{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T09:42:59Z","timestamp":1791020579086,"version":"4.1.0"},"reference-count":32,"publisher":"BMJ","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Fam Plann Reprod Health Care"],"accepted":{"date-parts":[[2001,6,24]]},"published-print":{"date-parts":[[2002,1]]},"abstract":"<jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Migraine in the pill-free interval of combined oral contraceptives is reported by many women, but there is little published information on possible mechanisms and treatments.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To determine whether the use of natural oestrogen patches affected the occurrence and severity of migraine during the pill-free interval.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>A double-blind, placebo-controlled, randomised, crossover study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>The City of London Migraine Clinic.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>Fourteen women with migraine during the pill-free interval.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Interventions<\/jats:title>\n                  <jats:p>50 \u03bcg oestradiol patches (Evorel\u2122) used during the pill-free interval for two cycles versus placebo for two cycles (total four cycles).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main outcome measures<\/jats:title>\n                  <jats:p>Number of pill-free intervals (zero, one or two) during which migraine occurred; number of days of migraine; severity of migraine; number of days of migraine accompanied by nausea, vomiting and\/or photophobia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Complete data were available for 12 women and for two cycles for one woman. Use of 50 \u03bcg oestrogen patches during the pill-free interval showed a trend towards reducing the frequency and severity of migraine.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>These results were not as good as expected. However, we had originally aimed for 20 eligible women to participate in the trial, but only 14 were recruited and only 12 completed the study with full data for analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The results of this pilot study suggest that use of 50 \u03bcg oestrogen patches during the pill-free interval may reduce the frequency and severity of migraine at that time. This study should be repeated with larger numbers of women and a higher dose of oestrogen.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1783\/147118902101195974","type":"journal-article","created":{"date-parts":[[2005,3,5]],"date-time":"2005-03-05T01:30:57Z","timestamp":1109986257000},"page":"27-31","source":"Crossref","is-referenced-by-count":48,"title":["Prevention of migraine in the pill-free interval of combined oral contraceptives: A double-blind, placebo-controlled pilot study using natural oestrogen supplements"],"prefix":"10.1136","volume":"28","author":[{"given":"E Anne","family":"MacGregor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Hackshaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2002,1,1]]},"reference":[{"key":"ref_1","first-page":"612","article-title":"Side effects of oral contraceptives","volume":"ii:","author":"Slugge, H.J.; Lawson, J.P.","year":"1967","unstructured":"Slugge HJ, Lawson JP. Side effects of oral contraceptives. Lancet 1967; ii: 612.","journal-title":"Lancet"},{"key":"ref_2","first-page":"66","article-title":"The 150\/30 formulation. Experience in the United Kingdom","volume":"1","author":"Guillebaud, J.","year":"1983","unstructured":"Guillebaud J. The 150\/30 formulation. Experience in the United Kingdom. J Rep Med 1983; 28 (Suppl. 1): 66\u201370.","journal-title":"J Rep Med"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/0010-7824(94)00010-T","article-title":"Twelve years of clinical experience with an oral contraceptive containing 30 microg ethinyl-estradiol and 150 microg desogestrel","volume":"51","author":"Fotherby, K.","year":"1998","unstructured":"Fotherby K. Twelve years of clinical experience with an oral contraceptive containing 30 microg ethinyl-estradiol and 150 microg desogestrel. Contraception 1998; 51: 3.","journal-title":"Contraception"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/0010-7824(92)90151-I","article-title":"Clinical experience and pharmacological effects of an oral