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July 24, 2018; 91 (4) Article

Female sex hormones in men with migraine

Willebrordus P.J. van Oosterhout, Guus G. Schoonman, Erik W. van Zwet, Olaf M. Dekkers, Gisela M. Terwindt, Antoinette MaassenVanDenBrink, Michel D. Ferrari
First published June 27, 2018, DOI: https://doi.org/10.1212/WNL.0000000000005855
Willebrordus P.J. van Oosterhout
From the Departments of Neurology (W.P.J.v.O., G.G.S., G.M.T, M.D.F.), Medical Statistics (E.W.v.Z.), and Endocrinology (O.M.D.), Leiden University Medical Center, Rotterdam; Department of Neurology (W.P.J.v.O.), OLVG Hospital, Amsterdam; Department of Neurology (G.G.S.), Elisabeth Tweesteden Hospital, Tilburg; and Department of Internal Medicine (A.M.), Division of Vascular Medicine and Pharmacology, Erasmus Medical Centre, Rotterdam, the Netherlands.
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Guus G. Schoonman
From the Departments of Neurology (W.P.J.v.O., G.G.S., G.M.T, M.D.F.), Medical Statistics (E.W.v.Z.), and Endocrinology (O.M.D.), Leiden University Medical Center, Rotterdam; Department of Neurology (W.P.J.v.O.), OLVG Hospital, Amsterdam; Department of Neurology (G.G.S.), Elisabeth Tweesteden Hospital, Tilburg; and Department of Internal Medicine (A.M.), Division of Vascular Medicine and Pharmacology, Erasmus Medical Centre, Rotterdam, the Netherlands.
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Erik W. van Zwet
From the Departments of Neurology (W.P.J.v.O., G.G.S., G.M.T, M.D.F.), Medical Statistics (E.W.v.Z.), and Endocrinology (O.M.D.), Leiden University Medical Center, Rotterdam; Department of Neurology (W.P.J.v.O.), OLVG Hospital, Amsterdam; Department of Neurology (G.G.S.), Elisabeth Tweesteden Hospital, Tilburg; and Department of Internal Medicine (A.M.), Division of Vascular Medicine and Pharmacology, Erasmus Medical Centre, Rotterdam, the Netherlands.
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Olaf M. Dekkers
From the Departments of Neurology (W.P.J.v.O., G.G.S., G.M.T, M.D.F.), Medical Statistics (E.W.v.Z.), and Endocrinology (O.M.D.), Leiden University Medical Center, Rotterdam; Department of Neurology (W.P.J.v.O.), OLVG Hospital, Amsterdam; Department of Neurology (G.G.S.), Elisabeth Tweesteden Hospital, Tilburg; and Department of Internal Medicine (A.M.), Division of Vascular Medicine and Pharmacology, Erasmus Medical Centre, Rotterdam, the Netherlands.
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Gisela M. Terwindt
From the Departments of Neurology (W.P.J.v.O., G.G.S., G.M.T, M.D.F.), Medical Statistics (E.W.v.Z.), and Endocrinology (O.M.D.), Leiden University Medical Center, Rotterdam; Department of Neurology (W.P.J.v.O.), OLVG Hospital, Amsterdam; Department of Neurology (G.G.S.), Elisabeth Tweesteden Hospital, Tilburg; and Department of Internal Medicine (A.M.), Division of Vascular Medicine and Pharmacology, Erasmus Medical Centre, Rotterdam, the Netherlands.
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Antoinette MaassenVanDenBrink
From the Departments of Neurology (W.P.J.v.O., G.G.S., G.M.T, M.D.F.), Medical Statistics (E.W.v.Z.), and Endocrinology (O.M.D.), Leiden University Medical Center, Rotterdam; Department of Neurology (W.P.J.v.O.), OLVG Hospital, Amsterdam; Department of Neurology (G.G.S.), Elisabeth Tweesteden Hospital, Tilburg; and Department of Internal Medicine (A.M.), Division of Vascular Medicine and Pharmacology, Erasmus Medical Centre, Rotterdam, the Netherlands.
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Michel D. Ferrari
From the Departments of Neurology (W.P.J.v.O., G.G.S., G.M.T, M.D.F.), Medical Statistics (E.W.v.Z.), and Endocrinology (O.M.D.), Leiden University Medical Center, Rotterdam; Department of Neurology (W.P.J.v.O.), OLVG Hospital, Amsterdam; Department of Neurology (G.G.S.), Elisabeth Tweesteden Hospital, Tilburg; and Department of Internal Medicine (A.M.), Division of Vascular Medicine and Pharmacology, Erasmus Medical Centre, Rotterdam, the Netherlands.
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Citation
Female sex hormones in men with migraine
Willebrordus P.J. van Oosterhout, Guus G. Schoonman, Erik W. van Zwet, Olaf M. Dekkers, Gisela M. Terwindt, Antoinette MaassenVanDenBrink, Michel D. Ferrari
Neurology Jul 2018, 91 (4) e374-e381; DOI: 10.1212/WNL.0000000000005855

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Abstract

Objective To assess the role of estradiol and testosterone in men with migraine.

Methods We measured 17β-estradiol (E2) and calculated free testosterone (Tf) in serum of 17 medication-free men with migraine and 22 men without migraine group-matched for age and body mass index (BMI), targeted at 20 to 28 kg/m2. Blood was sampled on a single, for migraineurs interictal, day at 9 am, 12 pm, 3 pm, and 6 pm. Migraineurs were subsequently measured 3 to 4 times daily until an attack occurred. Clinical androgen deficiency was assessed with the Androgen Deficiency of Ageing Men questionnaire and the Aging Males' Symptoms (AMS) scale. We analyzed interictal data (mean ± standard error) with repeated-measures analysis of covariance and longitudinal data by generalized estimated equations models.

Results Compared to controls, men with migraine had a lower interictal Tf/E2 ratio (3.9 ± 0.4 vs 5.0 ± 0.3, p = 0.03) due to higher E2 (96.8 ± 6.1 vs 69.1 ± 5.6 pmol/L, p = 0.001) and similar Tf (357.5 ± 21.4 vs 332.6 ± 18.7 pmol/L, p = 0.35) levels. Preictal Tf levels were increased in men with migraine reporting premonitory symptoms (p = 0.03). Men with migraine more frequently reported symptoms of androgen deficiency (11 of 18 [61.1%] vs 6 of 22 [27.3%], p = 0.031), which were also more frequently severe (p = 0.006); their age- and BMI-adjusted AMS scores were higher (27.0 ± 1.2 vs 21.0 ± 1.0, p = 0.002).

Conclusions In this study, nonobese men with migraine exhibited increased levels of the sex hormone estradiol and showed clinical evidence of relative androgen deficiency. The role of estradiol in modulating migraine susceptibility and activity in men deserves further investigations.

Glossary

ADAM=
Androgen Deficiency of Ageing Men;
AMS=
Aging Males' Symptoms;
BMI=
body mass index;
CSD=
cortical spreading depolarization;
LUMINA=
Leiden University Medical Centre Migraine Neuro Analysis;
SHBG=
sex hormone–binding globulin;
Tf=
free testosterone

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received November 24, 2017.
  • Accepted in final form April 19, 2018.
  • © 2018 American Academy of Neurology
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