Role of sex hormones in lung cancer

Lung cancer represents the world’s leading cause of cancer deaths. Sex differences in the incidence and mortality rates for various types of lung cancers have been identified, but the biological and endocrine mechanisms implicated in these disparities have not yet been determined. While some cancers such as lung adenocarcinoma are more commonly found among women than men, others like squamous cell carcinoma display the opposite pattern or show no sex differences. Associations of tobacco product use rates, susceptibility to carcinogens, occupational exposures, and indoor and outdoor air pollution have also been linked to differential rates of lung cancer occurrence and mortality between sexes. While roles for sex hormones in other types of cancers affecting women or men have been identified and described, little is known about the influence of sex hormones in lung cancer. One potential mechanism identified to date is the synergism between estrogen and some tobacco compounds, and oncogene mutations, in inducing the expression of metabolic enzymes, leading to enhanced formation of reactive oxygen species and DNA adducts, and subsequent lung carcinogenesis. In this review, we present the literature available regarding sex differences in cancer rates, associations of male and female sex hormones with lung cancer, the influence of exogenous hormone therapy in women, and potential mechanisms mediated by male and female sex hormone receptors in lung carcinogenesis. The influence of biological sex on lung disease has recently been established, thus new research incorporating this variable will shed light on the mechanisms behind the observed disparities in lung cancer rates, and potentially lead to the development of new therapeutics to treat this devastating disease.

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Cyclic Adenosine Monophosphate Eliminates Sex Differences in Estradiol-Induced Elastin Production from Engineered Dermal Substitutes

International Journal of Molecular Sciences ◽

10.3390/ijms22126358 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6358

Author(s):

Andreja Moset Zupan ◽

Carolyn Nietupski ◽

Stacey C. Schutte

Keyword(s):

Sex Differences ◽

Sex Hormones ◽

Elastic Fibers ◽

Skin Substitutes ◽

Estradiol Treatment ◽

Male And Female ◽

Female Sex ◽

Dermal Substitutes ◽

Female Sex Hormones ◽

17Β Estradiol

Lack of adult cells’ ability to produce sufficient amounts of elastin and assemble functional elastic fibers is an issue for creating skin substitutes that closely match native skin properties. The effects of female sex hormones, primarily estrogen, have been studied due to the known effects on elastin post-menopause, thus have primarily included older mostly female populations. In this study, we examined the effects of female sex hormones on the synthesis of elastin by female and male human dermal fibroblasts in engineered dermal substitutes. Differences between the sexes were observed with 17β-estradiol treatment alone stimulating elastin synthesis in female substitutes but not male. TGF-β levels were significantly higher in male dermal substitutes than female dermal substitutes and the levels did not change with 17β-estradiol treatment. The male dermal substitutes had a 1.5-fold increase in cAMP concentration in the presence of 17β-estradiol compared to no hormone controls, while cAMP concentrations remained constant in the female substitutes. When cAMP was added in addition to 17β-estradiol and progesterone in the culture medium, the sex differences were eliminated, and elastin synthesis was upregulated by 2-fold in both male and female dermal substitutes. These conditions alone did not result in functionally significant amounts of elastin or complete elastic fibers. The findings presented provide insights into differences between male and female cells in response to female sex steroid hormones and the involvement of the cAMP pathway in elastin synthesis. Further explorations into the signaling pathways may identify better targets to promote elastic fiber synthesis in skin substitutes.

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Endocrine regulation of lung disease and inflammation

Experimental Biology and Medicine ◽

10.1177/1535370218816653 ◽

2018 ◽

Vol 243 (17-18) ◽

pp. 1313-1322 ◽

Cited By ~ 11

Author(s):

Nathalie Fuentes ◽

Patricia Silveyra

Keyword(s):

