Sex disparities in cystic fibrosis: review on the effect of female sex hormones on lung pathophysiology and outcomes

Abstract

Sex differences in morbidity and mortality have been reported in the cystic fibrosis (CF) population worldwide. However, it is unclear why CF women have worse clinical outcomes than men. In this review, we focus on the influence of female sex hormones on CF pulmonary outcomes and summarise data from in vitro and in vivo experiments on how oestrogen and progesterone might modify mucociliary clearance, immunity and infection in the CF airways. The potential for novel sex hormone-related therapeutic interventions is also discussed.

FIGURE 1

Changes in oestrogen and progesterone levels in the context of clinical, infectious and inflammatory findings during the menstrual cycle. During the menstrual phase, both oestrogen and progesterone levels are low. In the follicular phase, oestrogen begins to rise and peak just prior to ovulation. Progesterone begins to rise shortly before ovulation and peak during the luteal phase. Oestrogen levels also increase during the luteal phase. Levels of both progesterone and oestrogen decline until the start of the next menstrual cycle. Forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) are both noted to be reduced during menstruation and ovulation but recover to baseline by the luteal phase. Rates of pulmonary exacerbations (PEx) are highest during the follicular phase, while markers of inflammation (tumour necrosis factor-α (TNF-α), interleukin-8 (IL-8) and free neutrophil elastase (NE)) and Pseudomonas aeruginosa (PsA) sputum bacterial load are highest during ovulation. PsA takes on the more virulent mucoid form during the follicular phase while reverting to the less virulent non-mucoid form during the luteal phase.