Abstract
Background
Polycystic ovary syndrome (PCOS) and migraine headaches are considered to be common health problems that may share some risk factors. This study aimed to discuss the possible association between migraine headache and polycystic ovary syndrome.
Methods and results
In this narrative review, PubMed, Scopus, Web of Science, and Google Scholar were systematically searched for retrieving and summarizing published studies up to January 2021 to explore the possible interplay between migraine headache and PCOS. We discuss the possible pathways that may explain the association between migraine headaches and PCOS signs/symptoms and complications. While genetic factors have profound effects on the pathogenesis of migraine headaches, sex hormones, including estrogen and progesterone may also play an important role in inducing migraine headaches. Some disorders, such as sleep apnea, amenorrhea, and vascular disease that are more likely to occur in women with PCOS, may cause or exacerbate migraine headaches in women with PCOS.
Conclusions
Future comprehensive studies are needed to investigate the exact underlining mechanisms related to the association between PCOS and migraine headaches.
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Data availability
No additional data are available.
References
Stovner L, Hagen K, Jensen R et al (2007) The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia 27:193–210
Togha M, Haghdoost F, Khorsha F, Jahromi SR, Ghorbani Z (2019) Body mass index and its association with migraine characteristics in female patients. Archiv Iran Med 22:554–559
Headache Classification Committee of the International Headache Society (IHS) (2018) The International Classification of Headache Disorders, 3rd edition. Cephalalgia 38:1–211
Arumugam M, Narayan SK (2019) Rethinking of the concepts: migraine is an autoimmune disease? Neurol Psychiatry Brain Res 31:20–26
Hashmat A, Jamil H, Inam SHA, Alamgir W, Hamid S (2019) Association between migraine and Body Mass Index in patients reporting at a military hospital, Rawalpindi. JPMA J Pakistan Med Assoc 69:1888–1890
Olesen J (2018) International classification of headache disorders. Lancet Neurol 17:396–397
Silberstein S, Patel S (2014) Menstrual migraine: an updated review on hormonal causes, prophylaxis and treatment. Expert Opin Pharmacother 15:2063–2070
Karlı N, Baykan B, Ertaş M et al (2012) Impact of sex hormonal changes on tension-type headache and migraine: a cross-sectional population-based survey in 2,600 women. J Headache Pain 13:557–565
Bigal ME, Liberman JN, Lipton RB (2006) Obesity and migraine—a population study. Neurology 66:545–550
Ali AT (2015) Polycystic ovary syndrome and metabolic syndrome. Ceska Gynekol 80:279–289
Shah D, Patil M, National PCOS Working Group (2018) Consensus statement on the use of oral contraceptive pills in polycystic ovarian syndrome women in India. J Hum Reprod Sci 11:96–118
Setji TL, Brown AJ (2014) Polycystic ovary syndrome: update on diagnosis and treatment. Am J Med 127:912–919
Baethge C, Goldbeck-Wood S, Mertens S (2019) SANRA—a scale for the quality assessment of narrative review articles. Res Integr Peer Rev 4:1–7
Cavestro C, Rosatello A, Micca G et al (2007) Insulin metabolism is altered in migraineurs: a new pathogenic mechanism for migraine? Headache 47:1436–1442
Colson N, Fernandez F, Griffiths L (2010) Genetics of menstrual migraine: the molecular evidence. Curr Pain Headache Rep 14:389–395
Broner SW, Bobker S, Klebanoff L (2017) Migraine in women. Semin Neurol 37:601–610
Li W, Diao XJ, Chen CF, Li CC, Zhang YB, Li YY (2018) Changes in hormones of the hypothalamic–pituitary–gonadal axis in migraine patients. J Clin Neurosci 50:165–171
