Sex differences and sex steroids in lung health and disease
Open accessAbstract
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.(Endocrine Reviews 33: 1-47, 2012) I. Introduction II.Sex Differences in Lung Structure and Function A. Measurement of lung structure and function B. Historical studies C. Sex differences in prenatal and early postnatal lung D. Sex differences in puberty and beyond III.Sex Differences in Lung Diseases A. Asthma B. Atopy and allergic rhinitis C. COPD and lung cancer D. Fibrotic diseases E. Pulmonary hypertension F. Other conditions IV. Sex Steroids in Lung Physiology and Pathophysiology A. Sex steroid signaling B. Upper and lower airways C. Lung parenchyma D. Pulmonary vasculature E. Immune cells and function V. Clinical Implications of Sex Differences and Sex Steroid Signaling VI.Future Directions VII. Conclusions
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The sex difference in pulmonary function may be largely explained by the androgen-sensitive sex difference in height, which is a strong predictor of lung capacity and function.
“The sex difference in pulmonary function may be largely explained by the androgen-sensitive sex difference in height, which is a strong predictor of lung capacity and function (149).”
From Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance (2018) · cites this paper as [149]
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17β-Estradiol Inhibits Phosphorylation of Stromal Interaction Molecule 1 (STIM1) Protein
Sheridan, J. T., Gilmore, R. C., Watson, M. J., Archer, C. B., & Tarran, R. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.486662 · Cited by 42 · see citing works
Tsiligianni, I., Mezzi, K., Fucile, S., Κostikas, Κ., Shen, S., Banerji, D. D., & Fogel, R. (2017) · COPD Journal of Chronic Obstructive Pulmonary Disease · doi:10.1080/15412555.2017.1324837 · Cited by 42 · see citing works
Aravamudan, B., Goorhouse, K. J., Unnikrishnan, G., Thompson, M. A., Pabelick, C. M., Hawse, J. R., Prakash, Y. S., & Sathish, V. (2016) · Journal of Cellular Physiology · doi:10.1002/jcp.25674 · Cited by 40 · see citing works
Interaction effects of polyfluoroalkyl substances and sex steroid hormones on asthma among children
Zhou, Y., Hu, L., Qian, Z. M., Geiger, S. D., Parrish, K. L., Dharmage, S. C., Campbell, B., Roponen, M., Jalava, P., Hirvonen, M.-R., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-01140-5 · Cited by 40 · see citing works
Chiarella, S. E., Cardet, J. C., & Prakash, Y. S. (2021) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2020.12.007 · Cited by 40 · see citing works
Espinoza, J., Montaño, L. M., & Perusquı́a, M. (2013) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2013.05.009 · Cited by 40 · see citing works
Developmental origin and sex-specific risk for infections and immune diseases later in life
Zazara, D. E., & Arck, P. (2018) · Seminars in Immunopathology · doi:10.1007/s00281-018-0713-x · Cited by 39 · see citing works
- Authors
- Townsend, E. A., Miller, V. M., & Prakash, Y. S.
- Affiliations
- Mayo Clinic (US)
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 2012-02
- Volume
- 33
- Issue
- 1
- Pages
- 1-47
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- PMC
- PMC3365843
- OpenAlex
- W2041568486
- Cited by
- 395
- References
- 494
- Citations by year
- 2026: 20 · 2025: 19 · 2024: 28 · 2023: 24 · 2022: 34 · 2021: 44 · 2020: 33 · 2019: 32 · 2018: 34 · 2017: 29 · 2016: 23 · 2015: 23 · 2014: 25 · 2013: 23 · 2012: 4
- FWCI
- 3.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrine Reviews (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL088029, HL056470, R01HL088029, R01HL056470)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- sex differences, sex steroids, lung health, lung disease, sex hormone receptors, asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer, pulmonary hypertension, puberty, pregnancy, menopause, aging, biomarkers
- MeSH terms
- Aging, Female, Humans, Lung, Lung Diseases, Male, Menopause, Pregnancy, Puberty, Sex Characteristics, Gonadal Steroid Hormones, Signal Transduction, Biomarkers
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