Testosterone therapy and cardiovascular risk (original) (raw)
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The Journal of Sexual Medicine, 2011
Increasing interest in the use of supplemental testosterone has led to a heightened focus on the safety of testosterone in elderly males, with a particular emphasis on cardiovascular risk. Aims. To evaluate, based on available clinical trial data, whether exogenous testosterone administration in middleaged to elderly men increases cardiovascular risk, and to assess whether these effects differ in hypogonadal vs. eugonadal subjects. Methods. MEDLINE search from 2004 to present of all meta-analyses and randomized, controlled clinical trials of testosterone administration in male subjects Ն45 years old that included measurements of cardiovascular outcomes or known cardiovascular risk factors before and after treatment with testosterone. Main Outcome Measures. The effects of testosterone treatment on cardiovascular events and cardiovascular risk factors were assessed. Results. In clinical trials where testosterone has been used in patients with preexisting cardiovascular conditions, the effect on disease symptoms has typically been either neutral or beneficial. Based on clinical trial data, testosterone treatment has minimal effect on cardiovascular risk factors with the exception of an increase in hematocrit, which is consistently seen with testosterone treatment, and a decrease in high-density lipoprotein cholesterol, which is an inconsistent response. Responses of hypogonadal and eugonadal men to testosterone treatment in terms of cardiovascular risk are generally similar. Testosterone treatment has not been reported to increase the incidence of cardiovascular events with the possible exception of one trial in frail elderly men. Conclusions. Available clinical trial data indicate that the use of testosterone in middle-aged to elderly men does not increase cardiovascular risk nor does it unfavorably modify cardiovascular risk profile. Prospective data from large, well-designed, long-term trials of testosterone treatment are lacking and will be required to verify the cardiovascular efficacy/safety of chronic treatment. Carson CC and Rosano G. Exogenous testosterone, cardiovascular events, and cardiovascular risk factors in elderly men: A review of trial data. J Sex Med 2012;9:54-67.
Testosterone and Cardiovascular Health
Mayo Clinic proceedings, 2018
There is an ongoing debate in the medical community regarding the effects of testosterone on cardiovascular (CV) health. For decades, there has been conflicting evidence regarding the association of endogenous testosterone levels and CV disease (CVD) events that has resulted in much debate and confusion among health care providers and patients alike. Testosterone therapy has become increasingly widespread, and after the emergence of studies that reported increased CVD events in patients receiving testosterone therapy, the US Food and Drug Administration (FDA) released a warning statement about testosterone and its potential risk regarding CV health. Some of these studies were later found to be critically flawed, and some experts, including the American Association of Clinical Endocrinologists and an expert panel regarding testosterone deficiency and its treatment, reported that some of the FDA statements regarding testosterone therapy were lacking scientific evidence. This article s...
Testosterone and cardiovascular disease - the controversy and the facts
Postgraduate medicine, 2015
Since November 2013, there has been a flurry of articles written in the media touting the risk of cardiovascular (CV) disease in men treated with testosterone, based on two recent reports. Since first synthesized in 1935, testosterone therapy has demonstrated substantial benefits for men with testosterone deficiency (also called hypogonadism). Testosterone has an acceptable safety profile and literature spanning more than 30 years, suggesting a decreased CV risk with low levels of testosterone and benefits associated with testosterone therapy. However, nonmedical media outlets have seized on reports of increased CV risk, and published scathing editorials impugning testosterone therapy as a dangerous and overprescribed treatment. Here, we review these recent studies, and find no scientific basis for assertions of increased CV risk. This article is intended to provide the clinician with the facts needed for an informed discussion with men who suffer from testosterone deficiency and wh...
The Effect of Testosterone on Cardiovascular Biomarkers in the Testosterone Trials
The Journal of Clinical Endocrinology and Metabolism, 2017
Context: Studies of the possible cardiovascular risk of testosterone treatment are inconclusive. Objective: To determine the effect of testosterone treatment on cardiovascular biomarkers in older men with low testosterone. Design: Double-blind, placebo-controlled trial. Setting: Twelve academic medical centers in the United States.
Testosterone: Friend or foe for the cardiovascular system in men?
Annals of Clinical and Analytical Medicine, 2020
Epidemiological studies showed that cardiovascular diseases occur 7-10 years earlier in men than in women. One in two men and one in three women will have coronary artery disease events at the age of 40, and this observation is attributed to many factors, including differences in the steroidal hormonal status. In experimental trials, testosterone showed both beneficial and deleterious effects on the cardiovascular system. In addition, some trials found low levels of serum testosterone in men with coronary artery disease or heart failure and that patients with hypogonadism are at higher risk of cardiovascular diseases than patients with a normal serum level of testosterone. Clinical studies demonstrated cardiovascular deleterious effects of hypogonadism but no improvement with testosterone replacement therapy. It is unclear whether the differences in cardiovascular risk between men and women are due to the hormonal status or socio-cultural status.
