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[PDF] Estrogeneration: How Estro


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It appears that estrogen is very likely to play a key role in migraine pathogenesis, but seems to affect patients in different ways depending on their past medical history, age, and use of hormonal therapy. Further research is warranted to isolate the effects of estrogen in each unique patient population, and we believe that studies comparing menstruating women to postmenopausal women could help shed light in this area.


As migraines are more frequent among females, a variety of hormones have been implicated in their pathogenesis; specifically, prior research has repeatedly shown evidence linking estrogen to migraine headaches [5]. Pringsheim highlighted this association when they found that the prevalence of migraines in male-to-female transgender individuals taking estrogen therapy was similar to the prevalence of migraines in females, and far higher than that in males [6]. Although numerous studies have suggested that estrogen plays a leading role in migraine pathogenesis, its specific role has yet to be fully understood. The purpose of this review is to investigate the specific roles of estrogen in the pathophysiology of migraine headaches to give providers and patients a better understanding of migraine pathology, treatment options, and areas of potential future research.


In our literature search, our primary focus was to find studies that investigated the role of estrogen in the pathogenesis of migraine. We kept our search broad and utilized the inclusion and exclusion criteria below to narrow down search results in accordance with our predetermined PICO framework.


A scoping review was undertaken to identify studies pertaining to estrogen and migraine headaches. PupMed and EMBASE were searched for articles published in the English language using keywords and the respective MESH and PICO search engines. Our data collection and extraction is highlighted below in Table 1 and the PRISMA 2009 Flow Diagram.


The PICO engine of EMBASE was utilized in order to retrieve articles. Our search terms included [transformed migraine OR migraine], [estrogen], [chronic OR persistent OR recurrent] and were kept purposefully broad in order to return as many relevant papers as possible. Suggested synonyms for each term were selected to be included in the search. Papers were then screened in accordance with our PICO framework and inclusion/exclusion criteria to narrow down the search results.


General searches were also conducted on PUBMED using the keywords migraine, estrogen, sex hormones, menstrual migraine, menstrual-associated migraine, menstrual-related migraine, migraine and estrogens, migraine and sex hormones, estrogen and headaches, and sex hormones and headaches. Bibliographies of relevant articles were also examined in order to identify other potentially pertinent articles.


A total of 246 studies were imported for initial screening. Abstracts were initially screened by two blinded reviewers. Each reviewer screened each abstract, and studies that were agreed on by both reviewers advanced to full-text screening. Seventy-seven full-text studies were reviewed by the two blinded reviewers. Each reviewer screened each full-text article and studies deemed appropriate by both reviewers were included in the final review. After excluding any nonclinical studies as well as studies that did not directly study estrogen, 19 studies were included in the final review. This process is summarized in the PRISMA flow diagram in Fig. 1. A summary of findings can be seen in Table 2.


Three studies assessed the effects of hormone replacement therapy (HRT) on migraine in postmenopausal women with results varying by estradiol dosing, but generally concluding that estrogen replacement increased the incidence of migraine [8, 11, 23]. Three other studies found that women with a history of migraine had an increased sensitivity to physiologic fluctuations in estradiol levels [12, 16, 21]. Lastly, four survey/diary-based studies suggested that migraines most




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