Sex differences in urinary mast cell mediators: Implications for diagnosing atopic and mast cell disorders

Urinary mast cell mediators aid in diagnosing atopic and mast cell disorders, yet sex differences in these mediators remain unreported despite known sex-specific variations in eicosanoid pathways.

To characterize sex differences in urinary mast cell mediators 2,3-dinor-11β-prostaglandin F2α (2,3-BPG), N-methylhistamine, and leukotriene E4 (LTE4).

This retrospective chart review of 4033 patients of all ages at Mayo Clinic from June 1, 2019 to May 31, 2024 including demographic and clinical data. Urine mast cell mediators 2,3-BPG, N-methylhistamine, and LTE4 were quantified using liquid chromatography-tandem mass spectrometry and normalized to creatinine levels. Statistical analyses were performed using R software (R Core Team, Vienna, Austria).

Among patients tested for urinary mast cell mediators, 78.8% were female sex. Compared with females, males were older at testing (mean 48.0 vs 40.1 years), more likely to report ever smoking (33.5% vs 22.7%), had higher body mass index (mean 28.6 vs 27.7), more often had an atopic condition (82.6% vs 71.0%) or comorbidity (46.1% vs 30.3%), and had higher median LTE4 levels (102.5 vs 90.0 pg/mg creatinine) (P < .001 for all). Males also more typically had elevated 2,3-BPG (8.0% vs 3.7%) and eosinophil counts (17.0% vs 5.9%) and higher median tryptase levels (5.1 vs 4.3 pg/mL) (P < .001 for all). Multivariable analysis revealed a sex-by-atopy interaction for LTE4, with higher levels in atopic males (male/female ratio 1.15 [95% CI: 1.07-1.25], P < .001) and higher levels in nonatopic females (male/female ratio 0.86 [95% CI: 0.76-0.97], P = .02).

Sex differences in testing rates and urinary mediator levels highlight the need to consider sex in optimizing the diagnostic utility of these mediators.