Pavlovic JM (2018) Evaluation and management of migraine in midlife women. Menopause J N Am Menopause Soc 25:927–929
Lieba-Samal D, Wöber C (2011) Sex hormones and primary headaches other than migraine. Curr Pain Headache Rep 15:407–414
Faubion SS, Casey PM, Shuster LT (2012) Hormonal contraception and migraine: clinical considerations. Curr Pain Headache Rep 16:461–466
Allais G, Chiarle G, Sinigaglia S, Airola G, Schiapparelli P, Benedetto C (2018) Estrogen, migraine, and vascular risk. Neurol Sci 39:11–20
Pavlović JM, Allshouse AA, Santoro NF et al (2016) Sex hormones in women with and without migraine. Neurology 87:49–56
Deligeoroglou E, Athanasopoulos N, Tsimaris P, Dimopoulos KD, Vrachnis N, Creatsas G (2010) Evaluation and management of adolescent amenorrhea. Ann N Y Acad Sci 1205:23–32
MacGregor EA, Frith A, Ellis J, Aspinall L, Hackshaw A (2006) Prevention of menstrual attacks of migraine—a double-blind placebo-controlled crossover study. Neurology 67:2159–2163
MacGregor EA, Frith A, Ellis J, Aspinall L, Hackshaw A (2006) Incidence of migraine relative to menstrual cycle phases of rising and falling estrogen. Neurology 67:2154–2158
Welch KMA, Brandes JL, Berman NEJ (2006) Mismatch in how oestrogen modulates molecular and neuronal function may explain menstrual migraine. Neurol Sci 27:s190–s192
Loder E, Rizzoli P, Golub J (2007) Hormonal management of migraine associated with menses and the menopause: a clinical review. Headache 47:329–340
Prestwood KM, Unson C, Kulldorff M, Cushman M (2004) The effect of different doses of micronized 17beta-estradiol on C-reactive protein, interleukin-6, and lipids in older women. J Gerontol A Biol Sci Med Sci 59:827–832
Sacco S, Ricci S, Degan D, Carolei A (2012) Migraine in women: the role of hormones and their impact on vascular diseases. J Headache Pain 13:177–189
Finocchi C, Ferrari M (2011) Female reproductive steroids and neuronal excitability. Neurol Sci 32:S31–S35
te Velde ER, Pearson PL (2002) The variability of female reproductive ageing. Hum Reprod Update 8:141–154
Peterlin BL, Rosso AL, Rapoport AM, Scher AI (2010) Obesity and migraine: the effect of age, gender and adipose tissue distribution. Headache 50:52–62
Chaudhari NK, Nampoothiri LP (2017) Neurotransmitter alteration in a testosterone propionate-induced polycystic ovarian syndrome rat model. Horm Mol Biol Clin Investig 29:71–77
Glaser R, Dimitrakakis C, Trimble N, Martin V (2012) Testosterone pellet implants and migraine headaches: a pilot study. Maturitas 71:385–388
Cairns BE, Gazerani P (2009) Sex-related differences in pain. Maturitas 63:292–296
Fargo KN, Foecking EM, Jones KJ, Sengelaub DR (2009) Neuroprotective actions of androgens on motoneurons. Front Neuroendocrinol 30:130–141
Mattsson P (2002) Serum levels of androgens and migraine in postmenopausal women. Clin Sci (Lond) 103:487–491
Glintborg D, Nybo M, Abrahamsen B, Andersen M (2015) Morbidity and medicine prescriptions in a nationwide Danish population of patients diagnosed with polycystic ovary syndrome. European journal of endocrinology 172:627–638
Pourabolghasem S, Najmi S, Arami MA (2009) Polycystic ovary syndrome and migraine headache, is there any correlation? Eur Neurol 61:42–45
Montalcini T, Migliaccio V, Ferro Y, Gazzaruso C, Pujia A (2012) Androgens for postmenopausal women’s health? Endocrine 42:514–520
Pluchino N, Carmignani A, Cubeddu A, Santoro A, Cela V, Errasti T (2013) Androgen therapy in women: for whom and when. Arch Gynecol Obstet 288:731–737
Martin VT, Behbehani M (2006) Ovarian hormones and migraine headache: understanding mechanisms and pathogenesis—part 2. Headache 46:365–386
Eikermann-Haerter K, Baum MJ, Ferrari MD, van den Maagdenberg A, Moskowitz MA, Ayata C (2009) Androgenic suppression of spreading depression in familial hemiplegic migraine type 1 mutant mice. Ann Neurol 66:564–568
