Menstrual Migraines...Are Your Migraines Caused by This Common Imbalance?
What Are Menstrual Migraines?
Menstrual migraines (MM) are a particular subtype of migraine that usually occur without aura in a predictable association with menstruation. MM generally occur within a 5-day window, spanning 2 days before the onset of menses through to day 3 of bleeding. These types of migraine are arguably the most common disabling condition encountered in women’s health as they are considered to be the most severe, last the longest and be the most resistant to standard treatment. MM can also occur alongside other symptoms including PMS (premenstrual syndrome), dysmenorrhea (painful menstruation) and nausea.
MM are divided into pure MM, accounting for less than 10% of migraines in women, and the more common menstrual-related migraines (MrM), which affect over 50% of female migraineurs. Pure MM occur only with menstruation whereas MrM occur both with menstruation and during the rest of the menstrual cycle.
Women in their 40s are most affected by MM, and the age range most at risk are women between 35 and 45 years old. Following menarche (the beginning of menstruation), the incidence and prevalence of migraine increases in girls and continues to increase until their mid-40s. Migraines as a whole affect 3 times as many women as men (post puberty). The cause of this increased prevalence is thought to be due to a genetic predisposition to migraines, which is triggered by fluctuating female sex hormones, among other non-hormonal triggers.
Menstrual Migraine Triggers
The key MM trigger appears to be sharp falls in oestrogen, which occur either during the natural menstrual cycle (around the time of menstruation), from taking hormonal contraceptives or in relation to the menopausal transition. Oestrogen is an important modulator in the body so a sudden decline can impact neurotransmitter systems and in particular the trigeminal nerve, a major pain pathway, leading to heightened sensations of pain. The normal release of inflammatory mediator prostaglandin during the first 48 hours of menstruation has also been implicated. Prostaglandins promote inflammation, muscle contractions (menstrual cramps), blood vessel constriction and pain, and they are released in large quantities by the endometrial cells that form the lining of the uterus during menstruation.
There are no tests available to confirm MM so the only accurate way to diagnose the condition is to keep a symptom diary for at least three months to ascertain a possible connection between migraine attacks and the menstrual cycle. This is also usual for identifying any non-hormonal triggers such as particular foods or lack of sleep.
As illustrated in the diagram below, showing the hormonal fluctuations during a healthy menstrual cycle, both oestrogen and progesterone are at their lowest levels just before and during menstruation, when MM tend to strike. Women who experience MM seem to have a greater % fall in oestrogen before menstruation and at the same time are more sensitive to migraine triggers such as stress, lack of sleep and certain foods. The combination of the rapid fall in oestrogen levels along with a particular trigger is thought to cause the MM.
Diagram 1: Hormonal Fluctuations During A Normal Menstrual Cycle
The question then becomes, why do these women experience a greater % fall in oestrogen in the first place and also why are they more sensitive to certain migraine triggers. Given the number of complex interactions that take place within the body, there are a whole host of factors to consider, however they mostly relate to excessive levels of oestrogen relative to progesterone. Important points to consider for each case of MM include:
1. An over-burdened liver; such as from a high toxic load or excessive alcohol consumption can lead to hormonal imbalances as the liver is responsible for metabolising most of the body’s hormones, preparing them for excretion from the body.
2. Gut dysbiosis; the gut microbiome, specifically the ‘estrobiome’, helps to regulate circulating oestrogen using the enzyme beta-glucuronidase. However with an imbalanced microbiome, such as with bacterial or candida over-growth, these enzymes cannot metabolize oestrogens properly so they are reabsorbed into the bloodstream via enterohepatic recycling rather than excreted.
3. Certain dietary & lifestyle factors; such as antibiotic use, poor nutrition and insufficient fibre intakes disrupt the bodily systems involved in the production, metabolism and excretion of oestrogen, including the gut microbiome and estrobiome, as well as other toxins in the body.
4. Glutamate accumulation; is strongly associated with migraines, with brain levels of glutamate found to be higher in migraineurs, particularly during attacks. Glutamate is the most important and widely distributed excitatory neurotransmitter in the central nervous system and substantial evidence connects it with migraine pathophysiology. Oestrogen and progesterone are important regulators of glutamate, and help to prevent it from accumulating. Interestingly, both magnesium and the migraine drug topiramate target glutamate receptors to prevent migraines.