Sex Differences ◽

Lung Function ◽

Lung Disease ◽

Sex Hormones ◽

Lung Diseases ◽

Endocrine Regulation ◽

Male And Female ◽

Female Sex ◽

Female Sex Hormones ◽

Chronic Lung Diseases

Sex-based disparities have been identified in respiratory physiology, and in many chronic lung diseases including asthma, chronic obstructive pulmonary disease, and cystic fibrosis. The observed sex differences in lung disease prevalence and incidence have been linked to changes in circulating levels of sex hormones that start after puberty and that have been shown to affect physiological and immunological functions. While the exact roles of male and female sex hormones in these processes have not been fully elucidated, it is now evident that these can target many lung cell types and affect several functions of the respiratory system. In this mini-review, we have summarized seminal studies aimed to understand the effects of the most relevant male and female sex hormones (estrogens, progesterone, and androgens) and their receptors on lung function. Moreover, we have reviewed the known influences of sex hormones and of the hypothalamic–pituitary–gonadal axis in lung disease and immunity. Understanding the roles of sex hormones in the regulation of lung function and inflammation is the first step for the potential development of more effective therapeutic options to prevent and treat lung disease in men and women. Impact statement Sex-differences in the incidence and severity of inflammatory lung diseases have been recognized for years. Women of reproductive age are more likely to suffer from chronic lung disease, with higher mortality rates than men. Physiological changes in hormone levels such as those occurring during the menstrual cycle, pregnancy, and menopause have been associated with lung function changes and asthma symptoms. Despite this, the roles of sex hormones in the mechanisms associated with lung diseases have not been fully elucidated. This review summarizes basic and clinical studies of sex hormones as potential modulators of lung function and inflammation. The information obtained from sex-specific research on lung physiology and pathology will potentially help in the development of sex-specific therapeutics for inflammatory lung disease that may account for the hormonal status of the patient.

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Sex Differences in Stroke

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2012.141 ◽

2012 ◽

Vol 32 (12) ◽

pp. 2100-2107 ◽

Cited By ~ 113

Author(s):

Roy AM Haast ◽

Deborah R Gustafson ◽

Amanda J Kiliaan

Keyword(s):

Sex Differences ◽

Sex Hormones ◽

Premenopausal Women ◽

Epidemiologic Studies ◽

Stroke Onset ◽

Effective Prevention ◽

Sex Steroid Hormone ◽

Incidence And Mortality ◽

Primary Focus ◽

The Impact

Sex differences in stroke are observed across epidemiologic studies, pathophysiology, treatments, and outcomes. These sex differences have profound implications for effective prevention and treatment and are the focus of this review. Epidemiologic studies reveal a clear age-by-sex interaction in stroke prevalence, incidence, and mortality. While premenopausal women experience fewer strokes than men of comparable age, stroke rates increase among postmenopausal women compared with age-matched men. This postmenopausal phenomenon, in combination with living longer, are reasons for women being older at stroke onset and suffering more severe strokes. Thus, a primary focus of stroke prevention has been based on sex steroid hormone-dependent mechanisms. Sex hormones affect different (patho)physiologic functions of the cerebral circulation. Clarifying the impact of sex hormones on cerebral vasculature using suitable animal models is essential to elucidate male–female differences in stroke pathophysiology and development of sex-specific treatments. Much remains to be learned about sex differences in stroke as anatomic and genetic factors may also contribute, revealing its multifactorial nature. In addition, the aftermath of stroke appears to be more adverse in women than in men, again based on older age at stroke onset, longer prehospital delays, and potentially, differences in treatment.

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Gender-Related Response of Body Systems in COVID-19 Affects Outcome

Russian Journal of Infection and Immunity ◽

10.15789/2220-7619-grr-1664 ◽

2021 ◽

Author(s):

M. Khaksari ◽

N. Sabet ◽

Z. Soltani ◽

H. Bashiri

Keyword(s):

Gender Differences ◽

Gender Difference ◽

Sex Hormones ◽

Myocardial Dysfunction ◽

Local Effect ◽

Multiple Organ ◽

Rapid Progression ◽

Female Sex ◽

Female Sex Hormones ◽

Incidence And Mortality

Severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) is the seventh member of the coronaviruses (CoVs) family that infects humans and causes coronavirus disease 2019 (COVID-19), which is currently a global pandemic. Widespread secretion of cytokines has been shown to occur early in severe cases of the disease and can be an effective factor in the rapid progression of the disease. The storm of cytokines including interleukin (IL)-1β, IL-2, IL-7, IL-6, IL-8, IL-10, IL-17, and gamma interferon (INF-ɣ) has been reported in several organ failures. Systemic inflammation indicates an advanced stage of acute disease, which is characterized by multiple organ failure and elevated key inflammatory markers. The important disturbances in the various body systems such as alveolar damage and pulmonary edema in the lung, increase of liver enzymes in the liver, decrease of microbiota and increase of mesenteric edema in the gastrointestinal system, increase of blood urea nitrogen (BUN), creatinine (Cr) and glomerular filtration rate (GFR) in the kidney, myocardial dysfunction, arrhythmia and cardiac enzymes elevation in the heart, blood brain barrier (BBB) disruption, brain edema and encephalopathy in the brain have been reported. Studies have shown a gender difference between the incidence and mortality of COVID-19. In this review, we investigated the gender difference in the systemic effects of COVID-19 and found that this gender difference exists especially in the respiratory, cardiovascular, liver, gastrointestinal and kidney systems. Due to the worse outcome of COVID in males, the role of female sex hormones in causing these gender differences is noticeable. There can be a systemic and local effect of female sex hormones, especially estrogen and possibly progesterone, on various cells. Among the effects of these hormones is the regulation of localized angiotensin-converting enzyme 2 (ACE2) levels. ACE2 is the route of entry for SARS-CoV-2 virus into the cell. It is hoped that this review would address gender differences for better management of COVID-19 treatment.

