title: Reduced trigeminovascular cyclicity in patients with menstrually related migraine.
abstract: OBJECTIVE
  A case-control study to investigate the effect of the menstrual cycle on trigeminal nerve-induced vasodilation in healthy women and patients with menstrually related migraine (MRM).
  
  
  METHODS
  Using a laser-Doppler imager, we compared the vasodilator effects of capsaicin application and electrical stimulation (ES) on the forehead skin, a trigeminal nerve-innervated dermatome, in premenopausal patients with MRM (n = 22), healthy controls (n = 20), and postmenopausal women without migraine (n = 22). Blood samples were collected for female sex hormone measurements.
  
  
  RESULTS
  Dermal blood flow (DBF) responses to capsaicin were higher in controls during days 1-2 than during days 19-21 of their menstruation cycle (mean Emax ± SEM: 203 ± 28 AU vs 156 ± 27 AU [p = 0.031] for 0.06 mg/mL capsaicin and 497 ± 25 AU vs 456 ± 24 AU [p = 0.009] for 6.0 mg/mL capsaicin). In contrast, patients with MRM demonstrated DBF responses without significant cycle-dependent variability (days 1-2 vs days 19-21: Emax 148 ± 20 AU vs 154 ± 20 AU [p = 0.788] for 0.06 mg/mL capsaicin and 470 ± 17 AU vs 465 ± 20 AU [p = 0.679] for 6.0 mg/mL capsaicin). DBF responses to ES were not different between either patients with MRM or controls, at either occasion. Estradiol levels on days 19-21 of the menstrual cycle were higher in healthy controls (mean ± SEM: 75 ± 8 pg/mL) than in patients with MRM (52 ± 4 pg/mL, p = 0.014). In postmenopausal women, DBF responses to capsaicin and ES, as well as estradiol levels at both visits, were all significantly reduced compared to patients with MRM and controls (in all cases, p < 0.05).
  
