As their natural production of testosterone (T) declines millions of American men have discovered the health benefits of replacing it with a prescription supplement. Testosterone replacement therapy (TRT) is booming, in part due to increased awareness, but also television commercials by drug companies aggressively hawking their TRT products. But, one study has suggested that TRT might increase the risk of heart disease. Do men taking TRT need to be concerned?
Results published in the Journal of the American Medical Association, by lead author Rebecca Vigen, MD, et al, showed that among men in the VA hospital system given TRT there was a 30% increased risk of heart disease during a 3 year follow up period. In this retrospective study, researchers focused on 8,709 men who had cardiac angiograms for various reasons, and 1,223 of the men who were later put on TRT were compared to 7,486 men who did not take TRT.
The men received TRT by injection, topical cream or topical patch. There was no indication that any consistent T level was established or monitored. The men who chose TRT were not randomized in a double-blind fashion, but were put on TRT based on a subjective decision by the patient and prescribing doctor.
Healthy aging men will have a predictable decline in the male sex hormone, testosterone, leading to decreased energy and fatigue, weight gain, loss of muscle mass, and loss of sex drive or erectile function. They will also have increasing risk for heart disease, diabetes, osteoporosis and dementia.
Men can supplement their hormones, just like women. The decline in male hormones is called andropause, with a decline in hormones similar to menopause in women, but it occurs over 10-15 years instead of the few years it takes for menopause.
Men don’t usually have hot flashes or night sweats and unlike the mood swings noted with the wildly fluctuating hormone levels during menopause, men tend to just get more and more apathetic, with decreasing motivation, security, and confidence. Feeling so blah causes many men to feel anxious or depressed.
T normally breaks down in the body to two main byproducts, estrogen (E) and di-hydro-testosterone (DHT). We know from observational studies that as men age and their T levels drop, sometimes either E or DHT will rise dramatically. With high DHT levels we observe a higher risk for enlarged prostate. With high E levels we observe men having increased risk for heart disease as well as prostate cancer.
The first issue I have with the study is that E and DHT levels were not measured. We always measure these byproducts and if either one becomes elevated we give enzyme inhibitors to block the conversion of T to the byproduct. In the case of high E, we know it is associated with more heart disease. This might be the main reason for increased heart disease in the men taking TRT.
Second, the men in the study were older, and most of them already had existing heart disease. We know from studies on women that estrogen replacement therapy (ERT) will prevent heart disease if started early before artery plaque has started, yet will agitate existing artery plaque. Thus it matters a great deal when the ERT is started. It may be TRT increases risk of heart disease only in men with existing heart disease when TRT is started.
Before starting women on ERT, if they have not been on hormones for more than 5 years or so, we always scan the arteries to check for plaque. If there is no plaque we start ERT. If there is plaque, we examine the causes thoroughly, then treat and stabilize the plaque prior to starting ERT.
I can only speculate, but I wonder if there is a similar, as yet unstudied, pattern in men such that TRT may prevent plaque, yet agitate existing unstable plaque. There was a similar study a few years ago done in a nursing home setting that showed increased risk of heart disease in men taking TRT. Again, these were much older men, many with pre-existing heart disease.
This is an area that deserves more specific research – does it matter when TRT is started, before artery disease is present, and does controlling E byproduct levels lower the risk of worsening heart disease.
Should Men Supplement T ?
TRT is a well-established science and there are hundreds of studies documenting the safety and effectiveness of TRT. Some of the largest studies simply observe that men who are low in testosterone have about a 50% increased death rate over the subsequent decade when compared to the same age men with normal testosterone levels.
There are also numerous studies showing TRT will help reduce the risk of getting diabetes, osteoporosis, and dementia, while TRT has also been shown to improve these conditions.
TRT helps maintain muscle mass, energy and stamina. It helps prevent frailty and the build up of fat, especially around the belly. It helps with sex drive and erectile function. It helps us build strong bones. It improves cognition and mood, especially abstract and spatial skills such as reading a map, coordination and balance, and motor control.
So where are we with TRT and the heart? Is this something men should be concerned about? There are numerous studies which show low T is associated with increased risk of heart disease, and that TRT will decrease the risk of heart disease.
According to one author, “it is becoming increasingly evident that the low serum levels of testosterone experienced by aging men are associated with increased all-cause mortality from heart disease and other vascular disorders. Achieving a normal physiological testosterone concentration through the administration of testosterone therapy has been shown to provide beneficial effects on the pathophysiological markers and clinical symptoms of heart disease” (Jones, Atherosclerosis, 2009).
A large European study examined over 11,000 men and found “in men, endogenous testosterone concentrations are inversely related to mortality due to cardiovascular disease and all causes. Low testosterone may be a predictive marker for those at high risk of cardiovascular disease” (Khaw, Circulation, 2007).
A recent French study found the extremes of both low and high T levels are associated with increased rates of heart disease (Soisson, Maturitas, 2013). I think this underscores the need for close monitoring of T levels in men taking TRT in order to insure the correct dose is being administered.
In summary, I think the study by Dr Vigen, et al, is a marginal study that raises some serious questions about the safety of TRT in relation to heart disease. It seems clear that in older men with existing heart disease there may be an increased risk to TRT, at least when administered and monitored as it was in this study. Many questions remain as to whether monitoring and treatment of high levels of E and DHT would lower the risk of heart disease, or whether there is a difference in starting TRT in younger men without pre-existing heart disease.
Scott Rollins, MD, is Board Certified with the American Board of Family Practice and the American Board of Anti-Aging and Regenerative Medicine. He specializes in bioidentical hormone replacement for men and women, thyroid and adrenal disorders, fibromyalgia and other complex medical conditions. He is founder and medical director of the Integrative Medicine Center of Western Colorado (www.imcwc.com) and Bellezza Laser Aesthetics (www.bellezzalaser.com). Call (970) 245-6911 for an appointment or more information.