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 recently appeared in PLOS One.*

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 of symptoms.

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 study recently reported a study of the risk of acute non-fatal myocardial infarction (MI) following an initial TT prescription (N = 55,593) in a large health-care database. We compared the incidence rate of MI in the 90 days following the initial prescription (post-prescription interval) with the rate in the one year prior to the initial prescription (pre-prescription interval) (post/pre).
The results of this study in all subjects revealed the rate ratio (RR) for TT prescription was 1.36. In men aged 65 years and older, the RR was 2.19 for TT prescription. The RR for TT prescription increased with age from 0.95 for men under age 55 years to 3.43 for those aged ≥75 years. In men under age 65 years, excess risk was confined to those with a prior history of heart disease.
The study summary stated that in older men, and in younger men with pre-existing diagnosed heart disease, the risk of MI following initiation of TT prescription is substantially increased.

Some comments about the study:

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.

There is no documentation as to whether or not Endocrine Association guidelines were followed, including morning testosterone level assessments and repeating the test at least once.

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 is associated with an increased risk of heart attack, stroke, and death.

Finally, the International Consultation in Sexual Medicine (J Sex Med 2010;7:1608) concluded that:
• Low endogenous testosterone levels correlate with an increased risk for adverse cardiovascular events
• High endogenous testosterone levels appear to be beneficially associated with decrease mortality due to all causes, including cardiovascular disease and cancer
• Testosterone supplementation in men is relatively safe in terms of cardiovascular health
• Testosterone use in men with low testosterone leads to inconsequential changes in blood pressure, glycemic control and all lipid fractions.
Bottom Line: Low testosterone levels are associated with increased atherosclerosis. Most studies confirm that administration of testosterone to men has neutral effects on cardiovascular risk factors and cardiac events. For men with a history of heart disease, a careful discussion between the doctor and patient should take place.

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