The role of female hormones on lung function in chronic lung diseases

Abstract

Background: The prevalence, morbidity, and mortality of inflammatory lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) are increasing in women. There is a dearth of data on the biological mechanisms to explain such observations. However, some large epidemiologic studies suggest that lung function fluctuates during the menstrual cycle in female patients with airways disease but not in women without disease, suggesting that circulating estradiol and progesterone may be involved in this process.

Discussion: In asthma, estradiol shuttles adaptive immunity towards the TH2 phenotype while in smokers estrogens may be involved in the generation of toxic intermediate metabolites in the airways of female smokers, which may be relevant in COPD pathogenesis. In CF, estradiol has been demonstrated to up-regulate MUC5B gene in human airway epithelial cells and inhibit chloride secretion in the airways. Progesterone may augment airway inflammation.

Summary: Taken together, clinical and in-vivo data have demonstrated a sex-related difference in that females may be more susceptible to the pathogenesis of lung diseases. In this paper, we review the effect of female sex hormones in the context of these inflammatory airway diseases.

Figure 1

Median survival ages in both sexes in CF from 1977-2002. Obtained from the Canadian Cystic Fibrosis Foundation, Report of the Canadian Patient Data Registry 2002, Toronto, Ontario [8].

Figure 2

Used with permission from the American Physiological Society. A) Overview of the sex steroid hormone biosynthetic pathway and associated nuclear receptors. P450ssc, P450-linked side chain cleaving enzyme; CYP17, cytochrome P450 17; 3β-HSD, 3β-hydroxysteroid dehydrogenase; 17β-HSD, 17β-hydroxysteroid dehydrogenase; PR, progesterone receptor; AR, androgen receptor; ER, estrogen receptor. B) Progesterone, C) estriol, D) estradiol, E) estrone [9].