If I have been prescribed testosterone replacement therapy should I stop?
If I have Low-T, is it safe for me take testosterone replacement therapy (TRT)?
What you need to know about Low-T and Cardiovascular Events
It is a common question by all men who are considering testosterone replacement therapy: Will testosterone replacement cause me to have a heart attack? Am I at an increased risk of having a heart attack if I get testosterone therapy?
To best answer this question lets first consider the history of testosterone therapy and its clinical use in managing patients with cardiovascular conditions. In the early 1930’s testosterone therapy was once considered a treatment for angina pectoris (chest pain) and peripheral vascular diseases. Physicians during this time injected testosterone to improve vascular flow to lower limbs in patients with intermittent claudication and peripheral vascular disease. In the 1940’s a variety of published studies observed testosterone’s ability to vasodilate (expand) small arteries and improve blood flow to areas of the body with diminished blood inflow. In men who presented with chest pain secondary to small vessel blockage or vessel wall spasm, testosterone was given during an acute chest pain attack (heart attack) as a treatment. Studies revealed “marked improvement” in patients’ symptoms and the use of testosterone was able to reduce not only the severity of attacks of chest pain but also the occurrences.
It was not until the early 1980’s, that testosterone deficiency (also known as Low-T) was being heralded as a new diagnosis in aging males. Testosterone therapy was becoming more popular as its effects to promote lean muscle mass, improving weight loss, cognition, sex drive, erectile function and improve the quality of life of men were becoming more apparent. The boom of the testosterone marketplace was announced as pharmacological companies began producing a variety testosterone formulations (patches, gels, pellets) to capitalize on this new and expanding marketplace. Given the media’s attention towards testosterone’s abilities and its new expansion in the medical area, so did much of the scrutiny surrounding testosterone replacement, especially that testosterone therapy can cause heart attacks. This culminated in the following FDA label change of testosterone in 2015.
FDA Testosterone Package Insert Warning 2015
Long term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men. To date, epidemiological studies and randomized controlled studies have been inconclusive for determining the risk of major adverse cardiovascular events (MACE), such as non-fatal myocardial infarction, non-fatal stroke, cardiovascular death with use of testosterone compared to non-use. Some studies, but not all, have reported an increased risk of MACE in association with use of testosterone replacement therapy in men.
Patient should be informed of this possible risk when deciding whether to use or to continue to use Androgel 1%.
What do the Testosterone studies show?
The risk factors for testosterone deficiency (Low-T) and risk factors for heart attacks are the same: obesity, hypertension, dyslipidemia, hyperglycemia, insulin resistance and metabolic syndrome.
Many men who are on testosterone also have and share risk factors for cardiovascular disease (CVD) and may already have underlying CVD prior to starting testosterone therapy.
There are a number of clinical studies and evidence that supports that low testosterone levels are a risk factor for cardiovascular disease and replacing testosterone can improve cardiac health. The following are statements with the number of supporting testosterone clinical studies:
· Low T increases incidence of coronary artery disease (6)
· Low T increases mortality (8)
· Low T correlates with increased severity of Coronary Artery Disease (4)
· TRT decreases obesity (6)
· TRT improves cholesterol levels (3)
· TRT improves glycemic control 6)
· TRT decreases markers of inflammation (8)
In the largest testosterone study to date, The Testosterone Trials (T-Trials), the risk of cardiovascular events ( such as a heart attack) is no different between men treated with testosterone or men not treated with testosterone.
What do the American Urologic Association Guidelines say about Testosterone Therapy risk and Heart Attack?
The American Urologic Association (AUA) identifies and has confirmed the following:
1) Low Testosterone is a risk factor for cardiovascular events. This includes heart attack, strokes and premature death.
2) There is no robust evidence to demonstrate that testosterone replacement therapy increases or decreases cardiovascular events while on testosterone therapy.
3) It is recommended that testosterone replacement therapy (TRT) not be prescribed to a man within 3-6 months of the occurrence of a cardiovascular event.
4) Intramuscular testosterone injection therapy can cause polycythemia. Current evidence does not link testosterone replacement therapy to an increased risk of venothromboembolic events (VTE).
5) Since the FDA testosterone label changes, 4 large observations studies have been published that show no increased risk of VTE with patients on testosterone therapy.
AUA 2018 Guidelines
· Clinicians should inform testosterone deficient patients that low testosterone is a risk factor for cardiovascular disease
· Prior to initiating treatment clinicians should counsel patients that, at this time, it cannot be stated definitively whether testosterone therapy increases or decreases the risk of cardiovascular events.
· Testosterone therapy should not be commenced for a period of three to six weeks in patients with a history of cardiovascular events.
Endocrine 2018 Guidelines
· We recommend against testosterone therapy in men with … heart failure, Myocardial infarction or stroke within at least 6 months (low quality of evidence)
· …there is no conclusive evidence that Testosterone supplementation is associated with increased cardiovascular risk in hypogonal men.
· Thus, there are insufficient data to establish a causal link between Testosterone therapy and cardiovascular events.
As It stands with our current literature and research, there can be no definitive statement if testosterone therapy increases or decreases the risk of a heart attack.
However, there is robust data from several clinical trials to state the following:
1) Low Testosterone is a risk factor for cardiovascular events such as a heart attack.
2) Testosterone therapy can improve the risk factors associated with heart attacks and cardiovascular events such as improving glycemic control, obesity and weight loss, cholesterol, reducing metabolic syndrome.
3) No current studies prove that testosterone replacement therapy will cause a heart attack or stroke.
If I have been prescribed testosterone replacement therapy should I stop?
If you are currently being prescribed testosterone replacement therapy and are under the care of a Urologist, there is no clear indication for you to stop therapy as a result of the current information. If you have an increased risk of heart disease such as a family history of heart disease or have medical conditions such as high blood pressure, high cholesterol or diabetes, discussing with your doctor the benefits of testosterone replacement therapy can be useful to optimize your health and safety.
Is testosterone replacement therapy safe?
All medical therapies have a risk. When a physician considers starting a patient on any therapy, a physician must ensure the benefits out way the risks. Pertaining to testosterone replacement therapy, testosterone administration is a safe medication if given under the guidance and monitoring of a trained urologic physician. Testosterone replacement risks include a rise in hemoglobin and hematocrit levels, rise in prostate specific antigen, gynecomastia, lower extremity swelling, acne, reduction in sperm production and possible reduction in testicular size. While the following risks are all reversible with cessation of testosterone administration, understanding these risks before undergoing therapy will help optimize therapy outcomes and mitigate risks.
Will I get prostate cancer if I take testosterone replacement therapy?
No. Testosterone replacement therapy does not increase the risk or cause the development of prostate cancer. While it was thought years ago that that prostate cancer could be caused by giving someone testosterone replacement, several clinical studies have proven this hypothesis to be false. There is no level one evidence that supports shows testosterone replacement causes or increases the risk of prostate cancer. On the contrary, there is supporting evidence that men who have low testosterone and an elevated PSA are at an increased risk of having a higher grade or more aggressive form of prostate cancer.
If a man currently has prostate or received prostate cancer and is now cancer free but also has a low testosterone level with associated symptoms, meeting with a urologist discuss the risk and benefits of testosterone replacement therapy would be advised.