Changes in Exhaled Nitric Oxide Related to Estrogen and Progesterone During the Menstrual Cycle

Background: Significant changes in asthma and atopy occur throughout the menstrual cycle. We hypothesized that the characteristics of asthma (eg, symptoms, exhaled nitric oxide [eNO] levels as a marker of airway inflammation, pulmonary function, and atopy) vary throughout the menstrual cycle in relation to changes in the levels of estrogen or progesterone and that this variation is attenuated in women using oral contraception (OC). Methods: Seventeen women with asthma were studied over the course of their menstrual cycle through daily measurements of symptoms, eNO, spirometry, 17 beta-estradiol, and progesterone levels, and through the performance of alternate-day allergy skin-prick tests (SPTs). Results: Of 534 potential daily visits, 526 (98.5%) were completed. Women not using OC (n = 8) had higher mean eNO levels (48.2 parts per billion [ppb]; 95% Cl, 43.1 ppb to 53.3 ppb) than women using OC (27.0 ppb; 95% CI, 24.2 ppb to 29.7 ppb; p <= 0.005). Among women not using OC, a 10 pmol/L increase in 17 beta-estradiol levels was associated with a 15.2-ppm decrease in eNO levels (95% CI, -23.4 ppb to -7.0 ppm; p < 0.005). In contrast, an increase in progesterone level of 0.5 nmol/L was significantly associated with a 10.0-ppb increase in eNO (95% CI, 1.2 ppb to 18.7 ppb; p <= 0.05). Consistent and significant results were found for 17 beta-estradiol and progesterone levels and SPT. There were no significant associations between sex hormones and markers of asthma among women using OC. Conclusion: During natural menstrual cycles, increases in estrogen levels were associated with decreased eNO levels, whereas increases in progesterone levels were associated with increased eNO levels and SPT wheal size. These effects were not observed among women using OC. (CHEST 2009; 136:1301-1307)