Testosterone is the principal male sex hormone and we know that in general, as men get above the age of 40, testosterone levels start dropping. We also know that as men get above the age of 40, their overall cardiac risk and overall risk of mortality starts increasing. So it appears that overall cardiac risk starts going up around about the same time as testosterone levels start falling. What we still don’t know is whether they are both simply a consequence of aging or whether in some way testosterone is protective for cardiac risk.
In this blog, I will review exactly what we know about testosterone and the heart so far.
Testosterone is produced in the male testes and about 98% binds to a carrier called SHBG (sex hormone binding globulin) and about 1-2% circulates unbound or ‘free’ The free testosterone is perhaps the most potent biological form.
Testosterone is responsible for development of primary and secondary sex characteristics and also increases both muscle mass and bone density.
When men become testosterone deficient, they often develop reduced libido, erectile dysfunction, reduced energy levels, bad mood and increased irritability. Overall sexuality, health status and quality of life all deteriorate.
The prevalence of testosterone in middle aged/older men is quoted in the literature as being anywhere between 2.1-12.8%.
Patients who are particularly vulnerable to being testosterone deficient include:
Chronic heart failure
Type 2 diabetes
Currently the way it is diagnosed is through an early morning blood test which measures total testosterone levels and if the level is less than 200 ng/mL then that is classed as testosterone deficiency. There is some controversy however over how good the assays are and especially if the value is at the lower levels of normal, what that means. Some scientists have suggested that maybe measuring the levels of free testosterone may be better but it is still unclear.
Testosterone and Overall/Cardiac mortality
There was a publication by Corona et al who summarised after studying 1178 articles about testosterone that testosterone deficiency was associated with both, an increased overall mortality and increased cardiac mortality too.
Testosterone and coronary artery disease
Testosterone has both a vasodilatory action as well as anti-inflammatory effects and small studies have suggested that there appears to be an inverse relationship between serumtestosterone levels and severity of coronary disease. A population of patients with the lowest testosterone levels are more likely to have more severe coronary disease.
Testosterone and congestive heart failure
When you look at all stages of heart failure, patients will in general have lower testosterone levels compared to an age matched population. Patients with lower testosterone levels seem to have a worse prognosis.
Testosterone and lipid levels
There are conflicting data and at present we are not sure of what effect testosterone has on cholesterol levels.
Testosterone and diabetics/metabolic syndrome patients
Men with type 2 diabetes in general have lower testosterone levels compared to non-diabetics.
In population studies it seems that patients with lowest levels of testosterone double their risk of developing type 2 diabetes.
So whilst these are useful observations, the more important question is whether replacing the testosterone will reduce these risks.
The effects of TRT(testosterone replacement therapy)
Testosterone deficient men have more fat and less muscle.
Obese patients are more likely to be testosterone deficient.
When TRT is used, we know that fat mass percentage drops by an average of 2%.
There are no large scale studies showing that testosterone replacement is beneficial or safe and therefore we can’t make definitive conclusions.
However there are plenty of small scale trials which suggest that we should treat testosterone deficiency with more respect. The FDA looked at all the data surrounding testosterone and found over 100 clinical studies which suggested benefit and 4 small scale studies which suggested harm (without any convincing proof).
The studies which suggested benefit largely showed the following:
There appears to be reduced cardiovascular risk in patients who have higher levels of endogenous testosterone
Testosterone replacement is associated with an improvement in cardiac risk factors
Patients who are testosterone deficient and undergo testosterone replacement seem to have reduced mortality compared to patients who are deficient but do not undergo thyroxine replacement.
Let’s look at specific groups:
TRT and coronary disease
There have been 3 randomised placebo controlled trials and they suggest that TRT reduces myocardial ischemia presumably through its vasodilatory actions
TRT and CCF
In heart failure patients, replacing testosterone in deficient patients is associated with improved exercise capacity and functional status. In one study there was a 16.7% improvement on exercise distance on a 6 minute walk test.
TRT and diabetes
In testosterone deficient diabetics, HbA1c and fasting sugar levels were improved with TRT
What about side effects and risks with TRT?
There has been some historical concern that TRT may be associated with prostate cancer. This was based on a study which suggested that patients on TRT had greater prostate related effects which included a combination od increased urinary frequency, cancer, more prostatic biopsies and an elevation in PSA levels. However further dissection of the data have failed to show any convinicing evidence that TRT is associated with an increased risk of prostate cancer
As testosterone could increase blood thickness one concern has been whether it increases risk of blood clots. There was a study by Ramasamy et al where they followed patients up for 3 years and found no increase in blood clots.
Testosterone does definitely increase the haematocrit or blood thickness levels. However again there is really very little evidence that that translates into dangerous events if done under close medical supervision.
So in summary
Testosterone deficiency is common and not only makes quality of life worse but can also impact adversely on length of life.
Doctors don’t routinely look for it especially in those who are most vulnerable to having it and replacement under medical supervision may not only improve quality of life but may even offer prognostic benefits.
It is generally quite difficult to find GPs and specialists within the NHS with an interest in testosterone. Some private companies like Balance My Hormones have considerable expertise with Testosterone replacement and can be contacted via firstname.lastname@example.org