Abstract
Background
Combined hormonal contraception might worsen migraine in sensitive women, especially
during the free-hormone interval, and raise concerns about the vascular risk. The
characteristics of a contraceptive pill containing estradiol valerate/dienogest (E2V/DNG)
might be of potential benefit in women with menstrually related migraine (MRM) who
choose to use oral contraception for birth control.
Study design
This was a prospective diary-based pilot study. Thirty-two women (age >35 years) [n=18 who had never used combined oral contraceptives (COCs) and n=14 who had previously used COCs] diagnosed with MRMs according to the International
Headache Society criteria were included. During the observational period, women filled
in a diary with the clinical characteristics of migraine attacks. After a three-cycle
run-in period, each subject received a COC containing E2V/DNG (Qlaira®/Natazia®; Bayer
HealthCare, Berlin, Germany) administered using an estrogen step-down and progestogen
step-up approach. Follow-up evaluations were scheduled at the last cycle of run-in
and at the third and sixth cycles of treatment.
Results
The number of migraine attacks was significantly reduced at the third (p<.001) and
sixth cycles (p<.001) in comparison with the run-in period. A similar result was evident
for the duration (p<.001 at the third and p<.001 at the sixth cycle) as well as for
the severity of head pain (p<.001 at the third and p<.001 at the sixth month). Indeed,
a significantly lower number of analgesics were used at the third cycle (p<.001) in
comparison with baseline, and a further decrease was evident at the sixth cycle (p<.001)
in comparison with the third cycle of E2V/DNG use. Interestingly, duration and severity
of head pain were significantly correlated with the number of days of dysmenorrhea
at the third cycle (r=.89, p=.000 and r=.67, p=.02; respectively) and at the sixth cycle (r=.76, p=.000 and r=.62, p=.04; respectively) in women without complete remission of menstrual cramps
during the study period.
Conclusions
The present diary-based pilot study indicates that the use of a pill containing EV2/DNG
for six cycles has a positive effect in women with MRM and suggests an association
between dysmenorrhea with COCs use as a potential feature of refractory head pain.
Keywords
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References
- Migraine and reproductive life.Handb Clin Neurol. 2010; 97: 303-322
The international classification of headache disorders, 2nd ed. Cephalalgia 2004;(suppl 1).
- Prevalence of migraine on each day of the natural menstrual cycle.Neurology. 2004; 63: 351-353
- Menstrual cycle and headache in a population sample of migraineurs.Neurology. 2000; 55: 1517-1523
- Migraine and menstruation: a pilot study.Cephalalgia. 1990; 10: 305-310
- Estrogen-withdrawal migraine.Neurology. 1975; 25: 239-244
- Menstrual migraine in a representative Dutch population sample: prevalence, disability and treatment.Cephalalgia. 2003; 23: 302-308
- Characteristics of menstrual and non-menstrual attacks in women with menstrually-related migraine.Cephalagia. 2004; 24: 707-716
- Migraine and use of combined hormonal contraceptives: a clinical review.J Fam Plann Reprod Health Care. 2007; 33: 159-169
- Headache and combination estrogen-progestin oral contraceptives: integrating evidence, guidelines, and clinical practice.Headache. 2005; 45: 224-231
- Headache as a side effect of combination estrogen-progestin oral contraceptives: a systematic review.Am J Obstet Gynecol. 2005; 193: 636-649
- Prevention of menstrual attacks of migraine: a double-blind placebo-controlled crossover study.Neurology. 2006; 67: 2159-2163
- Estradiol supplementation modulates neuroendocrine response to M-chlorophenylpiperazine in menstrual status migrainosus triggered by oral contraception-free interval.Hum Reprod. 2005; 20: 3423-3428
- Combined oral contraceptives in women with menstrual migraine without aura.Fertil Steril. 2011; 96: 917-920
- Acceptance of altering the standard 21-day/7-day oral contraceptive regimen to delay menses and reduce hormone withdrawal symptoms.Am J Obstet Gynecol. 2002; 18: 1142-1149
