Higher-dose estrogen patch may prevent migraine: after medical oophorectomy

OB/GYN News, Oct 1, 2003 by Patrice G.W. Norton

CHICAGO -- Dosage maybe an important factor in the use of transdermal estradiol for prevention of headache in female migraineurs, Dr. Vincent T. Martin said at the annual meeting of the American Headache Society.

He reported new evidence from a long-term follow-up study showing that a trans dermal 100-[micro]g transdermal estradiol-17[beta] patch prevented headaches in migraineurs who had undergone medical oophorectomy. Yet a 50-[micro]g estradiol patch was not preventive, when compared with placebo.

This study is one of the first to suggest that the dosage of transdermal estradiol may play an important role in migraine prevention. If confirmed in larger-scale studies, the findings could suggest that higher doses of transdermal estrogen are required to prevent headache in premenopausal women with migraine, said Dr. Martin of the University of Cincinnati.

Currently, conflicting evidence suggests that higher doses of oral estrogen replacement therapy can both prevent and provoke headaches. In one study, a higher dose of estrogen replacement therapy was more effective in headache prevention than a lower dose (Am. J. Obstet. Gynecol. 111[2]:178-86, 1971). Others have reported a worsening of the aura (Headache 39[9]:674-78, 1999) and headache phases of migraine headaches (Cephalalgia 21[4]: 448-49, 2001) with higher doses of estrogen replacement therapy.

Evidence from a growing number of studies suggests an advantage of the transdermal estradiol patch over oral estrogen replacement therapy in the prevention of migraine.

Transdermal delivery might provide more constant estradiol levels and be less likely to provoke migraine, Dr. Martin said. More natural forms of estrogen, such as estradiol-17[beta], may be preferable to oral conjugated estrogen.

His study was a continuation of a randomized controlled study examining the effects of medical oophorectomy with and without estrogen add-back in the prevention of migraine. The 21 women in the study were not required to have menstrual-related migraine, but many were convinced that they had menstrual-related migraines, and their migraines occurred almost exclusively during menses. The study included a 2.5-month placebo run-in phase, a 1-month phase during which a medical oophorectomy was induced, and a 2-month phase in which patients were randomized to a 100-[micro]g patch of estradiol-17[beta] or matching placebo.

After completing the study, 11 of the women volunteered to participate in the 1-year follow-up study and were randomized to 50-[micro]g or 100-[micro]g estradiol-17[beta] patch. Both groups maintained medical oophorectomy with monthly injections of goserelin, a GnRH agonist. A 4% vaginal progesterone cream was administered for the first 10 days of each month to prevent endometrial hyperplasia.

The women recorded headache severity (0-10 scale) and disability (0-5) three times per day in a headache diary. The primary outcome Was the headache index, defined as the mean of the pain severity ratings.

As Dr. Martin and his colleagues reported earlier, the 100-[micro]g estradiol patch in the short-term study reduced the headache index by 33% in female migraineurs who had undergone medical oophorectomy, compared with severity ratings during the 2.5-month placebo run-in phase prior to the medical oophorectomy.

In the follow-up study, the magnitude of improvement with the 100-[micro]g patch (31%) was similar to the improvement seen in the original study. This suggests that the improvement is maintained over time and also that the introduction of vaginal progesterone did not adversely affect outcomes, he said.