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Transgender and Migraine

  • E. Anne MacGregorEmail author
  • Antoinette Maassen van den Brink
Chapter
Part of the Headache book series (HEAD)

Abstract

Migraine is known to be affected by sex hormones, with the higher prevalence in women during the reproductive years considered to be due to the effects of oestrogen. Hence, migraine is likely to be affected by hormones used for transgender treatment. Of the very limited data available, the prevalence of migraine increases in transgender women using oestrogen and reduces in transgender men using testosterone. The increased prevalence of migraine aura in transgender women may be associated with high oestrogen dosing, particularly of oral oestrogen. Risks can be reduced by using transdermal hormones, which result in stable physiologic levels. In patients with aura, modifiable risk factors for stroke should be managed, particularly smoking cessation. Otherwise migraine management should follow national guidelines.

Keywords

Transgender Transsexual Migraine Oestrogen Testosterone 

References

  1. 1.
    Hembree WC, Cohen-Kettenis PT, Gooren L, Hannema SE, Meyer WJ, Murad MH, et al. Endocrine treatment of gender-dysphoric/gender-incongruent persons: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2017;102(11):3869–903.PubMedGoogle Scholar
  2. 2.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013.Google Scholar
  3. 3.
    Collin L, Reisner SL, Tangpricha V, Goodman M. Prevalence of transgender depends on the “case” definition: a systematic review. J Sex Med. 2016;13(4):613–26.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Winter S, Diamond M, Green J, Karasic D, Reed T, Whittle S, et al. Transgender people: health at the margins of society. Lancet. 2016;388(10042):390–400.PubMedGoogle Scholar
  5. 5.
    Gender Identity Development Service. Accessed on 18 Jan 2018. Available from: http://gids.nhs.uk/number-referrals.
  6. 6.
    Vetvik KG, MacGregor EA. Sex differences in the epidemiology, clinical features, and pathophysiology of migraine. Lancet Neurol. 2017;16(1):76–87.Google Scholar
  7. 7.
    MacGregor EA. Oestrogen and attacks of migraine with and without aura. Lancet Neurol. 2004;3(6):354–61.PubMedGoogle Scholar
  8. 8.
    Pringsheim T, Gooren L. Migraine prevalence in male to female transsexuals on hormone therapy. Neurology. 2004;63(3):593–4.PubMedGoogle Scholar
  9. 9.
    Launer LJ, Terwindt GM, Ferrari MD. The prevalence and characteristics of migraine in a population-based cohort: the GEM study. Neurology. 1999;53(3):537–42.PubMedGoogle Scholar
  10. 10.
    Aloisi AM, Bachiocco V, Costantino A, Stefani R, Ceccarelli I, Bertaccini A, et al. Cross-sex hormone administration changes pain in transsexual women and men. Pain. 2007;132(Suppl 1):S60–7.PubMedGoogle Scholar
  11. 11.
    World Professional Association for Transgender Health. Standards of care for the health of transsexual, transgender, and gender nonconforming people. 2011. Accessed on 18 Jan 2018. Available from: https://s3.amazonaws.com/amo_hub_content/Association140/files/Standards%20of%20Care%20V7%20-%202011%20WPATH%20(2)(1).pdf.
  12. 12.
    Sanchez NF, Sanchez JP, Danoff A. Health care utilization, barriers to care, and hormone usage among male-to-female transgender persons in New York City. Am J Public Health. 2009;99(4):713–9.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Mepham N, Bouman WP, Arcelus J, Hayter M, Wylie KR. People with gender dysphoria who self-prescribe cross-sex hormones: prevalence, sources, and side effects knowledge. J Sex Med. 2014;11(12):2995–3001.PubMedGoogle Scholar
