Endogenous and exogenous sex steroid hormones in asthma and allergy in females: A systematic review and meta-analysis

To the Editor: Asthma and allergy are more common in males than in females during early childhood, but the incidence, severity, and impact on quality of life are greater in postpubertal females than in males. Female sex steroid hormones may partly explain these differences. In 2 previous systematic reviews, early menarche (<12 years) was associated with an increased asthma risk, whereas no significant association was found betweenmenopause and asthma, although subgroup analyses indicated an increased risk in postmenopausal women using hormone replacement therapy (HRT). Consideration of other hormonal factors, along with the full spectrum of relevant outcomes, is necessary for a comprehensive appreciation of the underlying evidence base. We therefore undertook a systematic review investigating the role of endogenous and exogenous hormonal factors in the development and clinical expression of asthma and allergy in females. Our methods were published a priori (PROSPERO: 2015:CRD42015026762). Further details are available in this article’s Online Repository at www.jacionline.org. We included experimental and analytical epidemiological studies of females from puberty to adulthood (<75 years). Exposures were puberty, menarche, menstruation, menopause, hormonal contraceptives, and HRT. Primary outcomes were self-reported or objectively defined incidence or prevalence of asthma, asthma exacerbations, asthma hospitalizations, and asthma medication use. We searched 11 bibliographic databases, databases of ongoing studies, and conference abstracts, and contacted experts for articles published between January 1990 and November 2015 with no language restrictions. N.M. and B.I.N. independently screened titles, abstracts, and full-text articles; extracted study data; and assessed risk of bias using the Cochrane Risk of Bias Tool (experimental studies) and the Effective Public Health Practice Project tool (observational studies). Discrepancies were resolved by discussion, or arbitration by A.S. Adjusted effect estimates were combined in random-effects meta-analyses, performed using Stata release 14 (StataCorp, College Station, Tex). Meta-analyses were possible for studies on menarche, menstruation, menopause, hormonal contraceptives, and HRT. Stratified analyses were performed by body mass index and smoking for HRT studies. Of 22,488 articles retrieved, 64 (reporting 57 studies; observational: 51; experimental: 6) were included with 554,293 participants analyzed (see references E5 and E10-E72 and Fig E1 in this article’s Online Repository at www.jacionline.org). Study characteristics are available on request. Detailed results are given in this article’s Online Repository at www.jacionline.org; here, we present key findings. Compared with typical menarche (11-13 years), early menarche