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Males had higher levels of urinary mast cell mediators—LTE4, 2,3-BPG, and tryptase—particularly in atopic individuals, compared to females. These sex-based differences suggest the need to account for sex in interpreting diagnostic biomarkers for mast cell and atopic disorders.

As per the study published in the June 2025 issue of Annals of Allergy, Asthma & Immunology, the researchers conducted a retrospective study to characterize sex differences in urinary mast cell mediators 2,3-dinor-11β-prostaglandin F2α (2,3-BPG), N-methylhistamine (NMH), and leukotriene E4 (LTE4).  

They reviewed 4,033 patients at Mayo Clinic from June 1, 2019, to May 31, 2024, which encompassed demographic and clinical data. Urinary mast cell mediators, specifically 2,3-BPG, NMH, and LTE4, were quantified using liquid chromatography-tandem mass spectrometry and normalized to creatinine (Cr) levels. Statistical analyses were performed using R.  

The results showed that 78.8% of patients tested for urinary mast cell mediators were female. Compared to females, males were older at testing (mean 48.0 vs 40.1 years), more frequently reported ever smoking (33.5% vs 22.7%), had a higher BMI (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 Cr) (P < 0.001 for all). Males also more commonly had elevated 2,3-BPG (8.0% vs 3.7%) and eosinophil counts (17.0% vs 5.9%), along with higher median tryptase levels (5.1 vs 4.3 pg/mL) (P < 0.001 for all). Multivariable analysis revealed a sex-by-atopy interaction for LTE4, with higher levels in atopic males (M/F ratio 1.15, [95% CI: 1.07–1.25], P < 0.001) and lower levels in non-atopic females (M/F ratio 0.86, [95% CI: 0.76–0.97], P = 0.02).  

Investigators concluded that sex differences in testing rates and urinary mediator levels highlighted the necessity of considering sex when optimizing the diagnostic utility of these mediators. 

Source: annallergy.org/article/S1081-1206(25)00270-4/abstract