Oral Contraceptives Associated With Increased Asthma Risk

Ingrid Hein

May 20, 2018

The risk for asthma is elevated in women taking oral contraceptives, new research shows.

"What can we do with this information? That is the tricky part," said Joe Zein, MD, from the Cleveland Clinic, who presented the finding at the American Thoracic Society 2018 International Conference in San Diego. "We need more data."

Because there are so many formulations of contraceptives, we don't have precise information on which formulation has an impact on which condition, he told Medscape Medical News.

"We are not making any recommendations, and we do not suggest that women stop taking oral contraceptives," he added. Rather, the recommendation is that doctors take oral contraceptives into consideration when they assess patients with asthma.

If a patient's asthma was previously well controlled but has become severe, the doctor should determine whether she has "started taking oral contraception or hormone therapy pills," Zein explained.

In their cross-sectional study, Zein and his colleague assessed the health records of women 20 to 50 years of age. They identified 6,524,990 women from 26 healthcare organizations in the United States.

Of these women, 2,116,000 (32.4%) were using oral contraceptives and 692,470 (10.6%) carried a diagnosis of lifetime asthma and had been treated with bronchodilators or inhaled corticosteroids.

The prevalence of asthma was significantly higher in women taking oral contraceptives than in those who were not (14.3% vs 8.8%; P < .001).

"There may be a correlation with sex hormones," Zein explained. "Our hypothesis is that it has something to do with increased estrogen, which may cause inflammation."

In general, women have a higher risk for autoimmune diseases and Crohn's disease, he noted. And a recent study showed that testosterone seems to protect males against the development of asthma (J Exp Med. 2017;214:1581-1592).

A large prospective study is needed to explore these findings in women of childbearing age who are and are not using oral contraceptives, Zein said, adding that it would need a 20-year follow-up.

The issue is "very complex," he said. "Is it estrogen? Is it progesterone? Is there a difference with injections? Even if it is estrogen, which formulation?"

Subgroups Might Benefit From Oral Contraceptives

In fact, oral contraceptives might be of benefit to some women with asthma. This makes it difficult to arrive at a recommendation, particularly when women's hormones change rapidly.

Subgroups of women experience exacerbations of asthma before their menstrual cycle, for example. "Taking oral contraception can blunt the sex hormones" during that time," Zein explained. But "again, that's a hypothesis; we don't know 100 %."

And studies have shown that polycystic ovary syndrome, when women have menstrual cycles without ovulation, might be associated with a higher risk for asthma, even when women are not taking oral contraceptives.

"We need to study this further," Zein told Medscape Medical News. "That's why we don't want to make any conclusions. But we do want doctors to be aware of the time-sensitivity of asthma exacerbations and oral contraception, and ask questions."

Not Just Estrogen

"In children, asthma is more prevalent in boys than girls, then around puberty it switches," said John Mastronarde, MD, from the Providence Portland Medical Center and The Oregon Clinic's Asthma Center. "This has always fuelled speculation that somehow sex hormones are involved."

Although there is evidence that some women get more frequent and severe asthma attacks when they are premenstrual, "if it was really just related to estrogen, this should be true for all women," he pointed out. "It's clearly not as simple as just estrogen."

The theory needs a lot more study, said Mastronarde. Although this was a very large dataset, the study had a lot of limitations.

"For example, there's been a lot of talk about the misdiagnosis of asthma," he told Medscape Medical News.

That being said, the large numbers provide fuel for future research. "This does raise more questions about the pathogenesis of sex hormones. We need prospective studies on this with asthma patients," he said.

Zein and Mastronarde have disclosed no relevant financial relationships.

American Thoracic Society (ATS) 2018 International Conference: Abstract P867. Presented May 20, 2018.

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