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

Management of Progesterone Hypersensitivity

The management of progesterone hypersensitivity requires suppression of endogenous progesterone production through gonadotropin-releasing hormone (GnRH) analogues as first-line therapy, with careful consideration of hormonal alternatives and desensitization protocols for refractory cases.

Diagnosis and Clinical Presentation

Progesterone hypersensitivity (PH) presents with a spectrum of symptoms ranging from:

• Urticaria with or without angioedema
• Dermatitis
• Systemic anaphylaxis
• Bronchospasm
• Cyclical symptoms correlating with the luteal phase of menstrual cycle

Key diagnostic elements:

• Timing of symptoms: Luteal phase (days 14-28) of menstrual cycle for endogenous PH
• Symptoms after exposure to exogenous progestins (contraceptives, IVF therapy)
• Resolution of symptoms during menses or with ovulation suppression

Management Algorithm

First-Line Treatment

1. GnRH Analogues

   • Initiate during days 1-3 of menstrual cycle to prevent initial agonistic effect 1
   • Suppresses ovulation and corpus luteum formation (source of endogenous progesterone)
   • Continue for initial 3 months to assess response
   • Add low-dose estradiol skin patch after 3 months if GnRH is effective, to prevent menopausal symptoms and bone loss 1
   • Treatment beyond 6 months requires estrogen supplementation 1

2. Contraceptive Management

   • Avoid progesterone-only contraceptives including implants and progesterone-containing IUDs 1
   • Safe alternatives:
     • Barrier methods (condoms)
     • Copper IUDs (non-hormonal) 1
     • Low-dose estrogen-progestin combinations may be trialed after 6 months of GnRH therapy 1

Second-Line Options

1. Symptom-Directed Therapy

   • Antihistamines for urticaria/angioedema
   • Topical corticosteroids for dermatitis
   • Epinephrine auto-injectors for patients with history of anaphylaxis

2. Desensitization Protocols

   • Consider for patients requiring fertility treatments or with refractory symptoms 2
   • Can be administered via oral (73%) or intramuscular (27%) routes 2
   • Has shown success in symptom control and fertility preservation
   • Should be performed under specialist supervision

3. Oophorectomy

   • Reserved as last resort for severe, refractory cases
   • Should not be considered unless there is another medical indication 1

Special Considerations

Fertility and Pregnancy

• Fertility-inducing drugs may precipitate acute symptoms 1
• Pre-conception evaluation recommended
• High-risk obstetric care during pregnancy
• Desensitization protocols may enable IVF treatment 2

Monitoring and Follow-up

• Follow-up within 1 month after initiating therapy to assess response
• Regular monitoring of symptoms during treatment
• If using GnRH analogues long-term, monitor for bone density loss
• Consider trial of low-dose estrogen-progestin combination after 6 months of GnRH therapy 1

Pitfalls and Caveats

1. Diagnostic challenges:

   • PH is often misdiagnosed due to heterogeneous presentation
   • Consider PH in women with cyclical hypersensitivity symptoms
   • Progesterone-specific IgE testing may assist in diagnosis 3

2. Treatment pitfalls:

   • Avoid estrogen-containing emergency contraceptive pills 1
   • Progestin-only emergency contraceptive pills may be tolerated by some patients 1
   • Cyproterone acetate (anti-androgenic progestin) may worsen symptoms 1

3. Pregnancy considerations:

   • Despite high progesterone levels during pregnancy, compensatory mechanisms may be protective 1
   • Attacks during pregnancy can be safely treated with appropriate medications 1
   • Monitor closely during post-partum period as attacks can occur 1

By following this structured approach to management, clinicians can effectively control symptoms and improve quality of life for patients with progesterone hypersensitivity while preserving fertility options when desired.