  14. 14.
    de Haan G, Santos GM, Arayasirikul S, Raymond HF. Non-prescribed hormone use and barriers to care for transgender women in San Francisco. LGBT Health. 2015;2(4):313–23.PubMedGoogle Scholar
  15. 15.
    Dittrich R, Binder H, Cupisti S, Hoffmann I, Beckmann MW, Mueller A. Endocrine treatment of male-to-female transsexuals using gonadotropin-releasing hormone agonist. Exp Clin Endocrinol Diabetes. 2005;113(10):586–92.PubMedGoogle Scholar
  16. 16.
    Asscheman H, Giltay EJ, Megens JA, de Ronde WP, van Trotsenburg MA, Gooren LJ. A long-term follow-up study of mortality in transsexuals receiving treatment with cross-sex hormones. Eur J Endocrinol. 2011;164(4):635–42.PubMedGoogle Scholar
  17. 17.
    Ho JY, Chen MJ, Sheu WH, Yi YC, Tsai AC, Guu HF, et al. Differential effects of oral conjugated equine estrogen and transdermal estrogen on atherosclerotic vascular disease risk markers and endothelial function in healthy postmenopausal women. Hum Reprod. 2006;21(10):2715–20.PubMedGoogle Scholar
  18. 18.
    Canonico M, Oger E, Plu-Bureau G, Conard J, Meyer G, Levesque H, et al. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation. 2007;115(7):840–5.PubMedGoogle Scholar
  19. 19.
    Vehkavaara S, Silveira A, Hakala-Ala-Pietila T, Virkamaki A, Hovatta O, Hamsten A, et al. Effects of oral and transdermal estrogen replacement therapy on markers of coagulation, fibrinolysis, inflammation and serum lipids and lipoproteins in postmenopausal women. Thromb Haemost. 2001;85(4):619–25.PubMedGoogle Scholar
  20. 20.
    Bergoglio MT, Gomez-Balaguer M, Almonacid Folch E, Hurtado Murillo F, Hernandez-Mijares A. Symptomatic meningioma induced by cross-sex hormone treatment in a male-to-female transsexual. Endocrinol Nutr. 2013;60(5):264–7.PubMedGoogle Scholar
  21. 21.
    Goh HH, Li XF, Ratnam SS. Effects of cross-gender steroid hormone treatment on prolactin concentrations in humans. Gynecol Endocrinol. 1992;6(2):113–7.PubMedGoogle Scholar
  22. 22.
    Bradshaw HB, Berkley KJ. The influence of ovariectomy with or without estrogen replacement on responses of rat gracile nucleus neurons to stimulation of hindquarter skin and pelvic viscera. Brain Res. 2003;986(1-2):82–90.PubMedGoogle Scholar
  23. 23.
    Gupta S, Villalon CM, Mehrotra S, de Vries R, Garrelds IM, Saxena PR, et al. Female sex hormones and rat dural vasodilatation to CGRP, periarterial electrical stimulation and capsaicin. Headache. 2007;47(2):225–35.PubMedGoogle Scholar
  24. 24.
    Eikermann-Haerter K, Dilekoz E, Kudo C, Savitz SI, Waeber C, Baum MJ, et al. Genetic and hormonal factors modulate spreading depression and transient hemiparesis in mouse models of familial hemiplegic migraine type 1. J Clin Invest. 2009;119(1):99–109.PubMedGoogle Scholar
  25. 25.
    Sacco S, Ricci S, Degan D, Carolei A. Migraine in women: the role of hormones and their impact on vascular diseases. J Headache Pain. 2012;13(3):177–89.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Gazerani P, et al. Pain. 2005;118:155–63.PubMedGoogle Scholar
  27. 27.
    Ibrahimi K, et al. Neurology. 2015;84(2):125–31.Google Scholar
  28. 28.
    Labastida-Ramirez A, Rubio-Beltran E, Villalon CM, MaassenVanDenBrink A. Gender aspects of CGRP in migraine. Cephalalgia. 2017.; 333102417739584.Google Scholar
  29. 29.
