Do Androgens Modulate the Pathophysiological Pathways of Inflammation? Appraising the Contemporary Evidence

Traish, Abdulmaged M.; Bolaños, José; Nair, Sunil; Saad, Farid; Morgentaler, Abraham

doi:10.3390/jcm7120549

Cited by 103 publications

(108 citation statements)

References 183 publications

(247 reference statements)

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“…We have demonstrated remarkable responses (clinical exam, mammography, ultrasound) of hormone receptor positive tumors to T + aromatase inhibitor implant therapy in the neoadjuvant setting, further confirming the direct beneficial effect of T at the AR [8,9]. T also improves glycemic control and attenuates the inflammatory process, both of which could have a beneficial effect on the incidence of breast cancer [14,15,32,33].…”

Section: Discussionsupporting

confidence: 58%

Incidence of invasive breast cancer in women treated with testosterone implants: a prospective 10-year cohort study

2019

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Background: Testosterone implants have been used for over eighty years to treat symptoms of hormone deficiency in pre and postmenopausal women. Evidence supports that androgens are breast protective. However, there is a lack of data on the long-term effect of testosterone therapy on the incidence of invasive breast cancer (IBC). This study was specifically designed to investigate the incidence of IBC in pre and postmenopausal women (presenting with symptoms of androgen deficiency) treated with subcutaneous testosterone implants or testosterone implants combined with anastrozole. Methods: The 10-year prospective cohort study was approved in March 2008 at which time recruitment was initiated. Recruitment was closed March 2013. Pre and postmenopausal women receiving at least two pellet insertions were eligible for analysis (N = 1267). Breast cancer incidence rates were reported as an unadjusted, un-weighted value of newly diagnosed cases divided by the sum of 'person-time of observation' for the at-risk population. Incidence rates on testosterone therapy were compared to age-specific Surveillance Epidemiology and End Results (SEER) incidence rates and historical controls. Bootstrap sampling distributions were constructed to verify comparisons and tests of significance that existed between our results and SEER data. Results: As of March 2018, a total of 11 (versus 18 expected) cases of IBC were diagnosed in patients within 240-days following their last testosterone insertion equating to an incidence rate of 165/100000 p-y, which is significantly less than the age-matched SEER expected incidence rate of 271/100000 p-y (p < 0.001) and historical controls. Conclusion: Long term therapy with subcutaneous testosterone, or testosterone combined with anastrozole, did not increase the incidence of IBC. Testosterone should be further investigated for hormone therapy and breast cancer prevention.

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Section: Discussionsupporting

confidence: 58%

Incidence of invasive breast cancer in women treated with testosterone implants: a prospective 10-year cohort study

2019

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“…During wound healing, androgens have been shown to increase the production of pro-inflammatory cytokines by macrophages. After traumatic hemorrhagic shock and burns, androgens also inhibited the production of cytokines [38]. All these findings suggest that androgens are necessary for maintaining overall inflammatory homeostasis.…”

Section: Discussionmentioning

confidence: 83%

“…Though there is considerable knowledge regarding the cellular and molecular pathways of the inflammatory process, much remains to be understood, including the role of sex steroid hormones in promoting or attenuating inflammatory responses. Several epidemiological, as well as clinical studies, show that androgens attenuate the expression of inflammatory biomarkers including TNF-α, IL-1β, and IL-6 in various chronic inflammatory diseases like Crohn's disease, psoriasis, rheumatoid arthritis and allergic asthma [38]. Androgens regulate a variety of molecular pathways involving a host of immune cells and biochemical factors that contribute to the regulation of the inflammatory process [39].…”

Section: Discussionmentioning

confidence: 99%

“…Various mechanisms are postulated to suggest the role of androgen in regulating the production of inflammatory molecules including its effect on the expression of toll-like receptor-4 (TLR-4), neutrophil-binding vascular adhesion molecule-1 (VCAM-1), suppression of monocyte chemoattractant protein-1 (MCP-1), IL-6 expression in 3T3-L1 adipocytes, etc. [38,40,41]. During wound healing, androgens have been shown to increase the production of pro-inflammatory cytokines by macrophages.…”