  
  CONCLUSIONS
  Our study provides evidence for a reduced menstrual cyclicity of both estradiol levels and the trigeminovascular vasodilator system in patients with MRM.
authors.affiliation: From the Division of Pharmacology and Vascular Medicine, Department of Internal Medicine (K.I., A.H.J.D., I.M.G., A.H.v.d.M., A.M.V.D.B.), and Departments of Gynaecology (W.v.D.), Psychiatry (S.A.K.), and Biostatistics (E.M.E.H.L.), Erasmus MC, Rotterdam; and Department of Neurology (W.P.J.v.O., G.M.T., M.D.F.), Leiden University Medical Center, the Netherlands.
authors.forename: Khatera
authors.initials: K
authors.lastname: Ibrahimi
authors.affiliation: From the Division of Pharmacology and Vascular Medicine, Department of Internal Medicine (K.I., A.H.J.D., I.M.G., A.H.v.d.M., A.M.V.D.B.), and Departments of Gynaecology (W.v.D.), Psychiatry (S.A.K.), and Biostatistics (E.M.E.H.L.), Erasmus MC, Rotterdam; and Department of Neurology (W.P.J.v.O., G.M.T., M.D.F.), Leiden University Medical Center, the Netherlands.
authors.forename: Willebrordus Petrus Johannes
authors.initials: WP
authors.lastname: van Oosterhout
authors.affiliation: From the Division of Pharmacology and Vascular Medicine, Department of Internal Medicine (K.I., A.H.J.D., I.M.G., A.H.v.d.M., A.M.V.D.B.), and Departments of Gynaecology (W.v.D.), Psychiatry (S.A.K.), and Biostatistics (E.M.E.H.L.), Erasmus MC, Rotterdam; and Department of Neurology (W.P.J.v.O., G.M.T., M.D.F.), Leiden University Medical Center, the Netherlands.
authors.forename: Wendy
authors.initials: W
authors.lastname: van Dorp
authors.affiliation: From the Division of Pharmacology and Vascular Medicine, Department of Internal Medicine (K.I., A.H.J.D., I.M.G., A.H.v.d.M., A.M.V.D.B.), and Departments of Gynaecology (W.v.D.), Psychiatry (S.A.K.), and Biostatistics (E.M.E.H.L.), Erasmus MC, Rotterdam; and Department of Neurology (W.P.J.v.O., G.M.T., M.D.F.), Leiden University Medical Center, the Netherlands.
authors.forename: A H Jan
authors.initials: AH
authors.lastname: Danser
authors.affiliation: From the Division of Pharmacology and Vascular Medicine, Department of Internal Medicine (K.I., A.H.J.D., I.M.G., A.H.v.d.M., A.M.V.D.B.), and Departments of Gynaecology (W.v.D.), Psychiatry (S.A.K.), and Biostatistics (E.M.E.H.L.), Erasmus MC, Rotterdam; and Department of Neurology (W.P.J.v.O., G.M.T., M.D.F.), Leiden University Medical Center, the Netherlands.
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Garrelds
authors.affiliation: From the Division of Pharmacology and Vascular Medicine, Department of Internal Medicine (K.I., A.H.J.D., I.M.G., A.H.v.d.M., A.M.V.D.B.), and Departments of Gynaecology (W.v.D.), Psychiatry (S.A.K.), and Biostatistics (E.M.E.H.L.), Erasmus MC, Rotterdam; and Department of Neurology (W.P.J.v.O., G.M.T., M.D.F.), Leiden University Medical Center, the Netherlands.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Kushner
authors.affiliation: From the Division of Pharmacology and Vascular Medicine, Department of Internal Medicine (K.I., A.H.J.D., I.M.G., A.H.v.d.M., A.M.V.D.B.), and Departments of Gynaecology (W.v.D.), Psychiatry (S.A.K.), and Biostatistics (E.M.E.H.L.), Erasmus MC, Rotterdam; and Department of Neurology (W.P.J.v.O., G.M.T., M.D.F.), Leiden University Medical Center, the Netherlands.
authors.forename: Emmanuel M E H
authors.initials: EM
authors.lastname: Lesaffre
authors.affiliation: From the Division of Pharmacology and Vascular Medicine, Department of Internal Medicine (K.I., A.H.J.D., I.M.G., A.H.v.d.M., A.M.V.D.B.), and Departments of Gynaecology (W.v.D.), Psychiatry (S.A.K.), and Biostatistics (E.M.E.H.L.), Erasmus MC, Rotterdam; and Department of Neurology (W.P.J.v.O., G.M.T., M.D.F.), Leiden University Medical Center, the Netherlands.
authors.forename: G M
authors.initials: GM
authors.lastname: Terwindt
authors.affiliation: From the Division of Pharmacology and Vascular Medicine, Department of Internal Medicine (K.I., A.H.J.D., I.M.G., A.H.v.d.M., A.M.V.D.B.), and Departments of Gynaecology (W.v.D.), Psychiatry (S.A.K.), and Biostatistics (E.M.E.H.L.), Erasmus MC, Rotterdam; and Department of Neurology (W.P.J.v.O., G.M.T., M.D.F.), Leiden University Medical Center, the Netherlands.
authors.forename: Michel D
authors.initials: MD
authors.lastname: Ferrari
authors.affiliation: From the Division of Pharmacology and Vascular Medicine, Department of Internal Medicine (K.I., A.H.J.D., I.M.G., A.H.v.d.M., A.M.V.D.B.), and Departments of Gynaecology (W.v.D.), Psychiatry (S.A.K.), and Biostatistics (E.M.E.H.L.), Erasmus MC, Rotterdam; and Department of Neurology (W.P.J.v.O., G.M.T., M.D.F.), Leiden University Medical Center, the Netherlands.
authors.forename: Anton H
authors.initials: AH
authors.lastname: van den Meiracker
authors.affiliation: From the Division of Pharmacology and Vascular Medicine, Department of Internal Medicine (K.I., A.H.J.D., I.M.G., A.H.v.d.M., A.M.V.D.B.), and Departments of Gynaecology (W.v.D.), Psychiatry (S.A.K.), and Biostatistics (E.M.E.H.L.), Erasmus MC, Rotterdam; and Department of Neurology (W.P.J.v.O., G.M.T., M.D.F.), Leiden University Medical Center, the Netherlands. a.vanharen-maassenvandenbrink@erasmusmc.nl.
authors.forename: Antoinette
authors.initials: A
authors.lastname: MaassenVanDenBrink
mesh_terms: D000328:Adult; D000368:Aged; D002211:Capsaicin / Q000494:pharmacology*; D016022:Case-Control Studies; D004558:Electric Stimulation; D004967:Estrogens / Q000097:blood; D005260:Female; D005546:Forehead; D006801:Humans; D008599:Menstruation Disturbances / Q000503:physiopathology*; D008875:Middle Aged; D008881:Migraine Disorders / Q000503:physiopathology*; D010507:Periodicity; D011374:Progesterone / Q000097:blood; D018689:Sensory System Agents / Q000494:pharmacology*; D012867:Skin / Q000098:blood supply*; D014276:Trigeminal Nerve / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D004967:Estrogens; D018689:Sensory System Agents; D011374:Progesterone; D002211:Capsaicin