The minimum exposure to estrogen required to cause estrogen-withdrawal migraine has been studied by giving long-acting estradiol valerate to four women and short-acting estradiol benzoate to two women. It was found that several days of exposure to high estrogen levels were needed to cause migraine on estrogen withdrawal. Oral administration of estrogen supplements in the form of estradiol valerate or as conjugated equine estrogens during the premenstrual phase in four women did not significantly affect plasma levels of estradiol, nor was it effective in preventing menstrual migraine.
Prophylaxis of menstrual migraine was attempted in five women, using estradiol implants. The treatment was successful in suppressing ovulation and in producing high, although fluctuating, levels of estradiol in the plasma. Clinically this was associated with severe menstrual disturbance. The regular periodicity of the headaches was lost, but clinical benefit was unpredictable, with some patients actually experiencing more headaches than before the treatment. The administration of progesterone against a background of prolonged exposure to high estrogen levels did not provoke migraine, nor in any case did its subsequent withdrawal result in migraine. These findings cast further doubt on the importance of progesterone withdrawal in the etiology of menstrual migraine.
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