# When Hormones Attack: A Literature Review of Progesterone-Induced Anaphylaxis

**Authors:** Roxana Silvia Bumbăcea, Denisa-Alexandra Băloiu, Mihaela Ruxandra Vintilă, Maria Lucia Toader, Selda Ali

PMC · DOI: 10.1007/s11882-026-01267-4 · 2026-03-19

## TL;DR

This review summarizes cases of severe allergic reactions to progesterone, highlighting the need for better awareness and management in reproductive-age women.

## Contribution

The paper compiles and analyzes 25 cases of progesterone-induced anaphylaxis, offering insights into diagnosis and treatment strategies.

## Key findings

- 25 cases of progesterone-induced anaphylaxis were identified, including severe grade 4 and grade 5 reactions.
- Diagnostic methods like skin testing and challenges were used, but protocols varied widely.
- Management included hormonal modulation, oophorectomy, monoclonal antibodies, and successful desensitization in some cases.

## Abstract

Progesterone hypersensitivity is a rare and underdiagnosed condition whose incidence is expected to rise due to the increasing use of assisted reproductive technologies and exogenous progesterone exposure. This review aims to summarize the reported cases of endogenous and exogenous progesterone-induced anaphylaxis, focusing on clinical manifestations, diagnostic strategies, and management options.

A literature search through three data bases identified 25 documented cases of progesterone-induced anaphylaxis. Both endogenous (n = 15) and exogenous (n = 10) exposures were implicated, with severe reactions including grade 4 (n = 12) and grade 5 (n = 1) anaphylaxis. Diagnostic evaluation commonly involved skin testing and challenge procedures, although heterogeneity in protocols was evident. Management strategies varied widely: some patients responded to hormonal modulation, while others required oophorectomy or treatment with monoclonal antibodies. Desensitization protocols were successfully implemented in selected cases, including in the context of in vitro fertilization.

PH should be recognized as a potentially life-threatening condition, particularly relevant for women of reproductive age undergoing assisted reproduction or hormonal therapy. By combining clinical insights with published examples of successful diagnostic and therapeutic strategies, this review aims to support clinicians in recognizing progesterone-induced anaphylaxis and implementing patient-centered management. Increased awareness is essential for early diagnosis and individualized treatment.

## Linked entities

- **Chemicals:** progesterone (PubChem CID 5994)
- **Diseases:** anaphylaxis (MONDO:0100053)

## Full-text entities

- **Genes:** GNRH1 (gonadotropin releasing hormone 1) [NCBI Gene 2796] {aka GNRH, GRH, LHRH, LNRH}, IGHE (immunoglobulin heavy constant epsilon) [NCBI Gene 3497] {aka IgE}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, LHCGR (luteinizing hormone/choriogonadotropin receptor) [NCBI Gene 3973] {aka HHG, LCGR, LGR2, LH/CG-R, LH/CGR, LHR}
- **Diseases:** syncope (MESH:D013575), maculopapular dermatitis (MESH:D003872), mast cell disorders (MESH:D000090362), hypotension (MESH:D007022), respiratory symptoms (MESH:D012818), WAO (MESH:D000092124), infertility (MESH:D007246), gastrointestinal (MESH:D005767), breathlessness (MESH:D004417), AIDS (MESH:D000163), IVF (MESH:C566179), weight gain (MESH:D015430), mast cell activation syndrome (MESH:D000090267), autoimmune (MESH:D001327), chest tightness (MESH:D002637), autoimmune progesterone dermatitis (MESH:C535299), ascites (MESH:D001201), muco-cutaneous symptoms (MESH:D012816), cancer (MESH:D009369), bronchospasm (MESH:D001986), vulvar swelling (MESH:D014845), uterine bleeding (MESH:D014592), menorrhagia (MESH:D008595), wheezing (MESH:D012135), pleural effusion (MESH:D010996), anorexia (MESH:D000855), Flushing (MESH:D005483), urticaria (MESH:D014581), Allergy (MESH:D004342), dermatoses (MESH:D012871), Anaphylaxis (MESH:D000707), systemic mastocytosis (MESH:D034721), drug eruption (MESH:D003875), angioedema (MESH:D000799), PH (MESH:C564871)
- **Chemicals:** cholesterol (MESH:D002784), GPAb (-), 17-hydroxyprogesterone (MESH:D019326), C-21 (MESH:C000711730), Omalizumab (MESH:D000069444), Norethindrone (MESH:D009640), carbon (MESH:D002244), megestrol acetate (MESH:D019290), estranes (MESH:D004962), ethanol (MESH:D000431), CS (MESH:D002586), Progesterone (MESH:D011374), epinephrine (MESH:D004837), ketone (MESH:D007659), azathioprine (MESH:D001379), estradiol (MESH:D004958), danazol (MESH:D003613), medroxyprogesterone (MESH:D008525), alfaxalone (MESH:C006477), polyethylene glycol 3350 (MESH:C000595212), diethylstilbestrol (MESH:D004054), Psoralen (MESH:D005363), E (MESH:D004540), polyethylene glycol (MESH:D011092), methylparaben (MESH:C015358), propylparaben (MESH:C006068), oil (MESH:D009821), pregnane (MESH:D011278), histamine (MESH:D006632), Drospirenone (MESH:C035144), steroid (MESH:D013256), alfadolone acetate (MESH:C033418), polysorbate 80 (MESH:D011136), Medroxyprogesterone Acetate (MESH:D017258), 19-nortestosterone (MESH:D009277), Alfathesin (MESH:D000530), spironolactone (MESH:D013148), desogestrel (MESH:D017135), P (MESH:D010758), water (MESH:D014867), dapsone (MESH:D003622)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13002717/full.md

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Source: https://tomesphere.com/paper/PMC13002717