Sixty percent of women who experience migraine headaches self report that the headaches worsen with their menstrual period. The current literature suggests these headaches may be related to rapidly falling estrogen levels on migraine headaches outside of the perimenstrual period.
The specific aims of this study are as follows: 1) To evaluate the effect of hormone fluctuations on the severity and disability of migraine headaches. 2) To determine the impact of pharmacologically reducing hormonal fluctuations, using a GnRH agonist, on headache severity and disability. 3) To evaluate if adding constant doses of estrogen to women on a GnRH agonist decreases headache severity and disability. 4) To compare if there is a difference in headache severity and disability in women treated with GnRH alone compared to those treated with GnRH and the estogen therapy. 5) To evaluate cerebral blood flow velocities (BFV's) and CO2 cerebrovascular reactivity (CVR) using transcranial Doppler studies (TCD) in female migraineurs at different phases of the menstrual cycle. 6) To study the effect of hormonal manipulation (GnRH/placebo and GnRH/estrogen groups) on BVF's and CVR as compared to baseline measures. After patients have recorded baseline headaches and severity scores (daily) for 2-1/2 months (phase 1) they will be randomized in a double blind parallel fashion to either GnRH + placebo patches or GnRH + 100 mcg estradiol patches (phase 3). Outcome measures will include the visual analogue scale to assess headache severity, the Henry Ford Hospital Headache Disability Index to assess disability and the SF-36 to assess quality of life in these participants. The principle dependent variable concerning severity of headache will be the Cumulative Daily Severity Score (CDSS) defined as the sum of disability scores obtained three times daily. A daily average CDSS and CDDS between phase 1 and phase 3 within a given patient will be calculated. Treatment A and B will be compared using a paired t-test or a nonparametric Wilcoxon test for small sample sizes. Six TCD studies will be performed during the study; three during a normal menstrual cycle and three during GnRH therapy. A longitudinal mixed model analysis will be used to determine if BFV's change during a menstrual cycle and with pharmacologic manipulation. To date we have seven patients actively enrolled into the study. Three patients have entered into phase 3, two patients have entered phase 2, and 2 patients have entered phase 1. The final patient is still in her lead-in-month prior to phase 1. Efforts of recruitment through our Headache Clinic continue. No significant adverse effects have occurred in any of our patients. However, only 4 of our patients have received active GnRH injections. We have noted greater than 90% compliance in filling out the headache daily log sheets as well as collecting daily urine samples for assay of estrone glucuronide and pregnanediol glucuronide. As an additional part of our study we plan to perform transcranial Doppler studies on patients during the various phases of our study. We are in the process of purchasing a transcranial Doppler machine and Dr. Nabiah Ramadan will coordinate the performance of such studies.

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Cincinnati Children's Hospital Medical Center
United States
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