Effect of a contraceptive pill containing estradiol valerate and dienogest (E2V/DNG) in women with menstrually-related migraine (MRM)

• Published in: Contraception (Stoneham) Vol. 88; no. 3; pp. 369 - 375
• Main Authors: Nappi, Rossella E., Terreno, Erica, Sances, Grazia, Martini, Ellis, Tonani, Silvia, Santamaria, Valentina, Tassorelli, Cristina, Spinillo, Arsenio
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.09.2013; Elsevier
• Subjects: Adult; Analgesics - administration & dosage; Biological and medical sciences; Bleeding; Body Mass Index; Contraceptives, Oral, Combined - administration & dosage; Dienogest; Dysmenorrhea; Dysmenorrhea - complications; Dysmenorrhea - drug therapy; Estradiol - administration & dosage; Estradiol - analogs & derivatives; Estradiol valerate; Female; Female genital diseases; Genital system. Reproduction; Gynecology. Andrology. Obstetrics; Hormonally associated headaches; Humans; Italy; Medical sciences; Menstruation; Migraine Disorders - drug therapy; Migraine Disorders - etiology; Migraine Disorders - physiopathology; Migraine without aura; Nandrolone - administration & dosage; Nandrolone - analogs & derivatives; Neurology; Non tumoral diseases; Obstetrics and Gynecology; Pharmacology. Drug treatments; Pilot Projects; Prospective Studies; Treatment Outcome; Vascular diseases and vascular malformations of the nervous system; Italy; Estradiol valerate; Migraine without aura; Hormonally associated headaches; Bleeding; Dysmenorrhea; Dienogest; Human; Menstruation disorders; Nervous system diseases; Migraine; Estrogen; Cardiovascular disease; Hemorrhage; Estrane derivatives; Female genital diseases; Cerebral disorder; Progestagen; Vascular disease; Pain; Central nervous system disease; Female; Contraceptive; Woman; Cerebrovascular disease
• ISSN: 0010-7824; 1879-0518; 1879-0518
• DOI: 10.1016/j.contraception.2013.02.001

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. 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. 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. 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.