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In contrast, other studies have found no statistically significant association between testosterone level and cardiovascular mortality. Studies have shown that TRT can improve heart rate variability in men with low testosterone levels. TRT involves administering testosterone through injections, patches, gels, or pellets to increase hormone levels to a healthy range. For men with low testosterone levels and decreased HRV, testosterone replacement therapy (TRT) may be recommended. Maintaining optimal testosterone levels can have several benefits for heart health. Research has shown that testosterone levels have a direct impact on heart rate variability.
In our opinion, the association between testosterone and T2DM is bidirectional and involves several organs. Several authors have demonstrated that the administration of testosterone in diabetic men improves the homeostatic model of insulin resistance, hemoglobin A1c, and fasting plasma glucose.26,68–72 The results of these studies are summarized in Table 4. The authors also noted that their analyses for total and free testosterone lost statistical significance after adjusting for waist circumference.66 Similarly, Vikan et al followed 1454 Swedish men for 11 years and discovered that men in the highest quartile of total testosterone were significantly less likely to develop T2DM. Laaksonen et al65 followed 702 Finnish men for 11 years and demonstrated that men in the lowest quartile of total testosterone, free testosterone, and SHBG were more likely to develop T2DM and metabolic syndrome. It has been well established that men with T2DM have lower levels of testosterone compared with nondiabetic men.
These factors are the subfraction of testosterone used to perform the analysis and the method used to account for subclinical CAD. The recent flurry of direct consumer advertising of testosterone products on television and in print is difficult to ignore. The accumulation of ROS over time may cause damage to the Leydig cell DNA and thereby render it incapable of producing testosterone.5 Reactive oxygen species (ROS), which are generated by the mitochondria of Leydig cells, are a normal byproduct of testosterone synthesis. With the exception of certain diagnostic test panels, list available here, the tests we offer access to are not intended to diagnose or treat disease. Everlywell offers health and wellness solutions including laboratory testing for wellness monitoring, informational and educational use.
The hazard ratio for CHF mortality per 1 standard deviation increase in free testosterone was calculated to be 0.37 (95% CI, 0.15 to 0.89) in the same study. No significant association was found between testosterone levels and the presence of severe abdominal aortic atherosclerosis in women by Hak et al. Although some authors have focused on the association between testosterone levels and IMT of the carotid artery, other authors have evaluated the association between endogenous testosterone levels and IMT of the aorta. CCS indicates case–control study; CIMT, carotid artery intima‐media thickness; DBPCC, double‐blind placebo‐controlled crossover study; DBRCT, double‐blind randomized controlled trial; HOMA‐IR, homeostatic model of insulin resistance; hsCRP, high‐sensitivity C‐reactive protein; IL‐10, interleukin‐10; IL‐1β, interleukin–1β; IL‐6, interleukin‐6; IM, intramuscular; PO, by mouth; SBRCT, single‐blind randomized controlled study; sICAM‐1, soluble intracellular adhesion molecule‐1; sVCAM‐1, soluble vascular cell adhesion molecule‐1; TD, transdermal; TG, triglycerides; TNF‐α, tumor necrosis factor–α; TRT, testosterone replacement therapy.
Toma et al. performed a meta-analysis of these studies and discovered that there was a net pooled improvement of 0.52 standard deviations in exercise capacity among those who received TRT. Testosterone replacement therapy has been shown to significantly improve exercise capacity without affecting left ventricular ejection fraction (LVEF). Emerging evidence indicates that congestive heart failure (CHF) is more than just a syndrome affecting a failing heart. In their 2013 review, Oskui and colleagues reported on evidence suggesting that men with lower levels of endogenous T are more likely to develop CAD during their lifetimes.11 The severity of CAD has also been investigated as a function of serum T concentrations. Populations at high risk for TD include men with CHF, type 2 diabetes, obesity, chronic obstructive pulmonary disorder, HIV, and chronic opioid use.7
A number of studies have examined the association between testosterone levels and carotid IMT, with all the studies showing an inverse correlation between these 2 variables.126–128,32,129–132 The results of these studies are summarized in Table 7. In a study of 11 nonobese men with hypogonadism, Charbit et al evaluated the effects of a single intramuscular injection of testosterone enanthate 250 mg on heart rate–independent QT interval length.115 The authors measured QT length at 3 points after the administration of testosterone. Likewise, no conclusion can be made regarding the association between testosterone replacement therapy and its effect on CRP levels.
