What components in progesterone (hormone) can cause allergic reactions?

Allergenic Components in Progesterone That Can Cause Allergic Reactions

The primary allergenic components in progesterone formulations that can cause allergic reactions are peanut oil in micronized progesterone capsules and the progesterone hormone itself, which can trigger autoimmune responses in susceptible individuals. 1, 2

Excipients in Progesterone Formulations

• Many formulations of micronized progesterone contain peanut oil as an excipient (inert material in which the drug is suspended), which can trigger severe allergic reactions including anaphylaxis in individuals with peanut allergies 1
• Individuals with severe peanut allergies should not receive micronized progesterone capsules due to the risk of anaphylactic reactions 1
• Vaginal gel formulations of progesterone do not contain peanut oil and can be safely used as an alternative in patients with peanut allergies 1

Autoimmune Reactions to Progesterone

• Some individuals may develop autoimmune reactions to progesterone itself, known as autoimmune progesterone dermatitis (APD) or autoimmune progesterone anaphylaxis (AIPA) 2, 3
• These reactions can occur in response to both endogenous progesterone produced naturally in the body and exogenous progesterone administered as medication 2, 4
• Symptoms typically present cyclically during the luteal phase of the menstrual cycle when progesterone levels are elevated 3, 4

Clinical Manifestations of Progesterone Allergy

• Skin manifestations are most common and include erythema multiforme, eczema, urticaria, and angioedema 2, 3
• More severe systemic reactions can involve respiratory symptoms such as dyspnea, cough, and respiratory distress, constituting autoimmune progesterone anaphylaxis 2
• Symptoms typically begin 3-10 days before menstruation and resolve 1-2 days after menstruation ceases 4

Diagnosis of Progesterone Allergy

• Diagnosis is based on the cyclic nature of symptoms corresponding to the luteal phase of the menstrual cycle 3, 4
• Confirmation can be made through intradermal skin testing using progesterone, with a positive test showing wheal formation (typically >10mm) after 15 minutes 2, 4
• The cyclic pattern helps differentiate progesterone allergy from other allergies or systemic diseases with skin manifestations 3

Cross-Reactivity Concerns

• Patients with allergies to progesterone may be at risk for developing allergies to corticosteroids due to structural similarities between sex hormones and corticosteroids 5
• Recent research suggests progesterone can amplify allergic inflammation in susceptible individuals, particularly affecting respiratory symptoms in conditions like asthma 6

Management Options

• For autoimmune progesterone reactions, inhibition of ovulation using oral conjugated estrogens (0.625 mg) or other hormonal contraceptives can prevent symptoms by reducing endogenous progesterone production 2, 3
• Gonadotropin-releasing hormone analogues have been used successfully to treat autoimmune progesterone dermatitis 4
• For patients requiring progesterone therapy who have peanut allergies, vaginal gel formulations should be used instead of oral micronized progesterone capsules 1

Important Considerations

• Hormone receptor-positive breast cancer is a contraindication to progesterone therapy regardless of allergy status 1
• When prescribing progesterone, clinicians should specifically inquire about peanut allergies to avoid potentially severe allergic reactions 1
• Patients with unexplained cyclic skin eruptions or allergic symptoms should be evaluated for possible progesterone allergy, especially if symptoms correlate with the menstrual cycle 2, 4