Testosterone and Heart Disease - Facts & Caveats
I have received numerous calls from men who have symptoms of low
testosterone, a documented decrease in their serum testosterone level, and who are receiving
testosterone replacement therapy regarding a study that appeared in a reputable medical journal
stating that treatment with testosterone increases the risk of heart disease. (JAMA.
Let's look at some facts. The human body is always
trying to achieve homeostasis which is defined as "the
ability or tendency of an organism or cell to maintain
internal equilibrium by adjusting its physiological
processes." What does this mean? It means that the
body is always trying to stay normal without deviations
from the norm. For example, if a man drinks too much
water, the kidneys will increase the excretion of water. If
a man is dehydrated, the kidneys will try and conserve
water to prevent the problems associated with
dehydration. If a man has diabetes, the doctor will
recommend a treatment to lower the blood sugar. If a man has high blood pressure, the doctor will recommend dietary changes, exercise, and perhaps
medication to lower the blood pressure. If a man has anemia or a low blood count because of iron
deficiency, the doctor will prescribe iron supplements. If a man has a deficiency in vitamin D, the
doctor will recommend increasing the consumption of this necessary vitamin. These actions are
what we do every day; we attempt to achieve a normal equilibrium in the body as this is the best
way to restore and maintain health. This same reasoning applies to men
who are deficient in testosterone. Testosterone is a necessary hormone
produced in the testicles that is responsible for a man's sex drive, muscle
mass, energy level, bone strength, and even a man's mood which may
cause depression if the hormone is low and not returned to normal. The
unstudied/published issue is what is the target value? Most experts feel that
there is no absolute "correct" value, but rather treatment is targeted at relief
There are more than 13 million men in the United States who reportedly suffer from testosterone deficiency. For men who receive treatment, they
usually report significant improvement in their symptoms. There are many
conflicting reports about testosterone and heart disease. There are even studies that support that
low testosterone increases the risk of heart disease and that treating the deficiency with hormone
replacement therapy may be protective of heart disease.
The list below outlines numerous comments about the Journal of the American Medical
Association (AMA) study in question:
Of the nearly 7,500 men who did not get extra T, about 1 in 5 had adverse cardiovascular
outcomes, including stroke, heart attack, or death. In the more than 1,200 men who got
testosterone, nearly 1 in 4 had those significant problems, with an increased risk of these
problems by nearly 30 percent. A well-powered scientific study has a similar number of study
patients in each group, not 7,500 of control group and 1,200 in the experimental group as is
present in this recent JAMA article. The researchers concluded that taking testosterone came
with an increased risk of an adverse outcome.
No follow-up or research was done on whether or not the men on testosterone therapy
achieved therapeutic levels or if they stayed on treatment. It is not accurate to assume that
all men treated had their testosterone levels elevated by therapy.
Very few of the patients studied were placed on 1.1% Testosterone gel (which is the most
common form of treatment in men under the age of 60 - they used an old formula for
Androgel that was not very effective in raising testosterone levels and led to the
re-formulization of the product). 35.7% of the men were on injection therapy which is
associated with spikes in testosterone levels in excess of over a 1,000 ng/dL as well as
nadirs below normal levels. The remaining patients were on the patch product, Androderm,
which is rarely used in private practice and also is shown to be poorly tolerated, rarely
prescribed, and minimally changed testosterone levels. Although there was no difference in
the results in any of these three therapeutic groups, there is no documentation as to whether
or not therapeutic levels were obtained and maintained for the period of the study.
There is no documentation as to whether or not Endrocrine Association guidelines were
followed, including morning testosterone level assessments and repeating the test at least
There is no way of knowing if the "untreated group" received testosterone therapy outside of
the VA hospital system.
Dr. Anne Cappola of the Perelman School of Medicine at the University of Pennsylvania
wrote in an accompanying editorial: "The most important question is the generalizability of
the results of this study to the broader population of men taking testosterone." The take
home message is that it is not possible to generalize from this study to the entire population
of men, some of whom may have had a low testosterone level.
This is a very big caveat: By definition, all the men in the study were older than 60 and all
had heart problems. It's still not clear whether those same risks apply to younger healthier
"These were sick, older veterans," Dr. Michael Ho, a cardiologist with the VA Eastern
Colorado Health Care System who helped direct the study, said in an interview. "Many were
obese, had diabetes and other ailments", he said. Obese men with diabetes and other
co-morbid conditions are certainly independently at higher risk for heart disease, stroke, and
I feel the Low T Centers and their advertisements for restoring youth, vigor and sexuality are
misleading, and not the standard of care for testosterone replacement therapy. At these centers,
Depo injections are given on a 7-10 day basis along with office visits and frequent in office testing of
testosterone and PSA. For my patients on injection therapy (primarily because of cost) we instruct
them on how to do the Depo injections at home and see them on an every 3 month basis to monitor
their levels, saving both the patients and the insurance companies significant amounts of money.
Additionally, we feel that the blood tests that these centers use are are not very reliable and are
technologies that were state-of-the-art 7-10 years ago.
In closing, a larger study in the Journal of Clinical Endocrinology and Metabolism showed that
among male veterans over 40, those on testosterone had lower rates of death than those that did
not. This certainly makes sense, since hypogonadism is associated with metabolic syndrome,
which, as you are aware, is associated with an increased risk of heart attack, stroke, and death.
Dr. Ken Goldberg
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