The indication of an association between testosterone therapy and risk for adverse cardiovascular events prompted the US Food and Drug Administration (FDA) to issue a safety warning on testosterone therapy for older men, which was followed by a reduction in testosterone prescriptions.30 The safety warning cautioned against the use of testosterone therapy for aging-related decline and reinforced the current approval of testosterone products for hypogonadal men only.30 However, it is important to note that the methodology and reliability of the aforementioned studies have since been questioned. Despite a lack of clarity on the relationship between endogenous testosterone and cardiovascular risk, testosterone replacement therapy (TRT) is widely used, especially in older men with low serum testosterone levels. This finding is consistent with results of the prospective Rotterdam study, which reported an inverse association between testosterone levels in older men and risk and progression of severe aortic atherosclerosis.15 The European Prospective Investigation Into Cancer in Norfolk (EPIC-Norfolk) study, a nested case–control study, similarly reported an inverse relationship between endogenous testosterone concentrations and all-cause mortality and CVD.15 Although it is well established that testosterone levels decline and cardiovascular mortality increases with age, the association between testosterone and CVD remains unclear. The effects of testosterone, the primary male sex hormone, on cardiovascular risk have been of special interest due to the increased risk of CVD in men. Optimal testosterone levels play a significant role in maintaining heart rate variability, a crucial indicator of cardiovascular health.
On the other hand, testosterone could be functioning as a marker for an underlying disease entity that results in increased mortality risk. The goal of this article is to provide a comprehensive review of the clinical literature that has examined the associations between testosterone and cardiovascular disease including incidence of coronary artery disease, severity of coronary artery disease, mortality secondary to cardiovascular disease, angina pectoris, vasomotor regulation of coronary arteries, congestive heart failure, and QT interval prolongation. Checking testosterone levels is important if you have symptoms or if you are on therapy that can affect your testosterone levels, due to the potential impacts on your heart and other health factors. Studies looking at the effects of testosterone replacement therapy have had mixed results when it comes to heart health.
This interaction may be a result of the promotion of lipolysis in abdominal adipose tissue by testosterone, which may in turn cause reduced abdominal adiposity. Malkin et al administered Sustanon 250 (testosterone propionate 30 mg, testosterone phenylpropionate 60 mg, testosterone isocaproate 60 mg, and testosterone decanoate 100 mg/mL) IM injection. Recently, Ding et al25 and Corona et al26 performed 2 meta‐analyses that combined the results of the above‐mentioned studies and have produced similar results. There is growing evidence from in vivo animal models and in vitro models that testosterone induces coronary vasodilation by modulating the activity of ion channels, such as potassium and calcium channels, on the surface of vascular smooth muscle cells. This observation is in agreement with the in vitro findings reported by Yue et al,57 who demonstrated that testosterone had no effect on endothelial nitric oxide activity. This finding is significant because it suggests that the effect of testosterone on coronary arteries is independent of vessel endothelium.
In our opinion, the association between testosterone and T2DM is bidirectional and involves several organs. Several authors have demonstrated that the administration of testosterone in diabetic men improves the homeostatic model of insulin resistance, hemoglobin A1c, and fasting plasma glucose.26,68–72 The results of these studies are summarized in Table 4. The authors also noted that their analyses for total and free testosterone lost statistical significance after adjusting for waist circumference.66 Similarly, Vikan et al followed 1454 Swedish men for 11 years and discovered that men in the highest quartile of total testosterone were significantly less likely to develop T2DM. Laaksonen et al65 followed 702 Finnish men for 11 years and demonstrated that men in the lowest quartile of total testosterone, free testosterone, and SHBG were more likely to develop T2DM and metabolic syndrome. It has been well established that men with T2DM have lower levels of testosterone compared with nondiabetic men.
These factors are the subfraction of testosterone used to perform the analysis and the method used to account for subclinical CAD. The recent flurry of direct consumer advertising of testosterone products on television and in print is difficult to ignore. The accumulation of ROS over time may cause damage to the Leydig cell DNA and thereby render it incapable of producing testosterone.5 Reactive oxygen species (ROS), which are generated by the mitochondria of Leydig cells, are a normal byproduct of testosterone synthesis. With the exception of certain diagnostic test panels, list available here, the tests we offer access to are not intended to diagnose or treat disease. Everlywell offers health and wellness solutions including laboratory testing for wellness monitoring, informational and educational use.
The hazard ratio for CHF mortality per 1 standard deviation increase in free testosterone was calculated to be 0.37 (95% CI, 0.15 to 0.89) in the same study. No significant association was found between testosterone levels and the presence of severe abdominal aortic atherosclerosis in women by Hak et al. Although some authors have focused on the association between testosterone levels and IMT of the carotid artery, other authors have evaluated the association between endogenous testosterone levels and IMT of the aorta. CCS indicates case–control study; CIMT, carotid artery intima‐media thickness; DBPCC, double‐blind placebo‐controlled crossover study; DBRCT, double‐blind randomized controlled trial; HOMA‐IR, homeostatic model of insulin resistance; hsCRP, high‐sensitivity C‐reactive protein; IL‐10, interleukin‐10; IL‐1β, interleukin–1β; IL‐6, interleukin‐6; IM, intramuscular; PO, by mouth; SBRCT, single‐blind randomized controlled study; sICAM‐1, soluble intracellular adhesion molecule‐1; sVCAM‐1, soluble vascular cell adhesion molecule‐1; TD, transdermal; TG, triglycerides; TNF‐α, tumor necrosis factor–α; TRT, testosterone replacement therapy.