Reviews in Endocrine and Metabolic Disorders, 2021
The cardiovascular (CV) benefit and safety of treating low testosterone conditions is a matter of debate. Although testosterone deficiency has been linked to a rise in major adverse CV events, most of the studies on testosterone replacement therapy were not designed to assess CV risk and thus excluded men with advanced heart failure or recent history of myocardial infarction or stroke. Besides considering observational, interventional and prospective studies, this review article evaluates the impact of testosterone on atherosclerosis process, including lipoprotein functionality, progression of carotid intima media thickness, inflammation, coagulation and thromboembolism, quantification of plaque volume and vascular calcification. Until adequately powered studies evaluating testosterone effects in hypogonadal men at increased CV risk are available (TRAVERSE trial), clinicians should ponder the use of testosterone in men with atherosclerotic cardiovascular disease and discuss benefit ...
Testosterone and cardiovascular disease
Current Opinion in Endocrinology & Diabetes and Obesity, 2014
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.
International Journal of Cardiovascular Medicine, 3(4), 2024
Background: Testosterone deficiency in men has historically been associated with an increased risk of cardiovascular disease (CVD), including myocardial infarction, heart failure, and mortality. The potential benefits of testosterone replacement therapy (TRT) on cardiovascular outcomes remain controversial. This systematic review and meta-analysis aimed to investigate if there could be potential benefits of TRT on cardiovascular disease risk and, if so, uncover the underlying mechanisms. Methods: A comprehensive literature search for Level A evidence in multiple databases (PubMed, Embase, Cochrane Library) was conducted, including randomized controlled trials (RCTs), systematic reviews, metaanalyses, cohort studies, review articles and experimental studies published between 1999 and 2024 that investigated the association between TRT and cardiovascular outcomes in men. The primary outcome was the risk of major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and cardiovascular mortality. Secondary outcomes included changes in ejection fraction, lipid profiles, side effects, and other cardiovascular risk factors. Results: From 3,727 records identified using the selected criteria, a total of 51 studies were selected for the metaanalysis, comprising 4 RCTs, 9 cohort studies, 6 experimental studies, 23 review articles, 4 systematic reviews, and 5 meta-analyses, with a combined sample size of approximately 3,134,054 men. The findings from the meta-analysis suggests an 18% reduction in the risk of cardiovascular events among men receiving TRT compared to those receiving a placebo. TRT was found to be associated with significant improvements in ejection fraction, lipid profiles (reduction in total cholesterol and low-density lipoprotein cholesterol), and other cardiovascular risk factors, including insulin resistance and inflammatory markers. Potential mechanisms underlying the cardioprotective effects of TRT include improvements in endothelial function, vasodilation, and myocardial remodeling. Subgroup analyses revealed that the beneficial effects of TRT were more pronounced in men with established cardiovascular disease or risk factors, such as diabetes or metabolic syndrome. Conclusion: This systematic review and meta-analysis of high-quality evidence suggest that testosterone deficiency is associated with an increased risk of cardiovascular disease. Conversely, TRT is associated with a reduced risk of cardiovascular events, particularly in men with pre-existing cardiovascular disease or risk factors. TRT was linked to a reduced risk of MACE, improved ejection fraction, and favorable changes in lipid profiles and other cardiovascular risk factors. Despite the relatively large sample size, further long-term studies are needed to confirm these findings and establish optimal dosing and monitoring strategies for TRT in cardiovascular disease prevention.
The Effect of Testosterone on Cardiovacular Biomarkers in the Testosterone Trials
The Journal of clinical endocrinology and metabolism, 2017
Studies of the possible cardiovascular risk of testosterone treatment are inconclusive. To determine the effect of testosterone treatment on cardiovascular (CV) biomarkers in older men with low testosterone. Double-blind, placebo-controlled trial. Twelve academic medical centers in the United States. 788 men ≥65 years old with an average of two serum testosterone levels <275 ng/dL who were enrolled in The Testosterone Trials. Testosterone gel, the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. Serum markers of cardiovascular risk, including lipids and markers of glucose metabolism, fibrinolysis, inflammation, and myocardial damage. Testosterone treatment, compared to placebo, significantly decreased total cholesterol (adjusted mean difference -6.1 mg/dL, p<0.001), high density lipoprotein (HDL) cholesterol (adjusted mean difference -2.0 mg/dL, p<0.001) cholesterol and low density lipoprotein (LDL) cholestero...
Cardiovascular effect of testosterone replacement therapy in aging male
Cardiovascular diseases (CVD) are the most important causes of morbidity and mortality in the developed and developing world. Particularly, coronary heart disease is the commonest cause of death worldwide. Testosterone (T) is an anabolic hormone with putative beneficial effects on men's health and restoration of normal T levels in deficient men represents an important key-point of male well-being. In the lasts years it has emerged a possible linkage between androgen deficiency and CVD. Many studies noted that T deficiency might contribute to increased risk of CVD. Furthermore, androgen deficiency is frequently associated with increased levels of glucose, total cholesterol, low-density lipoprotein, increased production of pro-inflammatory cytokines, and increased thickness of the arterial wall that all contribute to worsen endothelial function. The clinical and epidemiological studies discussed in this section give an update on the interplay between late onset hypogonadism (LOH) and CVD. The linkage between androgen deficiency and men's vascular health has a great impact in the modern approach to the ageing male, and should be further investigated to determine the therapeutic potential of androgens in men with vascular disease. (www.actabiomedica.it)