The cystic fibrosis gender gap: Potential roles of estrogen

Abstract

Cystic fibrosis (CF) is a complex, multi-system, autosomal recessive disease predominantly affecting Caucasians that leads to vigorous airway inflammation and chronic respiratory infection, commonly with Pseudomonas aeruginosa. A variety of factors significantly modify the progression and severity of CF lung disease and the timing of the resulting mortality. We summarize here data indicating that there is in CF a female disadvantage in survival and morbidity, called the "CF gender gap". Although controversy exists regarding the nature and relative importance of the various contributing mechanisms involved, gender affects the progression of CF disease with respect to lung infection, decline in pulmonary function and nutritional status. These interrelated factors in turn have a negative impact on survival. This review will emphasize the increasing evidence that suggest a role for the effects of gender, and particularly the female sex hormone estrogen, on infection, inflammation and transepithelial ion transport, all major determinants of CF lung disease. Future elucidation of the pathophysiology of hormonal aggravation of CF lung disease may pave the way for novel therapeutic interventions. This, combined with the magnitude of the gender gap in CF mortality, strongly suggests that further work in this field is well justified.

Impact of Osteopathic Treatment on Pain in Adult Patients with Cystic Fibrosis – A Pilot Randomized Controlled Study

“…Indeed, in CF there is a female disadvantage in terms of survival and morbidity, called the “CF gender gap” [28], which might be due to the female sex hormone estrogen. Nevertheless, it is unclear from the literature whether women with CF are in greater pain than men with CF.…”

Lung transplantation and gender effects on survival of recipients with cystic fibrosis

“…[1, 2] The exact reason for this gender gap remains unclear; and various factors such as sex hormones, differences in immune responses, socio-economic factors, and variations in airway diameter have all been implicated. [1][2][3][4] Lung transplantation (LT) is a widely accepted modality of treatment for select CF patients with progressive disease. In the United States, donors and recipients are matched based on ABO compatibility, size, virtual crossmatch, and need for single versus bilateral lungs.…”

End-stage cystic fibrosis lung disease is characterised by a diverse inflammatory pattern: an immunohistochemical analysis

“…Given the lack of apparent differences in patient characteristics between male and female CF patients in our population which may account for the observed female predominance in airway inflammation, there is some room for speculation. It has been shown that oestrogen has a complex immunomodulatory effect on inflammation and mucoid P. aeruginosa density [19]. Human CF patients whose lungs are actively infected with P. aeruginosa have elevated sputum levels of IL-23 and IL-17 which decrease dramatically following antibiotic treatment [20, 21].…”

“…Sex hormones also modulate autoimmunity. Autoimmune diseases are a class of illnesses associated with increased Th17 activity and showing distinct gender-based differences in prevalence [19]. The gender-based difference in inflammation in our CF population may be the result of overstimulation of Th17 activity by oestrogens similar to what is seen in autoimmune diseases.…”