Estradiol supplementation modulates neuroendocrine response to M-chlorophenylpiperazine in menstrual status migrainosus triggered by oral contraception-free interval

R. E. Nappi, G. Sances, B. Brundu, S. De Taddei, A. Sommacal, N. Ghiotto, F. Polatti, G. Nappi

Research output: Contribution to journalArticle

Abstract

Background: Migraine triggered by oral contraception (OC)-free interval is very common and may be extremely severe, long-lasting and poorly responsive to analgesics (status migrainosus). The serotoninergic (5-HT) system is crucially involved in pain threshold and it is sensitive to estradiol (E2). Therefore, we aimed to assess neuroendocrine correlates of OC status migrainosus in response to the direct central 5-HT agonist meta-chlorophenylpiperazine (m-CPP) and to test the effect of transdermal E2 supplementation of the OC-free interval. Methods: Clinical investigative protocol, single-blinded placebo-controlled treatment. Oral m-CPP (0.5 mg/kg body weight) challenge test was performed in 10 patients with status migrainosus occurring within 48 h of the discontinuation of a monophasic pill (30 μg of ethinyl estradiol and 150 μg of desogestrel) and in six healthy women assuming the same OC as controls. In a consecutive menstrual cycle, patients with OC status migrainosus underwent to the same test after they were blindly treated with 2.0 g of percutaneous E2 gel or placebo daily during the pill-free interval. Plasma prolactin and cortisol levels and clinical characteristics of migraine attacks were evaluated. Results: Women with OC-status migrainosus showed a derangement of prolactin release (F = 4.8; P <0.01) and a lack of cortisol response (F = 5.8; P <0.001) after m-CPP in comparison with controls. Transdermal E2 during the pill-free interval significantly restored prolactin (F = 2.8; P <0.01) and cortisol responses (F = 18.9; P <0.001) against placebo and positively affected the duration (P <0.001), the number of hours in which pain intensity prohibits daily activity (P <0.001), the episodes of vomiting (P <0.001) and the consumption of analgesics (P <0.001). Conclusions: Status migrainosus triggered by OC-free interval is associated with impaired prolactin and cortisol responses following m-CPP challenge. Transdermal E2 supplementation is able to restore neuroendocrine response to this specific 5-HT agent, exerting a positive clinical effect on the course of menstrually related migraine.

Original languageEnglish
Pages (from-to)3423-3428
Number of pages6
JournalHuman Reproduction
Volume20
Issue number12
DOIs
Publication statusPublished - Dec 2005

Fingerprint

Migraine Disorders
Contraception
Estradiol
Prolactin
Hydrocortisone
Placebos
Analgesics
Serotonin
Desogestrel
Serotonin Receptor Agonists
Ethinyl Estradiol
Pain Threshold
Menstrual Cycle
Clinical Protocols
Vomiting
Gels
Body Weight
Pain
1-(3-chlorophenyl)piperazine

Keywords

  • Estradiol
  • Meta-chlorophenylpiperazine test
  • Oral contraception
  • Pill-free interval
  • Status migrainosus

ASJC Scopus subject areas

  • Physiology
  • Developmental Biology
  • Obstetrics and Gynaecology
  • Reproductive Medicine

Cite this

Estradiol supplementation modulates neuroendocrine response to M-chlorophenylpiperazine in menstrual status migrainosus triggered by oral contraception-free interval. / Nappi, R. E.; Sances, G.; Brundu, B.; De Taddei, S.; Sommacal, A.; Ghiotto, N.; Polatti, F.; Nappi, G.

In: Human Reproduction, Vol. 20, No. 12, 12.2005, p. 3423-3428.

Research output: Contribution to journalArticle

@article{2fcc408d6f9740de943201617afe9628,
title = "Estradiol supplementation modulates neuroendocrine response to M-chlorophenylpiperazine in menstrual status migrainosus triggered by oral contraception-free interval",
abstract = "Background: Migraine triggered by oral contraception (OC)-free interval is very common and may be extremely severe, long-lasting and poorly responsive to analgesics (status migrainosus). The serotoninergic (5-HT) system is crucially involved in pain threshold and it is sensitive to estradiol (E2). Therefore, we aimed to assess neuroendocrine correlates of OC status migrainosus in response to the direct central 5-HT agonist meta-chlorophenylpiperazine (m-CPP) and to test the effect of transdermal E2 supplementation of the OC-free interval. Methods: Clinical investigative protocol, single-blinded placebo-controlled treatment. Oral m-CPP (0.5 mg/kg body weight) challenge test was performed in 10 patients with status migrainosus occurring within 48 h of the discontinuation of a monophasic pill (30 μg of ethinyl estradiol and 150 μg of desogestrel) and in six healthy women assuming the same OC as controls. In a consecutive menstrual cycle, patients with OC status migrainosus underwent to the same test after they were blindly treated with 2.0 g of percutaneous E2 gel or placebo daily during the pill-free interval. Plasma prolactin and cortisol levels and clinical characteristics of migraine attacks were evaluated. Results: Women with OC-status migrainosus showed a derangement of prolactin release (F = 4.8; P <0.01) and a lack of cortisol response (F = 5.8; P <0.001) after m-CPP in comparison with controls. Transdermal E2 during the pill-free interval significantly restored prolactin (F = 2.8; P <0.01) and cortisol responses (F = 18.9; P <0.001) against placebo and positively affected the duration (P <0.001), the number of hours in which pain intensity prohibits daily activity (P <0.001), the episodes of vomiting (P <0.001) and the consumption of analgesics (P <0.001). Conclusions: Status migrainosus triggered by OC-free interval is associated with impaired prolactin and cortisol responses following m-CPP challenge. Transdermal E2 supplementation is able to restore neuroendocrine response to this specific 5-HT agent, exerting a positive clinical effect on the course of menstrually related migraine.",
keywords = "Estradiol, Meta-chlorophenylpiperazine test, Oral contraception, Pill-free interval, Status migrainosus",
author = "Nappi, {R. E.} and G. Sances and B. Brundu and {De Taddei}, S. and A. Sommacal and N. Ghiotto and F. Polatti and G. Nappi",
year = "2005",
month = "12",
doi = "10.1093/humrep/dei260",
language = "English",
volume = "20",
pages = "3423--3428",
journal = "Human Reproduction",
issn = "0268-1161",
publisher = "Oxford University Press",
number = "12",

