Estrogen aggravates cystic fibrosis reports new study

Robin Wulffson MD's picture
cystic fibrosis, CF, estrogen, Pseudomonas aeruginosa, gender difference

Cystic fibrosis (CF) is a genetic disorder, which results in thick mucus secretions that most critically affects the lungs, and also the pancreas, liver, and intestines. It is known that females affected with the disorder often fare worse than males. A new study has unearthed a possible cause for the discrepancy: estrogen. Irish researchers published their findings on May 24 in The New England Journal of Medicine.

Due to the thick mucus secretions, individuals with CF are prone to pulmonary infections with organisms such as Pseudomonas aeruginosa. Pseudomonas aeruginosa bacteria play a primary role in the infections, exacerbations(episodes of increased symptoms), and lung damage characteristic of CF. Noel McElvaney, MD, professor of medicine at Beaumont Hospital in Dublin, Ireland, and colleagues evaluated the effects of estradiol and its metabolite estriol (both are types of estrogen) on P. aeruginosa in vitro (laboratory) and in vivo (female subjects).

They determined the effect of estradiol on disease exacerbations in women with cystic fibrosis.


The researchers found that P aeruginosa transforms into its more virulent mucoid form after prolonged exposure to estradiol. In addition, they discovered that women who experience high levels of estrogen (during the follicular phase of a normal menstrual cycle or during pregnancy) are more likely to be infected with the mucoid form of P aeruginosa than women with lower estrogen levels. (The follicular phase of the menstrual cycle is the period where the follicles in the ovary mature; the hormone controlling this phase is estradiol.) The investigators conducted a
review of the Cystic Fibrosis Registry of Ireland and found that the use of oral contraceptives was associated with a decreased need for antibiotics. Predominantly nonmucoid P. aeruginosa (a born of the bacterium not harmful to CF sufferers) was isolated from sputum during exacerbations in the luteal phase of the menstrual cycles when estradiol levels are low. In contrast, increased proportions of mucoid bacteria were isolated during exacerbations occurring in the follicular phase (high estradiol).

The authors concluded that: “estradiol and estriol induced mucoid conversion of P. aeruginosa in women with cystic fibrosis through a mutation of mucA in vitro and were associated with selectivity for mucoid isolation, increased exacerbations, and mucoid conversion in vivo.”

Several decades ago, CF victims often succumbed from the disease before they were of elementary school age. Currently, primarily through symptomatic treatment of the symptoms, many are surviving into adulthood; however, their life expectancy is curtailed. Genetic research is approaching cures for the many variants of CF. Each variant requires a specific therapy. Millions of Americans carry the defective CF gene; however they do not have any symptoms. That is because a person with CF must inherit two defective CF genes: one from each parent. An estimated 1 in 29 Caucasian Americans have the CF gene. The disease is the most common, deadly, inherited disorder affecting Caucasians in the U.S. and is more common among those of Northern or Central European descent. Thus, the Irish population (where this study was conducted) contains a higher proportion of CF sufferers than many other regions of the globe. Most children with CF are diagnosed by age two. However, a small number are not diagnosed until age 18 or older. These individuals usually have a milder form of the disease.

Take home message: This study suggests that women with cystic fibrosis will benefit from oral contraceptives, whether or not they require pregnancy protection. For more information regarding cystic fibrosis, click on this link.

Reference: The New England Journal of Medicine.