Objective:

To evaluate sex disparities in cystic fibrosis (CF) outcomes before and after the introduction of highly effective modulator therapy.

Key Findings:

• Female patients with CF experience worse pulmonary morbidity and earlier mortality compared to male patients.
• Female sex remains an independent risk factor for death even after adjusting for comorbidities and chronic airway infection.
• Female patients have more frequent pulmonary exacerbations, longer treatment courses, and are less likely to recover baseline lung function post-exacerbation.
• Common airway pathogens are acquired earlier by female patients, leading to accelerated lung function decline.
• Estrogen may negatively impact CF lung disease through various airway-level effects.

Interpretation:

Limitations:

• Many findings are based on mechanistic, in vitro, animal, or observational studies, which may not fully reflect clinical physiology.
• Existing studies on the effects of oral contraceptives and hormonal states on CF outcomes show inconsistent results.

Conclusion: