Gender-based Asthma Mysteries

Vol. 20 • Issue 6 • Page 8

Allergy and asthma

Asthma is known to play favorites in the gender department.

In young childhood, asthma is much more common in males. As children near puberty, asthma is much more common in females. Then, at about the age of puberty, the prevalence is equal in males and females. Finally, after puberty, it is more common in females. Why is there a variance in asthma prevalence according to age and gender?

“That’s what everyone is trying to figure out,” said Jennifer McCallister, MD, assistant professor in the division of pulmonary medicine at Ohio State University (OSU) Medical Center, Columbus, Ohio. She is leading a pilot study dealing with gender-based asthma profiling. “Intuitively researchers and asthma clinicians want to place all the blame on sex hormones, since this transition in asthma prevalence occurs at a key time – puberty – when these hormones are becoming key players in the reproductive lives of women.”

But it’s not quite that simple. Not all research has supported a direct causal relationship between sex hormones and symptom exacerbation.

“Some literature suggests that at menopause the use of hormone replacement therapy is associated with an increase in asthma prevalence in older women. That would support the relationship between asthma and sex hormones,” Dr. McCallister said. “However, in women of childbearing potential there has been research using manipulation of the hormones, specifically the administration of oral contraceptives, to try to decrease asthma symptoms. The majority of this research fails to show any relationship between the use of oral contraceptives in women and asthma. It seemed clear cut before that.”

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Up to 40 percent of women with asthma note an increase of symptoms prior to menses, according to McCallister. “Prior to menstruation, there is an abrupt drop in sex hormones. That has led some researchers to hypothesize that it is the change in the level of sex hormones that may be directly linked and not so much the amount.”

Tom Utigard, RRT, director of respiratory care at Yakima Regional Medical & Cardiac Center, has dealt with post-pubescent girls throughout his career while providing therapy at an asthma camp. He has seen the cycle-based flare-ups all too often.

“Either right before their period or during their period the girls’ symptoms seem to worsen, and they require more treatments than they did a day or two before when they were having as much or more activity,” Utigard noted. “How come all of a sudden? For one or two to have those issues would be one thing, but it is a fairly common occurrence.”

Pilot study at OSU

McCallister will do her part to unravel the gender-based mysteries surrounding asthma by leading a pilot study funded by the Center for Women’s Health and the Center for Clinical and Translational Science at OSU. The study will concentrate on that 40 percent sub-population of women who have a worsening of asthma symptoms at the time of menses in hopes of discovering why some, but not all, women experience this.

Some 20 women, 10 with self-described premenstrual worsening of asthma and 10 without, will be enrolled for evaluation of inflammatory markers, including leukotrienes, known to be elevated in patients with asthma. In addition, micro-RNA will be examined to evaluate the patients’ genetic makeup.

The researchers will look at participants at two points during their menstrual cycle: one midway through their menstrual cycle, when hormones are most stable; the second point will be right before the onset of menses. Blood tests will be done to compare the leukotriene level at those two points in the two patient populations.

The study’s findings could hold important implications for treatment going forward. “There are asthma medications now that specifically target the leukotriene pathway,” Dr. McCallister said. “If research shows a spike in leukotrienes among women with premenstrual worsening of symptoms, we as clinicians would know they would be potentially excellent candidates for these medications.”

Utigard would welcome research that could shed light on the issue, as a way to reinforce medication compliance among the female campers with asthma. “It would be helpful to be able to pinpoint a specific time of the month and stress; this is the most important time to stay on therapies and medicines to stay out of trouble,” Utigard said.

While Dr. McCallister and fellow researchers are anxious to get the study into full gear, they’re struggling to find young menstruating women to participate. “OSU is a huge university with over 50,000 students, so you’d think it would be easy to get the right participants,” she said. “But with the birth control pills available today, many young women don’t menstruate. They take pills that allow them to have a period every four to six months.”

Valerie Neff Newitt can be reached at [email protected].