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Sex Differences in Otolaryngology: Focus on the Emerging Role of Estrogens in Inflammatory and Pro-Resolving Responses

International Journal of Molecular Sciences ◽

10.3390/ijms22168768 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8768

Author(s):

Sheng-Dean Luo ◽

Tai-Jan Chiu ◽

Wei-Chih Chen ◽

Ching-Shuen Wang

Keyword(s):

Sex Differences ◽

Sex Hormones ◽

Immune Cells ◽

Vocal Fold ◽

Hormone Receptors ◽

Inflammatory Responses ◽

Proinflammatory Responses ◽

Males And Females ◽

Nose And Throat

Otolaryngology (also known as ear, nose, and throat (ENT)) diseases can be significantly affected by the level of sex hormones, which indicates that sex differences affect the manifestation, pathophysiology, and outcomes of these diseases. Recently, increasing evidence has suggested that proinflammatory responses in ENT diseases are linked to the level of sex hormones. The sex hormone receptors are present on a wide variety of immune cells; therefore, it is evident that they play crucial roles in regulating the immune system and hence affect the disease progression of ENT diseases. In this review, we focus on how sex hormones, particularly estrogens, regulate ENT diseases, such as chronic rhinosinusitis, vocal fold polyps, thyroid cancer, Sjögren’s syndrome, and head and neck cancers, from the perspectives of inflammatory responses and specialized proresolving mediator-driven resolution. This paper aims to clarify why considering sex differences in the field of basic and medical research on otolaryngology is a key component to successful therapy for both males and females in the future.

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Common risk factors of Lung cancer, an observational study in a National Institute, Dhaka

Community Based Medical Journal ◽

10.3329/cbmj.v8i1.55666 ◽

2019 ◽

Vol 8 (1) ◽

pp. 23-29

Author(s):

MM Bodiuzzaman ◽

Muhammad Zubaer Hussain ◽

SM Munawar Morshed ◽

Md Rafiqul Islam ◽

- Md Akhtaruzzaman ◽

...

Keyword(s):

Risk Factors ◽

Lung Cancer ◽

Observational Study ◽

Tobacco Smoking ◽

Age Groups ◽

Malignant Neoplasm ◽

Preventive Measure ◽

Occupational Exposures ◽

Lung Carcinogenesis ◽

Common Risk Factors

Lung cancer is the most prevalent malignant neoplasm in most of the countries, and is leading cause of mortality worldwide. Till date tobacco consumption is the main etiological factor in lung carcinogenesis. Other factors such as genetic susceptibility, poor diet, occupational exposures and air pollution may act independently. Treatment of lung cancer is time consuming, costly and need special care during its management. Post treatment complications also more and sometimes it is more serious and becomes life threatening to the patients. The study was done to find out the most common risk factors of lung cancer, for this we can take necessary preventive measure from those risk factors to prevent health burden and mortality from lung cancer.This observational study was done in the department of Medical Oncology, National Institute of Cancer Research and Hospital (NICRH), Mohakhali, Dhaka, from January 2012 to May 2012. One hundred and six (106) patients, aged over 30 years, included all sexes, were diagnosed as a lung cancer by histopathology and came for chemotherapy, were selected randomly in this study after informed written consent. In this study we found males are predominantly affected (92.45%) by lung cancer and common age groups affected are between 51-60 years (39.62%). Among the occupation farmers are more affected (77.35%) and most of them were active smokers (64.15%). In our study we found that right side of lung is more affected (58.49%) than left side and adenocarcinoma was predominant (35.84%). Control of tobacco smoking is the most important preventive measure. This study may help us to identify the etiological aspect and future preventive efforts and research be needed to focus on tobacco smoking and non-cigarette tobacco smoking products, as well as better understanding of risk factors underlying lung carcinogenesis in never-smokers. CBMJ 2019 January: vol. 08 no. 01 P: 23-29

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