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      Effects of Exogenous Androgens on Platelet Activity and Their Thrombogenic Potential in Supraphysiological Administration: A Literature Review

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          Abstract

          Anabolic androgenic steroids (AAS), simply called “androgens”, represent the most widespread drugs used to enhance performance and appearance in a sporting environment. High-dosage and/or long-term AAS administration has been associated frequently with significant alterations in the cardiovascular system, some of these with severe endpoints. The induction of a prothrombotic state is probably the most life-threatening consequence, suggested by numerous case reports in AAS-abusing athletes, and by a considerable number of human and animal studies assessing the influence of exogenous androgens on hemostasis. Despite over fifty years of research, data regarding the thrombogenic potential of exogenous androgens are still scarce. The main reason is the limited possibility of conducting human prospective studies. However, human observational studies conducted in athletes or patients, in vitro human studies, and animal experiments have pointed out that androgens in supraphysiological doses induce enhanced platelet activity and thrombopoiesis, leading to increased platelet aggregation. If this tendency overlaps previously existing coagulation and/or fibrinolysis dysfunctions, it may lead to a thrombotic diathesis, which could explain the multitude of thromboembolic events reported in the AAS-abusing population. The influence of androgen excess on the platelet activity and fluid–coagulant balance remains a subject of debate, urging for supplementary studies in order to clarify the effects on hemostasis, and to provide new compelling evidence for their claimed thrombogenic potential.

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          Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline

          To update the "Testosterone Therapy in Men With Androgen Deficiency Syndromes" guideline published in 2010.
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            Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials

            Background Testosterone therapy is increasingly promoted. No randomized placebo-controlled trial has been implemented to assess the effect of testosterone therapy on cardiovascular events, although very high levels of androgens are thought to promote cardiovascular disease. Methods A systematic review and meta-analysis was conducted of placebo-controlled randomized trials of testosterone therapy among men lasting 12+ weeks reporting cardiovascular-related events. We searched PubMed through the end of 2012 using “(“testosterone” or “androgen”) and trial and (“random*”)” with the selection limited to studies of men in English, supplemented by a bibliographic search of the World Health Organization trial registry. Two reviewers independently searched, selected and assessed study quality with differences resolved by consensus. Two statisticians independently abstracted and analyzed data, using random or fixed effects models, as appropriate, with inverse variance weighting. Results Of 1,882 studies identified 27 trials were eligible including 2,994, mainly older, men who experienced 180 cardiovascular-related events. Testosterone therapy increased the risk of a cardiovascular-related event (odds ratio (OR) 1.54, 95% confidence interval (CI) 1.09 to 2.18). The effect of testosterone therapy varied with source of funding (P-value for interaction 0.03), but not with baseline testosterone level (P-value for interaction 0.70). In trials not funded by the pharmaceutical industry the risk of a cardiovascular-related event on testosterone therapy was greater (OR 2.06, 95% CI 1.34 to 3.17) than in pharmaceutical industry funded trials (OR 0.89, 95% CI 0.50 to 1.60). Conclusions The effects of testosterone on cardiovascular-related events varied with source of funding. Nevertheless, overall and particularly in trials not funded by the pharmaceutical industry, exogenous testosterone increased the risk of cardiovascular-related events, with corresponding implications for the use of testosterone therapy.
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              Testosterone and Cardiovascular Disease.

              Testosterone (T) is the principal male sex hormone. As men age, T levels typically fall. Symptoms of low T include decreased libido, vasomotor instability, and decreased bone mineral density. Other symptoms may include depression, fatigue, erectile dysfunction, and reduced muscle strength/mass. Epidemiology studies show that low levels of T are associated with more atherosclerosis, coronary artery disease, and cardiovascular events. However, treating hypogonadism in the aging male has resulted in discrepant results in regard to its effect on cardiovascular events. Emerging studies suggest that T may have a future role in treating heart failure, angina, and myocardial ischemia. A large, prospective, long-term study of T replacement, with a primary endpoint of a composite of adverse cardiovascular events including myocardial infarction, stroke, and/or cardiovascular death, is needed. The Food and Drug Administration recently put additional restrictions on T replacement therapy labeling and called for additional studies to determine its cardiac safety.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                04 January 2021
                January 2021
                : 10
                : 1
                : 147
                Affiliations
                [1 ]Division of Physiology and Neuroscience, Department of Functional Sciences, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; suzana.voiculescu@ 123456umfcd.ro (S.E.V.); leon.zagrean@ 123456umfcd.ro (L.Z.)
                [2 ]Victor Babeş National Institute of Research-Development in the Pathology Domain, 050096 Bucharest, Romania; bogdan_ovidiu_popescu@ 123456yahoo.com
                [3 ]Department of Cardiology, Emergency University Hospital of Bucharest, 050098 Bucharest, Romania
                [4 ]Department of Hematology, Carol Davila University of Medicine and Pharmacy, Emergency University Hospital of Bucharest, 050098 Bucharest, Romania; ahmititelu@ 123456yahoo.com (A.M.); minodorel@ 123456yahoo.com (M.O.)
                [5 ]Department of Neurology, Carol Davila University of Medicine and Pharmacy, Colentina Clinical Hospital, 020125 Bucharest, Romania
                [6 ]Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, C.I. Parhon National Institute of Endocrinology, 11863 Bucharest, Romania; badicrin@ 123456yahoo.co.uk
                [7 ]Division of Physiology, Department of Fundamental Disciplines, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; costin.caruntu@ 123456gmail.com
                [8 ]Department of Dermatology, “Prof. N.C. Paulescu” National Institute of Diabetes, Nutrition and Metabolic Diseases, 011233 Bucharest, Romania
                [9 ]Department of Gastroenterology, Carol Davila University of Medicine and Pharmacy, Elias Clinical Hospital, 011461 Bucharest, Romania; serbangologan@ 123456gmail.com
                [10 ]Department of Surgery, Carol Davila University of Medicine and Pharmacy, “Sf. Ioan” Clinical Hospital, 042122 Bucharest, Romania; mirica_rm@ 123456yahoo.com
                Author notes
                Author information
                https://orcid.org/0000-0002-8087-8125
                https://orcid.org/0000-0003-4530-7965
                https://orcid.org/0000-0002-7272-4513
                Article
                jcm-10-00147
                10.3390/jcm10010147
                7795962
                33406783
                964a9b08-d4d5-49ab-99f8-936437d4c457
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 19 November 2020
                : 28 December 2020
                Categories
                Review

                anabolic androgenic steroids,aas,androgens,testosterone,hemostasis/haemostasis,platelet activity,platelet reactivity,platelet aggregation,thrombopoiesis,platelet count,prothrombotic state,thrombotic diathesis,thrombosis

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