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US-POLITICS-BIDEN

Srdjan Stepic

In January, Jess Johnson woke in the middle of the night struggling to breathe. While lying in bed, she could not stop coughing or wheezing.

“My inhaler would not work, nothing was working,” Johnson recalls.

Her first thought was the <a href="https://www.washingtonpost.com/coronavirus/" target="_blank" class="contextual_link">coronavirus</a>. But then the North Carolina resident remembered she was due to get her period that week.

When she was in fifth grade, Johnson was diagnosed with <a href="https://www.lung.org/lung-health-diseases/lung-disease-lookup/asthma/learn-about-asthma" target="_blank">asthma, a chronic condition characterized by lung inflammation</a>. That inflammation, which can be caused by genetic and environmental factors, often makes it hard to breathe.

About 17 years later, Johnson started noticing that, for a few days each month, her asthma would flare and tasks as simple as folding laundry or talking on the phone would leave her breathless. Today, Johnson, 33, still finds herself relying heavily on her inhaler the week before her period.

For some, bodily changes around menstruation bypass discomfort and careen into danger territory. Research shows that anywhere from <a href="https://err.ersjournals.com/content/errev/30/162/210067.full.pdf" target=_blank>10 to 40 percent of women experience worsening of asthma symptoms just before and during menstruation</a>. (Experts think the true number lies somewhere in the middle.) The worsening of asthma symptoms can have serious consequences: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1747196/pdf/v060p00806.pdf" target=_blank>Women visiting the emergency department for asthma attacks</a> are often within a few days of getting their periods, researchers say.

Aggravation of symptoms around menstruation is just one part of a larger puzzle of the role sex differences play in asthma. In general, the different levels of sex hormones in males vs. females seem to cause an increase in the number and severity of asthma cases in adult women. And the rise and fall of hormones during the menstrual cycle seems to exacerbate asthma symptoms, too.

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Differences related to asthma between males and females start early and shift dramatically as people age. While more adult women live with asthma than do men, the trend is flipped for children: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629917/pdf/nihms907289.pdf" target=_blank>Before puberty, boys are 1.5 times more likely to have asthma than are girls</a>, and twice as likely to be hospitalized for their symptoms. Experts attribute this in part to structural differences in the lungs, since boys have airways that are disproportionately narrow compared with the large volume of their lungs.

When puberty hits, though, children’s systems are flooded with sex-specific hormones. Females get higher levels of estrogen and progesterone, and males get higher levels of testosterone. The change in hormonal milieu drives what researchers call the “puberty switch,” when women overtake men in the number of new asthma cases, with about two adult women diagnosed for every one man.

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The ways that each of the sex hormones affects the lungs are complex, and their effect varies depending on which cells are involved. On balance, though, the testosterone that kicks in after puberty in males helps protect against asthma by decreasing inflammation. Estrogen and progesterone, on the other hand, increase inflammation and can therefore worsen asthma, says <a href="https://www.mayoclinic.org/biographies/chiarella-sergio-e-m-d/bio-20487817">Sergio Chiarella</a>, an allergist-immunologist at the Mayo Clinic.

For example, progesterone can impair the hairlike structures that line the airways. Those structures — called cilia, Latin for eyelash — undulate back and forth to propel inhaled debris out of the lungs. Researchers have shown that <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359952/pdf/AJRCMB464446.pdf" target=_blank>progesterone decreases the cilia’s movement</a> and makes it harder to expel outside particles that wander into the body. Those outside particles can then nestle into the lungs and worsen the inflammatory response in women with asthma.

But while female hormones increase the risk for asthma overall, the picture gets more complicated when looking at the day-to-day experiences of women with asthma, whose symptoms can change over the course of their menstrual cycles.

Heather Dunham

Lynn Johnson, a board member for the <a href="https://www.aafa.org/">Asthma and Allergy Foundation of America</a> who lives in Alabama, was diagnosed with asthma at age 45. After her diagnosis, Johnson began charting her asthma symptoms and menstrual cycle on a spreadsheet. She noticed, as Jess Johnson had, that they intensified just before her period — a phenomenon experts call “perimenstrual asthma.”

