ArticleResearch square2026
Metabolomic signatures of the steroid biosynthesis driving sex differences in clinical asthma subtypes.
Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00000575 (Childhood Asthma Management Program), which is not on this map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Childhood Asthma Management Program
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Authors and funding
8 authors.
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Abstract
Background: Asthma is a heterogeneous disease with well-documented sex differences in prevalence. However, the sex-specific and pubertal effects of inhaled corticosteroids on endogenous steroid metabolites and their relationship with asthma-related clinical outcomes remain poorly understood. Methods: Targeted whole-blood plasma profiling of the steroid biosynthesis pathway was generated by Precion Inc. (NC, USA). Sixteen metabolites from the steroid biosynthesis pathway were quantified at baseline and end-of-trial in children with asthma from the Childhood Asthma Management Program (CAMP; n=1,041), aged 5-12 years. Linear mixed models and generalized linear models were used to evaluate sex-specific longitudinal and endpoint responses of steroid metabolites and clinical outcomes with inhaled corticosteroid (ICS) use, adjusting for age, sex, race, height, and body mass index. Results: ICS use in males was associated with significantly lower cortisol and cortisone levels at Year 4 (end of trial). In females, cortisol and cortisone showed more stable trajectories with ICS use, which resulted in a non-significant reduction at year 4. Males receiving ICS showed suggestive positive longitudinal associations for 17α-hydroxyprogesterone, estrone, and testosterone, while females showed a suggestive positive trajectory for androstenedione. ICS exposure modified the associations between metabolites and clinical outcomes (FEV1, FVC, eosinophils, and airway hyperresponsiveness) in a pathway- and sex-specific manner. Overall, ICS attenuated longitudinal associations between endogenous steroids and clinical outcomes, particularly in females, while selected relationships from the androgen-lung function associations were preserved at the end of the trial. Conclusion: We identify sex-specific differences in ICS-associated metabolite profiles and clinical outcomes, supporting the need for further investigation into sex-informed approaches to corticosteroid use in pediatric asthma. Trial registration: Clinicaltrials.gov: NCT00000575; registered 1999-10-27.
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