstrual cycles without variation in cycle length), perimenopausal (cycle lengths varied by 7 or more days or periods of amenorrhea lasting 2-11 months) and postmenopausal (absent menstrual periods for at least 12 months) based upon responses to the questionnaire.
  • Women also completed the Patient Health Questionnaire Depression module (PHQ-9) and 3) and Allodynia Symptom Checklist-12 (ASC-12).  

The study authors conclusions were as follows:

  • To our knowledge, ours is the first study to demonstrate that high frequency headache is increased by 40-60% in women during the perimenopause and postmenopause compared to the premenopause.
  • The effect of the menopause and postmenopause on headache frequency is robust to adjustment by depression and allodynia.
  • The strongest predictor of high frequency headache was depression, with odds of high frequency headache being 131% higher for those with depression than without.
  • It is quite likely that the changes in ovarian hormones that occur during the perimenopause and the early postmenopause trigger headaches in these women.

"Persistance in scientific research leads to what I call instinct for truth." -Louis Pasteur

In a press release from the  AHS, Dr. Martin, study lead author, is quoted as saying, "These results validate the belief by many women that their headaches worsen during the transition into menopause." He adds, "We hope our work spurs researchers to develop novel treatments for migraine during this period given that many of the headaches encountered are thought to be hormonally triggered." Dr. Richard Lipton, study co-author adds, "We believe that both declining estrogen levels that occur at the time of menstruation as well as low levels that are encountered during the menopause are triggers of migraine in some women."

To appreciate the significance of the results and conclusions in this study, as well as the implications these findings have for our unique journeys with migraine, this article addresses:

  • the influence of estrogen on migraine.
  • depression and migraine.
  • association of allodynia in migraine with mood disorders and other chronic pain conditions.
  • perimenopause, menopause and migraine.

The influence of estrogen on migraine

Although the association between estrogen and migraine warrants further research, some of the explanations of how estrogen influences migraine that we need to be aware of include:

  • Genetic predisposition (MacGregor, 2010, Sacco et al, 2012). 
  • Estrogens may interfere with cellular excitability (MacGregor, 2009, Sacco et al, 2012). 
  • Estrogen is thought to influence the pain pathway associated with migraine by binding to its receptors on the trigeminal nerves. The trigeminovascular system consists of a network of cranial vessels and their trigeminal innervations that convey pain information to the central nervous system where pain is perceived. The pain response increases by the release of vasodilating neuropeptides especially calcitonin gene-related peptide-CGRP (Milan, 2012, and Sacco et al, 2012).
  • There is an interrelationship between estrogen and brain neurotransmitters, including serotonin, dopamine, norepinephrine, and endorphins. In particular, estrogen is believed to have a potent effect on the serotonergic system (Sacco et al, 2012).
  • Estrogen is associated with increased production of serotonin, reduced serotonin reuptake and decreased serotonin degradation (MacGregor, 2010).
  • Low serotonin levels have been linked to migraine.
  • Because serotonin enhances endorphins (natural analgesic found in the gray matter of the brain), low levels can increase sensitivity to pain. 

Depression and migraine

At this point, it is helpful for us to take a quick look at serotonin. Serotonin is a neurotransmitter in our brain important for managing mood, appetite, sleep and dreaming. For example, high levels make make us feel full, calm, relaxed and even drowsy. Low levels may cause us to feel anxious, irritable and depressed. 

Given the strongest predictor of high frequency headache in this study was depression, we need to know that several studies have linked migraine with mood and anxiety disorders. Some studies suggest mood and anxiety disorders are 2-10 times more prevalent among persons with migraine (comorbid) than in the general population. As well, increased migraine frequency (chronic migraine) is associated with higher rates of depression. (Buse et al, 2012). It has been suggested:

  • serotonergic and dopaminergic dysfunction underlies the comorbidity of depression and migraine (Buse et al, 2012), and
  • "conditions that are comorbid with migraine such as depression and anxiety have presumptive serotonergic mechanisms "(Shapiro, 2008, p 29).

Keeping these things in mind, we also need to be aware that a recent study on "Depression in women: windows of vulnerability and new insights into the link between estrogen and serotonin", (Lokuge, 2011), suggests the effects of estrogen on serotonin may have implications on female mood disorders such as premenstrual disorders and depression during pregnancy, postpartum, and during the menopausal transition.

Association of alloydynia in migraine with mood disorders and other chronic pain conditions

Now, let's peek at cutaneous allodynia (CA). CA is thought to be a result of central nervous system sensitization, which makes us hyperresponsive to otherwise innocuous tactile stimuli. For example, it may hurt to brush our hair or try to put it into a ponytail. As an attack progresses, we may experience sensitivity on extracranial locations such as the arm (Shapiro, 2008, p. 30).  Here, we should be aware that in an estimation of the prevalence and severity of  CA in headache sufferers, results of the AMPP Study (2008) showed CA was more common among migraineurs with female sex, high attack frequency, increased body mass index, disability and depression. 

