First report of linzagolix as bridge therapy for progesterone hypersensitivity, an ultra-rare disorder

PURPOSE: ), an oral GnRH antagonist, to manage progesterone hypersensitivity, an ultra-rare disorder with fewer than 200 cases reported worldwide. METHODS: A 23-year-old woman presented with severe cyclic luteal-phase symptoms from menarche: vulvar edoema, recurrent cystitis, fever (38-42 °C), urticaria, angioedema, and systemic inflammation. Diagnosis was confirmed by positive intradermal progesterone testing (1:10 dilution) and elevated IgE (1,010 IU/mL). Combined oral contraceptives were ineffective. Linzagolix 200 mg daily was started in May 2025 under exceptional approval granted by a government pharmaceutical inspector (off-label use), achieving partial symptom control. Progesterone desensitisation in July 2025 triggered an anaphylactic reaction (hypotension 80/40 mmHg, tachycardia 120 bpm). Anakinra (an IL-1 receptor antagonist) was subsequently added. RESULTS: Linzagolix induced ovarian suppression and clinical improvement. Following anaphylaxis, combination therapy with linzagolix and anakinra achieved complete symptom resolution. Multidisciplinary collaboration enabled monitoring. CONCLUSIONS: To our knowledge, this is the first use of linzagolix for progesterone hypersensitivity, suggesting GnRH antagonists may serve as bridge therapy. Multi-disciplinary care proved essential.