5. Histamine intolerance or overload; is often observed in cases of high oestrogen. Substantial evidence shows that histamine may elicit, maintain and aggravate migraines to play a crucial role in migraine pathogenesis via the neurogenic inflammation pathway. Oestrogen triggers mast cells to release histamine and it also down-regulates the DAO enzyme, which breaks down histamine. Conversely progesterone is needed to upregulate DAO (see my separate blog post for more on this topic!)
6. Hormonal therapies; such as the oral contraceptive pill and hormonal replacement therapy (HRT) contain synthetic forms of oestrogen which increase the body’s oestrogen levels while depleting progesterone. Synthetic hormones can also be quite toxic as they are not easily metabolized by the liver (therefore contribute to an over-burdened liver) while also depleting the body of essential nutrients and disrupting the gut microbiome.
7. Stress; chronic stress depletes progesterone as the body uses progesterone instead to make the stress hormone cortisol during times of stress. High cortisol levels also disrupt the functioning of the hypothalamic-pituitary-gonadal axis, causing increased levels of oestrogen and less progesterone. Stress also depletes zinc, which is needed to make progesterone, and as zinc is depleted copper levels rise, which leads to both more oestrogen and histamine.
8. Mineral deficiencies; both zinc and copper are required at certain levels for the proper functioning of oestrogen and progesterone. Elevated copper levels along with corresponding low levels of zinc (due to their reciprocal relationship) are often seen in cases of high oestrogen.
9. Excess body fat; especially when stored in the hips, waist and thighs, is one of the leading causes of oestrogen dominance. Not only does fat tissue absorb and store oestrogen circulating in the bloodstream, it also synthesizes new oestrogen. In addition, high levels of oestrogen stimulate the body to produce more fat cells, which then synthesise even more oestrogen in a vicious cycle. Obesity is also linked with insulin resistance, which promotes increased aromatase activity (to convert androgens such as testosterone to oestrogen) as well as uncontrolled inflammation.
10. Endocrine-disrupting xenoestrogens; these industrial chemicals that mimic oestrogen, including widely used PCBs, BPA and phthalates, are found in increasingly larger quantities in our environment from plastics and pesticides (therefore our food and water!) to soaps, clothing and flame-retardant materials. By exerting an oestrogenic effect in the body, xenoestrogens imbalance hormones and can suppress ovulation thereby preventing progesterone production.
11. Heavy metal toxicity; heavy metals such as cadmium, lead and mercury also have oestrogen-mimicking properties so can contribute to hormonal imbalances and oestrogen dominance.
Oestrogen Dominance & Migraine
Oestrogen dominance (OD), or progesterone deficiency, occurs when the normal healthy balance between oestrogen and progesterone begins to shift in favour of oestrogen. This can happen as a result of excessive oestrogen production or poor elimination, exposure to xenoestrogens, not ovulating (which is when progesterone is produced) or producing insufficient amounts of progesterone. OD can present with symptoms such as migraine, weight gain, severe menstrual cramps, heavy bleeds, irregular cycles, low libido, fatigue, mood swings, polycystic ovarian syndrome (PCOS) and endometriosis. OD also increases the risk of developing several chronic health conditions, including autoimmunity, thyroid dysfunction and some cancers.
OD is considered the most common cause of hormonal headaches and MM. Higher levels of oestrogen causes increased histamine production, which in turn leads to even more oestrogen (another very interesting topic so…another bog post!). Oestrogen also promotes fluid retention, increasing intercranial pressure; causes blood vessel constriction followed by rebound dilation; and depletes magnesium, which is essential for healthy blood vessel tone and reducing spasm.
Migraines that occur after menstruation have a very different pathogenesis to MM. These are generally caused from the menstrual blood loss which causes reduced iron levels and triggers a brief iron-deficiency anaemia. Treatment for these migraines should therefore focus on increasing iron levels from foods (e.g. organ meats, oysters, lentils) and taking a high-quality iron supplement.
