Your postmenopausal patient reports a history of migraine

Related article: The gynecologist's role in managing menstrual migraine Anne H. Calhoun, MD

Migraine and the risk of stroke
Migraine with aura has been associated with an increased risk of stroke and other cerebral vascular events,⁷ and that risk is further elevated in patients treated with OCs.⁸ Although migraine without aura also may be associated with an elevated risk of stroke, OCs do not further increase that risk.

Andrew M. Kaunitz, MD:
The elevated risk of stroke associated with use of OCs by women with migraine with aura appears to relate, in particular, to older, higher-dose OC formulations.^9,10

Some practitioners assume that the data on the risk of stroke associated with OC use also applies to hormone therapy, but there is no evidence that HT, in which doses of estrogen are far lower than in OCs, increases the risk of stroke in migraineurs to any greater degree than would be expected in unselected populations (ie, as noted in the Women’s Health Initiative, Nurses Health Study, or other large investigations). Therefore, HT would be an appropriate option for this patient if her very slight risk of stroke on HT would be acceptable to the practitioner and patient.

JoAnn V. Pinkerton, MD:
The route of administration is critical here. In relatively healthy postmenopausal women (average age, 63), combined continuous oral HT significantly increased the risk of stroke. After 3 years of use, the absolute risk was 18 cases of stroke per 1,000 HT users (95% confidence interval [CI], 14–23). And oral estrogen-only therapy increased the risk of stroke after 7 years of use, with an absolute risk of 32 cases per 1,000 HT users (95% CI, 25–40).¹¹

The limited clinical evidence available on the effects of tramsdermal estradiol on stroke risk indicates that the risk is not increased.¹²

Choosing an HT formulation

Consider the pharmacokinetic profile. Many oral estrogen HT products have rapid-release characteristics that make them likely to contribute to rapid rises and falls in the user’s estrogen level. Oral estrogens also are associated with procoagulant properties that may increase the risk of thrombosis and thromboembolism. Nonoral estrogens do not appear to increase these risks.¹³

Nonoral estrogens (patches, gels, sprays, lotions, and vaginal rings) provide a more stable pharmacokinetic profile, as do some oral products with controlled-release properties.

As for progestins, some formulations (medroxyprogesterone acetate) tend to cause vasoconstriction, whereas others (micronized progesterone) tend to be vasodilators. Whether these properties affect the rate of migraine or risk of stroke is unclear.

My management approach for this patient
In the absence of any systematic data on the use of HT in this clinical setting, and without any concrete suggestions from migraine experts, I would take the following three-step approach:

1. I would begin with a low-dose nonoral estradiol formulation, prescribing it without a progestin even in a woman who still has a uterus. My aim: to determine the lowest effective dose of HT for this particular patient. I would follow the patient on this dose for 3 months.

JoAnn V. Pinkerton, MD:
Another goal is to determine whether transdermal estradiol increases headaches. Before settling on a therapy, however, I would ask how long this patient has been postmenopausal, how long she has been experiencing vasomotor symptoms, and how severe those symptoms are. For example, is she having 7 or 8 hot flashes per day and waking from night sweats once or twice per night? I also would ask her how long she remained on the venlafaxine. The additional information would allow me to fine-tune her treatment.

2. If this formulation is tolerated, I would add micronized progesterone (oral or vaginal) for endometrial protection.

JoAnn V. Pinkerton, MD:
I would give oral progesterone if it is FDA approved for postmenopausal use, vaginal progesterone if it isn’t.

3. I would follow the patient’s clinical response—specifically, her vasomotor symptoms and rate of migraine with or without aura.

Hormone therapy is one option for postmenopausal migraineurs with bothersome vasomotor symptoms
Many women with a history of migraine move into menopause expecting their condition to improve, says headache expert Anne H. Calhoun, MD, a founder of the Carolina Headache Institute in Chapel Hill, North Carolina.

“Over the years, these women have heard that things get better with menopause.”

For women with a history of episodic migraine, that expectation is realistic, Calhoun says. “But for women with chronic migraine, who may experience a low-grade headache on a daily, or almost daily basis, with 10 or 12 severe headaches in a month, things usually get worse after menopause because the sleep issues of menopause are superimposed on the migraine.”

Dr. Calhoun observes that hormone therapy (HT) has never been contraindicated in women with migraine, although many neurologists are hesitant to prescribe any hormones for this population.

Before prescribing HT to a postmenopausal migraineur, Dr. Calhoun considers a range of variables, including sleep patterns, current medications, anxiety, frequency and severity of vasomotor symptoms, and any other problems the patient may be experiencing.

“It’s basically the same assessment as with any postmenopausal patient—to determine whether HT is a reasonable option,” she says.

And when she determines that HT is appropriate, “I almost exclusively use transdermal HT. I also am more likely to prescribe continuous use of a transdermal patch or skin gel, as I want to achieve very consistent hormone levels, day in and day out,” she says.