Changes in <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3747720/pdf/chest_143_4_984.pdf" target=_blank>asthma symptoms align with the ebb and flow of estrogen and progesterone during the menstrual cycle</a>, which usually lasts 28 days, researchers say. Typically, when the symptoms of people like Jess Johnson and Lynn Johnson start to worsen, they are about a week away from starting their period. At that point, their levels of progesterone and estrogen have begun to plummet. Asthma exacerbations persist as the levels of hormones fall to their lowest point during menstruation, when women get their periods.

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These changes in symptoms during the menstrual cycle are confusing given what researchers know about the role of sex hormones in males and females. Female sex hormones can increase inflammation in and around the lungs, “but the times in which the symptoms appear are when [levels of hormones] are lower,” says <a href="https://www.vumc.org/pmi-education/person/dawn-c-newcomb-phd">Dawn Newcomb</a>, associate professor at Vanderbilt University Medical Center, who studies the role of sex hormones in asthma. “That doesn’t make a lot of sense.”

The best explanation experts have is that the fluctuations in levels of sex hormones underlie perimenstrual asthma, says <a href="https://profiles.dom.pitt.edu/paccm/faculty_info.aspx/Wenzel5445">Sally Wenzel</a>, a pulmonologist and director of the University of Pittsburgh Asthma &amp; Environmental Lung Health Institute.

As for why the change in hormones matters more than absolute amounts, researchers are less sure. The fall in progesterone before menstruation seems to play an important role in triggering perimenstrual asthma. But “exactly how it triggers it again, I think, is pretty unclear,” Wenzel says.

Because hormone fluctuations seem to trigger perimenstrual asthma, researchers suspected that therapies providing constant amounts of hormones — such as some types of oral birth control — might temper symptoms. But “it’s kind of a mixed bag” when it comes to the scientific evidence in support of that prediction, says <a href="https://my.clevelandclinic.org/staff/16187-joe-zein">Joe Zein</a>, a pulmonologist and researcher at the Cleveland Clinic. One <a href="https://www.atsjournals.org/doi/10.1164/ajrccm.155.4.9105066?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed">study</a> found that hormonal contraception improves symptoms; <a href="https://accpjournals.onlinelibrary.wiley.com/doi/abs/10.1592/phco.23.5.561.32201?sid=nlm%3Apubmed">another</a> did not.

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Part of the reason for the haziness about oral birth control’s efficacy for asthma symptoms might have to do with when the studies were conducted. Most of the research on oral birth control is decades old, when the amounts of hormones in the pills were different from all the options available today.

“It’s a study begging to be done again, but using different hormonal combinations,” Wenzel says.

Plus, there is a lot of variation between people in terms of levels of sex hormones, types of asthma and exposure to risk factors. And there are additional factors that influence the immune system — and indirectly, asthma — such as the genes contained on X vs. Y chromosomes. That makes it hard to speak in generalizations such as “birth control is bad” or “birth control is good,” Chiarella says. “It’s very context dependent.”

Personalized medicine, or tailoring the therapy to the unique context of the patient, makes the most sense, he says.

That is the approach that finally helped Lynn Johnson. When Johnson was hospitalized for respiratory failure five years after her diagnosis, she told her pulmonologist about her spreadsheet. They looked at the document, and Johnson’s doctor agreed that there was an association between her menstrual cycle and asthma symptoms.

Together they made a plan. During a normal week, Johnson would use her nebulizer — a way to self-administer asthma medication — each morning, adding an extra dose a couple of times a week as needed. Before her period, however, she would ramp up her medications. Based on her doctor’s advice, she would dose herself with one kind of asthma medication every four hours round-the-clock, and another every eight.

“It’s helped me plan and manage my asthma a whole lot better,” Johnson says.

But doctors and researchers still have many questions about the links between asthma and sex hormones. And when, historically, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835077/">two times</a> more women have died of asthma than men, answering those questions is important. Without more research to fill in those gaps, doctors and patients must continue operating without “clear-cut recommendations,” Zein said.

Emily Harris

Asthma symptoms worsen before and during menstruation for some women