The cardiovascular effects of testosterone and testosterone therapy are subject to intense investigation in medical research and have recently generated heated discussions among healthcare professionals.
While the main focus has been on testosterone per se, it is important to remember that testosterone is both a hormone in its own right, and a pro-hormone that gets converted to both estradiol and DHT (dihydrotestosterone). Estradiol and DHT exert effects themselves that are different from the effects of testosterone.
Therefore, when analyzing the effects of testosterone, especially supplemental testosterone administered as testosterone replacement therapy, it is critical to take into consideration how it affects downstream testosterone metabolites like estradiol and DHT.
Here I will present results from a recent systematic review and meta-analysis that specifically investigated how different routes of testosterone therapy administration (i.e different testosterone preparations) affect blood levels of testosterone and espcially DHT , and how this in turn relates to cardiovascular adverse events.
It is well documented that obesity may cause hypogonadism, and that hypogonadism may cause obesity [1-4] This has generated debate about what condition comes first; obesity or hypogonadism? And what should be the first point of intervention?
In this article I will summarize data from several reviews on the associations of hypogonadism and obesity [1-4], and make the case that these conditions create a self-perpetuating vicious circle. Once a vicious circle has been established, it doesn’t matter where one intervenes; one can either treat the obese condition or treat hypogonadism first. The critical issue is to break the vicious circle as soon as possible before irreversible health damage arises.
Nevertheless, as I will explain here, treating hypogonadism first with testosterone replacement therapy may prove to be a more effective strategy because it to a large extent “automatically” takes care of the excess body fat and metabolic derangements. In addition, treating hypogonadism first also confers psychological benefits that will help obese men become and stay more physically active.
In a previous article "Combined Testosterone and GH therapy for best results on body composition and safety profiles" I covered a study showing that testosterone replacement therapy alone produced significant gains in total lean body mass, leg/arm muscle mass, strength and aerobic endurance, together with significant reductions in whole-body and trunk fat. 
In the same study, addition of GH (growth hormone) further enhanced these beneficial results.
In a follow-up to that that study, the researchers looked deeper into the data with the following analyses: 
- Pathway analysis to test the hypothesis that testosterone and GH affected muscle mass directly and that a threshold change in lean tissue (muscle) mass was needed to generate significant improvements in muscle performance and physical function.
- Bootstrap analysis to determine threshold hormone levels associated with threshold changes in whole-body and appendicular lean mass that would be necessary for improving muscle performance and functional outcomes.
Here I report on the results of this insighful analysis...
Testosterone deficiency is especially common in men who are obese and/or have the metabolic syndrome or diabetes, with a prevalence ranging from 35% to almost 80%.[1-5] However, there is a subgroup of non-obese men who have low testosterone levels and suffer from typical symptoms of low-T, but who do not (yet) have any co-morbidities.
Many studies show that suboptimal testosterone levels may contribute to the development of obesity (including abdominal obesity) [6, 7], metabolic syndrome [8-13] and/or diabetes.[9, 14-20] Therefore, testosterone therapy in non-obese men with testosterone deficiency may be an effective intervention to correct not only symptoms associated with hypogonadism, but also prevent the development of obesity, metabolic syndrome and/or diabetes.
A notable study was set out to specifically investigate this…
A rapidly growing body of medical research is showing that testosterone deficiency (aka hypogonadism and low-T) is strongly associated with a wide range of detrimental health outcomes [1, 2], and that testosterone replacement therapy improves those health parameters that are negatively affected by testosterone deficiency.[2, 3]
Therefore, leading testosterone scientists now view testosterone deficiency as a cardiovascular risk factor that contributes to the development of cardiovascular disease.[4-7]
As general practitioners and cardiologists primarily care for these patients with cardiovascular disease, a survey study was conducted to assess their knowledge, beliefs and clinical practice with respect to testosterone deficiency and cardiovascular health.
During testosterone therapy, total and free estradiol (the main form of estrogen) levels increase dose-dependently in both young (aged 19-35 year old) and 52 older (aged 59-75 year old) men, and more so in older men compared to younger men.
The potential clinical consequences of higher estradiol levels and higher estradiol-to-testosterone ratios in older men remains poorly understood, and the optimal management of high-normal or elevated estrogens is controversial among clinicians.
Interestingly, in some patients, an initial elevation in estradiol is followed by decreased estradiol after prolonged testosterone therapy.[3, 4] This may be due to reduced body fat mass or decreased testosterone levels over time with fixed dose treatments.
Here you will get advice on how to best approach estrogen management while on testosterone therapy…
Accumulating evidence shows beneficial effect of testosterone therapy on a wide range of health outcomes, including inflammation, insulin sensitivity, muscle mass, body fat mass, lipid profiles, endothelial, bone mineral density, energy and vitality, mood, sexual function and overall quality of life. [1-9]
Despite this, concerns have been raised that testosterone therapy could have detrimental effects on cardiovascular disease.
In this article I summarize results from a comprehensive systematic review and meta-analysis, the largest to date, of all placebo-controlled randomized clinical trials (RCTs) on the effect of testosterone therapy on cardiovascular-related outcomes.
One of the major concerns among doctors and patients with testosterone therapy is its allegedly negative effect on the prostate. However, according to the current ISA, ISSAM, EAU, EAA, ASA clinical guidelines, there is no conclusive evidence that testosterone therapy increases the risk of prostate cancer or benign prostatic hyperplasia.
The guidelines also state that there is also no evidence that testosterone treatment will convert subclinical prostate cancer to clinically detectable prostate cancer.
Despite this, many men are being denied testosterone therapy because of undue fears that it would cause harm to the prostate. Here I summarize the results from a study that investigated incidence of prostate cancer with testosterone therapy for up to 17 years.
Testosterone therapy confers a wide range of health benefits for hypogonadal men, including improvements in body composition (reduction in body fat, increase in muscle mass), lipid profile cardiovascular function, insulin sensitivity/glucose metabolism, bone mineral density, inflammatory parameters, quality of life and longevity.
Despite this, there is a high discontinuation rate with testosterone therapy.[2, 3]
In this article I summarize results from two studies that investigated adherence to testosterone therapy and treatment patterns.[2, 3]
Since its approval in 2004, many clinical studies have been conducted with testosterone undecanoate, the first long-acting injectable form of testosterone.
Testosterone undecanoate has been proven to have an excellent safety profile and need only be administered four times annually to produce stable testosterone levels.
Long-term studies have validated the clinical efficacy of testosterone undecanoate in maintaining stable therapeutic levels of testosterone and safely conferring the desired benefits of androgen replacement.
Here I summarize the results from a comprehensive meta-analysis of all uncontrolled and placebo-controlled randomized clinical trials (RCTs) demonstrating the effect of injectable testosterone undecanoate on multiple clinical outcomes.