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

Before puberty, asthma and allergy are more common in males than in females, but these conditions become more common in females than in males during adulthood until around the time of menopause.(1-7) The disease severity, healthcare utilisation and impact on health-related quality of life (HRQoL) are also considerably higher in post-pubertal females than in males.(1-7) Although the specific mechanisms for these differences are unclear, it has been suggested that female sex steroid hormones may have a role.(1,2) Higher disease risk in females appears to follow key hormonal transitional time points in a female's reproductive life cycle, such as puberty, menarche, menstruation and menopause.(1,2) These hormonal transitional points may increase the risk of asthma and poor asthma outcomes in females.(8-10) In contrast, external suppression of endogenous sex hormone production with hormonal contraceptives may improve asthma outcomes,(9-14) but the evidence is inconsistent,(13,14) with evidence suggesting that hormone replacement therapy (HRT) may increase the risk of poor outcomes.(15-22) A clearer understanding of the role of sex steroid hormones in the development of asthma and allergy in females and their impact on asthma exacerbation, use of healthcare, and HRQoL will help to provide new insights into disease mechanisms and essential preliminary data to inform the development of primary prevention interventions and hormonal-based management strategies. We plan to undertake a systematic synthesis of the evidence to provide a comprehensive, unbiased estimate of the actual effects of sex steroid hormones on the development and clinical expression of asthma and allergy in females. The only relevant previous systematic review on this topic was confined to investigating the role of menopausal transition; this review focussed on asthma incidence as the sole outcome of interest.(23) Consequently, that study does not allow a thorough appraisal of this evidence base, given that key endogenous and exogenous hormonal factors, as well as other essential asthma and allergy outcomes, were not considered. There is therefore the need to undertake a more comprehensive synthesis of the effect of the various endogenous and exogenous hormonal factors on the full spectrum of asthma outcomes in females.