That said, in a study examining the relationship of migraine with comorbid mood disorders and other chronic pain conditions, (Tietjen et al, 2009), results demonstrated symptoms of CA in migraine were associated with current anxiety, depression, and several chronic pain conditions, including irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome.   

Peri-menopause, menopause and migraine

Holding on to what we have learned so far, it's time to review some general information about perimenopause, menopause, and migraine. To begin with, let's take a brief look at what happens to every women during perimenopause and menopause.

We need to know that as we age and enter perimenopause, our ovaries lose their ability to undergo ovulation and produce estrogen and progesterone. Our pituitary gland, via the hypothalamic-pituitary-ovarian axis, attempts to compensate by releasing follicle-stimulating hormone (FSH) to stimulate an ovarian follicle to produce estrogen. Transient increases of estrogen can occur during this time as FSH surges to stimulate remaining follicles. Menstrual irregularities occur, with sometimes prolonged and heavy menstruation mixed with periods of amenorrhea. When no more follicles remain for stimulation, estrogen levels dramatically decline and menstruation ceases.

Approximately 75-80% of women experience perimenopausal and menopausal symptoms.  Sources vary, but, in general, symptoms are thought to emerge up to 4 years prior to cessation of menses (perimenopause) and may persist for several years postmenopause. Symptoms are believed to be related to the withdrawal of estrogen. Many of them are thought to be associated with resultant changes in the central nervous system neurotransmitters, including serotonin, dopamine and norepinephrine.; and, serum electrolytes, including calcium, magnesium, sodium and potassium. They include:

  • Vasomotor disturbances ("hot flashes", "night sweats"). Although the exact cause is not known, vasomotor disturbances are believed to be caused by a narrowing of the thermoneutral zone in the brain related to the central nervous system neurotransmitters (Archer et al, 2011). In other words "our thermostat is broken". The feeling of intense heat that begins in our upper chest or neck, proceeds up to our face and head and may spread throughout our body, can last for several seconds or minutes and be accompanied by profuse perspiration. When "hot flashes" occur at night, they interrupt our sleep (insomnia). We need to know that they can be precipitated by heat, alcohol, spicy foods, and stress.
  • Sleep impairment.
  • Fatigue.
  • Depression, irritability and other mood disturbances.
  • Cognitive difficulties (loss of concentration, poor memory).
  • Weight gain. Numerous factors may be involved, including decreased metabolism; decreased serotonin levels, with resultant increase in food cravings; and, increased sympathetic nervous system activity, with resultant fluctuation in hormones like cortisol. It is important for us to know that weight gain during this period is often associated with fat deposit in the abdomen, which can increase our risk for developing insulin resistance, diabetes, hypertension and heart disease. Hypothyroidism may become prevalent and exacerbate symptoms like fatigue, weight gain, and mood changes.
  • Sexual dysfunction, including decreased libido.
  • Urinary incontinence.
  • Musculoskeletal pain.
  • Osteoporesis.

Now, let's relate these symptoms to migraine. As you can see, many of these symptoms are the same as (and may be easy to confuse with and exacerbate) migraine triggers (e.g., sleep impairment and fatigue), migraine symptoms (e.g. cognitive difficulties, musculoskeletal pain), and comorbidities (e.g. depression and anxiety).

To add to our discomfort, perimenopause and menopause are the very busiest years of our lives. Many of us are juggling family and career responsibilities, or perhaps, financial worries about college for our children and retirement for ourselves and our partners. The added stress can contribute to migraine as a trigger and a factor that makes us more susceptible to all of our triggers. When chronic, stress can deplete our estrogen levels, decrease our serotonin levels, increase anxiety and depression, and increase the frequency of our attacks. In addition, chronic stress may precipitate an earlier perimenopause and menopause.

"Are you ready for the ride of your life"?

Given I went through a surgical menopause at the age of 42 because of an ovarian cancer scare, I was not prepared for the "ride of my life". Twelve years later, I was diagnosed with chronic migraine, accompanied by medication overuse headaches.

Acknowledging surgical menopause has more severe consequences, to help you prepare and "cushion your ride" through a natural perimenopause and menopause, along with an accurate diagnosis for migraine, it would seem appropriate for you to know where you sit in the menopausal transition:

  • "Despite the increased prevalence of headache and migraine in women in their 40s, migraine is underdiagnosed in this population" (MacGregor, 2009).
  • If you have symptoms suggestive of perimenopause and menopause, along with headaches and other symptoms of migraine, it is important to talk to your doctor about all of your symptoms so they can be managed effectively, with the potential to reduce progression to chronic migraine, comorbidities like depression, unpleasant symptoms such as allodynia, and resultant disability. Blood tests to measure FSH and estrogen levels can determine where you are at in the menopausal transition.
  • The lack of an accurate diagnosis for migraine has been shown to be a barrier to our care,  which may include pharmacological and non-pharmacological interventions. (Buse. et al, 2014).

That said, while we wait for novel treatments to emerge, current pharmacological and non-pharmacological  management of migraine in perimenopause and menopause addresses the same issues as management of migraine at any time, with perhaps the addition of hormone replacement therapy (HRT) at the lowest dose possible to maintain a stable estrogen environment (MacGregor, 2012). It is important for you to know that the benefits and risks of HRT vary with the individual and warrant a thorough discussion with your physician.