Davison SL, Bell R, Donath S, Montalto JG, Davis SR (2005) Androgen levels in adult females: changes with age, menopause, and oophorectomy. J Clin Endocrinol Metab 90:3847–3853
Galluzzo A, Amato MC, Giordano C (2008) Insulin resistance and polycystic ovary syndrome. Nutr Metab Cardiovasc Dis 18:511–518
Buccola JM, Reynolds EE (2003) Polycystic ovary syndrome: a review for primary providers. Prim Care 30:697–710
Patel S (2018) Polycystic ovary syndrome (PCOS), an inflammatory, systemic, lifestyle endocrinopathy. J Steroid Biochem Mol Biol 182:27–36
Dearborn JL, Schneider AL, Gottesman RF et al (2014) Adiponectin and leptin levels in migraineurs in the Atherosclerosis Risk in Communities Study. Neurology 83:2211–2218
Macut D, Bjekić-Macut J, Rahelić D, Doknić M (2017) Insulin and the polycystic ovary syndrome. Diabetes Res Clin Pract 130:163–170
Moghetti P (2016) Insulin resistance and polycystic ovary syndrome. Curr Pharm Des 22:5526–5534
Guldiken B, Guldiken S, Taskiran B et al (2009) Migraine in metabolic syndrome. Neurologist 15:55–58
Bhoi SK, Kalita J, Misra UK (2012) Metabolic syndrome and insulin resistance in migraine. J Headache Pain 13:321–326
Porte D Jr, Baskin DG, Schwartz MW (2005) Insulin signaling in the central nervous system: a critical role in metabolic homeostasis and disease from C. elegans to humans. Diabetes 54:1264–1276
Masharani U, Gjerde C, Evans JL, Youngren JF, Goldfine ID (2010) Effects of controlled-release alpha lipoic acid in lean, nondiabetic patients with polycystic ovary syndrome. J Diabetes Sci Technol 4:359–364
Golbidi S, Badran M, Laher I (2011) Diabetes and alpha lipoic Acid. Front Pharmacol 2:69
Bernecker C, Ragginer C, Fauler G et al (2011) Oxidative stress is associated with migraine and migraine-related metabolic risk in females. Eur J Neurol 18:1233–1239
Yilmaz N, Aydin O, Yegin A, Tiltak A, Eren E, Aykal G (2011) Impaired oxidative balance and association of blood glucose, insulin and HOMA-IR index in migraine. Biochem Med (Zagreb) 21:145–151
Cavestro C, Bedogni G, Molinari F, Mandrino S, Rota E, Frigeri MC (2018) Alpha-lipoic acid shows promise to improve migraine in patients with insulin resistance: a 6-month exploratory study. J Med Food 21:269–273
Šenk B, Goričar K, Kravos NA, Jensterle Sever M, Janež A, Dolžan V (2018) SLC6A4 5HTTLPR Polymorphism affects insulin secretion in patients with polycystic ovary syndrome. Int J Endocrinol. https://doi.org/10.1155/2018/6130487
Fava A, Pirritano D, Consoli D et al (2014) Chronic migraine in women is associated with insulin resistance: a cross-sectional study. Eur J Neurol 21:267–272
Sacco S, Altobelli E, Ornello R, Ripa P, Pistoia F, Carolei A (2014) Insulin resistance in migraineurs: results from a case-control study. Cephalalgia 34:349–356
Özcan RK, Özmen SG (2019) The association between migraine, metabolic syndrome, insulin resistance, and obesity in women: a case–control study. Sisli Etfal Hastan Tip Bul 53:395–402
Farello G, Ferrara P, Antenucci A, Basti C, Verrotti A (2017) The link between obesity and migraine in childhood: a systematic review. Italian J Pediatrics 43:27
Téllez-Zenteno JF, Pahwa DR, Hernandez-Ronquillo L, García-Ramos G, Velázquez A (2010) Association between body mass index and migraine. Eur Neurol 64:134–139
Ornello R, Ripa P, Pistoia F et al (2015) Migraine and body mass index categories: a systematic review and meta-analysis of observational studies. J Headache Pain 16:27
Peterlin BL, Rosso AL, Williams MA et al (2013) Episodic migraine and obesity and the influence of age, race, and sex. Neurology 81:1314–1321
