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Testosterone Replacement Therapy

Testosterone replacement therapy comes in forms such as gels, patches, pellets and injections. While the FDA has approved some of these treatments, the products can pose serious health risks like heart problems and blood clots.

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Testosterone replacement therapy (TRT), also known as androgen replacement therapy, is an FDA-approved medical treatment for men of any age who have low testosterone, a hormone necessary for male sexual development. Some of the more popular brand names of TRTs include AndroGel, AndroDerm, Testim and Axiron.

FDA-approved testosterone products are approved for men with low testosterone who have an associated medical condition. Use of testosterone products by men with normal levels of testosterone can be very risky. Additionally, some testosterone products have undergone recalls.

Studies have shown that nearly a quarter of men prescribed testosterone do not have their levels tested. Many men have received testosterone prescriptions for “lifestyle” reasons, which goes against physician guidelines. Testosterone treatments should only be used under a doctor’s supervision to raise testosterone to normal levels.

An enormous industry has sprung up to capitalize on the alleged low testosterone problem, and has contributed to a potentially dangerous rise in the unregulated sale and use of testosterone supplements. Also, the government does not regulate the sale or use of products containing compounds that get converted into testosterone. Testosterone precursors should only be used under a doctor’s supervision.

Testosterone Replacement Therapy Benefits

Appropriately prescribed testosterone may be advantageous for some men. Studies have indicated that TRT may offer a wide range of benefits for men with hypogonadism, including the following:

  • Improved libido (interest in sex), mood and cognition (mental ability)
  • Increased muscle mass
  • Greater bone density to help prevent osteoporosis
  • Higher red blood cell production

The value each person receives from testosterone treatments may differ on a case by case basis.

Types of Testosterone Replacement Therapy

FDA-approved testosterone formulations include:

  • Topical gel applied to the skin, usually on the upper arms or shoulders

  • Transdermal patch, also applied to the skin

  • Buccal system attached to the upper gum or inner cheek

  • Subcutaneous pellets inserted beneath the skin

  • Injection

Adverse Events Linked to TRT

FDA officials have expressed concern over recent studies that show possible adverse results associated with testosterone replacement therapy.

Recent studies
A 2010 trial of 209 men over 65 years of age with low testosterone levels hinted at an increased risk of cardiovascular adverse events in the treatment group, and the safety board monitoring the trial halted it due to the health dangers. 1
Another trial, published in the Journal of the American Medical Association, found that testosterone therapy given to veterans at medical centers run by the U.S. Department of Veterans Affairs was associated with increased risk of heart attack, stroke, death and other potentially harmful effects. 2
In 2013, a meta-analysis published in BMC Medicine reviewed 27 trials of older men. Testosterone therapy was found to increase the risk of a cardiovascular-related event. 3
A 2014 study of more than 55,000 men observed that both older men and younger men with pre-existing diagnosed heart disease have a higher risk of a heart attack following the start of testosterone therapy. 4

This study, funded by the National Institutes of Health, suggested that men aged 65 years and older were twice as likely to have a heart attack after taking testosterone treatment therapy drugs. 5

A 2015 study involving more than 150,000 men uncovered compelling evidence of a connection between first-time testosterone use and elevated risk of myocardial infarction, according to the journal Pharmacotherapy. 6

The investigators who conducted the study concluded that, until more is known about this link between testosterone replacement therapy and myocardial infarction, the only men who should be taking this product are those with “clinically symptomatic and biochemically proven” hypogonadism. 6

However, even with the results of these studies, more research is needed to understand the long-term effects of testosterone replacement therapy. Some investigations into the safety of TRT have revealed conflicting results, and researchers have advocated for both observational studies and large-scale randomized clinical trials to further examine potentially adverse effects of TRT.

Blood Clot Risks

The risk of venous blood clots is included in the labeling of testosterone products as a possible consequence of polycythemia (increase in red blood cells).

But, due to reports of venous blood clots unrelated to polycythemia, as of June 19, 2014, the FDA is requiring testosterone manufacturers to include a general warning in the drug labeling of all approved testosterone products about the risk of venous thromboembolism (VTE) which is blood clots in the veins: deep vein thrombosis (DVT) and pulmonary embolism (PE).