contraceptive containing 20 micrograms oestrogen","volume":"46","author":"Fotherby, K.","year":"1992","unstructured":"Fotherby K. Clinical experience and pharmacological effects of an oral contraceptive containing 20 micrograms oestrogen. Contraception 1992; 46: 477\u2013488.","journal-title":"Contraception"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/j.1600-0404.1970.tb05792.x","article-title":"Headache and treatment with oral contraceptives","volume":"46","author":"Larsson-Cohn, U.; Lundberg, P.O.","year":"1970","unstructured":"Larsson-Cohn U, Lundberg PO. Headache and treatment with oral contraceptives. Acta Neurol Scand 1970; 46: 267\u2013278.","journal-title":"Acta Neurol Scand"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/j.1526-4610.1975.hed1501036.x","article-title":"The relationship of headache frequency to hormone use in migraine","volume":"15","author":"Kudrow, L.","year":"1975","unstructured":"Kudrow L. The relationship of headache frequency to hormone use in migraine. Headache 1975; 15: 37\u201340.","journal-title":"Headache"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1111\/j.1526-4610.1978.hed1706250.x","article-title":"A controlled study of the effects of oral contraceptives in migraine","volume":"17","author":"Ryan, R.E.","year":"1978","unstructured":"Ryan RE. A controlled study of the effects of oral contraceptives in migraine. Headache 1978; 17: 250\u2013252.","journal-title":"Headache"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1136\/bmj.2.5597.99","article-title":"Oral contraceptive drugs and migraine","volume":"2","author":"Philips, B.M.","year":"1968","unstructured":"Philips BM. Oral contraceptive drugs and migraine. Br Med J 1968; 2: 99.","journal-title":"Br Med J"},{"key":"ref_9","first-page":"856","article-title":"The effect of oral contraceptives on migraine","volume":"i:","author":"Whitty, C.W.M.; Hockaday, J.M.; Whitty, M.M.","year":"1966","unstructured":"Whitty CWM, Hockaday JM, Whitty MM. The effect of oral contraceptives on migraine. Lancet 1966; i: 856\u20139.","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.1526-4610.1976.he1504247.x","article-title":"Migraine and oral contraceptives","volume":"15","author":"Dalton, K.","year":"1976","unstructured":"Dalton K. Migraine and oral contraceptives. Headache 1976; 15: 247\u2013251.","journal-title":"Headache"},{"key":"ref_11","first-page":"405","article-title":"Possible role of gonadal hormones as triggering factors in migraine","volume":"1","author":"Horowski, R.; Runge, I.","year":"1986","unstructured":"Horowski R, Runge I. Possible role of gonadal hormones as triggering factors in migraine. Funct Neurol 1986; 1: 405\u201314.","journal-title":"Funct Neurol"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1046\/j.1468-2982.1996.1601011.x","article-title":"\u2018Menstrual\u2019 migraine: towards a definition","volume":"16","author":"MacGregor, E.A.","year":"1996","unstructured":"MacGregor EA. \u2018Menstrual\u2019 migraine: towards a definition. Cephalalgia 1996; 16: 11\u201321.","journal-title":"Cephalalgia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1212\/WNL.22.4.355","article-title":"The role of estradiol withdrawal in the etiology of menstrual migraine","volume":"22","author":"Somerville, B.W.","year":"1972","unstructured":"Somerville BW. The role of estradiol withdrawal in the etiology of menstrual migraine. Neurology 1972; 22: 355\u2013365.","journal-title":"Neurology"},{"issue":"239\u2013244","key":"ref_14","first-page":"15","article-title":"Duration of exposure required and attempted prophylaxis by premenstrual estrogen administration","volume":"25","author":"Epstein, M.T.; Hockaday, J.M.; Hockaday, T.D.R.","year":"1975","unstructured":"Duration of exposure required and attempted prophylaxis by premenstrual estrogen administration. Neurology 1975; 25: 239\u2013244. 