Women with Endometriosis Are More Likely to Suffer from Migraines: A Population-Based Study

Women with Endometriosis Are More Likely to Suffer

from Migraines: A Population-Based Study

Meng-Han Yang

, Peng-Hui Wang

, Shuu-Jiun Wang

, Wei-Zen Sun

, Yen-Jen Oyang

, Jong-Ling

Fuh

*

1 Department of Computer Science and Information Engineering, National Taiwan University, Taipei City, Taiwan, Republic of China, 2 Department of Obstetrics and Gynecology, Taipei-Veterans General Hospital, Taipei City, Taiwan, Republic of China,3 Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei City, Taiwan, Republic of China,4 Department of Neurology, Neurological Institute, Taipei-Veterans General Hospital, Taipei City, Taiwan, Republic of China, 5 Brain Research Center, National Yang-Ming University Schools of Medicine, Taipei City, Taiwan, Republic of China,6 Department of Anesthesiology, National Taiwan University Hospital, Taipei City, Taiwan, Republic of China,7 Graduate Institutes of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei City, Taiwan, Republic of China

Abstract

Previous research suggests that a co-morbid relationship exists between migraine and endometriosis; however, results have

been inconsistent. In addition, female hormones, which are important in the pathogenesis and management of

endometriosis, have been reported to precipitate migraine attacks and may confound the results. The aim of this

population-based cohort study was to explore the relationship between migraine and endometriosis in women of

reproductive age (18–51 years). Data were derived from the National Health Insurance Research Database of Taiwan, which

contains outpatient and inpatient records from 2000 to 2007. Our study cohort included 20,220 endometriosis patients and

263,767 controls without endometriosis. We analyzed the prevalence of migraine in these women as recorded during the

eight years of the database. Our results found that patients with endometriosis were more likely to suffer migraine

headaches compared to controls (odds ratio [OR], 1.70; 95% confidence interval [CI] [1.59, 1.82]; p,0.001). In addition, the

co-morbid association between migraine and endometriosis remained significant after the data were controlled for age and

frequently utilized hormone therapies (OR, 1.37; 95% CI, [1.27, 1.47]; p,0.001). The results of this cohort study support the

existence of a co-morbid relationship between migraine and endometriosis, even after adjusting for the possible effects of

female hormone therapies on migraine attacks.

Citation: Yang M-H, Wang P-H, Wang S-J, Sun W-Z, Oyang Y-J, et al. (2012) Women with Endometriosis Are More Likely to Suffer from Migraines: A Population-Based Study. PLoS ONE 7(3): e33941. doi:10.1371/journal.pone.0033941

Editor: Yiqing Song, Brigham & Women’s Hospital, and Harvard Medical School, United States of America Received June 29, 2011; Accepted February 21, 2012; Published March 19, 2012

Copyright: ß 2012 Yang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This study was supported in part by grants from the National Science Council of Taiwan and Taipei Veterans General Hospital (V100C-059). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.

Competing Interests: Dr. Shuu-Jiun Wang has served on the advisory boards of Pfizer, Allergan, Daichi-Sankyo and Elli Lilly Taiwan. He has received speaking honoraria from local companies (Taiwan branches) of Pfizer, Elli Lilly, Boehringer Ingelheim and GSK. He has received research grants from the Taiwan National Science Council, Taipei-Veterans General Hospital, Pfizer and MSD Taiwan.

* E-mail: jlfuh@vghtpe.gov.tw

Introduction

Endometriosis is a gynecological disorder defined by the

presence of viable, extrauterine, endometrial tissue. This tissue

arises only in women of menstrual age, can grow or bleed

cyclically, and may cause adhesions. Typical symptoms include

pelvic pain, dysmenorrhea, and infertility [1]. Endometriosis

affects 6–10% of women of reproductive age, 50–60% of women

and teenage girls with pelvic pain, and up to 50% of women with

infertility [2].

Migraine is a neurological disorder that also commonly occurs

in women of reproductive age. An important advance in the

standardization of migraine diagnosis was the publication of

operational criteria by the Headache Classification Committee of

the International Headache Society (IHS) in 1988 [3]. Physicians

diagnose migraine according to the clinical symptoms. Migraines

typically present as recurrent episodic headaches and frequently

have the following pain characteristics: a unilateral location, a

pulsating quality, moderate-to-severe intensity, and aggravation by

routine physical activity. In addition, the attacks may be associated

with nausea, photophobia, or phonophobia symptoms.