    Puri V, Cui L, Liverman CS, Roby KF, Klein RM, Welch KMA, et al. Ovarian steroids regulate neuropeptides in the trigeminal ganglion. Neuropeptides. 2005;39(4):409–17.PubMedGoogle Scholar
  30. 30.
    Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S. Pathophysiology of migraine: a disorder of sensory processing. Physiol Rev. 2017;97(2):553–622.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Labruijere S, van Houten EL, de Vries R, Musterd-Bagghoe UM, Garrelds IM, Kramer P, et al. Analysis of the vascular responses in a murine model of polycystic ovary syndrome. J Endocrinol. 2013;218(2):205–13.PubMedGoogle Scholar
  32. 32.
    Valenti S, Fazzuoli L, Giusti M. Circulating nitric oxide levels increase after anti-androgen treatment in male-to-female transsexuals. J Endocrinol Invest. 2003;26(6):522–6.PubMedGoogle Scholar
  33. 33.
    New G, Duffy SJ, Harper RW, Meredith IT. Long-term oestrogen therapy is associated with improved endothelium-dependent vasodilation in the forearm resistance circulation of biological males. Clin Exp Pharmacol Physiol. 2000;27(1-2):25–33.PubMedGoogle Scholar
  34. 34.
    Stanzani Maserati M. Migraine attacks, aura, and polycythemia: a vasculoneural pathogenesis? J Neural Transm (Vienna). 2011;118(4):545–7.Google Scholar
  35. 35.
    Michiels JJ, Berneman Z, Gadisseur A, Lam KH, De Raeve H, Schroyens W. Aspirin-responsive, migraine-like transient cerebral and ocular ischemic attacks and erythromelalgia in JAK2-positive essential thrombocythemia and polycythemia vera. Acta Haematol. 2015;133(1):56–63.PubMedGoogle Scholar
  36. 36.
    Cairns BE, Gazerani P. Sex-related differences in pain. Maturitas. 2009;63(4):292–6.PubMedGoogle Scholar
  37. 37.
    Gupta S, McCarson KE, Welch KM, Berman NE. Mechanisms of pain modulation by sex hormones in migraine. Headache. 2011;51(6):905–22.PubMedGoogle Scholar
  38. 38.
    Fink G, Sumner B, Rosie R, Wilson H, McQueen J. Androgen actions on central serotonin neurotransmission: relevance for mood, mental state and memory. Behav Brain Res. 1999;105(1):53–68.PubMedGoogle Scholar
  39. 39.
    Eikermann-Haerter K, Baum MJ, Ferrari MD, van den Maagdenberg AM, Moskowitz MA, Ayata C. Androgenic suppression of spreading depression in familial hemiplegic migraine type 1 mutant mice. Ann Neurol. 2009;66(4):564–8.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Lichten EM, Bennett RS, Whitty AJ, Daoud Y. Efficacy of danazol in the control of hormonal migraine. J Reprod Med. 1991;36(6):419–24.PubMedGoogle Scholar
  41. 41.
    Glaser R, Dimitrakakis C, Trimble N, Martin V. Testosterone pellet implants and migraine headaches: a pilot study. Maturitas. 2012;71(4):385–8.PubMedGoogle Scholar
  42. 42.
    Merki-Feld GS, Imthurn B, Langner R, Seifert B, Gantenbein AR. Positive effects of the progestin desogestrel 75 mg on migraine frequency and use of acute medication are sustained over a treatment period of 180 days. J Headache Pain. 2015;16:522.Google Scholar
  43. 43.
    Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38(1):1–211.Google Scholar
  44. 44.
    Lipton RB, Dodick D, Sadovsky R, Kolodner K, Endicott J, Hettiarachchi J, et al. A self-administered screener for migraine in primary care: the ID Migraine validation study. Neurology. 2003;61(3):375–82.PubMedGoogle Scholar
  45. 45.
    Dodick DW. Pearls: headache. Semin Neurol. 2010;30(1):74–81.PubMedGoogle Scholar
  46. 46.
    Blau JN. Migraine: theories of pathogenesis. Lancet. 1992;339(8803):1202–7.PubMedGoogle Scholar
  47. 47.