Section: Discussionmentioning

confidence: 99%

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Effect of DHT-Induced Hyperandrogenism on the Pro-Inflammatory Cytokines in a Rat Model of Polycystic Ovary Morphology

et al. 2020

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Background and Objectives: Polycystic ovary syndrome (PCOS) is one of the most prevalent disorders among women of reproductive age. It is considered as a pro-inflammatory state with chronic low-grade inflammation, one of the key factors contributing to the pathogenesis of this disorder. Polycystic ovary is a well-established criterion for PCOS. The present investigation aimed at finding the role of hyperandrogenism, the most important feature of PCOS, in the development of this inflammatory state. To address this problem, we adopted a model system that developed polycystic ovary morphology (PCOM), which could be most effectively used in order to study the role of non-aromatizable androgen in inflammation in PCOS. Materials and Methods: Six rats were used to induce PCOM in 21-days-old female Wistar albino rats by using a pre-determined release of dihydrotestosterone (DHT), a potent non-aromatizable androgen, achieved by implanting a DHT osmotic pump, which is designed to release a daily dose of 83 μg. Results: After 90 days, the rats displayed irregular estrous cycles and multiple ovarian cysts similar to human PCOS. Elevated serum inflammatory markers such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and the presence of a necrotic lesion in the liver, osteoclast in the femur, multinucleated giant cells and lymphocytes in the ovary based on histopathological observation of DHT-treated rats clearly indicated the onset of inflammation in the hyperandrogenic state. Our results show no significant alterations in serum hormones such as luteinizing hormone (LH), follicle stimulating hormone (FSH), insulin, and cortisol between control and hyperandrogenised rats. DHT was significantly elevated as compared to control. mRNA studies showed an increased expression level of TNF-α and IL-1β, further, the mRNA expression of urocortin 1 (Ucn-1) was stupendously elevated in the liver of hyperandrogenised rats. Conclusions: Thus, results from this study provide: (1) a good PCOM model system in order to study the inflammatory changes in PCOS aspects, (2) alteration of inflammatory markers in PCOM rats that could be either due to its direct effect or by the regulation of various inflammatory genes and markers in the liver of hyperandrogenic state suggesting the regulatory role of DHT, and (3) alteration in stress-related protein in the liver of PCOM rats.

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“…With SARS-CoV, viral titers and the accumulation of inflammatory monocytes and neutrophils in the lungs was higher among men. Estrogen receptor signaling may play a protective role (105), and low testosterone levels have been implicated in reduced immunity (106). Accordingly, investigation of inflammatory responses, viral loads and immune response patterns across sex and age with RNA viral infections are required.…”

Section: Innate Immunosenescence Inflammation and Inflammasomesmentioning

confidence: 99%

COVID-19 and Crosstalk between the Hallmarks of Aging

Salimi¹,

Hamlyn²

2020

Preprint

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Within the past several decades, the emergence of new viral diseases with more severe health complications and mortality, primarily in older adults with comorbidities, is evidence of an age-dependent, compromised bodily response to abrupt stress with concomitant reduced immunity. The emergence of new infectious coronaviruses such as SARS-CoV-2 has resulted in the coronavirus disease 2019 (COVID-19). The result is increased morbidity and mortality in persons with underlying chronic diseases and among those with compromised defense mechanisms, regardless of age and among older adults who are more likely to fit these categories. COVID-19 appears to be primarily an upper respiratory disease. While SARS-CoV-2 is highly virulent, there is variability in the severity of the disease and its complications in humans. Severe pneumonia, acute respiratory distress syndrome (ARDS), lung fibrosis, cardiac t complication, acute kidney injury, hospitalization, and high mortality have been reported in older adults with COVID-19, that result from pathogen-host interactions. Here, we review potential interactions of the coronavirus and host cellular responses in relation to hallmarks of aging including genomic instability, telomere attrition, impaired autophagy, mitochondrial dysfunction, innate immunosenescence, inflammation and inflammasomes, adaptive immunosenescence, and epigenetic alterations, that likely contribute to the increased pathophysiological responses to SARS-CoV-2 among older adults.

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Do Androgens Modulate the Pathophysiological Pathways of Inflammation? Appraising the Contemporary Evidence

Cited by 103 publications

References 183 publications

Incidence of invasive breast cancer in women treated with testosterone implants: a prospective 10-year cohort study

Incidence of invasive breast cancer in women treated with testosterone implants: a prospective 10-year cohort study

Effect of DHT-Induced Hyperandrogenism on the Pro-Inflammatory Cytokines in a Rat Model of Polycystic Ovary Morphology

COVID-19 and Crosstalk between the Hallmarks of Aging

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