Endometriosis and migraine share many similarities in

epide-miology, pathogenesis, and the physical or psychiatric

co-morbidities that can accompany them [4,5,6,7,8]. For example,

early menarche, a well-known risk factor for endometriosis, is also

associated with an increased risk of migraine [9]. Similarly,

menorrhagia, a frequent complaint of women with endometriosis,

is also common in women with migraine, with 63% of migraine

patients reporting a recent history of menorrhagia, compared to

37% of controls [10]. In addition, migraine patients with

endometriosis are more likely to have mood and pain-related

disorders than migraine patients without endometriosis [11].

Men also suffer from migraines; however, both the age-adjusted

prevalence of migraine (among men 8% and among women 26%)

and age of onset for migraine (among men 20% in the first

decennium, and 23% in the second and third decennium; among

women 9% in the first decennium, 34% in the second, and 30% in

the third) differ significantly between men and women [12,13].

chart evidence of the prescription of female hormones (or other

drugs) does not verify that the drugs were actually taken by the

patient. Therefore, our results may have underestimated the effects

of medication on our subjects. Third, the administrative claims

data from the NHIRD did not include detailed personal

information (e.g., body mass index, living habits, or laboratory

test results), which may add confounding factors to the relation of

migraine or endometriosis. Fourth, the prevalence of migraines in

this cohort was 3.1%, which is much lower than the 14.4%

estimated prevalence for the community [13]. A previous study

suggested that many patients with migraines fail to seek medical

help [38], which may explain the discrepancy in our findings.

Nonetheless, we should use caution when applying our conclusions

to the community population as a whole. Fifth, we did not control

all the potential risk factors of endometriosis and migraine which

might influence their co-morbidities. A final limitation of our study

pertains to the treatments used for women diagnosed with

endometriosis. Transient menopause is a common consequence

of the management of endometriosis and is triggered either by the

surgical ablation of the ovarian function or the use of

menopause-inducing medications, such as gonadotropin releasing hormone

(GnRH) agonist. Unfortunately, we were unable to determine

whether the patients in our study were being treated with GnRH,

as the NHI Bureau did not cover this prescription.

In conclusion, the results of this population-based cohort study

support the existence of a co-morbid relationship between

migraine and endometriosis. This co-morbid association exists

after adjusting the influences of pelvic pain symptoms or hormone

therapies on migraine. Although endometriosis is associated with a

higher risk of migraines, additional studies are needed to delineate

the pathophysiological pathways underlying this co-morbid

relationship.

Author Contributions

Conceived and designed the experiments: MHY PHW SJW WZS YJO JLF. Performed the experiments: MHY YJO JLF. Analyzed the data: MHY PHW SJW JLF. Contributed reagents/materials/analysis tools: MHY WZS YJO JLF. Wrote the paper: MHY PHW SJW YJO JLF.

References

1. Kennedy S, Bergqvist A, Chapron C, D’Hooghe T, Dunselman G, et al. (2005) ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod 20: 2698–2704.

2. Giudice LC (2010) Clinical practice. Endometriosis. N Engl J Med 362: 2389–2398.

3. (1988) Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Headache Classification Committee of the International Headache Society. Cephalalgia 8 Suppl 7: 1–96.

4. Sepulcri Rde P, do Amaral VF (2009) Depressive symptoms, anxiety, and quality of life in women with pelvic endometriosis. Eur J Obstet Gynecol Reprod Biol 142: 53–56.

5. Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P (2002) High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod 17: 2715–2724.

6. Hagen K, Einarsen C, Zwart JA, Svebak S, Bovim G (2002) The co-occurrence of headache and musculoskeletal symptoms amongst 51 050 adults in Norway. Eur J Neurol 9: 527–533.

7. Levy D, Burstein R, Strassman AM (2006) Mast cell involvement in the pathophysiology of migraine headache: A hypothesis. Headache 46 Suppl 1: S13–18.

8. Buse DC, Manack A, Serrano D, Turkel C, Lipton RB (2010) Socio-demographic and comorbidity profiles of chronic migraine and episodic migraine sufferers. J Neurol Neurosurg Psychiatry 81: 428–432.

9. Aegidius KL, Zwart JA, Hagen K, Dyb G, Holmen TL, et al. (2011) Increased headache prevalence in female adolescents and adult women with early menarche. The Head-HUNT Studies. Eur J Neurol 18: 321–328.

10. Tietjen GE, Conway A, Utley C, Gunning WT, Herial NA (2006) Migraine is associated with menorrhagia and endometriosis. Headache 46: 422–428. 11. Tietjen GE, Bushnell CD, Herial NA, Utley C, White L, et al. (2007)

Endometriosis is associated with prevalence of comorbid conditions in migraine. Headache 47: 1069–1078.

12. Rasmussen BK (1993) Migraine and tension-type headache in a general population: precipitating factors, female hormones, sleep pattern and relation to lifestyle. Pain 53: 65–72.

