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Estrogen May Explain Why Women With Cystic Fibrosis Suffer More
Date:11/20/2008

Study found high levels of hormone worsened respiratory disease

THURSDAY, Nov. 20 (HealthDay News) -- Higher levels of estrogen during ovulation may explain why women with cystic fibrosis tend to fare worse than men with the respiratory disease, researchers at the University of North Carolina report.

The authors of the study, published in the Nov. 20 issue of the Journal of Clinical Investigation, suggest that drugs that reduce estrogen levels, such as tamoxifen, might be helpful in fighting this devastating disease.

The evidence is still preliminary, however.

"There's not an immediate clinical connection to this," said Dr. Michael Konstan, director of the Cystic Fibrosis Center at Rainbow Babies & Children's Hospital, University Hospitals Case Medical Center in Cleveland. "We need to understand a lot more about the role estrogen plays in cystic fibrosis. What this clearly does is raise our awareness that there are sex-related differences."

Women with cystic fibrosis tend to have worse disease and shorter life spans than men. Although members of both genders generally now live into their 30s, men live an average of about three years longer, said senior study author Robert Tarran, an assistant professor in the Cystic Fibrosis/Pulmonary Research & Treatment Center at the University of North Carolina, Chapel Hill.

That gap has narrowed, largely thanks to more aggressive infection treatment in women.

People with cystic fibrosis have mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which reduces the ability of chloride ions to travel across cell membranes, the researchers said.

Chloride helps hydrate the lungs by bringing water along with it, basically to hydrate the mucous so that mucous keeps moving through the airways, taking disease-causing bacteria and other organisms with it.

In a person without cystic fibrosis, the chloride channel is wide open, allowing chloride to enter the lungs. Not so in cystic fibrosis patients. Due to a lack of hydration, mucous gets thicker and doesn't move, essentially trapping bacteria, allowing it to linger and fester illness.

Luckily, there is a second, "rescue" chloride channel that can take up some of the slack for cystic fibrosis patients.

"When people get cystic fibrosis, they don't just die after birth. The rescue channel keeps them limping on and provides enough hydration," Tarran explained. "The hypothesis is that that's OK until there's a catastrophic event like a viral infection."

Tarran and his colleagues hypothesized that estrogen might affect chloride secretion, thus explaining more severe illness in women. They measured the ability of chloride to move in and out of cells in women with cystic fibrosis who were not taking any birth control or other hormonal treatments.

While estrogen was low, there was no effect on the nasal passages. But high levels of estrogen while a woman was ovulating inhibited the rescue channel by about 50 percent.

"For a normal woman, it's no big deal because the other, huge channel is doing its job," Tarran said. "But in cystic fibrosis it is a big deal. The airway is cut by half, so maybe for four to five days each month there is a reduced ability to hydrate the airways. For a few days every month, it becomes a statistical lottery, if you happen to breathe in something nasty on those days."

Tarran's group next plans to test lung function in healthy women taking tamoxifen, the breast cancer drug that interferes with the activity of estrogen.

Dr. John Saito is assistant professor of pediatrics at Texas A&M Health Science Center College of Medicine, and director of the Cystic Fibrosis Center at Scott & White Hospital. "Everyone has suspected differences but nailing this down is difficult to do. This [new research] offers some insight as to what's going on at a molecular level."

There may be ways to use this new information now, Saito said. "There are other medicines that patients with cystic fibrosis inhale that replenish the airway surface layer," he said. Women patients might be able to use the intervention at the appropriate times of the month to reduce the likelihood of infection.

More information

To learn more visit the Cystic Fibrosis Foundation.



SORCES: Robert Tarran, Ph.D., assistant professor, Cystic Fibrosis/Pulmonary Research & Treatment Center, University of North Carolina, Chapel Hill; Michael Konstan, M.D., director, Cystic Fibrosis Center, Rainbow Babies & Children's Hospital, University Hospitals Case Medical Center, Cleveland; John Saito, M.D., assistant professor of pediatrics at Texas A&M Health Science Center College of Medicine, and director of the Cystic Fibrosis Center, Scott & White Hospital; Nov. 20, 2008, Journal of Clinical Investigation


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