}

TY - JOUR

T1 - Estradiol supplementation modulates neuroendocrine response to M-chlorophenylpiperazine in menstrual status migrainosus triggered by oral contraception-free interval

AU - Nappi, R. E.

AU - Sances, G.

AU - Brundu, B.

AU - De Taddei, S.

AU - Sommacal, A.

AU - Ghiotto, N.

AU - Polatti, F.

AU - Nappi, G.

PY - 2005/12

Y1 - 2005/12

N2 - Background: Migraine triggered by oral contraception (OC)-free interval is very common and may be extremely severe, long-lasting and poorly responsive to analgesics (status migrainosus). The serotoninergic (5-HT) system is crucially involved in pain threshold and it is sensitive to estradiol (E2). Therefore, we aimed to assess neuroendocrine correlates of OC status migrainosus in response to the direct central 5-HT agonist meta-chlorophenylpiperazine (m-CPP) and to test the effect of transdermal E2 supplementation of the OC-free interval. Methods: Clinical investigative protocol, single-blinded placebo-controlled treatment. Oral m-CPP (0.5 mg/kg body weight) challenge test was performed in 10 patients with status migrainosus occurring within 48 h of the discontinuation of a monophasic pill (30 μg of ethinyl estradiol and 150 μg of desogestrel) and in six healthy women assuming the same OC as controls. In a consecutive menstrual cycle, patients with OC status migrainosus underwent to the same test after they were blindly treated with 2.0 g of percutaneous E2 gel or placebo daily during the pill-free interval. Plasma prolactin and cortisol levels and clinical characteristics of migraine attacks were evaluated. Results: Women with OC-status migrainosus showed a derangement of prolactin release (F = 4.8; P <0.01) and a lack of cortisol response (F = 5.8; P <0.001) after m-CPP in comparison with controls. Transdermal E2 during the pill-free interval significantly restored prolactin (F = 2.8; P <0.01) and cortisol responses (F = 18.9; P <0.001) against placebo and positively affected the duration (P <0.001), the number of hours in which pain intensity prohibits daily activity (P <0.001), the episodes of vomiting (P <0.001) and the consumption of analgesics (P <0.001). Conclusions: Status migrainosus triggered by OC-free interval is associated with impaired prolactin and cortisol responses following m-CPP challenge. Transdermal E2 supplementation is able to restore neuroendocrine response to this specific 5-HT agent, exerting a positive clinical effect on the course of menstrually related migraine.

AB - Background: Migraine triggered by oral contraception (OC)-free interval is very common and may be extremely severe, long-lasting and poorly responsive to analgesics (status migrainosus). The serotoninergic (5-HT) system is crucially involved in pain threshold and it is sensitive to estradiol (E2). Therefore, we aimed to assess neuroendocrine correlates of OC status migrainosus in response to the direct central 5-HT agonist meta-chlorophenylpiperazine (m-CPP) and to test the effect of transdermal E2 supplementation of the OC-free interval. Methods: Clinical investigative protocol, single-blinded placebo-controlled treatment. Oral m-CPP (0.5 mg/kg body weight) challenge test was performed in 10 patients with status migrainosus occurring within 48 h of the discontinuation of a monophasic pill (30 μg of ethinyl estradiol and 150 μg of desogestrel) and in six healthy women assuming the same OC as controls. In a consecutive menstrual cycle, patients with OC status migrainosus underwent to the same test after they were blindly treated with 2.0 g of percutaneous E2 gel or placebo daily during the pill-free interval. Plasma prolactin and cortisol levels and clinical characteristics of migraine attacks were evaluated. Results: Women with OC-status migrainosus showed a derangement of prolactin release (F = 4.8; P <0.01) and a lack of cortisol response (F = 5.8; P <0.001) after m-CPP in comparison with controls. Transdermal E2 during the pill-free interval significantly restored prolactin (F = 2.8; P <0.01) and cortisol responses (F = 18.9; P <0.001) against placebo and positively affected the duration (P <0.001), the number of hours in which pain intensity prohibits daily activity (P <0.001), the episodes of vomiting (P <0.001) and the consumption of analgesics (P <0.001). Conclusions: Status migrainosus triggered by OC-free interval is associated with impaired prolactin and cortisol responses following m-CPP challenge. Transdermal E2 supplementation is able to restore neuroendocrine response to this specific 5-HT agent, exerting a positive clinical effect on the course of menstrually related migraine.

KW - Estradiol

KW - Meta-chlorophenylpiperazine test

KW - Oral contraception

KW - Pill-free interval

KW - Status migrainosus

UR - http://www.scopus.com/inward/record.url?scp=28544433510&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=28544433510&partnerID=8YFLogxK

U2 - 10.1093/humrep/dei260

DO - 10.1093/humrep/dei260

M3 - Article

C2 - 16123089

AN - SCOPUS:28544433510

VL - 20

SP - 3423

EP - 3428

JO - Human Reproduction

JF - Human Reproduction

SN - 0268-1161

IS - 12

ER -