13. Wang SJ, Fuh JL, Young YH, Lu SR, Shia BC (2000) Prevalence of migraine in Taipei, Taiwan: a population-based survey. Cephalalgia 20: 566–572. 14. Brandes JL (2006) The influence of estrogen on migraine: a systematic review.

JAMA 295: 1824–1830.

15. Misakian AL, Langer RD, Bensenor IM, Cook NR, Manson JE, et al. (2003) Postmenopausal hormone therapy and migraine headache. J Womens Health (Larchmt) 12: 1027–1036.

16. Massiou H, MacGregor EA (2000) Evolution and treatment of migraine with oral contraceptives. Cephalalgia 20: 170–174.

17. Aegidius K, Zwart JA, Hagen K, Schei B, Stovner LJ (2006) Oral contraceptives and increased headache prevalence: the Head-HUNT Study. Neurology 66: 349–353.

18. Lichten EM, Bennett RS, Whitty AJ, Daoud Y (1991) Efficacy of danazol in the control of hormonal migraine. J Reprod Med 36: 419–424.

19. Harris M, Kaneshiro B (2009) An evidence-based approach to hormonal contraception and headaches. Contraception 80: 417–421.

20. Ferrero S, Pretta S, Bertoldi S, Anserini P, Remorgida V, et al. (2004) Increased frequency of migraine among women with endometriosis. Hum Reprod 19: 2927–2932.

21. Nyholt DR, Gillespie NG, Merikangas KR, Treloar SA, Martin NG, et al. (2009) Common genetic influences underlie comorbidity of migraine and endometriosis. Genet Epidemiol 33: 105–113.

22. Karp BI, Sinaii N, Nieman LK, Silberstein SD, Stratton P (2011) Migraine in women with chronic pelvic pain with and without endometriosis. Fertil Steril 95: 895–899.

23. Bureau of National Health Insurance, Department of Health, Executive Yuan http:// www.nhi.gov.tw/Resource/webdata/13767_1_NHI%20IN%20TAIWAN%202011% 20ANNUAL%20REPORT.pdf (accessed 2012 February 24).

24. Berkley KJ, Rapkin AJ, Papka RE (2005) The pains of endometriosis. Science 308: 1587–1589.

25. Chacur M, Milligan ED, Gazda LS, Armstrong C, Wang H, et al. (2001) A new model of sciatic inflammatory neuritis (SIN): induction of unilateral and bilateral mechanical allodynia following acute unilateral peri-sciatic immune activation in rats. Pain 94: 231–244.

26. D’Cruz OJ, Uckun FM (2007) Targeting mast cells in endometriosis with janus kinase 3 inhibitor, JANEX-1. Am J Reprod Immunol 58: 75–97.

27. Kempuraj D, Papadopoulou N, Stanford EJ, Christodoulou S, Madhappan B, et al. (2004) Increased numbers of activated mast cells in endometriosis lesions positive for corticotropin-releasing hormone and urocortin. Am J Reprod Immunol 52: 267–275.

28. MacGregor A (1999) Estrogen replacement and migraine aura. Headache 39: 674–678.

29. MacGregor EA (2006) Migraine and the menopause. J Br Menopause Soc 12: 104–108.

30. Nappi RE, Cagnacci A, Granella F, Piccinini F, Polatti F, et al. (2001) Course of primary headaches during hormone replacement therapy. Maturitas 38: 157–163.

31. Dawood MY (1985) Dysmenorrhea. J Reprod Med 30: 154–167.

32. Johannes CB, Linet MS, Stewart WF, Celentano DD, Lipton RB, et al. (1995) Relationship of headache to phase of the menstrual cycle among young women: a daily diary study. Neurology 45: 1076–1082.

33. MacGregor EA (2010) Prevention and treatment of menstrual migraine. Drugs 70: 1799–1818.

34. Bigal ME, Kurth T, Santanello N, Buse D, Golden W, et al. (2010) Migraine and cardiovascular disease: a population-based study. Neurology 74: 628–635. 35. Nelson HD, Humphrey LL, Nygren P, Teutsch SM, Allan JD (2002) Postmenopausal hormone replacement therapy: scientific review. JAMA 288: 872–881.

36. Wang SJ, Fuh JL, Huang SY, Yang SS, Wu ZA, et al. (2008) Diagnosis and development of screening items for migraine in neurological practice in Taiwan. J Formos Med Assoc 107: 485–494.

37. Chu KK, Chen FP, Chang SD (1995) Prevalence of endometriosis among women undergoing laparoscopic procedures. Diagn Ther Endosc 2: 35–37. 38. Wang SJ, Fuh JL, Young YH, Lu SR, Shia BC (2001) Frequency and predictors

of physician consultations for headache. Cephalalgia 21: 25–30.

Migraine and Endometriosis