Testosterone and Cardiovascular Disease

Tambo, Amos; Roshan, Mohsin H. K; Pace, Nikolai Paul

doi:10.2174/1874192401610010001

Cited by 17 publications

(12 citation statements)

References 62 publications

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“…Epidemiological studies identified TD as a risk factor for CVD. 88 Furthermore, TTh improves CBV perfusion and improves mood in men with TD and low T levels predict a poor CV risk profile. 89 , 90 We should point out that we made no attempts to monitor changes in lifestyle, simply because when this registry study was initiated, there was no expectation that men would lose weight, lose WC, and experience improvement in lifestyle.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Testosterone Therapy Improves Cardiometabolic Function and Reduces Risk of Cardiovascular Disease in Men with Hypogonadism

Traish

Haider²,

Haider³

et al. 2017

J Cardiovasc Pharmacol Ther

117

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Objectives:In the absence of large, prospective, placebo-controlled studies of longer duration, substantial evidence regarding the safety and risk of testosterone (T) therapy (TTh) with regard to cardiovascular (CV) outcomes can only be gleaned from observational studies. To date, there are limited studies comparing the effects of long-term TTh in men with hypogonadism who were treated or remained untreated with T, for obvious reasons. We have established a registry to assess the long-term effectiveness and safety of T in men in a urological setting. Here, we sought to compare the effects of T on a host of parameters considered to contribute to CV risk in treated and untreated men with hypogonadism (control group).Patients and Methods:Observational, prospective, cumulative registry study in 656 men (age: 60.7 ± 7.2 years) with total T levels ≤12.1 nmol/L and symptoms of hypogonadism. In the treatment group, men (n = 360) received parenteral T undecanoate (TU) 1000 mg/12 weeks following an initial 6-week interval for up to 10 years. Men (n = 296) who had opted against TTh served as controls. Median follow-up in both groups was 7 years. Measurements were taken at least twice a year, and 8-year data were analyzed. Mean changes over time between the 2 groups were compared by means of a mixed-effects model for repeated measures, with a random effect for intercept and fixed effects for time, group, and their interaction. To account for baseline differences between the 2 groups, changes were adjusted for age, weight, waist circumference, fasting glucose, blood pressure, and lipids.Results:There were 2 deaths in the T-treated group, none was related to CV events. There were 21 deaths in the untreated (control) group, 19 of which were related to CV events. The incidence of death in 10 patient-years was 0.1145 in the control group (95% confidence interval [CI]: 0.0746-0.1756; P < .000) and 0.0092 in the T-treated group (95% CI: 0.0023-0.0368; P < .000); the estimated difference between groups was 0.0804 (95% CI: 0.0189-0.3431; P < .001). The estimated reduction in mortality for the T-group was between 66% and 92%. There were also 30 nonfatal strokes and 26 nonfatal myocardial infarctions in the control group and none in the T-treated group.Conclusion:Long-term TU was well tolerated with excellent adherence suggesting a high level of patient satisfaction. Mortality related to CV disease was significantly reduced in the T-group.

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Section: Discussionmentioning

confidence: 99%

Long-Term Testosterone Therapy Improves Cardiometabolic Function and Reduces Risk of Cardiovascular Disease in Men with Hypogonadism

Traish

Haider²,

Haider³

et al. 2017

J Cardiovasc Pharmacol Ther

117

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“…24 The Leydig cells, which are located between the seminiferous tubules of the testis, are responsible for the synthesis and secretion of testosterone. 24 The Leydig cells, which are located between the seminiferous tubules of the testis, are responsible for the synthesis and secretion of testosterone.…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that testosterone is essential for multiple physiological pathways including male secondary sexual development and fertility. 24 The Leydig cells, which are located between the seminiferous tubules of the testis, are responsible for the synthesis and secretion of testosterone. [25][26][27] Several studies have reported that dietary factors such as high-fat diets and high-calorie diets could inhibit Leydig cell steroidogenesis.…”

Section: Discussionmentioning

confidence: 99%

HC diet inhibited testosterone synthesis by activating endoplasmic reticulum stress in testicular Leydig cells

