Women with cystic fibrosis have inflammatory biomarker fluctuations in the lungs that correlate with changes in lung function, opening the possibility of sex hormone linked changes, according to the results of a recent study published in the Annals of the American Thoracic Society.

In this single center, prospective, observational pilot study (ClinicalTrials.gov Identifier: NCT02036879), investigators measured lung function, symptom questionnaires, sweat tests, blood hormone levels, and sputum inflammatory markers in women with cystic fibrosis who were not taking hormonal contraceptives and reported regular menstrual cycles. Associations were examined between lung function and estrogen levels over time.

Among the 23 women with cystic fibrosis, the average age was 29 years and baseline forced expiratory volume in 1 second (FEV1) percent predicted was 58.2. Several participants were taking modulator therapy at the time of the study: 2 were taking ivacaftor, 2 were taking tezacaftor/ivacaftor, and 2 were taking lumacaftor/ivacaftor. A total of 13 participants went on to take the oral hormonal contraceptive therapy, ethinyl estradiol-norethindrone, as part of the substudy. The researchers noted that 1 woman could not complete the substudy because a pulmonary embolism that had developed after oral contraception initiation, which left 12 women in the substudy.

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Hormone levels fluctuated as expected and in a manner consistent with hormone patterns of women without cystic fibrosis throughout the ovulatory cycle. At ovulation (a time of peak estrogen), there was a significant increase in pro-inflammatory cytokines and decrease in lung function. Furthermore, among the women who started oral hormonal contraceptive therapy, pro-inflammatory cytokines improved (eg, interleukin-8, tumor necrosis factor-alpha, and neutrophil free elastase).

Regarding clinical symptoms, there were no differences reported between the revised Cystic Fibrosis Questionnaire (CFQ-R) respiratory domain and the other domain scores during the natural cycle. However, when women were placed on oral contraceptive therapy, they reported an 8.54 improvement relative to menses in the health perception domain of the CFQ-R (P =.04). Women taking oral contraceptive therapy also reported a “trend toward improvement” in respiratory symptoms, treatment burden, and health perceptions, relative to the time of ovulation.

The major study limitation was the small sample size and that it was restricted to adult women with cystic fibrosis with regular menstrual cycles who were not currently taking hormonal contraception.

“These findings provide insight into the real time changes that may be occurring in women, particularly in regards to inflammation, and suggest that hormonal contraception may have beneficial effects,” the study authors wrote. “These data underscore the need for a larger, multicenter study to further explore the physiologic effects of hormone changes in women with [cystic fibrosis].”


Holtrop M, Heltshe S, Shabanova V, et al. A prospective study of the effects of sex hormones on lung function and inflammation in women with cystic fibrosis. Ann Am Thorac Soc. Published online February 5, 2021. doi:10.1513/AnnalsATS.202008-1064OC