Barbara Boughton

June 08, 2012

June 8, 2012 (San Francisco, California) — Estrogen is associated with poorer outcomes in women with cystic fibrosis, according to a study presented here at the American Thoracic Society 2012 International Conference. The results, which were published in the May 24 issue of the New England Journal of Medicine, might explain why women with cystic fibrosis tend to fare worse than men with the disease.

Pseudomonas aeruginosa bacteria play a primary role in the infections, exacerbations, and lung damage that mark cystic fibrosis. In their study, Noel McElvaney, MD, professor of medicine at Beaumont Hospital in Dublin, Ireland, and colleagues found that P aeruginosa transforms into its more virulent mucoid form after prolonged exposure to estradiol.

Moreover, the investigators found 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.

"We found that females are more likely to get P aeruginosa infections at certain times of the menstrual cycle (when estrogen is highest) and are more likely to be infected with mucoid P aeruginosa than nonmucoid P aeruginosa," Dr. McElvaney said.

To test whether exacerbations are related to women's hormonal cycles, the investigators assessed 139 exacerbations in 44 women with cystic fibrosis at Beaumont Hospital over the 24-month study period. In 23 of these women, they found a significant increase in the number of exacerbations during the follicular phase, when estradiol levels peak (P < .05).

They also found that serum estradiol levels were significantly higher in women with exacerbations than in those with stable disease (777 vs 303 pmol/L; P < .008).

To test the association between estrogen and the mucoid form of P aeruginosa, the investigators analyzed data from 2006 to 2009 on the use of oral contraceptives from the cystic fibrosis registry in Ireland. Of the 239 women 18 years or older in the registry, 15.1% used oral contraceptives. When the investigators compared these 239 women with 41 women in the registry who did not use contraceptives, they found that women using oral contraception were less likely to require antibiotics for the treatment of exacerbations.

In a final step of their analysis, the investigators analyzed all cystic fibrosis registry data up to December 2010, which included information on 455 women and 554 men. The women were significantly more likely to have P aeruginosa infections than the men (absolute difference, 11.9%; P < .001), and acquired P aeruginosa infections 2.3 years earlier than men (age, 19.7 vs 22.0 years; P = .01).

Data from the Irish registry on 14 pregnancies from 2001 to 2010 revealed that 5 of 7 pregnant women (71.4%) acquired the mucoid form of P aeruginosa within a year of delivery, and that 6 of 7 (85.7%) did so within 2 years.

"This study gives us insight into the pathogenesis of cystic fibrosis, the inflammatory response, and what elicits the inflammatory response," Dr. McElvaney said. "This is the first time that research has shown that a hormone can produce a change in bacteria," he noted.

Dr. McElvaney noted that the research might open up treatment options for women with cystic fibrosis, if bolstered by further randomized controlled trials. "One question our research raises is whether manipulating estrogen in women with cystic fibrosis — say with oral contraceptives — would have an effect on outcome," he said. "To really investigate that questions, you'd have to do a randomized trial with different types of birth control pills," he said.

"This is very exciting research and it explains what clinicians have observed for years — that women with cystic fibrosis tend to do worse than men," said Jerry A. Nick, MD, director of the adult cystic fibrosis program at the National Jewish Medical and Research Center in Denver, Colorado, who was not involved with the study.

"The research correlates well with what we see in women with cystic fibrosis. They tend to convert to the mucoid form [of P aeruginosa] earlier than males — around puberty — and have a less favorable response to antibiotics and a faster decline in lung function, Dr. Nick said.

Dr. McElvaney and Dr. Nick have disclosed no relevant financial relationships.

N Engl J Med. 2012;366:1978-1986. Abstract

American Thoracic Society (ATS) 2012 International Conference: Session A12. Presented May 20, 2012.

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