Toma et al. performed a meta-analysis of these studies and discovered that there was a net pooled improvement of 0.52 standard deviations in exercise capacity among those who received TRT. Testosterone replacement therapy has been shown to significantly improve exercise capacity without affecting left ventricular ejection fraction (LVEF). Emerging evidence indicates that congestive heart failure (CHF) is more than just a syndrome affecting a failing heart. In their 2013 review, Oskui and colleagues reported on evidence suggesting that men with lower levels of endogenous T are more likely to develop CAD during their lifetimes.11 The severity of CAD has also been investigated as a function of serum T concentrations. Populations at high risk for TD include men with CHF, type 2 diabetes, obesity, chronic obstructive pulmonary disorder, HIV, and chronic opioid use.7
A number of studies have examined the association between testosterone levels and carotid IMT, with all the studies showing an inverse correlation between these 2 variables.126–128,32,129–132 The results of these studies are summarized in Table 7. In a study of 11 nonobese men with hypogonadism, Charbit et al evaluated the effects of a single intramuscular injection of testosterone enanthate 250 mg on heart rate–independent QT interval length.115 The authors measured QT length at 3 points after the administration of testosterone. Likewise, no conclusion can be made regarding the association between testosterone replacement therapy and its effect on CRP levels.
The indication of an association between testosterone therapy and risk for adverse cardiovascular events prompted the US Food and Drug Administration (FDA) to issue a safety warning on testosterone therapy for older men, which was followed by a reduction in testosterone prescriptions.30 The safety warning cautioned against the use of testosterone therapy for aging-related decline and reinforced the current approval of testosterone products for hypogonadal men only.30 However, it is important to note that the methodology and reliability of the aforementioned studies have since been questioned. Despite a lack of clarity on the relationship between endogenous testosterone and cardiovascular risk, testosterone replacement therapy (TRT) is widely used, especially in older men with low serum testosterone levels. This finding is consistent with results of the prospective Rotterdam study, which reported an inverse association between testosterone levels in older men and risk and progression of severe aortic atherosclerosis.15 The European Prospective Investigation Into Cancer in Norfolk (EPIC-Norfolk) study, a nested case–control study, similarly reported an inverse relationship between endogenous testosterone concentrations and all-cause mortality and CVD.15 Although it is well established that testosterone levels decline and cardiovascular mortality increases with age, the association between testosterone and CVD remains unclear. The effects of testosterone, the primary male sex hormone, on cardiovascular risk have been of special interest due to the increased risk of CVD in men. Optimal testosterone levels play a significant role in maintaining heart rate variability, a crucial indicator of cardiovascular health.
On the other hand, testosterone could be functioning as a marker for an underlying disease entity that results in increased mortality risk. The goal of this article is to provide a comprehensive review of the clinical literature that has examined the associations between testosterone and cardiovascular disease including incidence of coronary artery disease, severity of coronary artery disease, mortality secondary to cardiovascular disease, angina pectoris, vasomotor regulation of coronary arteries, congestive heart failure, and QT interval prolongation. Checking testosterone levels is important if you have symptoms or if you are on therapy that can affect your testosterone levels, due to the potential impacts on your heart and other health factors. Studies looking at the effects of testosterone replacement therapy have had mixed results when it comes to heart health.
This interaction may be a result of the promotion of lipolysis in abdominal adipose tissue by testosterone, which may in turn cause reduced abdominal adiposity. Malkin et al administered Sustanon 250 (testosterone propionate 30 mg, testosterone phenylpropionate 60 mg, testosterone isocaproate 60 mg, and testosterone decanoate 100 mg/mL) IM injection. Recently, Ding et al25 and Corona et al26 performed 2 meta‐analyses that combined the results of the above‐mentioned studies and have produced similar results. There is growing evidence from in vivo animal models and in vitro models that testosterone induces coronary vasodilation by modulating the activity of ion channels, such as potassium and calcium channels, on the surface of vascular smooth muscle cells. This observation is in agreement with the in vitro findings reported by Yue et al,57 who demonstrated that testosterone had no effect on endothelial nitric oxide activity. This finding is significant because it suggests that the effect of testosterone on coronary arteries is independent of vessel endothelium.