15 Epstein MT, Hockaday JM, Hockaday TDR. Migraine and reproductive hormones throughout the menstrual cycle. Lancet 1975;i: 543\u2013548.","journal-title":"Neurology; Migraine and reproductive hormones throughout the menstrual cycle"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1046\/j.1526-4610.1996.3606367.x","article-title":"The confirmation of a biochemical marker for women\u2019s hormonal migraine: the depo-oestradiol challenge test","volume":"36","author":"Lichten, E.; Lichten, J.; Whitty, A.","year":"1996","unstructured":"Lichten E, Lichten J, Whitty A, et al. The confirmation of a biochemical marker for women\u2019s hormonal migraine: the depo-oestradiol challenge test. Headache 1996; 36: 367\u2013371.","journal-title":"Headache"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1212\/WNL.25.3.245","article-title":"Estrogen-withdrawal migraine II. Attempted prophylaxis by continuous estradiol administration","volume":"25","author":"Somerville, B.W.","year":"1975","unstructured":"Somerville BW. Estrogen-withdrawal migraine II. Attempted prophylaxis by continuous estradiol administration. Neurology 1975; 25: 245\u2013250.","journal-title":"Neurology"},{"key":"ref_17","first-page":"1450","article-title":"Prevention of menstrual migraine by percutaneous oestradiol","volume":"293","author":"de Ligni\u00e8res B; M, Vincens; P, Mauvais-Jarvis","year":"1986","unstructured":"de Ligni\u00e8res B, Vincens M, Mauvais-Jarvis P, et al. Prevention of menstrual migraine by percutaneous oestradiol. Br Med J 1986; 293: 1450.","journal-title":"Br Med J"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"113","DOI":"10.3109\/09513598809023619","article-title":"Menstrual migraine: a double-blind trial of percutaneous estradiol","volume":"2","author":"Dennerstein, L.; Morse, C.; Burrows, G.","year":"1988","unstructured":"Dennerstein L, Morse C, Burrows G, et al. Menstrual migraine: a double-blind trial of percutaneous estradiol. Gynaecol Endocrinol 1988; 2: 113\u2013120.","journal-title":"Gynaecol Endocrinol"},{"key":"ref_19","first-page":"244","article-title":"Efficacy and safety of percutaneous estradiol vs placebo in menstrual migraine","volume":"13","author":"Pfaffenrath, V.","year":"1993","unstructured":"Pfaffenrath V. Efficacy and safety of percutaneous estradiol vs placebo in menstrual migraine. Cephalalgia 1993; 13 (Suppl. 13): 244.","journal-title":"Cephalalgia"},{"key":"ref_20","first-page":"129","article-title":"Correlation between oestradiol plasma level and therapeutic effect on menstrual migraine","volume-title":"New advances in headache research., Clifford Rose F","author":"Pradalier, A.; Vincent, D.; Ph, Beaulieu","year":"1994","unstructured":"Pradalier A, Vincent D, Beaulieu Ph, et al. Correlation between oestradiol plasma level and therapeutic effect on menstrual migraine. In: New advances in headache research., Clifford Rose F (ed.). London: Smith-Gordon, 1994; 129\u2013132."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1526-4610.1994.hed3402103.x","article-title":"Perimenstrual migraine: effect of Estraderm TTSS\u00ae and the value of contingent negative variation and exteroceptive temporalis muscle suppression test","volume":"34","author":"Smits, M.G.; van der Meer, Y.G.; Pfeil, J.P.J.M.","year":"1994","unstructured":"Smits MG, van der Meer YG, Pfeil JPJM, et al. Perimenstrual migraine: effect of Estraderm TTSS\u00ae and the value of contingent negative variation and exteroceptive temporalis muscle suppression test. Headache 1994; 34: 103\u2013106.","journal-title":"Headache"},{"key":"ref_22","first-page":"294","article-title":"Estrogen-deprivation headaches","volume":"32","author":"Eichner, E.","year":"1968","unstructured":"Eichner E. Estrogen-deprivation headaches. Obstet Gynecol 1968; 32: 294.","journal-title":"Obstet Gynecol"},{"key":"ref_23","article-title":"A (eds). Handbook of family planning and reproductive health care","author":"Loudon, N.; Glasier, A.; Gebbie","year":"1995","unstructured":"Loudon N, Glasier A, Gebbie A (eds). Handbook of family planning and reproductive health care (3rd edn). Edinburgh: Churchill Livingstone, 1995.","edition":"3rd edn"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1136\/bmj.284.6324.1213","article-title":"Influence of contraceptive pill and menstrual cycle on serum lipids and high-density lipoprotein cholesterol concentrations","volume":"284","author":"AF, Demacker P.N.Schade R.W.Stalenhoef","year":"1982","unstructured":"Demacker PN. Schade RW. Stalenhoef AF, et al. Influence of contraceptive pill and menstrual cycle on serum lipids and high-density lipoprotein cholesterol concentrations. Br Med J 1982; 284: 1213\u2013215.","journal-title":"Br Med J"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1136\/bmj.310.6983.830","article-title":"Case-control study of migraine and risk of ischaemic stroke in young