Menopausal Transition & Migraine
The menopause transition period is a time of considerable and often turbulent changes in female sex hormones. The prevalence of migraine attacks generally peak during the latter part of the perimenopausal period, when periods become increasingly more erratic and often heavier, and particularly in those with a history of premenstrual syndrome and stress. These attacks often occur more frequently and sometimes last longer. Towards the end of the menopause transition however as periods lessen, migraines generally become less frequent. The cause of this increase is thought to be due to falling oestrogen levels, heavier blood flows leading to iron deficiency, disrupted sleep (a common migraine trigger) and increased prostaglandin release (causing inflammation).
The post-menopause period can be a blessing, particularly for those women who experienced MM pre-menopause, as migraine is very likely to improve. This may however take 2-3 years after a women’s final period, whilst the hormones are settling. Non-hormonal triggers can still persist after menopause though so in these instances, migraine attacks may continue.
There are plenty of natural treatments to support the menopause transition, which help to balance the female sex hormones and prevent excessive declines in their levels.
Conventional Drug Treatments
Conventional doctors and headache specialists often overlook hormonal imbalances as a possible cause for migraines so MM are usually treated the same as regular migraines. Even when doctors do recognise a hormonal element, very little is offered by way of a long-term solution, with most prescribing pain relievers or birth control pills. Unfortunately these drugs only suppress the issue and also often cause medication-rebound or oestrogen-induced headaches, as well as liver toxicity, chronic inflammation and leaky gut.
High oestrogen pills are particularly problematic for migraines and also carry a higher stroke risk for women who suffer from migraines, so these should definitely be avoided. The Mirena IUD is also associated with causing intracranial hypertension and throbbing-type headaches.
The goal of hormonal-based natural therapy is to minimize the premenstrual decline in oestrogen that is believed to precipitate MM. By reducing the magnitude of decline in oestrogen concentrations, MM can be prevented and the frequency of migraines with aura reduced (since these are associated with higher oestrogen levels).
Treatments are aimed at lowering oestrogen levels by reducing exogenous intakes, inhibiting excessive aromatase activity, which increases the synthesis of oestrogen (due to factors such as uncontrolled inflammation and nutritional deficiencies), and supporting more effective oestrogen metabolism and excretion.
Specific strategies include:
1. Maintain a healthy weight to avoid additional oestrogen production from adipose tissue
2. Avoid xenoestrogens as much as possible; use of BPA-free drink bottles (preferably glass or stainless steel), eat organic foods and choose natural beauty and cleaning products
3. Support optimal liver function to ensure proper metabolism and clearance of sex hormones
4. Address gut dysbiosis and support gastrointestinal tract integrity to ensure proper excretion of conjugated hormone metabolites, which are also toxic to the body
5. Stress management to prevent excess cortisol levels contributing to oestrogen dominance
6. Increase exercise to enhance insulin sensitivity (and for weight loss if overweight). Obesity and insulin resistance are key factors in excess aromatase activity and inflammation
7. Address mineral imbalances, particularly high copper:zinc ratio and magnesium deficiency
8. Address histamine sensitivities and/or overload by reducing histamine-containing and producing foods as well as supporting the pathways that inactivate histamine
9. Focus on eating a high fibre, low GI diet with plenty of brightly coloured plant foods and omega 3 fatty acids, while avoiding excessive omega-6 consumption and reducing trans fats. This will improve excretory pathways, reduce inflammation and increase antioxidant status
10. Increase intake of particular anti-inflammatory and antioxidant ingredients such as curcumin, resveratrol, grapeseed, fish oil and prebiotic fibre; supplementing if required
11. Increase intakes of high-quality phytoestrogens such as non-GMO soy isoflavones as “weak” dietary phytoestrogens can reduce and even prevent MM associated with the physiological oestrogen decline. Commence consumption 3-4 days pre-menstrually until day 3 of the cycle
12. Take oestrogen-modulating herbal medicines such as Hops, Red Clover and Dong Quai in the lead up to menstruation as a prophylactic preventative treatment for MM
13. Use natural progesterone (in capsule or cream form) to counter oestrogen dominance and prevent MM. Bioidentical progesterone calms the brain, reduces histamine and shelters the brain from oestrogen declines. Note that hormonal contraceptives contain synthetic progestins rather than progesterone, which do not offer the same benefits (and often have adverse effects in the body, opposite to the protective effects of progesterone)
14. Address heavy metal toxicity using relevant tests such as hair mineral analyses, followed by a specific metal detoxification treatment protocol to resolve the toxicity
15. Use seed cycling during the menstrual cycle to help rebalance the female sex hormones: eat 1-2 tablespoons each of raw, fresh ground flaxseeds and pumpkin seeds during Days 1-14; and eat 1-2 tablespoons each of raw, fresh ground sunflower and sesame seeds during days 15-28 (adjusted for the actual menstrual cycle duration) (more detailed blog post to follow!)