In  conclusion, keep in mind our migraine brain likes peace and harmony (homeostasis). Avoiding your other migraine triggers, maintaining a healthy diet and lifestyle habits, and participating in a regular exercise program, along with stress management strategies like mind-body and relaxation techniques, and other modalities like acupuncture, can help you decrease the influence of perimenopause and menopause on your migraine attacks, take control of your attacks and, as I do now, assist you to live a happy and healthy third stage of your life, with migraine.

Sharron :)


American Headache Society. "Women With Migraine Experience More Headaches During The Menopausal Transition: Results From The American Migraine Prevalence And Prevention (AMPP) Study." Press Release: Wednesday, June 25, 2014, !2:01 a.m. EDT

Archer, D. F., Sturdee, D. W., et al (2011). "Menopausal hot flushes and night sweats: where are we now?" Climateric.  Oct 14;(5):515-28 doi: 10.3109/13697137.2011.608596. 

Bigal, M. E., Ashina, S., et al (2008). "Prevalence and characteristics of allodynia in headache sufferers: a population study. Neurology. Apr 22;70(17):1525-33. doi: 10.12/01.wnl.000031064

Buse, D. C., Silberstein, S. D., et al (2013). "Psychiatric comorbidities of episodic and chronic migrane." J. Neurol. Aug;260(8):1960-9. doi: 10.1007/s00415-012-6725-x.

Buse, D. C., Lipton, R., et al (2014). "Barriers to Chronic Migraine Care: Results of the CaMEO (Chronic Migraine Epidemiology & Outcomes) study." Poster presented at the 66th Annual Academy of Neurology Annual Scientific Meeting, Philadelphia, PA. April26-May 3.

Edyta, J. Frackiewicz, N. R., Cutler. (2000). "Women's Health Care During the Perimenopause." J Am Pharm Assoc. 40(6).  

Lanje, M. A., Dr., Bhutey, A. K., Dr. et al (2010). "Serum Electrolytes During Different Phases of Menstrual Cycle." International Journal of Pharma Sciences and Research.  Vol.1(10), 435-437. ISSN: 0975-9492.

Lokuge, S., Frey, B. N., et al (2011). "Depression in women: windows of vulnerability and new insights into the link between estrogen and serotonin." J Clin Psychiatry.  Nov;73(11):e1563-9. doi: 10.4088/JCP.11com07089.  

MacGregor, E. A. (2009). "Estrogen replacement and migraine." Maturitas. May 20;63(1):51-5. doi: 10.1016/j.maturitas.2009.03.016.   

MacGregor, E. A. (2009). "Migraine Headache in perimenopausal and menopausal women. " CurrPain Headache Rep. Oct;13(5):399-403.

MacGregor, E. A. (2010). "Menstrual Migraine: Therapeutic Approaches." Ther Adv Neurol Disord.  May;3(3):197.

MacGregor, E. A. (2012). "Perimenopaual migraine in women with vasomotor symptoms." Maturitas. Jan;71(1):79-82. doi: 1016/j.maturitas.2011.11.001.

Martin, V. T., Pavlovic, M. J., et al (2014). "The menopausal transition is associated with higher headache frequencies in women with migraine: Results from the American Migraine Prevalence and Prevention (AMPP) Study." Poster presented at the 56th Annual Meeting of the American Headache Society. Los Angeles, CA. June 25-29th. 

Milan, A., Puri, V., Puri, S., PhD.(2012). "Effects of estrogen on the serotonergic system and calcitonin gene-related peptide in trigeminal ganglia of rats." Ann Neurosci. Oct;19(4): 151-157. doi: 10.5214/ans.0972.7531.190403.

Murray, S., M.S., R.N. Migraine: Identify Your Triggers, Break Your Dependence on Medication, Take Back Your Life-An Integrative Self-Care Plan For Wellness. San Francisco: Conari Press, 2013.

Sacco, S., Ricci, S. et al (2012). "Migraine in women: the role of hormones and their impact on vascular diseases." J Headache Pain. Apr;13(3): 177-189. doi: 10.1007/s10194-012-0424-y.

Shapiro, R. E. (2008). "Pathophysiology and Genetics of Migraine and Cluster Headache." In M. Levin (Ed.), Comprehensive Review of Headache Medicine. (pp 21-32). New York: Oxford University Press.

Tietjen, G. E., Brandes, J. L., et al (2009). Allodynia in migraine: association with comorbid conditions." Headache. Oct;49(9): 13333-44. doi: 10.1111/j.1526-4610.2009.01521.x.

Sharron is a health and wellness author. A person with migraines herself, her most recent book is, "Migraine..."

Follow Sharron on twitter @murraysharron, her Facebook page SharronMurray, MS, RN, and her website

This article is not intended as a subsitute for medical advice. If you have concerns about your health or nutrition, please see a qualified professional.

Copyright, October: 2014, Sharron E. Murray 

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