Clinical Manifestations of Progesterone Hypersensitivity
Progesterone hypersensitivity (PH) presents with a spectrum of symptoms ranging from cutaneous eruptions to systemic anaphylaxis, typically occurring cyclically in correlation with progesterone levels during the menstrual cycle or after exposure to exogenous progesterone. 1, 2, 3
Cutaneous Manifestations
- Urticaria and angioedema: Most common presentation, typically occurring during the luteal phase of the menstrual cycle 1, 4
- Dermatitis/eczematous eruptions: Can appear on extremities, trunk, and face 5
- Erythema multiforme: Characterized by target-like lesions 3
- Fixed drug eruptions: Recurrent lesions at the same sites 3
- Pemphigoid-like eruptions: Rare presentation with blistering 5
Systemic Manifestations
- Respiratory symptoms: Bronchospasm, asthma-like symptoms, and throat tightness 4
- Gastrointestinal symptoms: Nausea, vomiting, and abdominal pain 3
- Cardiovascular symptoms: Hypotension and tachycardia in severe cases 4
- Anaphylaxis: Life-threatening systemic reaction in severe cases 4
Timing and Pattern of Symptoms
- Cyclical pattern: Symptoms typically begin a few days before menstruation and resolve after the menstrual period 1
- Persistent symptoms: Some patients may experience continuous symptoms, especially with exogenous progesterone exposure 3
- Exacerbation during pregnancy: Due to increased endogenous progesterone levels 4
Triggers
- Endogenous progesterone: Natural hormone surges during the luteal phase of the menstrual cycle 2, 3
- Exogenous progesterone exposure: From oral contraceptives, fertility treatments, or hormone replacement therapy 1, 2
- Cross-reactivity: Some patients may react to multiple progestogens 3
Risk Factors
- Previous exposure to exogenous progesterone: May sensitize individuals 1
- Reproductive age: Most commonly affects women of childbearing age 4
- History of atopy: May increase susceptibility to progesterone hypersensitivity 3
Diagnostic Considerations
- Timing correlation: Symptoms that worsen during the luteal phase of the menstrual cycle or after progesterone administration 1
- Partial response to antihistamines: Unlike typical allergic reactions, PH may only partially respond to standard antihistamine therapy 1
- Improvement with hormonal suppression: Symptoms typically improve with medications that suppress ovulation 1, 4
Pitfalls in Diagnosis
- Delayed diagnosis: Due to the rarity of the condition and variable presentation, diagnosis is often delayed 1
- Misdiagnosis: Often confused with chronic urticaria, angioedema, or other dermatological conditions 3
- Limited awareness: General lack of knowledge about PH among healthcare providers 3
- Testing limitations: Lack of standardized commercial tests for progesterone-specific IgE 3
PH should be considered in the differential diagnosis for any woman of reproductive age presenting with cyclic hypersensitivity reactions, particularly when symptoms correlate with the luteal phase of the menstrual cycle or after exposure to exogenous progesterone. Early recognition can lead to appropriate management and improved quality of life for affected patients.