Sex Differences in the Pharmacokinetics of Antidepressants: Influence of Female Sex Hormones and Oral Contraceptives

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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Sex Disparities in Cystic Fibrosis: Review on the Effect of Female Sex Hormones on Lung Pathophysiology and Outcomes

ERJ Open Research ◽

10.1183/23120541.00475-2020 ◽

2020 ◽

pp. 00475-2020

Author(s):

G.Y. Lam ◽

J. Goodwin ◽

P.G. Wilcox ◽

B.S. Quon

Keyword(s):

Cystic Fibrosis ◽

Sex Differences ◽

Sex Hormones ◽

Mucociliary Clearance ◽

Therapeutic Interventions ◽

Female Sex ◽

Female Sex Hormones ◽

Sex Disparities

Sex differences in morbidity and mortality have been reported in the cystic fibrosis (CF) population worldwide. However, it is unclear why CF women have worse clinical outcomes than men. In this review, we focus on the influence of female sex hormones on CF pulmonary outcomes and summarise data from in vitro and in vivo experiments on how estrogen and progesterone might modify mucociliary clearance, immunity and infection in the CF airways. The potential for novel sex hormone related therapeutic interventions is also discussed.

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Association between asthma and female sex hormones

Sao Paulo Medical Journal ◽

10.1590/1516-3180.2016.011827016 ◽

2017 ◽

Vol 135 (1) ◽

pp. 4-14 ◽

Cited By ~ 5

Author(s):

Raquel Prudente de Carvalho Baldaçara ◽

Ivaldo Silva

Keyword(s):

Sex Hormones ◽

Oral Contraceptives ◽

Nk Cell ◽

Hormone Replacement ◽

Cell Activity ◽

Interferon Γ ◽

Medical Subject Headings ◽

Female Sex ◽

Female Sex Hormones ◽

Tnf Α

ABSTRACT CONTEXT AND OBJECTIVE: The relationship between sex hormones and asthma has been evaluated in several studies. The aim of this review article was to investigate the association between asthma and female sex hormones, under different conditions (premenstrual asthma, use of oral contraceptives, menopause, hormone replacement therapy and pregnancy). DESIGN AND SETTING: Narrative review of the medical literature, Universidade Federal do Tocantins (UFT) and Universidade Federal de São Paulo (Unifesp). METHODS: We searched the CAPES journal portal, a Brazilian platform that provides access to articles in the MEDLINE, PubMed, SciELO, and LILACS databases. The following keywords were used based on Medical Subject Headings: asthma, sex hormones, women and use of oral contraceptives. RESULTS: The associations between sex hormones and asthma remain obscure. In adults, asthma is more common in women than in men. In addition, mortality due to asthma is significantly higher among females. The immune system is influenced by sex hormones: either because progesterone stimulates progesterone-induced blocking factor and Th2 cytokines or because contraceptives derived from progesterone and estrogen stimulate the transcription factor GATA-3. CONCLUSIONS: The associations between asthma and female sex hormones remain obscure. We speculate that estrogen fluctuations are responsible for asthma exacerbations that occur in women. Because of the anti-inflammatory action of estrogen, it decreases TNF-α production, interferon-γ expression and NK cell activity. We suggest that further studies that highlight the underlying physiopathological mechanisms contributing towards these interactions should be conducted.

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Beneficial and Deleterious Effects of Female Sex Hormones, Oral Contraceptives, and Phytoestrogens by Immunomodulation on the Liver

International Journal of Molecular Sciences ◽

10.3390/ijms20194694 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4694

Author(s):

Luis E. Soria-Jasso ◽

Raquel Cariño-Cortés ◽

Víctor Manuel Muñoz-Pérez ◽

Elizabeth Pérez-Hernández ◽

Nury Pérez-Hernández ◽

...

Keyword(s):

Sex Hormones ◽

Oral Contraceptives ◽

Endocrine System ◽

Sexually Dimorphic ◽

Systemic Immune Response ◽

Physiological Importance ◽

Female Sex ◽

Female Sex Hormones ◽

Liver Functions ◽

Health And Disease

The liver is considered the laboratory of the human body because of its many metabolic processes. It accomplishes diverse activities as a mixed gland and is in continuous cross-talk with the endocrine system. Not only do hormones from the gastrointestinal tract that participate in digestion regulate the liver functions, but the sex hormones also exert a strong influence on this sexually dimorphic organ, via their receptors expressed in liver, in both health and disease. Besides, the liver modifies the actions of sex hormones through their metabolism and transport proteins. Given the anatomical position and physiological importance of liver, this organ is evidenced as an immune vigilante that mediates the systemic immune response, and, in turn, the immune system regulates the hepatic functions. Such feedback is performed by cytokines. Pro-inflammatory and anti-inflammatory cytokines are strongly involved in hepatic homeostasis and in pathological states; indeed, female sex hormones, oral contraceptives, and phytoestrogens have immunomodulatory effects in the liver and the whole organism. To analyze the complex and interesting beneficial or deleterious effects of these drugs by their immunomodulatory actions in the liver can provide the basis for either their pharmacological use in therapeutic treatments or to avoid their intake in some diseases.

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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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P3382 Protective effect of female sex hormones against pulmonary hypertension in Bolivian high altitude natives

European Heart Journal ◽

10.1016/s0195-668x(03)96008-8 ◽

2003 ◽

Vol 24 (5) ◽

pp. 650

Author(s):

Y ALLEMANN

Keyword(s):

Pulmonary Hypertension ◽

Protective Effect ◽

High Altitude ◽

Sex Hormones ◽

Female Sex ◽

Female Sex Hormones ◽

High Altitude Natives

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Female Sex Hormones and Epilepsy

The Bangkok Medical Journal ◽

10.31524/bkkmedj.2015.09.013 ◽

2015 ◽

Vol 10 (01) ◽

pp. 65-71

Author(s):

Chakorn Chansakul

Keyword(s):

Sex Hormones ◽

Female Sex ◽

Female Sex Hormones

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Role of sex hormones in lung cancer

Experimental Biology and Medicine ◽

10.1177/15353702211019697 ◽

2021 ◽

pp. 153537022110196

Author(s):

Nathalie Fuentes ◽

Miguel Silva Rodriguez ◽

Patricia Silveyra

Keyword(s):

Lung Cancer ◽

Sex Differences ◽

Sex Hormones ◽

Hormone Receptors ◽

Occupational Exposures ◽

Lung Carcinogenesis ◽

Male And Female ◽

Female Sex ◽

Incidence And Mortality ◽

Cancer Rates

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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