Alternatives to Testosterone Replacement Therapy

Men who lack energy should first see their doctor and ask about screening for stress, depression, and other conditions—such as thyroid disease or B12 deficiency—that could also be the cause. In some cases, medical or psychological treatment for other conditions can help raise testosterone levels.

Other alternatives to testosterone replacement therapy
Exercise Moderate exercise can raise testosterone levels to some degree. However, it is important to know that extreme exercise can actually reduce testosterone levels.
Varicocele surgery Swollen veins (varicoceles) in the scrotum can cause pain, reduce male fertility and lower testosterone. Correcting a varicocele could help increase testosterone levels.
Weight loss Extra fat on the body, especially around the abdomen, can act like a sponge, taking testosterone out of the blood. Losing weight may help keep testosterone available in the bloodstream.
Clomiphene Citrate (Clomid) and human chorionic gonadotropin (HCG) Both of these treatments can boost testosterone levels indirectly and help avoid some of the side effects of TRT.

Men who suspect they may have low testosterone should consult with their doctors before attempting any of these or other alternatives to testosterone treatment therapy.

In 2013, an investigative article published by the New York Times claimed that advertising by large pharmaceutical companies “promotes excessive and inappropriate” use of testosterone treatments and other drugs, which could lead to potentially dangerous side effects.

Controversy about Low Testosterone Levels

There is some debate among medical professionals about what level of testosterone is considered “low” in older men. Furthermore, some professionals believe that there is not enough evidence to advise the use of testosterone treatment therapy, and at least one review has asserted that there are few properly controlled studies on such treatments for men regardless of age. Also, symptoms of low testosterone are sometimes indistinguishable from symptoms of other medical problems or conditions. 7

In 2013, an investigative article published by the New York Times claimed that advertising by large pharmaceutical companies “promotes excessive and inappropriate” use of testosterone treatments and other drugs, which could lead to potentially dangerous side effects. 8 Such advertising may also drive men to seek out expensive drugs and treatments. In this vein, in 2013 the U.S. Supreme Court ruled that the Federal Trade Commission could sue pharmaceutical companies that prevent development of cheaper generic versions of their drugs, including testosterone therapy treatments like AndroGel. 9

Recalls of Testosterone Products

Although the FDA has not yet issued any recalls of testosterone due to potentially lethal heart attacks, strokes, or sudden death, a number of testosterone products have been recalled for various reasons, many relating to potential contamination or other impurities in the medications. In 2013 alone, at least five compounding pharmacies announced recalls for batches of their testosterone products.

  1. Basaria S. et al. Adverse events associated with testosterone administration. (July 8, 2010). New England Journal of Medicine. Accessed on July 28, 2014.
  2. Vigen R. et al. from https://jamanetwork.com/journals/jama/fullarticle/1764051
  3. Xu L. et al. Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. BMC Medicine. (April 18, 2013). Accessed July 29, 2014.
  4. Finkle W. D., et al. Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men. (January 29, 2014). PLoS ONE. Accessed July 29, 2014. 
  5. O’Connor, Anahad. New Concern About Testosterone and Heart Risks. (Jan. 29, 2014). New York Times: Well Blog. Accessed July 25, 2014.
  6. Etminan M., et al,, Testosterone Therapy and Risk of Myocardial Infarction: A Pharmacoepidemiologic Study, http://onlinelibrary.wiley.com/doi/10.1002/phar.1534/full 35 Pharmacotherapy 72-78 Accessed January 2015.
  7. Swerdloff, Ronald and Christina Wang. Testosterone Treatment of Older Men—Why Are Controversies Created? (Jan. 2011) Accessed July 25, 2014. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3038475/
  8. Rosenthal, Elisabeth. A Push to Sell Testosterone Gels Troubles Doctors. (Oct. 15, 2013). New York Times. Accessed July 25, 2014. http://www.nytimes.com/2013/10/16/us/a-push-to-sell-testosterone-gels-troubles-doctors.html?pagewanted=all&_r=0
  9. Hurley, Lawrence and Diane Bartz. Supreme court says FTC can sue over deals that delay generic drug sales. (June 17, 2013). Reuters. Accessed July 25, 2014. http://www.reuters.com/article/2013/06/17/us-usa-court-drugs-idUSBRE95G0JM20130617