Is testosterone therapy safe for you? New data has emerged regarding the potential risks of testosterone replacement therapy (TRT). Because of the issues recently raised by two new studies, on January 31, 2014, the FDA announced plans for a reassessment of the risks and safety issues related to TRT. The FDA advised doctors to “consider whether the benefits of FDA-approved testosterone treatment is likely to exceed the potential risks of treatment.” They have not, however, urged patients to discontinue therapy without discussing concerns with their physician.
Two recent and separate studies have suggested an increased risk of cardiovascular events that prompted the review from the FDA. The most recent study was published online January 29, 2014 in PLoS One. This study compiled data from the medical records of almost 56,000 men who had been given TRT from across the country and about 48,000 were under the age of 65. These were men reported as starting new prescriptions for TRT. The nearly 56,000 men were compared to just over 167,000 that filled prescriptions for either Tadalafil (Cialis) and sildenafil (Viagra). They did not report any increased risk of MI before or after filling the prescriptions for the above mentioned ED meds (Viagra and Cialis).
In this most recent study, for all men over the age of 65 using TRT, the risk of heart attack d(MI) was just over twofold higher in the first 90 days of using the medication. The investigators separated the men younger than 65 years of age into two groups, those with and those without a prior known history of coronary heart disease. In men younger than 65 without a history of existing coronary heart disease, there was not a correlation of increased risk of new cardiac events (MI). However, in the men younger than 65 with an existing history of cardiac disease, the use of TRT was associated with an approximate twofold increased risk of MI. When they continued to follow the men for another 90 days, the risk appeared to decline back to the level it was at the start for the men who did not refill the script.
This study raised the level of concern — that the use of TRT may raise the risk of future events (MI) particularly during the first 90 days — for all men with known cardiovascular disease. This increased risk of MI was also seen in men over the age of 65 even without a known history of cardiac disease.
Experts and the FDA are now debating the various issues raised in this and prior studies regarding TRT. Is TRT safe for use in men with a history of heart disease? What is the potential importance of the first 90 days of therapy? If there is a correlation between the use of TRT and increased cardiac events, could this in fact be related to increased levels of estrogen in men? A portion of testosterone is in fact broken down to a form of estrogen called 17-beta estradiol. Increased estrogen—which has been linked to blood clots in both men and women, could be a factor in this current study researchers have pointed out. Testosterone may also change certain factors related to the clotting of blood which could further increase the risk of MI.
Experts are also pointing to numerous other studies that have shown a significant link with low levels of circulating testosterone and increased cardiac risk and even an increased risk of mortality. Low levels of testosterone have been also linked to a variety of diseases, conditions and symptoms to include metabolic syndrome, fatigue, muscle wasting, depression, increased fat deposition, osteoporosis, cognitive decline as well as a myriad of issues related to sexual dysfunction.
This debate is complex and will take considerable time and more studies to determine the best course of action for many men. The FDA has not disclosed how long before it will provide more guidance for physicians. In the interim, it is increasingly important that patients considering TRT have an informed discussion with their physician regarding the risks and benefits of therapy. Men should seek guidance from physicians with particular knowledge and experience in evaluation and treatment of low testosterone. This appears particularly critical for patients over the age of 65 and younger patients with an existing heart history.