Hormonal Modulation of Airway Inflammation in Asthma: A Systematic Review

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Introduction: Asthma is a chronic inflammatory disease of the airways characterized by variable airflow obstruction and marked clinical heterogeneity, with important differences observed according to sex, age, and hormonal phases. Growing evidence indicates that the endocrine axis, particularly sex hormones, plays a modulatory role in type 2 airway inflammation, lung function, and asthma control. Sex-specific patterns after puberty, as well as variations related to the menstrual cycle, pregnancy, menopause, and metabolic factors, suggest a relevant interaction between the endocrine and immune systems in asthma pathophysiology. Objective: This systematic review identifies and synthesize evidence on hormonal modulation of airway inflammation in asthma, focusing on differences by sex, age, hormonal phases, and the influence of metabolic factors on clinical outcomes. Methodology: This systematic review was conducted in accordance with the PRISMA 2020 guidelines. Searches were performed in the PubMed, MEDLINE, and SciELO databases, including full-text human studies published within the last ten years. MeSH terms related to “asthma”, “sex hormones”, “endocrine system”, “airway inflammation”, “estrogen”, “progesterone”, “testosterone”, and “androgen receptor” were used. Observational studies, clinical cohorts, population-based analyses, and mechanistic reviews were included. After screening and removal of duplicates, 22 studies met the eligibility criteria and were included in the qualitative synthesis. Results: The reviewed studies consistently demonstrated that estrogen and progesterone are associated with increased type 2 airway inflammation and poorer asthma control, particularly in women after puberty and during the perimenstrual period. In contrast, androgens such as testosterone and dehydroepiandrosterone (DHEA) were recurrently associated with improved lung function, reduced airway inflammation, lower fractional exhaled nitric oxide (FeNO) levels, and fewer asthma exacerbations. Sex-related differences across the life course were evident, with higher asthma prevalence in boys during childhood and a predominance in women during adulthood. Metabolic factors, including obesity and sex hormone-binding globulin (SHBG) levels, were shown to modulate hormone bioavailability and influence asthma severity and clinical behavior. Conclusion: The evidence indicates that the endocrine axis plays a significant role in asthma pathophysiology and clinical control, contributing to sex-related and life stage–dependent heterogeneity. Integrating hormonal and metabolic contexts into clinical assessment may support more individualized management strategies. Despite substantial advances, important gaps remain, highlighting the need for longitudinal studies and clinical trials to better define the therapeutic implications of hormonal modulation in asthma.

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