Jiang

Zhang

et al. 2019

J Cellular Molecular Medi

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Emerging epidemiological studies indicate that hypercholesterolaemia is a risk factor for testosterone deficiency. However, the underlying mechanism is unclear. Testicular Leydig cells are the primary source of testosterone in males. To identify the effect and mechanism of cholesterol overload on Leydig cell function, rats were fed with a HC (HC) diet to induce hypercholesterolaemia. During the 16‐week feeding period, serum testosterone levels were reduced in a time‐dependent manner in rats fed the HC diet. Accordingly, these steroidogenic enzymes within the Leydig cells, including steroidogenic acute regulatory protein (StAR), cholesterol side‐chain cleavage cytochrome P450 (P450scc) and 3β‐hydroxysteroid dehydrogenase (3β‐HSD), were down‐regulated. Notably, the HC‐fed rats showed evident endoplasmic reticulum (ER) stress in the testis, including a dilated ER as an evident pathological change in the Leydig cell ultrastructure, up‐regulated ER stress biomarker (binding immunoglobulin protein) levels and activation of the activating transcription factor 6 (ATF6)‐related unfolded protein response pathway. Further analysis showed that when 4‐phenyl butyric acid (4‐PBA) was used to block ER stress in HC‐fed rats for 8 weeks, the testosterone deficiency was significantly alleviated. Our findings suggested that high dietary cholesterol intake affected serum testosterone levels by down‐regulating steroidogenic enzymes and that activated ER stress might serve as the underlying mechanism.

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“…Numerous studies have shown that males with low levels of testosterone were prone to cardiovascular diseases [14, 15]. Furthermore, low levels of endogenous testosterone are directly linked to male infertility, erectile dysfunction and oligospermia.…”

Section: Testosterone and Its Functionsmentioning

confidence: 99%

The role of testosterone in colorectal carcinoma: pathomechanisms and open questions

2016

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Colorectal cancer (CRC) is the fourth commonest type of malignancy after breast, lung and prostate in the USA and accounts for approximately 49,190 deaths annually in USA alone. The 5-year survival rate of CRC has increased over the past decades, in part, due to greater awareness and the widespread implementation of national screening programmes. Recently, a number of studies reported that males have a higher risk of developing CRC due to the action of testosterone.Testosterone is an androgen that is responsible for the development of male secondary sex characteristics and for spermatogenesis. Studies on rats with mutated Apc tumour-suppressor gene subjected to either ovariectomy or orchidectomy exhibit different risks of CRC. Female rats subjected to ovariectomy are at higher risk of CRC, whereas orchidectomised male rats exhibit a lower risk of developing CRC. Sex hormones, in particular estrogen and testosterone, play a significant role in the development of CRC since the anti-neoplastic effect of estrogen lost during ovariectomy increases the risk of females developing CRC. Male mice exposed to testosterone after orchidectomy were also at greater risk than those who were orchidectomised but administered placebo only. Moreover, the recently established role of membrane androgen receptors in regression of CRC via non-genomic androgen-dependent action sets these receptors apart from intracellular androgen receptors (iARs) which themselves promote CRC development. In addition, testosterone-albumin conjugates are selective to membrane androgen receptors (mARs) and lead to apoptosis via caspase-3 activation. Akt kinases promote invasion of colon cancer cells when phosphorylated. These kinases are dephosphorylated upon activation of mARs, thereby reducing colon cancer cell motility and invasiveness.Testosterone similarly plays important roles in human CRC. Long cytosine-adenine-guanine (CAG) repeats in the gene for the androgen receptors have been associated with a poor 5-year survival compared to shorter CAG repeats. Very recently, the measurement of serum unbound testosterone has been suggested as a novel biomarker along with carcinoembryonic antigen in CRC. In conclusion, testosterone may promote the development of CRC via a number of pathways, which may place males at greater risk. Testosterone holds promise as a potential biomarker in CRC risk prediction; however, further studies are required to better define its role in colorectal neoplasia.

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Testosterone and Cardiovascular Disease

Cited by 17 publications

References 62 publications

Long-Term Testosterone Therapy Improves Cardiometabolic Function and Reduces Risk of Cardiovascular Disease in Men with Hypogonadism

Long-Term Testosterone Therapy Improves Cardiometabolic Function and Reduces Risk of Cardiovascular Disease in Men with Hypogonadism

HC diet inhibited testosterone synthesis by activating endoplasmic reticulum stress in testicular Leydig cells

The role of testosterone in colorectal carcinoma: pathomechanisms and open questions

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