Medical Oophorectomy With and Without Estrogen Add-Back Therapy in the Prevention of Migraine Headache


Address all correspondence to Dr. Vincent T. Martin, Division of General Internal Medicine, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 6603, Cincinnati, OH 45267-4217.


Objectives.—To determine the preventive benefit of “medical oophorectomy” and transdermal estradiol in women with migraine.

Background.—Epidemiological studies have demonstrated that declines in serum estrogen levels occurring during normal menstrual cycles can trigger headache in women with migraine. Prior to this study, no randomized controlled trials have evaluated whether minimizing these hormonal changes pharmacologically can prevent headache.

Methods.—Twenty-one women with regular menstrual cycles and a diagnosis of migraine headache were enrolled. After a 2.5-month placebo run-in phase, all patients received a subcutaneous goserelin implant (a gonadotropin-releasing hormone agonist) to induce a medical oophorectomy. One month later, while continuing goserelin, participants were randomized to receive a transdermal patch containing 100 μg of estradiol-17β (gonadotropin-releasing hormone agonist/estradiol group, n  =  9) or a placebo patch (gonadotropin-releasing hormone agonist/placebo group, n  =  12) during a 2-month treatment phase. The primary outcome measure was the headache index, which was defined as the mean of pain severity ratings (0 to 10 scale) recorded three times per day by daily diary. Secondary outcome measures included headache disability, headache severity, headache frequency, and the percentage of headaches with a pain severity rating of 7 or greater.

Results.—The headache index was significantly lower during the treatment period in the gonadotropin-releasing hormone agonist/estradiol group than in the gonadotropin-releasing hormone agonist/placebo group (P  =  .025). Similar improvements were observed in the gonadotropin-releasing hormone agonist/estradiol group for all secondary outcome measures with the exception of headache frequency, which was unchanged between the groups. Within the gonadotropin-releasing hormone agonist/estradiol group, there was a 33.7% reduction (95% confidence interval, −64.4 to −3.0) in the headache index during the treatment phase when compared with the placebo run-in phase; no difference was seen between those phases within the gonadotropin-releasing hormone agonist/placebo group.

Conclusions.—Minimization of hormonal fluctuations with gonadotropin-releasing hormone agonist therapy alone is inadequate to prevent headache in women who are premenopausal with migraine. The addition of transdermal estradiol to existing gonadotropin-releasing hormone agonist therapy provides a modest preventive benefit.