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Original Research: ASTHMA |

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

Piush J. Mandhane, MD, PhD; Steven E. Hanna, PhD; Mark D. Inman, MD, PhD; Joanne M. Duncan, BSc; Justina M. Greene, Dip Comp Sys; Hong-Yu Wang, MD, PhD; Malcolm R. Sears, MB
Author and Funding Information

Affiliations: From the Firestone Institute for Respiratory Health (Drs. Mandhane, Inman, Wang, and Sears, Ms. Duncan, and Ms. Green), St. Joseph's Healthcare, Hamilton, ON, Canada; the Department of Medicine (Drs. Mandhane, Inman, Wang, and Sears, Ms. Duncan, and Ms. Green), and the Department of Clinical Epidemiology and Biostatistics (Dr. Hanna), School of Rehabilitation Science, McMaster University, Hamilton, ON, Canada.

Correspondence to: Piush Mandhane, MD, PhD, Aberhart Centre No. 1, Room 7316A, 11402 University Ave, Edmonton, AB, Canada T6G 2J3; e-mail: mandhane@ualberta.ca


Funding/Support: This study was funded by the Canadian Institute for Health Research (CIHR) and by an unrestricted grant from the AstraZeneca/Firestone Institute for Respiratory Health collaboration. Dr. Mandhane was a CIHR Strategic Training Fellow in the Canadian Child Health Clinician Scientist Program and received an award from the CHEST Foundation. Dr. Sears holds the AstraZeneca Chair in Respiratory Epidemiology, McMaster University.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).


© 2009 American College of Chest Physicians


Chest. 2009;136(5):1301-1307. doi:10.1378/chest.09-0604
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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, 17β-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% CI, 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 17β-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 17β-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.

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