Experiencing MM or any form of hormonal headache is more than just a monthly inconvenience, they are a real sign by the body that there is an underlying imbalance, which needs to be addressed. It really is important that sufferers seek to resolve the problem rather than just suppressing the symptoms with a pharmaceutical band-aid. Talk to your local natural health practitioner who will be able to support you in regaining your health and well-being, and hopefully make you migraine-free! 😊
Bonds, R. S., & Midoro-Horiuti, T. (2013). Estrogen effects in allergy and asthma. Current Opinion in Allergy and Clinical Immunology. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3537328/
Briden, L. (2016). The Curious Link Between Estrogen and Histamine Intolerance. Retrieved August 15, 2016 from http://www.larabriden.com/the-curious-link-between-estrogen-and-histamine-intolerance/
Calhoun, A. (2010) The Gynecologist’s Role in Managing Menstrual Migraine. Clinical Review. OBG Management. 2010 April;22(4):30-42
Ede, G. (n.d.). Histamine Intolerance: Understanding the Science. Retrieved August 15, 2016 from http://www.diagnosisdiet.com/histamine-intolerance-science/
Gasparini, C. F., & Griffiths, L. R. (2013). The biology of the glutamatergic system and potential role in migraine. International journal of biomedical science : IJBS, 9(1), 1–8.
Hoffmann, J., Charles, A. Glutamate and Its Receptors as Therapeutic Targets for Migraine. Neurotherapeutics 15, 361–370 (2018). https://doi.org/10.1007/s13311-018-0616-5
Maintz, L., Schwarzer, V., Bieber, T., van der Ven, K., & Novak, N. (2008). Effects of Histamine and diamine oxidase activities on pregnancy: a critical review. Human Reproduction Update, 14(5), 485-495. http://humupd.oxfordjournals.org/content/14/5/485.full
Marrion, G. (2018) The Relationship Between Histamine, Oestrogen, Progesterone and Cortisol. fxMedicine.com
Munoz-Cruz, S., Mendoza-Rodriguez, Y., Nava-Castro, K., Yepez-Mulia, L., & Morales-Montor, J. (2015). Gender-Related Effects of Sex Steroids on Histamine Release and FcεRI Expression in Rat
National Clinical Guideline Centre (UK). Headaches: Diagnosis and Management of Headaches in Young People and Adults. London: Royal College of Physicians (UK); 2012 Sep. Prophylactic pharmacological treatment of menstrual migraine. www.ncbi.nlm.nih.gov/books/NBK327493/
Peritoneal Mast Cells. Journal of Immunology Research, 2015 (2015). http://www.hindawi.com/journals/jir/2015/351829/
Sullivan, E., & Bushnell, C. (2010). Management of menstrual migraine: a review of current abortive and prophylactic therapies. Current pain and headache reports, 14(5), 376–384. https://doi.org/10.1007/s11916-010-0138-2
Witteveen, H., van den Berg, P., & Vermeulen, G. (2017). Treatment of menstrual migraine; multidisciplinary or mono-disciplinary approach. The journal of headache and pain, 18(1), 45. https://doi.org/10.1186/s10194-017-0752-z
Yuan, H. and Silberstein, S.D. (2018), Histamine and Migraine. Headache: The Journal of Head and Face Pain, 58: 184-193. doi:10.1111/head.13164
Zierau, O., Zenclussen, A. C., & Jensen, F. (2012). Role of sex hormones, estradiol and progesterone, in mast cell behavior. Frontiers in Immunology, 3(169). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377947/
Zlotnik, A. et al (2011) The Effects of Estrogen and Progesterone on Blood Glutamate Levels: Evidence from Changes of Blood Glutamate Levels During the Menstrual Cycle in Women, Biology of Reproduction, Volume 84, Issue 3, 1 March 2011, Pages 581–586, https://doi.org/10.1095/biolreprod.110.088120