Correlating Menstrual Cycles and Cystic Fibrosis Symptoms in the Era of Highly Effective Modulators: Findings of the MENSTRUAL Study

Abstract

Objectives

Chronic disease symptoms fluctuate across the menstrual cycle, but such patterning is understudied in cystic fibrosis (CF), particularly in the post–cystic fibrosis transmembrane conductance regulator modulator (CFTRm) era. This study examined how CF symptoms change across the cycle, identifying which symptoms worsen, how severe they get, and when they occur.

Methods

Menstruating cisgender women with CF (ages 18-45) completed surveys and tracked 40 CF and menstrual symptoms daily using a customized app. We assessed symptom periodicity over a 28-day cycle using a cumulative link mixed-effects model and evaluated the effects of CFTRm use and cycle phase, while adjusting for multiple covariates. We interviewed 20 participants using a constructivist grounded theory approach.

Results

Sixty-four participants (89%) contributed 3 cycles of symptom data; most (87%) used CFTRm and reported mild symptoms. Across multiple statistical models, menstrual cycle phase significantly affected CF symptoms, including gastrointestinal symptoms (eg, bloating, gas, stomachache, and bowel movement pain) and pulmonary/sinus symptoms (eg, coughing up mucus, migraine, and runny, stuffy nose). A phase effect on CF symptoms remains even after adjusting for CFTRm use. Qualitative findings corroborate these patterns, with interviewees reporting improvements in coughing, coughing mucus, and joint pain with CFTRm, though some experienced intensified gastrointestinal symptoms.

Conclusions

CF symptom severity varied across the menstrual cycle, even after accounting for CFTRm. While menstruation was associated with the highest symptom burden, other cycle phases showed significantly reduced symptom severity, which varies by symptom. Clinicians should encourage females with CF to track symptoms to support phasic CF management strategies.