What are the treatment options for endometriosis in a patient who experiences migraines with aura?

Treatment Options for Endometriosis in Patients with Migraine with Aura

Progestin-only therapies are the recommended first-line medical treatment for endometriosis in patients with migraine with aura, as combined hormonal contraceptives containing estrogen are absolutely contraindicated due to compounded stroke risk. 1, 2

Why Estrogen-Containing Therapies Are Contraindicated

• Women with migraine with aura have a significantly elevated baseline risk of ischemic stroke compared to those without aura 1, 2, 3
• The American College of Obstetricians and Gynecologists and the American Headache Society explicitly state that all combined hormonal contraceptives containing estrogen are contraindicated in women with migraine with aura due to this compounded stroke risk 1, 2
• This contraindication eliminates combined oral contraceptives, which are typically first-line therapy for endometriosis in women without migraine with aura 4, 5

Safe and Effective Treatment Options

First-Line: Progestin-Only Therapies

Progestin-only contraceptives are generally considered safe alternatives for women with migraine with aura because they do not carry the same stroke risk as estrogen-containing products 1, 2

Specific progestin-only options include:

• Oral medroxyprogesterone acetate: 5-10 mg daily for 5-10 days for abnormal bleeding; can be used for planned menstrual cycling 4, 6
• Depot medroxyprogesterone acetate (DMPA): Injectable formulation, though requires monitoring for fluid retention which may influence migraine 7
• Norethindrone acetate: Initial dose 5 mg daily for 2 weeks for endometriosis, increasing by 2.5 mg every 2 weeks up to 15 mg daily, maintained for 6-9 months 6
• Progestin-only pills: Including newer formulations like Slinda, are appropriate alternatives when combined hormonal contraceptives are contraindicated 1

Important Caveat About Progestins and Migraine

• Medroxyprogesterone acetate may cause fluid retention, which requires careful observation in patients with migraine 7
• Patients with a history of depression should be carefully observed, as progestins may worsen depression, which could indirectly affect migraine management 7

Second-Line: GnRH Agonists

GnRH agonists are highly effective for endometriosis pain relief and do not carry stroke risk, making them suitable for patients with migraine with aura 4

• Treatment with a GnRH agonist for at least 3 months appears equally effective as danazol for pain relief 4
• Add-back therapy is essential: When continued GnRH agonist therapy is needed, add-back therapy reduces or eliminates bone mineral loss without reducing pain relief efficacy 4
• This option is particularly valuable for severe endometriosis where medical treatment alone with progestins may not be sufficient 4

Third-Line: Danazol

• Danazol for at least 6 months is equally effective as GnRH agonists for pain relief 4
• However, androgenic side effects may limit tolerability 4

Surgical Management

Surgical excision by a specialist is considered the definitive treatment for endometriosis and is not contraindicated by migraine with aura 4

• Surgery is associated with significant pain reduction during the first 6 months following surgery 4
• Up to 44% of women experience symptom recurrence within one year, so this should be discussed during shared decision-making 4
• Preoperative imaging (expanded protocol transvaginal ultrasound or MRI) is associated with decreased morbidity and mortality and reduces the need for repeat surgeries 4

Post-Surgical Hormone Therapy Considerations

• After hysterectomy with bilateral salpingo-oophorectomy: Hormone replacement therapy with estrogen is not contraindicated, though this applies to postmenopausal hormone replacement, not contraceptive doses 4
• For women with endometriosis who required oophorectomy, combined estrogen/progestogen therapy can be effective for vasomotor symptoms and may reduce disease reactivation risk 4
• However, in the context of ongoing migraine with aura, transdermal estradiol (not ethinylestradiol) would be preferred if estrogen is used, as it carries lower thrombotic risk 4

Concurrent Migraine Management

While treating endometriosis, optimize migraine management:

• Acute treatment: Start NSAIDs or aspirin as soon as possible during the aura phase to prevent or diminish the subsequent headache 1, 2, 3
• If NSAIDs fail, use triptans when the headache begins—but not during the aura phase itself 1, 2, 3
• Preventive treatment: First-line options include propranolol (80-160 mg daily), metoprolol (50-100 mg twice daily), or topiramate (50-100 mg daily) 1, 2

Clinical Correlation Between Conditions

• Migraine is significantly more prevalent in endometriosis patients (29.9% vs. 12.1% in controls), particularly in advanced-stage disease 8, 9
• Women with both conditions report higher pain intensity, more monthly migraine days, and increased disability scores compared to those with endometriosis alone 8
• Severe adenomyosis and deep infiltrating endometriosis occur more frequently in women with migraine 8

Expectant Management

• For asymptomatic patients with endometriosis, expectant management may be appropriate, as endometriosis is often unpredictable and may regress 4
• This avoids medication exposure in patients who may not require treatment