- Combined hormonal contraceptives: is it time to reassess their role in migraine?.Headache. 2012; 52: 648-660
- Oral contraceptives in migraine.Expert Rev Neurother. 2009; 9: 381-393
- The evolution of combined oral contraception: improving the risk-to-benefit ratio.Contraception. 2011; 84: 19-34
- The use of newer progestins for contraception.Contraception. 2010; 82: 410-417
- Pharmacokinetics of an oral contraceptive containing oestradiol valerate and dienogest.Eur J Contracept Reprod Health Care. 2009; 14: 221-232
- Bleeding pattern and cycle control with an estradiol-based oral contraceptive: a seven-cycle, randomized comparative trial of estradiol valerate/dienogest and ethinyl estradiol/levonorgestrel.Contraception. 2009; 80: 436-444
- Effective treatment of heavy and/or prolonged menstrual bleeding with an oral contraceptive containing estradiol valerate and dienogest: a randomized, double-blind Phase III trial.Hum Reprod. 2011; 26: 2698-2708
- Hormone withdrawal-associated symptoms (headache and pelvic pain) in women taking combined oral contraceptives: comparison of oestradiol valerate/dienogest versus ethinylestradiol/levonorgestrel.Eur J Contracept Reprod Health Care. 2012; 17 (ABSTR P092)
- Menstrual-related pain conditions: dysmenorrhea and migraine.J Womens Health. 2008; 17: 879-891
- Diaries and calendars for migraine. A review..Cephalalgia. 2006; 26: 905-916
- Metabolic and haemostatc effects of estradiol valerate/dienogest, a novel oral contraceptive: a randomized, open-label, single-centre study.Clin Drug Investig. 2011; 31: 573-584
- Effects of a monophasic combined oral contracetive containing nomegestrol acetate and 17b-oestradiol compared with one containing levonorgestrel and ethynilestradiol on haemostasis, lipids and carbohydrate metabolism.Eur J Contracept Reprod Health Care. 2011; 16: 444-457
- Surrogate end points in women's health research: science, protoscience and pseudoscience.Fertil Steril. 2010; 93: 1731-1734
- Pituitary, ovarian and additional contraceptive effects of an estradiol-based combined oral contraceptive: results of a randomized, open-label study.Contraception. 2012; (pii: S0010-7824(12)00674-9)https://doi.org/10.1016/j.contraception.2012.07.008
- Ovarian hormones and migraine headache: understanding mechanisms and pathogenesis — part 2.Headache. 2006; 46: 365-386
- Changes in salivary prostaglandin levels during menstrual migraine with associated dysmenorrhea.Headache. 2010; 50: 844-851
- Combination treatment for menstrual migraine and dysmenorrhea using sumatriptan–naproxen: two randomized controlled trials.Obstet Gynecol. 2009; 114: 106-113
- Nonsteroidal anti-inflammatory drugs for dysmenorrhoea.Cochrane Database Syst Rev. 2010 Jan 20; 1: CD001751
- Nonsteroidal anti-inflammatory drugs for heavy menstrual bleeding.Cochrane Database Syst Rev. 2007 Oct 17; 4: CD000400
- The pharmacology of dienogest.Maturitas. 2012; 71: 337-344
- Dienogest inhibits aromatase and cyclooxygenase-2 expression and prostaglandin E2 production in human endometriotic stromal cells in spheroid culture.Fertil Steril. 2012; 97: 477-482
- Normalization of blood loss in women with heavy menstrual bleeding treated with an oral contraceptive containing estradiol valerate/dienogest.Contraception. 2012; 86: 96-101
- Endometriosis and headache.Curr Pain Headache Rep. 2011; 15: 415-419
- Menstrual migraine: update on pathophysiology and approach to therapy and management.Curr Treat Options Neurol. 2012; 14: 1-14
Article info
Publication history
Published online: March 04, 2013
Accepted:
February 2,
2013
Received in revised form:
January 24,
2013
Received:
October 28,
2012
Footnotes
☆Conflicts of interest: During the past 2 years, Professor R.E. Nappi had a financial relationship (lecturer, member of advisory boards and/or consultant) with Bayer-Schering Pharma, Eli Lilly, Gedeon Richter, Merck Sharpe & Dohme, Novo Nordisk, Pfizer Inc. and Teva/Theramex.
Identification
Copyright
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
