ACAAI 2011: Pregnancy and Hormonal Effects on Asthma

Carlos Camargo, MD, DrPH, Associate Professor of Medicine and Epidemiology at Harvard Medical School, and Director of the Emergency Medicine Network (EMNet) Coordinating Center at Massachusetts General Hospital, spoke today at the American College of Allergy, Asthma and Immunology Annual Meeting in Boston. His lecture, "Effect of Pregnancy and Hormonal Changes on Asthma" reviewed recent studies on the effects of menarche, menopause, and pregnancy on asthma, and described the implications for patients with asthma.

Dr. Camargo began by noting the variety of influences on asthma, including social, environmental, genetic, and hormonal factors, and the often complex interrelationships they have. For example, asthma is more prevalent in young males compared with females, until approximately mid-adolescence. Asthma is more prevalent in females until approximately age 70 and beyond. Compared with men, women also have higher symptom frequency and intensity, more ED visits and hospitalizations, and more asthma-related deaths. Dr. Camargo cited social factors (including diagnostic bias), environmental factors (eg, obesity, sedentary lifestyle, smoking), genetics, and sex hormones as potential explanations for these differences.

Regarding female sex hormones, Dr. Camargo explained that estrogen has both immunostimulatory and immunosuppressive effects, and an association is unclear between its levels and airway hyperresponsiveness (AHR) or asthma severity/control. Progesterone, which reduces uterine smooth muscle contractility in pregnancy, may also relax bronchial smooth muscle. Like estrogen, any relationship between progesterone levels and AHR or asthma severity/control is unclear.

Menarche has an influence on asthma. An increased risk of incident asthma is well known to occur after menarche. Premenstrual asthma is common, said to account for one-third of asthmatic women. It is believed to be a subset with more severe asthma, and its peak symptoms occur 2-3 days before menses. About 10 years ago, Dr. Camargo and colleagues published a paper that contradicts these points of conventional wisdom, finding more emergency department (ED) visits by women in the first half of the menstrual cycle (when there is unopposed estrogen) and the lowest was near the end of the cycle. Maybe there is a group that becomes more bronchospastic when given estrogen. In a study 5 years later, Dr. Camargo’s group noted symptom onset peak was at the beginning of the menstrual cycle.

To examine bronchial hyperreactivity (BHR) over the menstrual cycle, Dr. Camargo presented a Swiss cohort study published last year on 571 menstruating women. The women did not receive hormonal treatment, and were 28-58 years of age. There were 143 women who were perimenstrual: 3 days before and after first day of menstruation. A methacholine challenge was given and BHR prevalence was 13%. They also looked at oral contraceptives (OC) as a possible effect modifier. A cyclic BHR pattern was observed, suggesting the relationship is complex, especially at midcycle, when estrogen concentration is higher.

Dr. Camargo then described a recent multicenter study that examined the relationship between age of menarche and adult lung function and asthma. The 3,354 women, aged 27—57 years, were participants in the European Community Respiratory Health Survey II. Of these women, 3.4% had an age of menarche ≤10 years of age. In these women with early menarche, FEV₁ and FVC were lower, and both asthma symptoms and asthma with BHR were more prevalent, compared with women with later menarche.

Moving to the effects of menopause on asthma, Dr. Camargo noted the following major conventional wisdom highlights. There’s a decrease of asthma prevalence in older women. Hormone replacement therapy (HRT) elevates risk of incident asthma. Lastly, there’s menopausal asthma is a subset with more severe asthma, and has an absence of atopy, without a family history of asthma.

Dr. Camargo commented that there were not many new papers on menopause and asthma. A 2008 paper used European Community Respiratory Health Survey II data from 1,274 women, age 45-56 years, not on HRT. Menopausal transition (MT) was defined as amenorrhea for the last 6 months. Across different countries, women in MT were more likely to have respiratory symptoms and decreased spirometry; moreover, this appeared to be observed in women with lower BMI. A 2010 paper found menopausal women had higher sputum neutrophils and more exhaled IL-6, whereas premenopausal women had higher sputum eosinophils, suggesting a menopausal asthma was a new phenotype.

There are also few new findings on how pregnancy affects asthma. Dr. Camargo noted that later pregnancies tend to have similar asthma course. Multiple studies support the importance of asthma control during pregnancy. One double-blind, parallel-group randomized controlled study measured fraction of exhaled nitric oxide (F_ENO) during pregnancy in 220 women. The F_ENO group had half the risk of asthma exacerbations relative to the placebo group, with the number needed to treat (NNT) = 6.