What is the management approach for a patient with suspected progesterone hypersensitivity?

Management of Progesterone Hypersensitivity

The primary management approach for progesterone hypersensitivity involves GnRH analogues initiated during days 1-3 of the menstrual cycle for an initial 3-month period to assess response, with consideration for low-dose estradiol patches after 3 months to prevent menopausal symptoms and bone loss. 1

Diagnostic Considerations

• Identify key timing patterns:

  • Endogenous form: Symptoms occur during luteal phase (days 14-28) of menstrual cycle
  • Exogenous form: Symptoms follow exposure to progestins
  • Resolution during menses or with ovulation suppression supports diagnosis 1, 2

• Clinical presentation spectrum:

  • Cutaneous: Urticaria, angioedema, dermatitis
  • Respiratory: Bronchospasm
  • Systemic: Anaphylaxis 3, 2

Treatment Algorithm

First-Line Therapy

1. GnRH analogues:
   • Initiate during days 1-3 of menstrual cycle
   • Continue for initial 3 months to assess response
   • Add low-dose estradiol skin patches after 3 months if effective
   • Treatment beyond 6 months requires estrogen supplementation 1

Contraceptive Management

• Avoid:

  • Progesterone-only contraceptives
  • Progestin implants
  • Progesterone-containing IUDs 1

• Safe alternatives:

  • Barrier methods
  • Copper IUDs
  • Low-dose estrogen-progestin combinations (may be trialed after 6 months of GnRH therapy) 1

Symptom-Directed Therapy

• Urticaria/angioedema: Antihistamines
• Dermatitis: Topical corticosteroids
• History of anaphylaxis: Prescribe epinephrine auto-injectors 1

Refractory Cases

1. Desensitization protocols:

   • Consider for patients requiring fertility treatments
   • Options include intramuscular or oral desensitization
   • Successful in symptom control and enabling IVF treatment 1, 4

2. Oophorectomy:

   • Last resort for severe, refractory cases
   • Only consider if other medical indications exist 1

Special Considerations

Fertility and Pregnancy

• Fertility-inducing drugs may trigger acute symptoms

• Pre-conception evaluation recommended

• High-risk obstetric care during pregnancy is necessary

• Desensitization protocols may enable IVF treatment 1, 4

• Despite high progesterone levels during pregnancy, compensatory mechanisms may be protective

• Attacks during pregnancy can be safely treated with appropriate medications 1, 5

Follow-up and Monitoring

• Schedule follow-up within 1 month after initiating therapy
• Regularly monitor symptoms during treatment
• If using GnRH analogues long-term, monitor bone density
• Consider trial of low-dose estrogen-progestin combination after 6 months of GnRH therapy 1

Clinical Pearls and Pitfalls

• Diagnostic challenges: PH can be difficult to recognize due to heterogeneous clinical presentation 3
• Mechanism: Primarily IgE-mediated, though other immune responses may be involved 3
• Rising prevalence: Increased use of oral contraceptives and IVF treatments has likely increased PH incidence 3, 4
• Terminology evolution: The condition has been renamed from "autoimmune progesterone dermatitis" to "progestogen hypersensitivity" to better reflect the diversity of presentations and triggers 4