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

PURPOSE: We report the first use of linzagolix (Yselty®), 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.