Sex Differences and Sex Steroids in Lung Health and Disease

Abstract

Sex differences in the biology of different organ systems and the influence of sex hormones in modulating health and disease are increasingly relevant in clinical and research areas. Although work has focused on sex differences and sex hormones in cardiovascular, musculoskeletal, and neuronal systems, there is now increasing clinical evidence for sex differences in incidence, morbidity, and mortality of lung diseases including allergic diseases (such as asthma), chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer, as well as pulmonary hypertension. Whether such differences are inherent and/or whether sex steroids play a role in modulating these differences is currently under investigation. The purpose of this review is to define sex differences in lung structure/function under normal and specific disease states, with exploration of whether and how sex hormone signaling mechanisms may explain these clinical observations. Focusing on adult age groups, the review addresses the following: 1) inherent sex differences in lung anatomy and physiology; 2) the importance of certain time points in life such as puberty, pregnancy, menopause, and aging; 3) expression and signaling of sex steroid receptors under normal vs. disease states; 4) potential interplay between different sex steroids; 5) the question of whether sex steroids are beneficial or detrimental to the lung; and 6) the potential use of sex steroid signaling as biomarkers and therapeutic avenues in lung diseases. The importance of focusing on sex differences and sex steroids in the lung lies in the increasing incidence of lung diseases in women and the need to address lung diseases across the life span.

Serum testosterone levels and excessive erythrocytosis during the process of adaptation to high altitudes

“…In fact, there is increasing clinical evidence for sex differences in the incidence, morbidity and mortality of lung diseases including allergic diseases (such as asthma), chronic obstructive pulmonary disease, pulmonary fibrosis and lung cancer, as well as pulmonary hypertension. 54,55 A recent study showed that the androgen receptor (AR) is expressed in type II pneumocytes and the bronchial epithelium of murine lung and that androgen treatment increases AR protein levels in lung cells, 56 suggesting an important role for androgens in lung function.…”

Decreased levels of circulating sex hormones as a biomarker of lung cancer in male patients with solitary pulmonary nodules

“…It has been reported that sex hormones influence almost every aspect of human physiological functions, activities, and behaviors (12). Sex hormones are thought to have a role in the etiology of some cancers; disturbance in sex hormones is an important feature of cancer pathophysiology (13). However, most studies have been done on sex hormone-sensitive cancers in reproductive organs such as breast, prostate, cervix and ovary.…”

Endocrine regulation of airway contractility is overlooked

“…For the purpose of clarity, the endocrine regulation of the lung immune system is not addressed in detail in the present review. Readers are referred to recent reviews that are covering this particular topic (Townsend et al 2012a, Wright 2012, Sood & Shore 2013.…”

“…The effect of sex hormones on asthma, airway responsiveness, and ASM contractility has received considerable interest (Townsend et al 2012a). The results obtained so far are informative and promising, but not yet permissive to conclusive statements due to reported discrepancies.…”