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July 05, 2016; 87 (1) Article

Sex hormones in women with and without migraine

Evidence of migraine-specific hormone profiles

Jelena M. Pavlović, Amanda A. Allshouse, Nanette F. Santoro, Sybil L. Crawford, Rebecca C. Thurston, Genevieve S. Neal-Perry, Richard B. Lipton, Carol A. Derby
First published June 1, 2016, DOI: https://doi.org/10.1212/WNL.0000000000002798
Jelena M. Pavlović
From the Departments of Neurology (J.M.P., R.B.L., C.A.D.) and Epidemiology and Population Health (R.B.L., C.A.D.), Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY; Department of Obstetrics and Gynecology (A.A.A., N.F.S.), University of Colorado Denver, Aurora; Division of Preventive and Behavioral Medicine (S.L.C.), Department of Medicine, University of Massachusetts Medical Center, Worcester; Department of Psychiatry (R.C.T.), University of Pittsburgh, PA; and Division of Reproductive Endocrinology and Infertility (G.S.N.-P.), Department of Obstetrics and Gynecology, University of Washington, Seattle.
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Amanda A. Allshouse
From the Departments of Neurology (J.M.P., R.B.L., C.A.D.) and Epidemiology and Population Health (R.B.L., C.A.D.), Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY; Department of Obstetrics and Gynecology (A.A.A., N.F.S.), University of Colorado Denver, Aurora; Division of Preventive and Behavioral Medicine (S.L.C.), Department of Medicine, University of Massachusetts Medical Center, Worcester; Department of Psychiatry (R.C.T.), University of Pittsburgh, PA; and Division of Reproductive Endocrinology and Infertility (G.S.N.-P.), Department of Obstetrics and Gynecology, University of Washington, Seattle.
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Nanette F. Santoro
From the Departments of Neurology (J.M.P., R.B.L., C.A.D.) and Epidemiology and Population Health (R.B.L., C.A.D.), Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY; Department of Obstetrics and Gynecology (A.A.A., N.F.S.), University of Colorado Denver, Aurora; Division of Preventive and Behavioral Medicine (S.L.C.), Department of Medicine, University of Massachusetts Medical Center, Worcester; Department of Psychiatry (R.C.T.), University of Pittsburgh, PA; and Division of Reproductive Endocrinology and Infertility (G.S.N.-P.), Department of Obstetrics and Gynecology, University of Washington, Seattle.
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Sybil L. Crawford
From the Departments of Neurology (J.M.P., R.B.L., C.A.D.) and Epidemiology and Population Health (R.B.L., C.A.D.), Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY; Department of Obstetrics and Gynecology (A.A.A., N.F.S.), University of Colorado Denver, Aurora; Division of Preventive and Behavioral Medicine (S.L.C.), Department of Medicine, University of Massachusetts Medical Center, Worcester; Department of Psychiatry (R.C.T.), University of Pittsburgh, PA; and Division of Reproductive Endocrinology and Infertility (G.S.N.-P.), Department of Obstetrics and Gynecology, University of Washington, Seattle.
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Rebecca C. Thurston
From the Departments of Neurology (J.M.P., R.B.L., C.A.D.) and Epidemiology and Population Health (R.B.L., C.A.D.), Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY; Department of Obstetrics and Gynecology (A.A.A., N.F.S.), University of Colorado Denver, Aurora; Division of Preventive and Behavioral Medicine (S.L.C.), Department of Medicine, University of Massachusetts Medical Center, Worcester; Department of Psychiatry (R.C.T.), University of Pittsburgh, PA; and Division of Reproductive Endocrinology and Infertility (G.S.N.-P.), Department of Obstetrics and Gynecology, University of Washington, Seattle.
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Genevieve S. Neal-Perry
From the Departments of Neurology (J.M.P., R.B.L., C.A.D.) and Epidemiology and Population Health (R.B.L., C.A.D.), Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY; Department of Obstetrics and Gynecology (A.A.A., N.F.S.), University of Colorado Denver, Aurora; Division of Preventive and Behavioral Medicine (S.L.C.), Department of Medicine, University of Massachusetts Medical Center, Worcester; Department of Psychiatry (R.C.T.), University of Pittsburgh, PA; and Division of Reproductive Endocrinology and Infertility (G.S.N.-P.), Department of Obstetrics and Gynecology, University of Washington, Seattle.
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Richard B. Lipton
From the Departments of Neurology (J.M.P., R.B.L., C.A.D.) and Epidemiology and Population Health (R.B.L., C.A.D.), Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY; Department of Obstetrics and Gynecology (A.A.A., N.F.S.), University of Colorado Denver, Aurora; Division of Preventive and Behavioral Medicine (S.L.C.), Department of Medicine, University of Massachusetts Medical Center, Worcester; Department of Psychiatry (R.C.T.), University of Pittsburgh, PA; and Division of Reproductive Endocrinology and Infertility (G.S.N.-P.), Department of Obstetrics and Gynecology, University of Washington, Seattle.
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Carol A. Derby
From the Departments of Neurology (J.M.P., R.B.L., C.A.D.) and Epidemiology and Population Health (R.B.L., C.A.D.), Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY; Department of Obstetrics and Gynecology (A.A.A., N.F.S.), University of Colorado Denver, Aurora; Division of Preventive and Behavioral Medicine (S.L.C.), Department of Medicine, University of Massachusetts Medical Center, Worcester; Department of Psychiatry (R.C.T.), University of Pittsburgh, PA; and Division of Reproductive Endocrinology and Infertility (G.S.N.-P.), Department of Obstetrics and Gynecology, University of Washington, Seattle.
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Citation
Sex hormones in women with and without migraine
Evidence of migraine-specific hormone profiles
Jelena M. Pavlović, Amanda A. Allshouse, Nanette F. Santoro, Sybil L. Crawford, Rebecca C. Thurston, Genevieve S. Neal-Perry, Richard B. Lipton, Carol A. Derby
Neurology Jul 2016, 87 (1) 49-56; DOI: 10.1212/WNL.0000000000002798