Cervoni C, Bond DS, Seng EK (2016) Behavioral weight loss treatments for individuals with migraine and obesity. Curr Pain Headache Rep 20:13
Bigal ME, Lipton RB, Holland PR, Goadsby PJ (2007) Obesity, migraine, and chronic migraine: possible mechanisms of interaction. Neurology 68:1851–1861
Miller VM, Duckles SP (2008) Vascular actions of estrogens: functional implications. Pharmacol Rev 60:210–241
Pezzini A, Granella F, Grassi M et al (2005) History of migraine and the risk of spontaneous cervical artery dissection. Cephalalgia 25:575–580
Tietjen EG (2007) Migraine and ischaemic heart disease and stroke: potential mechanisms and treatment implications. Cephalalgia 27:981–987
Glintborg D, Andersen M (2017) Management of endocrine disease: morbidity in polycystic ovary syndrome. Eur J Endocrinol 176:R53-Rr65
Spector JT, Kahn SR, Jones MR, Jayakumar M, Dalal D, Nazarian S (2010) Migraine headache and ischemic stroke risk: an updated meta-analysis. Am J Med 123:612–624
Lidegaard Ø, Løkkegaard E, Jensen A, Skovlund CW, Keiding N (2012) Thrombotic stroke and myocardial infarction with hormonal contraception. N Engl J Med 366:2257–2266
Allais G, Chiarle G, Sinigaglia S, Benedetto C (2018) Menstrual migraine: a review of current and developing pharmacotherapies for women. Expert Opin Pharmacother 19:123–136
Schürks M, Rist PM, Bigal ME, Buring JE, Lipton RB, Kurth T (2009) Migraine and cardiovascular disease: systematic review and meta-analysis. BMJ 339:1015
Kurth T, Gaziano JM, Rexrode KM et al (2005) Prospective study of body mass index and risk of stroke in apparently healthy women. Circulation 111:1992–1998
Bond DS, Roth J, Nash JM, Wing RR (2011) Migraine and obesity: epidemiology, possible mechanisms and the potential role of weight loss treatment. Obes Rev 12:e362–e371
Tietjen GE, Khubchandani J (2009) Platelet dysfunction and stroke in the female migraineur. Curr Pain Headache Rep 13:386–391
Jernej B, Vladić A, Cicin-Sain L et al (2002) Platelet serotonin measures in migraine. Headache 42:588–595
Gasparini CF, Smith RA, Griffiths LR (2017) Genetic and biochemical changes of the serotonergic system in migraine pathobiology. J Headache Pain 18:20
Klein DA, Paradise SL, Reeder RM (2019) Amenorrhea: a systematic approach to diagnosis and management. Am Fam Physician 100:39–48
McIver B, Romanski SA, Nippoldt TB (1997) Evaluation and management of amenorrhea. Mayo Clin Proc 72:1161–1169
Meczekalski B, Podfigurna-Stopa A, Warenik-Szymankiewicz A, Genazzani AR (2008) Functional hypothalamic amenorrhea: current view on neuroendocrine aberrations. Gynecol Endocrinol 24:4–11
Prabhakar VK, Davis JR (2008) Hyperprolactinaemia. Best Pract Res Clin Obstet Gynaecol 22:341–353
Ripa P, Ornello R, Degan D et al (2015) Migraine in menopausal women: a systematic review. Int J Womens Health 7:773–782
Rains JC (2018) Sleep and migraine: assessment and treatment of comorbid sleep disorders. Headache 58:1074–1091
Vgontzas A, Pavlović JM (2018) Sleep disorders and migraine: review of literature and potential pathophysiology mechanisms. Headache 58:1030–1039
Young JO, Geurts A, Hodges MR, Cummings KJ (2017) Active sleep unmasks apnea and delayed arousal in infant rat pups lacking central serotonin. J Appl Physiol 123:25–834
Scher AI, Midgette LA, Lipton RB (2008) Risk factors for headache chronification. Headache 48:16–25
Scher AI, Stewart WF, Ricci JA, Lipton RB (2003) Factors associated with the onset and remission of chronic daily headache in a population-based study. Pain 106:81–89
Ødegård SS, Engstrøm M, Sand T, Stovner LJ, Zwart JA, Hagen K (2010) Associations between sleep disturbance and primary headaches: the third Nord-Trøndelag Health Study. J Headache Pain 11:197–206
