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, 17beta-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 <or= 0.005). Among women not using OC, a 10 pmol/L increase in 17beta-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 <or= 0.05). Consistent and significant results were found for 17beta-estradiol and progesterone levels and SPT. There were no significant associations between sex hormones and markers of asthma among women using OC.


CONCLUSIONS
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.
Mandhane
Piush J
PJ
Department of Medicine, School of Rehabilitation Science, McMaster University, Hamilton, ON, Canada; Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, ON, Canada. Electronic address: mandhane@ualberta.ca.
Hanna
Steven E
SE
Department of Clinical Epidemiology and Biostatistics, School of Rehabilitation Science, McMaster University, Hamilton, ON, Canada.
Inman
Mark D
MD
Department of Medicine, School of Rehabilitation Science, McMaster University, Hamilton, ON, Canada; Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, ON, Canada.
Duncan
Joanne M
JM
Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, ON, Canada; Department of Medicine, School of Rehabilitation Science, McMaster University, Hamilton, ON, Canada.
Greene
Justina M
JM
Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, ON, Canada; Department of Medicine, School of Rehabilitation Science, McMaster University, Hamilton, ON, Canada.
Wang
Hong-Yu
HY
Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, ON, Canada; Department of Medicine, School of Rehabilitation Science, McMaster University, Hamilton, ON, Canada.
Sears
Malcolm R
MR
Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Hamilton, ON, Canada; Department of Medicine, School of Rehabilitation Science, McMaster University, Hamilton, ON, Canada.
D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D003276:Contraceptives, Oral; D004958:Estradiol / Q000032:analysis; D045853:Exhalation / Q000502:physiology*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008597:Menstrual Cycle / Q000502:physiology*; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis*; D011374:Progesterone / Q000032:analysis*; D012463:Saliva / Q000502:physiology; D013147:Spirometry
D003276:Contraceptives, Oral; D009569:Nitric Oxide; D011374:Progesterone; D004958:Estradiol