Testosterone and dihydrotestosterone reduce platelet activation and reactivity in older men and women

Karolczak, Kamil; Konieczna, Lucyna; Kostka, Tomasz; Witas, Piotr J; Sołtysik, Bartłomiej K.; Bączek, Tomasz; Watała, Cezary

doi:10.18632/aging.101438

Cited by 37 publications

(30 citation statements)

References 51 publications

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“…We also identified platelet activation as one of the pathways that may be modulated by gut microbiota-miRNAs cross-talk in response to sex steroid-related alterations. In fact, it was recently shown that T reduces platelet activation in elderly people [ 37 ]. Taking into account the decline in T seen in aging [ 6 ], a potential role of the gut microbiota through miRNA actions inducing changes in blood platelets might be suggested.…”

Section: Discussionmentioning

confidence: 99%

Interplay between gonadal hormones and postnatal overfeeding in defining sex-dependent differences in gut microbiota architecture

Santos-Marcos¹,

Barroso²,

Rangel‐Zúñiga³

et al. 2020

aging

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Aging is associated with a decline in sex hormones, variable between sexes, that has an impact on many different body systems and might contribute to age-related disease progression. We aimed to characterize the sex differences in gut microbiota, and to explore the impact of depletion of gonadal hormones, alone or combined with postnatal overfeeding, in rats. Many of the differences in the gut microbiota between sexes persisted after gonadectomy, but removal of gonadal hormones shaped several gut microbiota features towards a more deleterious profile, the effect being greater in females than in males, mainly when animals were concurrently overfed. Moreover, we identified several intestinal miRNAs as potential mediators of the impact of changes in gut microbiota on host organism physiology. Our study points out that gonadal hormones contribute to defining sex-dependent differences of gut microbiota, and discloses a potential role of gonadal hormones in shaping gut microbiota, as consequence of the interaction between sex and nutrition. Our data suggest that the changes in gut microbiota, observed in conditions of sex hormone decline, as those caused by ageing in men and menopause in women, might exert different effects on the host organism, which are putatively mediated by gut microbiota-intestinal miRNA cross-talk.

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Section: Discussionmentioning

confidence: 99%

Interplay between gonadal hormones and postnatal overfeeding in defining sex-dependent differences in gut microbiota architecture

Santos-Marcos¹,

Barroso²,

Rangel‐Zúñiga³

et al. 2020

aging

View full text Add to dashboard Cite

show abstract

“…T augments activation and aggregation of platelets by increasing platelet expression of thromboxane A2 receptors [36]. In contrast, a negative correlation between serum T levels and platelet reactivity has been discovered by an ex vivo study [37]. T enhancestheproduction of endothelial nitric oxide, a potent vasodilator and inhibitor of plateletrecruitment.Mean platelet volume, a biological indicator of platelet activation, is seen to be increased in hypogonadal males [38].…”

Section: Role Of Sex Hormonesmentioning

confidence: 99%

The Role of Sex in the Risk of Mortality From COVID-19 Amongst Adult Patients: A Systematic Review

Kelada¹,

Anto²,

Dave³

et al. 2020

Cureus

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A worldwide outbreak of coronavirus disease 2019 (COVID-19), identified as being caused by the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), was classified as a Public Health Emergency of International Concern by the World Health Organisation (WHO) on January 30, 2020. Initial sex-disaggregated mortality data emerging from the Wuhan province of China identified male sex as a risk factor for increased COVID-19 mortality. In this systematic review, we aimed to assess the role of sex in the risk of mortality from COVID-19 in adult patients through comparison of clinical markers and inflammatory indexes. A systematic search was conducted on the following databases:PubMed, WHO COVID-19 database, Ovid MEDLINE, andWeb of Science between the dates of June 15, 2020, and June 30, 2020.Key search terms used included: "sex", "gender", "SARS-COV-2","COVID" and "mortality".We accepted the following types of studiesconcerning adult COVID-19 patients: retrospectivecohort, observationalcohort, case series, and applied research.Further studies were extracted from referencesearching.The risk of bias was determined using theNational Institutes of Health Quality Assessment Tool for Observational Cohort, Cross-Sectional Studies, and Case Series. We identified a total of 16 studies published between January 2020 and June 2020 for analysis in this systematic review. Our study population consisted of 11 cohort studies,four case series, andonegenetic study, including a total of 76,555 participants. Ten of the studiesincluded in this review observeda higher risk of mortality amongmalescompared to females, and eight of these studies found this risk to be statistically significant.

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“…This study showed that low levels of T and dihydrotestosterone (DHT) were significantly related to platelet activation and reactivity 103 . Moreover, an in vitro model has confirmed that both T and DHT significantly inhibit platelet aggregation triggered by arachidonate or collagen 103 . However, a recent study failed to show any difference in the procoagulant state of treated or untreated men with Klinefelter syndrome (KS) but demonstrated that thrombin generation in men with KS was inversely associated with androgen action and that it was lower in treated subjects than in untreated subjects 104 .…”

Section: Methodsmentioning

confidence: 99%

Late‐onset hypogonadism: Reductio ad absurdum of the cardiovascular risk‐benefit of testosterone replacement therapy

et al. 2020

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Background Low testosterone (T) level is considered a marker of poor cardiovascular health. Ten years ago, the Testosterone in Older Men with Mobility Limitations (TOM) trial was discontinued due to a higher number of adverse events in men receiving T compared with placebo. Since then, several studies have investigated the risks of T replacement therapy (TRT) in late‐onset hypogonadism (LOH). Objective To review the mechanism by which TRT could damage the cardiovascular system. Materials and methods Comprehensive literature search of recent clinical and experimental studies. Results The mechanisms of T‐mediated coronary vasodilation were reviewed with emphasis on calcium‐activated and ATP‐sensitive potassium ion channels. We showed how T regulates endothelial nitric oxide synthase (eNOS) and phosphoinositide 3‐kinase/protein kinase B/eNOS signaling pathways in vessel walls and its direct effects on cardiomyocytes via β1‐adrenergic and ryanodine receptors and provided data on myocardial infarction and heart failure. Vascular smooth muscle senescence could be explained by the modulation of growth factors, matrix metalloproteinase‐2, and angiotensin II by T. Furthermore, leukocyte trafficking, facilitated by changes in TNF‐α, could explain some of the effects of T on atheromatous plaques. Conflicting data on prothrombotic risk linked to platelet aggregation inhibition via NO‐triggered arachidonate synthesis or increased aggregability due to enhanced thromboxane A in human platelets provide evidence regarding the hypotheses on plaque maturation and rupture risk. The effects of T on cardiac electrophysiology and oxygen delivery were also reviewed. Discussion The effects of TRT on the cardiovascular system are complex. Although molecular studies suggest a potential benefit, several clinical observations reveal neutral or occasionally detrimental effects, mostly due to confounding factors. Conclusions Attempts to demonstrate that TRT damages the cardiovascular system via systematic analysis of the putative mechanisms led to the contradiction of the initial hypothesis. Current evidence indicates that TRT is safe once other comorbidities are addressed.

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Testosterone and dihydrotestosterone reduce platelet activation and reactivity in older men and women

Cited by 37 publications

References 51 publications

Interplay between gonadal hormones and postnatal overfeeding in defining sex-dependent differences in gut microbiota architecture

Interplay between gonadal hormones and postnatal overfeeding in defining sex-dependent differences in gut microbiota architecture

The Role of Sex in the Risk of Mortality From COVID-19 Amongst Adult Patients: A Systematic Review

Late‐onset hypogonadism: Reductio ad absurdum of the cardiovascular risk‐benefit of testosterone replacement therapy

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