A Novel Specific Prophylaxis for Menstrual-Associated Migraine
A Novel Specific Prophylaxis for Menstrual-Associated Migraine
Objectives: Few migraine prophylactic therapies have demonstrated a 50% reduction in headaches. Even when successful, the economic burden of prophylaxis can discourage widespread usage. This article presents a pilot study of a novel, effective, specific, and inexpensive prophylactic strategy for menstrual-associated migraine.
Materials and Methods: Eleven women with menstrual-associated migraine and fewer than 14 days of headache per month were identified from prospective enrollment at a gynecology practice and retrospective chart review at a headache center. Exclusion criteria included current use of prophylactic therapy for migraine.
Methods: Patients received open-label therapy with an oral contraceptive containing 20 µg ethinyl estradiol on days 1 to 21, supplemented with 0.9 mg conjugated equine estrogens on days 22 to 28. Headache intensity and bleeding were recorded in diaries that plotted headache days by oral contraceptive pill days.
Results: All of the patients achieved at least a 50% reduction in number of headache days per cycle (mean 77.9% reduction); 10 of the 11 women achieved at least a 50% reduction in weighted headache score (mean 76.3% reduction).
Conclusions: All currently available estrogen-containing oral contraceptives produce a premenstrual fall in ethinyl estradiol concentration equal to or greater than 20 µg. Estrogen supplementation during the placebo week can reduce the magnitude of this fall to less than 20 µg. When the decline is limited to the equivalent of 10 µg ethinyl estradiol, menstrual-associated migraine is prevented. At an average cost of six dollars per headache-day prevented, this represents an effective and inexpensive strategy for a common migraine trigger.
The predominance of migraine in reproductive-aged women and its associated clinical, social, and economic burden make it one of the most important medical issues in women's health. By the conclusion of reproductive years this common headache disorder has affected up to 40.9% of women. With up to 70% of female migraineurs noting relationship of their migraines to menses, menstruation is arguably the most common migraine trigger of all.
Few migraine prophylactic therapies demonstrate a 50% reduction in headaches. Even when successful, the economic burden of prophylaxis can be substantial, ranging as high as $138 per headache-day prevented. This article presents a small open-label pilot study of a novel specific therapy for prevention of menstrual-associated migraine (MAM) that is highly effective, inexpensive, and well-tolerated.
Hormonal-associated migraine occurs in many settings. It may occur exclusively with menses and be the only migraine that a woman experiences: the so-called true menstrual migraine. It may be predictable, but only one of several migraines in a month: the menstrual-associated migraine. Migraines may occur with scheduled withdrawals from exogenous estrogen-containing products such as oral contraceptives (OCs), postmenopausal estrogen therapy, or hormone therapy. In addition, they may occur with unintentional estrogen withdrawal on these products. These withdrawals may be secondary to missed doses, delayed doses, or increased metabolism of the estrogen component of the OC via cytochrome P450 3A4 or 1A2 interactions.
Hormonal association of headaches is exceedingly common. In a population of 262 women seen in a gynecology clinic for refill or initiation of OCs, 70% experienced headache during the placebo week of their OC. Reports have stated the prevalence of menstrual association in female migraineurs as high as 70%.
In the natural menstrual cycle, the late luteal phase decline in estradiol concentration is equivalent to a decline of 20 to 25 µg of the synthetic estrogen, ethinyl estradiol (EE) (Fig. 1). In a previous pilot study, the author found that reducing the premenstrual fall in estradiol to the equivalent of 10 µg EE or less was beneficial in preventing menstrual migraine. In that study, a variety of hormonal strategies were utilized, each of which accomplished the critical reduction in the magnitude of the premenstrual estradiol decline. This study investigates a single prophylactic strategy.
(Enlarge Image)
Physiologic premenstrual decline in estradiol concentration is equivalent to 20-25 µg ethinyl estradiol, and precipitates menstrual-associated migraine in susceptible women.
Objectives: Few migraine prophylactic therapies have demonstrated a 50% reduction in headaches. Even when successful, the economic burden of prophylaxis can discourage widespread usage. This article presents a pilot study of a novel, effective, specific, and inexpensive prophylactic strategy for menstrual-associated migraine.
Materials and Methods: Eleven women with menstrual-associated migraine and fewer than 14 days of headache per month were identified from prospective enrollment at a gynecology practice and retrospective chart review at a headache center. Exclusion criteria included current use of prophylactic therapy for migraine.
Methods: Patients received open-label therapy with an oral contraceptive containing 20 µg ethinyl estradiol on days 1 to 21, supplemented with 0.9 mg conjugated equine estrogens on days 22 to 28. Headache intensity and bleeding were recorded in diaries that plotted headache days by oral contraceptive pill days.
Results: All of the patients achieved at least a 50% reduction in number of headache days per cycle (mean 77.9% reduction); 10 of the 11 women achieved at least a 50% reduction in weighted headache score (mean 76.3% reduction).
Conclusions: All currently available estrogen-containing oral contraceptives produce a premenstrual fall in ethinyl estradiol concentration equal to or greater than 20 µg. Estrogen supplementation during the placebo week can reduce the magnitude of this fall to less than 20 µg. When the decline is limited to the equivalent of 10 µg ethinyl estradiol, menstrual-associated migraine is prevented. At an average cost of six dollars per headache-day prevented, this represents an effective and inexpensive strategy for a common migraine trigger.
The predominance of migraine in reproductive-aged women and its associated clinical, social, and economic burden make it one of the most important medical issues in women's health. By the conclusion of reproductive years this common headache disorder has affected up to 40.9% of women. With up to 70% of female migraineurs noting relationship of their migraines to menses, menstruation is arguably the most common migraine trigger of all.
Few migraine prophylactic therapies demonstrate a 50% reduction in headaches. Even when successful, the economic burden of prophylaxis can be substantial, ranging as high as $138 per headache-day prevented. This article presents a small open-label pilot study of a novel specific therapy for prevention of menstrual-associated migraine (MAM) that is highly effective, inexpensive, and well-tolerated.
Hormonal-associated migraine occurs in many settings. It may occur exclusively with menses and be the only migraine that a woman experiences: the so-called true menstrual migraine. It may be predictable, but only one of several migraines in a month: the menstrual-associated migraine. Migraines may occur with scheduled withdrawals from exogenous estrogen-containing products such as oral contraceptives (OCs), postmenopausal estrogen therapy, or hormone therapy. In addition, they may occur with unintentional estrogen withdrawal on these products. These withdrawals may be secondary to missed doses, delayed doses, or increased metabolism of the estrogen component of the OC via cytochrome P450 3A4 or 1A2 interactions.
Hormonal association of headaches is exceedingly common. In a population of 262 women seen in a gynecology clinic for refill or initiation of OCs, 70% experienced headache during the placebo week of their OC. Reports have stated the prevalence of menstrual association in female migraineurs as high as 70%.
In the natural menstrual cycle, the late luteal phase decline in estradiol concentration is equivalent to a decline of 20 to 25 µg of the synthetic estrogen, ethinyl estradiol (EE) (Fig. 1). In a previous pilot study, the author found that reducing the premenstrual fall in estradiol to the equivalent of 10 µg EE or less was beneficial in preventing menstrual migraine. In that study, a variety of hormonal strategies were utilized, each of which accomplished the critical reduction in the magnitude of the premenstrual estradiol decline. This study investigates a single prophylactic strategy.
(Enlarge Image)
Physiologic premenstrual decline in estradiol concentration is equivalent to 20-25 µg ethinyl estradiol, and precipitates menstrual-associated migraine in susceptible women.
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