TABLE 1

Summary of animal and human studies in cystic fibrosis (CF) examining the effects of female sex hormones or cystic fibrosis transmembrane conductance regulator (CFTR) modulators

InterventionStudy designStudy model or number of subjectsOutcomesRef.
Animal studies
 OestradiolIn vivoCFTR-deficient mouse model (CFTRtm1UNC)
  • Decreased survival when infected with Pseudomonas aeruginosa due to reduced bacterial killing compared to progesterone treatment

[48]
Ex vivoCFTR-deficient mouse model (CFTRtm1UNC)
  • Increased IL-23 and IL-17 expression in BAL and lung tissue post P. aeruginosa infection

    Increased P. aeruginosa load

    Decreased antimicrobial peptide, lactoferrin

[46]
Human studies
 Pre-clinical studies
  OestradiolIn vitroHuman CF bronchial epithelial cell line (CFBE41o-)
  • Upregulated SLPI and inhibited IL-8 production

[47]
In vitroHuman CF bronchial epithelial cell line (CuFi-1)
  • Reduced intensity of ciliary beat frequency

    Upregulated P. aeruginosa virulence factors to promote motility and biofilm formation

[40]
In vitroHuman CF bronchial epithelial cell lines (CFBE41o- and IB3-1)
  • Reduced chloride transport in a CFTR-independent manner

[66]
In vitroPrimary human CF bronchial epithelium (HBECs)
  • Inhibited Ca2+ influx

    Reduced Cl secretion and ASL volume

[36]
  TamoxifenIn vitroHuman CF bronchial epithelial cell lines (CFBE41o- and IB3-1)
  • Improved chloride transport in a CFTR-independent manner

[66]
  Tamoxifen and ICI182780In vitroHuman CF bronchial epithelial cell line (CuFi-1)
  • Counteracted oestrogen-mediated increase in P. aeruginosa virulence

[40]
In vitroPrimary human CF bronchial epithelium (HBECs)
  • Increased Cl secretion and ASL volume

[36]
 Clinical studies
  IvacaftorRetrospective case control144 (77 males; 67 females)
  • Decreased PEx rates in females to a greater extent than males and to a rate similar to that of males post-IVA

    Greater improvement in sweat chloride in females compared to males 3 months post-IVA

    No significant sex-related differences in changes in FEV1 or BMI post-IVA

[67]
  OCPRetrospective77 (36 on OCP)
  • Reduced antibiotics requirement

[49]
Retrospective114 (57 on OCP)
  • Unchanged FEV1, BMI or number of PEx

[61]
Prospective cohort23 (13 on OCP)
  • Improved CFQ-R scores

[62]
Prospective cohort23 (13 on OCP)
  • Reduced sputum inflammatory biomarkers and P. aeruginosa load

    Increased FEV1

[31]

IL: interleukin; BAL: bronchoalveolar lavage; SLPI: secretory leukoprotease inhibitor; ASL: airway surface liquid; PEx: pulmonary exacerbation; IVA: ivacaftor; OCP: oral contraceptive pill; FEV1: forced expiratory volume in 1 s; BMI: body mass index; CFQ-R: cystic fibrosis questionnaire revised.