Are migraines with aura a contraindication to Depo-Provera (medroxyprogesterone acetate)?

Depo-Provera and Migraine with Aura: No Contraindication

No, migraine with aura is NOT a contraindication to Depo-Provera (medroxyprogesterone acetate). The stroke risk associated with migraine with aura is specifically linked to estrogen-containing contraceptives, and Depo-Provera is a progestin-only method that does not contain estrogen 1.

Key Distinction: Estrogen vs. Progestin-Only Methods

The critical issue is understanding that the increased stroke risk in migraine with aura patients applies exclusively to combined hormonal contraceptives containing estrogen, not to progestin-only methods:

• Estrogen-containing contraceptives increase stroke risk 7-fold (RR 7.02; 95% CI 1.51-32.68) in women with migraine with aura 2, 3
• The American Heart Association/American Stroke Association explicitly recommends absolute contraindication to estrogen in migraine with aura patients 2
• Multiple guidelines classify combined hormonal contraceptives as contraindicated specifically due to estrogen's thrombogenic effects 4, 5

Why Depo-Provera is Safe in Migraine with Aura

Depo-Provera contains only medroxyprogesterone acetate (a progestin) with no estrogen component 1. The FDA labeling for medroxyprogesterone acetate injectable suspension lists specific contraindications, and migraine with aura is notably absent 1:

• Active thrombophlebitis or thromboembolic disorders 1
• Known or suspected breast malignancy 1
• Significant liver disease 1
• Undiagnosed vaginal bleeding 1

The only vascular contraindication listed is active or history of thromboembolic disorders, not migraine with aura 1.

Clinical Algorithm for Contraceptive Selection in Migraine with Aura

When counseling patients with migraine with aura on contraception:

1. Absolutely avoid all estrogen-containing methods (combined oral contraceptives, patches, rings) 2, 3
2. Progestin-only methods are appropriate options, including:
   • Depo-Provera (medroxyprogesterone acetate injection) 1
   • Progestin-only pills 4
   • Levonorgestrel or etonogestrel implants 4
   • Progestin IUDs 4
3. Screen for additional stroke risk factors that would warrant heightened caution even with progestin-only methods:
   • Smoking (catastrophic when combined with migraine: RR 9.03) 2, 3
   • Hypertension 4
   • Thrombophilia 4, 5
   • Age >45 years 3
   • High migraine frequency (>weekly attacks: HR 4.25) 3, 4

Important Caveats About Depo-Provera

While Depo-Provera is not contraindicated in migraine with aura, counsel patients about its specific risks unrelated to migraine:

• Bone mineral density loss is the primary concern, particularly in adolescents and young adults 1
• Use longer than 2 years is not recommended unless other methods are inadequate 1
• BMD should be evaluated for long-term users 1
• Consider alternative progestin-only methods (implants, IUDs) that don't carry the same BMD concerns for patients requiring long-term contraception 1

Common Pitfall to Avoid

Do not conflate the contraindication for combined hormonal contraceptives with all hormonal contraception. The evidence consistently shows that estrogen is the culprit in stroke risk amplification 2, 6, 7. Research from 2023 demonstrates that even among combined hormonal contraceptive users, higher estrogen doses (≥30 μg) carry greater stroke risk than lower doses 6. Progestin-only methods like Depo-Provera do not share this mechanism and are appropriate choices 4, 1.