Headache is among the most common neurological conditions with a current worldwide prevalence in the general population of 47%.1 The Global Burden of Disease Study 2015 ranks headache disorders (migraine, tension type headache, and medication overuse headache) as the third leading cause of life lost to disability worldwide in the 15- to-49 age group.2 Women have more frequent headaches, in part because of the higher prevalence of migraines in them (18%) compared to men (6%).3 Hormonal fluctuations during adolescence, pregnancy, and menopause, as well as use of oral contraceptive (OC) pills and postmenopausal hormone therapy are known to impact migraine frequency and intensity throughout a woman’s lifetime. This article reviews how migraines in women are impacted by the fluctuating hormone levels they experience throughout their lifecycle.
Migraine is characterized as recurrent moderate to severe headache made worse with activity and associated with sensitivity to light, sound, nausea and vomiting.4 Approximately 1 in 4 migraineurs have aura, which are fully reversible visual, sensory, or speech symptoms lasting between 5 and 60 minutes prior to onset of head pain. Visual symptoms are most common and may include either loss of vision or additional symptoms such as lights, lines spreading peripherally, or a combination of loss of vision and additional symptoms. Sensory symptoms include spreading numbness or tingling and speech disturbances such as word-finding difficulties.
Migraine is considered an inherited neurovascular disorder in which activation of the trigeminovascular pain pathway results in release of neuro peptides such as calcitonin gene-related peptide and substance P.3 Changes in levels of serotonin, estrogen, progesterone, melatonin and nitric oxide also influence the occurrence of migraine. Concerning features in evaluation of headache disorders that necessitate neuroimaging with magnetic resonance imaging of the brain include a significant change in attack frequency or severity and new clinical features such as changes in vision, speech, weakness, numbness, and tingling (Table 1). Other concerning features include a sudden, abrupt and quickly escalating headache, impaired alertness, confusion, and presence of systemic symptoms and secondary headache risk factors such as fever, weight loss, cancer, or retroviral disease.5
Menstrual migraines can be divided into 2 categories: pure menstrual migraine and menstrually related migraine (Table 2). About 14% of women have pure menstrual migraine, which is migraine only in association with menses with no other episodes of it throughout the month. In contrast, menstrually related migraine occurs in about 60% of women and is defined as migraines that occur consistently during the menstrual cycle in a patient who also has migraines with nonhormonal triggers throughout the month.6 The International Classification of Headache Disorders 3 Beta defines menstrual migraine as occurring from 2 days prior to onset of menses until 3 days after onset of menses.4
Menstrual migraine is thought to occur due to the abrupt drop in estrogen that occurs with menses each month, which is further supported through studies showing that perimenstrual treatment with estrogen can prevent development of menstrual migraine but not menses.7,8 Menstrual migraines typically are not associated with aura, are associated with more disability and more severe, and they usually are more resistant to treatment.6 Nonsteroidal anti-inflammatory drugs (NSAIDs), triptans—5HT1B and 5HT1D agonists that are US Food and Drug Administration (FDA)-approved for acute treatment of migraine — dihydroergotamine, combination analgesics (acetaminophen, aspirin, caffeine), and antiemetics (prochlorperazine, promethazine, metoclopramide) can be used acutely to manage migraine-related pain, photophobia, phonophobia, nausea, and vomiting.9 The goal of acute treatment is pain freedom in 2 hours and control of associated symptoms of nausea, vomiting, photophobia, and phonophobia.
When migraine frequency is greater than 6 days per month, daily preventative agents should be considered, such as propranolol, topiramate and valproate, to decrease both the number and the intensity of acute escalations.9 For women who have regular menstrual cycles with significant disability associated with menstrual migraine, short-term prophylaxis or mini-prophylaxis should be considered. The goal of short-term prophylaxis is decreasing duration, frequency, intensity, and disability of menstrual migraine. Options include using NSAIDs (naproxen) or triptans (frovatriptan, naratriptan, zolmitriptan) daily starting 2 to 3 days prior to onset of menses up to 3 to 7 days post-onset of menses. There is Level A evidence for use of Frovatriptan and Level B evidence for use of naratriptan and zolmitriptan (Table 3). Adverse effects associated with use triptans for short-term prophylaxis are similar to those seen with use of these drugs for acute treatment. Hormonal treatments can alter the menstrual cycle and, therefore, occurrence of menstrual migraines. Level C evidence exists for estradiol gel 1.5 mg or an estrogen patch used for 7 days starting from 2 to 5 days prior to onset of menses to maintain the estradiol level and prevent the estrogen drop that triggers menstrual migraine.6 Another approach is to use combined hormonal contraceptive pills continuously, eliminating placebo pills for 3 consecutive packs and eliminating menses once every 3 months. During the weeks when placebo pills are taken, patients can then be placed on short-term migraine prophylaxis. Irregular bleeding may be a complication of this protocol.6 Identifying the role that monthly hormonal fluctuations play in a patient’s headache pattern and targeting treatment to that pattern can significantly improve menstrual migraine control.