women","volume":"310","author":"Tzourio, C.; Tehindrazanarivelo, A.; Igl\u00e9sias, S.","year":"1995","unstructured":"Tzourio C, Tehindrazanarivelo A, Igl\u00e9sias S, et al. Case-control study of migraine and risk of ischaemic stroke in young women. Br Med J 1995; 310: 830\u2013833.","journal-title":"Br Med J"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/j.1471-0528.1995.tb09070.x","article-title":"Oral contraceptives, pregnancy and the risk of cerebral thromboembolism: the influence of diabetes, hypertension, migraine and previous thrombotic disease","volume":"102","author":"Lidegaard, O.","year":"1995","unstructured":"Lidegaard O. Oral contraceptives, pregnancy and the risk of cerebral thromboembolism: the influence of diabetes, hypertension, migraine and previous thrombotic disease. Br J Obstet Gynaecol 1995; 102: 153\u2013159.","journal-title":"Br J Obstet Gynaecol"},{"key":"ref_27","first-page":"13","article-title":"World Health Organisation Collaboration Study of Cardiovascular Disease and Steroid Hormone Contraception. Migraine and stroke in young women: case-control study","volume":"318","year":"1999","unstructured":"Chang CL, Donaghy M, Poulter N and World Health Organisation Collaboration Study of Cardiovascular Disease and Steroid Hormone Contraception. Migraine and stroke in young women: case-control study. Br Med J 1999; 318: 13\u201318.","journal-title":"Br Med J"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1136\/bmj.297.6647.519","article-title":"Postmenopausal oestrogen treatment and stroke: a prospective study","volume":"297","author":"Paganini-Hill, A.; Ross, R.K.; Henderson, B.E.","year":"1988","unstructured":"Paganini-Hill A, Ross RK, Henderson BE. Postmenopausal oestrogen treatment and stroke: a prospective study. Br Med J 1988; 297: 519\u2013522.","journal-title":"Br Med J"},{"key":"ref_29","first-page":"31","article-title":"Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain","volume":"\"(Suppl.\" # \"1\u201396\" # \"ii:\"","author":"Hamilton, M.","year":"1998","unstructured":"Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 1998; 8 (Suppl. 7): 1\u201396 31 Hamilton M. Computer programmes for the medical man: a solution. Br Med J 1965; ii: 1048\u20131050.","journal-title":"Cephalalgia; Computer programmes for the medical man: a solution"},{"key":"ref_30","first-page":"99","article-title":"Recruiting migraine patients to clinical trials by advertisement. In: Headache treatment: trial methodology and new drugs","author":"Lassen, L.H.; Ulrich, V.; Daugaard, D.","year":"1997","unstructured":"Lassen LH, Ulrich V, Daugaard D, et al. Recruiting migraine patients to clinical trials by advertisement. In: Headache treatment: trial methodology and new drugs, Olesen J, TfeltHansen P (eds). Philadelphia: Lippincott-Raven Publishers, 1997; 99\u2013102."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/0378-5122(90)90003-O","article-title":"Pharmacokinetics of oestrogens and progestogens","volume":"12","author":"Kuhl, H.","year":"1990","unstructured":"Kuhl H. Pharmacokinetics of oestrogens and progestogens. Maturitas 1990; 12: 171\u2013197.","journal-title":"Maturitas"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.1468-2982.1991.1101001.x","article-title":"Society Committee on Clinical Trials in Migraine. Guidelines for controlled trials of drugs in migraine. First edition","volume":"11","author":"International Headache","year":"1991","unstructured":"International Headache Society Committee on Clinical Trials in Migraine. Guidelines for controlled trials of drugs in migraine. First edition. Cephalalgia 1991; 11: 1\u201312.","journal-title":"Cephalalgia"}],"container-title":["Journal of Family Planning and Reproductive Health Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1783\/147118902101195974","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T19:14:46Z","timestamp":1757099686000},"score":1,"resource":{"primary":{"URL":"https:\/\/jfprhc.bmj.com\/lookup\/doi\/10.1783\/147118902101195974"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,1]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2002,1,1]]},"published-print":{"date-parts":[[2002,1]]}},"alternative-id":["10.1783\/147118902101195974"],"URL":"https:\/\/doi.org\/10.1783\/147118902101195974","relation":{},"ISSN":["1471-1893","2045-2098"],"issn-type":[{"value":"1471-1893","type":"print"},{"value":"2045-2098","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,1]]}}}