How to induce menses in a patient with amenorrhea (absence of menstruation) who has not responded to Medroxyprogesterone Acetate (MPA) and has a history of migraine with aura?

Management of Amenorrhea in Patients with Migraine with Aura After Failed MPA Treatment

For patients with amenorrhea who have failed medroxyprogesterone acetate (MPA) treatment and have a history of migraine with aura, a progestin-only pill (POP) is the recommended hormonal option to induce menses while maintaining safety.

Understanding the Contraindications

When managing amenorrhea in a patient with migraine with aura, safety considerations are paramount:

• Combined hormonal contraceptives (CHCs) are absolutely contraindicated in women with migraine with aura due to significantly increased stroke risk 1
• The Nature Reviews Neurology guidelines explicitly state that "combined hormonal contraceptives are contraindicated in women with migraine with aura regardless of any association with their menstrual cycle, owing to an associated increase in the risk of stroke" 1
• This contraindication receives a Category 4 classification (unacceptable health risk) in the US Medical Eligibility Criteria for Contraceptive Use 1

First-Line Treatment Option

1. Desogestrel 75 mcg/day (progestin-only pill)
   • Demonstrated effectiveness in inducing menses in women with amenorrhea 2
   • Safe in women with migraine with aura (Category 2 - benefits outweigh risks) 1
   • Shown to reduce migraine attack frequency, duration, and intensity 2
   • Low discontinuation rate (<10%) due to side effects 2

Alternative Options (If POP is Ineffective)

1. Cyclofem (monthly injectable containing estrogen and progestin)

   • Effective for DMPA-induced amenorrhea with 82% of users experiencing vaginal bleeding within 6 months 3
   • CAUTION: Only use if patient's migraine with aura is fully resolved and no other stroke risk factors exist
   • Monitor closely for return or worsening of aura symptoms

2. Non-hormonal options to consider:

   • NSAIDs for 5-7 days (can reduce menstrual blood loss by 26-60%) 4
   • Tranexamic acid for 4-5 days (reduces menstrual blood loss by ~50%) 4
   • NOTE: While these medications manage bleeding, they may not reliably induce menses in amenorrhea

Monitoring and Follow-up

• Evaluate response to treatment within 2-3 months 1
• Use headache calendars to track migraine frequency, severity, and relationship to hormonal treatment 1
• Monitor for any new or worsening aura symptoms, which would necessitate immediate discontinuation of any hormonal treatment

Important Considerations

• Progestin-only methods (POP, implant, DMPA) are all Category 2 (benefits outweigh risks) for women with migraine with aura 1
• If structural causes of amenorrhea are suspected, transvaginal ultrasonography should be performed before hormonal treatment 4
• Unexplained vaginal bleeding requires thorough evaluation before starting hormonal treatments 4

Pitfalls to Avoid

1. Never prescribe combined hormonal contraceptives (pills, patches, rings) to patients with migraine with aura, even if they have been amenorrheic
2. Do not confuse migraine with aura with general premonitory symptoms of migraine - true aura involves focal neurological symptoms, typically visual 5
3. Do not attribute amenorrhea solely to hormonal causes without ruling out other etiologies like thyroid dysfunction, hyperprolactinemia, or structural abnormalities 4
4. Avoid assuming that all progestin-based treatments are equally effective - evidence specifically supports desogestrel 75 mcg/day for this indication 2

The evidence strongly supports using progestin-only methods for women with migraine with aura who need to induce menses after failed MPA treatment, with desogestrel POP showing the most promising results for both menstrual regulation and potential migraine improvement.