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Abstract

Objective: To compare daily sex hormone levels and rates of change between women with history of migraine and controls.

Methods: History of migraine, daily headache diaries, and daily hormone data were collected in ovulatory cycles of pre- and early perimenopausal women in the Study of Women's Health Across the Nation. Peak hormone levels, average daily levels, and within-woman day-to-day rates of decline over the 5 days following each hormone peak were calculated in ovulatory cycles for conjugated urinary estrogens (E1c), pregnanediol-3-glucuronide, luteinizing hormone, and follicle-stimulating hormone. Comparisons were made between migraineurs and controls using 2-sample t tests on the log scale with results reported as geometric means.

Results: The sample included 114 women with history of migraine and 223 controls. Analyses of within-woman rates of decline showed that E1c decline over the 2 days following the luteal peak was greater in migraineurs for both absolute rate of decline (33.8 [95% confidence interval 28.0–40.8] pg/mgCr vs 23.1 [95% confidence interval 20.1–26.6] pg/mgCr, p = 0.002) and percent change (40% vs 30%, p < 0.001). There was no significant difference between migraineurs and controls in absolute peak or daily E1c, pregnanediol-3-glucuronide, luteinizing hormone, and follicle-stimulating hormone levels. Secondary analyses demonstrated that, among migraineurs, the rate of E1c decline did not differ according to whether a headache occurred during the cycle studied.

Conclusions: Migraineurs are characterized by faster late luteal phase E1c decline compared to controls. The timing and rate of estrogen withdrawal before menses may be a marker of neuroendocrine vulnerability in women with migraine.

GLOSSARY

BMI=
body mass index;
DHS=
Daily Hormone Study;
E1c=
conjugated urinary estrogens;
ELA=
evidence of luteal activity;
FSH=
follicle-stimulating hormone;
ICHD=
International Classification of Headache Disorders;
LH=
luteinizing hormone;
MHx=
women with history of migraine;
Pdg=
pregnanediol-3-glucuronide;
SWAN=
Study of Women's Health Across the Nation

Footnotes

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

  • Supplemental data at Neurology.org

  • Received September 9, 2015.
  • Accepted in final form March 17, 2016.
  • © 2016 American Academy of Neurology
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