    Kurth T, Chabriat H, Bousser MG. Migraine and stroke: a complex association with clinical implications. Lancet Neurol. 2012;11(1):92–100.PubMedGoogle Scholar
  48. 48.
    Gervil M, Ulrich V, Olesen J, Russell M. Screening for migraine in the general population: validation of a simple questionnaire. Cephalalgia. 1998;18:342–8.PubMedGoogle Scholar
  49. 49.
    Kuhl H. Pharmacokinetics of oestrogen and progestogens. Maturitas. 1990;12:171–97.PubMedGoogle Scholar
  50. 50.
    MacGregor A. Estrogen replacement and migraine aura. Headache. 1999;39:674–8.PubMedGoogle Scholar
  51. 51.
    Somerville BW. The role of estradiol withdrawal in the etiology of menstrual migraine. Neurology. 1972;22(4):355–65.PubMedGoogle Scholar
  52. 52.
    Lichten EM, Lichten JB, Whitty A, Pieper D. The confirmation of a biochemical marker for women’s hormonal migraine: the depo-estradiol challenge test. Headache. 1996;36(6):367–71.PubMedGoogle Scholar
  53. 53.
    van Kesteren PJ, Asscheman H, Megens JA, Gooren LJ. Mortality and morbidity in transsexual subjects treated with cross-sex hormones. Clin Endocrinol (Oxf). 1997;47(3):337–42.Google Scholar
  54. 54.
    Schurks M, Rist PM, Bigal ME, Buring JE, Lipton RB, Kurth T. Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ. 2009;339:b3914.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Spector JT, Kahn SR, Jones MR, Jayakumar M, Dalal D, Nazarian S. Migraine headache and ischemic stroke risk: an updated meta-analysis. Am J Med. 2010;123(7):612–24.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Etminan M, Takkouche B, Isorna FC, Samii A. Risk of ischaemic stroke in people with migraine: systematic review and meta-analysis of observational studies. BMJ. 2005;330(7482):63–5.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Kurth T, Schurks M, Logroscino G, Gaziano JM, Buring JE. Migraine, vascular risk, and cardiovascular events in women: prospective cohort study. BMJ. 2008;337:a636.PubMedPubMedCentralGoogle Scholar
  58. 58.
    Bigal ME, Kurth T, Santanello N, Buse D, Golden W, Robbins M, et al. Migraine and cardiovascular disease: a population-based study. Neurology. 2010;74(8):628–35.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Li L, Schulz UG, Kuker W, Rothwell PM, Oxford Vascular S. Age-specific association of migraine with cryptogenic TIA and stroke: population-based study. Neurology. 2015;85(17):1444–51.PubMedPubMedCentralGoogle Scholar
  60. 60.
    Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288(3):321–33.Google Scholar
  61. 61.
    Clarke MP, Coughlin JR. Prevalence of smoking among the lesbian, gay, bisexual, transsexual, transgender and queer (LGBTTQ) subpopulations in Toronto--the Toronto Rainbow Tobacco Survey (TRTS). Can J Public Health. 2012;103(2):132–6.PubMedGoogle Scholar
  62. 62.
    O’Donnell MJ, Xavier D, Liu L, Zhang H, Chin SL, Rao-Melacini P, et al. Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study. Lancet. 2010;376(9735):112–23.PubMedGoogle Scholar
  63. 63.
    Scher AI, Terwindt GM, Picavet HS, Verschuren WM, Ferrari MD, Launer LJ. Cardiovascular risk factors and migraine: the GEM population-based study. Neurology. 2005;64(4):614–20.PubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • E. Anne MacGregor
    • 1
    Email author
  • Antoinette Maassen van den Brink
    • 2
  1. 1.Barts Health NHS TrustLondonUK
  2. 2.Division of Vascular Medicine and Pharmacology, Department of Internal MedicineErasmus University Medical CenterRotterdamThe Netherlands

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