Kahal H, Kyrou I, Uthman O et al (2018) The association between obstructive sleep apnea and metabolic abnormalities in women with polycystic ovary syndrome: a systematic review and meta-analysis. Sleep. https://doi.org/10.1093/sleep/zsy085
Kim C, Siscovick DS, Sidney S, Lewis CE, Kiefe CI, Koepsell TD (2002) Oral contraceptive use and association with glucose, insulin, and diabetes in young adult women: the CARDIA Study. Coronary Artery Risk Dev Young Adults Diabetes Care 25:1027–1032
Macgregor EA, Rosenberg JD, Kurth T (2011) Sex-related differences in epidemiological and clinic-based headache studies. Headache 51:843–859
Lay CL, Broner SW (2009) Migraine in women. Neurol Clin 27:503–511
Vetvik KG, MacGregor EA, Lundqvist C, Russell MB (2014) Contraceptive-induced amenorrhoea leads to reduced migraine frequency in women with menstrual migraine without aura. J Headache Pain 15:30
De Leo V, Scolaro V, Musacchio MC, Di Sabatino A, Morgante G, Cianci A (2011) Combined oral contraceptives in women with menstrual migraine without aura. Fertil Steril 96:917–920
Allais G, Gabellari IC, Mana O, Schiapparelli P, Terzi MG, Benedetto C (2008) Migraine and stroke: the role of oral contraceptives. Neurol Sci 29(Suppl 1):S12–S14
Gillum LA, Mamidipudi SK, Johnston SC (2000) Ischemic stroke risk with oral contraceptives—a meta-analysis. JAMA J Am Med Assoc 284:72–78
Diamond M (2007) The impact of migraine on the health and well-being of women. J Womens Health (Larchmt) 16:1269–1280
Etminan M, Takkouche B, Isorna FC, Samii A (2005) Risk of ischaemic stroke in people with migraine: systematic review and meta-analysis of observational studies. BMJ 330:63
Karamustafaoglu Balci B, Kabakci Z, Guzey DY, Avci B, Guler M, Attar E (2019) Association between endometriosis, headache, and migraine. J Endometriosis Pelvic Pain Disord 11:19–24
Coffee AL, Sulak PJ, Hill AJ, Hansen DJ, Kuehl TJ, Clark JW (2014) Extended cycle combined oral contraceptives and prophylactic frovatriptan during the hormone-free interval in women with menstrual-related migraines. J Womens Health (Larchmt) 23:310–317
Sam S, Ehrmann DA (2019) Pathogenesis and consequences of disordered sleep in PCOS. Clin Med Insights Reprod Health 13:1179558119871269
Wittert G (2014) The relationship between sleep disorders and testosterone. Curr Opin Endocrinol Diabetes Obes 21:239–243
Faryal U, Rashid S, Hajra B, Hassan M, Saqib J, Ali MA (2016) Effect of hormonal contraceptives on serum serotonin in females of reproductive age group. J Ayub Med Coll Abbottabad 28:56–58
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The study has been supported and funded by the Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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SN: concepts, design, definition of intellectual content, research studies, manuscript preparation, manuscript editing, manuscript review, data acquisition; FRT: concepts, design, definition of intellectual content, research studies, manuscript preparation, manuscript editing, manuscript review, data acquisition, guarantor; ERN: literature search, manuscript preparation, manuscript editing, manuscript review; MN: literature search, data acquisition, manuscript preparation, manuscript review, FM: manuscript editing, manuscript review, data acquisition, manuscript review; MSG: manuscript editing, manuscript review, data acquisition, manuscript review.
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Sarahian, N., Noroozzadeh, M., Saei Ghare Naz, M. et al. Is there any association between migraine headache and polycystic ovary syndrome (PCOS)? A review article. Mol Biol Rep 49, 595–603 (2022). https://doi.org/10.1007/s11033-021-06799-8
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DOI: https://doi.org/10.1007/s11033-021-06799-8