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Rates of testosterone replacement therapy (TRT) prescriptions have increased markedly in recent years, with global testosterone sales growing twelvefold from 2000 to 2011. Higher growth rates have been seen in the United States and Canada than in other Western countries. 1
Detrimental Effects for Unapproved Uses
Even though testosterone treatment is increasingly promoted by direct-to-consumer advertising, the FDA has only approved TRT for men who physiologically produce no or low amounts of testosterone, citing concerns about detrimental effects in people who do not need the therapy.
In addition, reports have indicated that children who come into contact with someone taking a topical testosterone therapy drug could be harmed, and all testosterone products carry black box warnings, the highest warning that can be given to a drug, in their labeling regarding the risks accompanying secondary exposure. 2
FDA Alerts Regarding Cardiovascular Events and Death
On January 31, 2014, based on studies that suggested an increased risk of cardiovascular events among groups of men who were prescribed testosterone therapy, the FDA issued a safety alert regarding an investigation into the risk of stroke, heart attack and death in men taking testosterone supplements. The agency has stated it will continue to monitor risks related to TRT. However, long-term effects are still unknown.
The alert also advises doctors and other medical professionals to take the risks and benefits of FDA-approved testosterone treatment under consideration before writing any prescriptions. Furthermore, patients should be sure to read drug labels and follow the medication directions accordingly. 3
On March 3, 2015, the FDA made publicly available an update about this Safety Communication. FDA requirements include a label change for all manufacturers regarding “the possible increased risk of heart attacks and strokes associated with testosterone use.” The FDA also advises for healthcare professionals to discuss this possibility with their patients when the medication is prescribed.
Heart Attack and Stroke Risks Related to Testosterone
The general consensus from this meeting regarding cardiovascular safety is that need for additional studies is critical and that the potential signal for cardiovascular risk should be added to approved prescription testosterone labeling.
The FDA states that a well-designed clinical trial needs to be conducted by approved prescription testosterone manufacturers to better determine if there is an increased risk of heart attack or stroke for testosterone product users. The FDA also states that the “benefit and safety of these medications have not been established for the treatment of low testosterone levels due to aging, even if a man’s symptoms seem related to low testosterone.” 4
This updated Safety Communication was issued after the FDA held a joint meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee on September 17, 2014 in Hyattsville, Maryland, in order to “discuss the appropriate indicated population for testosterone replacement therapy and the potential for adverse cardiovascular outcomes associated with this use.” The general consensus from this meeting regarding cardiovascular safety is that need for additional studies is critical and that the potential signal for cardiovascular risk should be added to approved prescription testosterone labeling. 5
The FDA has also recently made public that it will be holding a joint meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee on September 17, 2014 in Hyattsville, Maryland, in order to “discuss the appropriate indicated population for testosterone replacement therapy and the potential for adverse cardiovascular outcomes associated with this use.” This meeting is open to the public and has time designated for approved members of the public who petition the FDA in writing for time to speak to voice their concerns regarding these issues.
Contamination and Testosterone Recalls
The nationwide recall included 21 testosterone products.
Although the FDA has not issued any recalls for testosterone due to the increased risks of heart attacks, strokes and even death, various compounding pharmacies have recalled testosterone products for other reasons.
In September 2013, University Compounding Pharmacy issued a recall of selected batches of testosterone that had been sent to pharmacies and consumers earlier in the year. Although the recall was voluntary, the company announced it only after the FDA had discovered a third-party company was improperly testing batches of testosterone, leading to the possibility of contamination. 6
In May 2013, Main Street Family Pharmacy, LLC, recalled a long list of drugs suspected of being contaminated after several reported cases of skin abscesses were discovered in patients using the drugs. The company stated in its press release that use of contaminated drugs could result in serious infections. The nationwide recall included 21 testosterone products. 7
Pallimed Pharmacy issued a recall in March 2013 of sterilized products distributed in January of the same year, including several testosterone supplies. According to the company press release, the FDA and the Massachusetts Board of Registration in Pharmacy found particulates that could potentially damage or clog blood vessels, trigger allergic reactions or induce tissue responses. 8
Handelsman, Daniel J. Global trends in testosterone prescribing, 2000–2011: expanding the spectrum of prescription drug misuse. (Aug. 4 2013). Accessed on July 28, 2014. ↩
U.S. Food and Drug Administration. Safety Concerns about Testosterone Gel. (Updated Dec. 7, 2013). Accessed July 28, 2014. ↩
U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA evaluating risk of stroke, heart attack and death with FDA-approved testosterone products. (Jan. 31, 2014). Accessed July 28, 2014. ↩
U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA cautions about using testosterone products for low testosterone due to aging; requires labeling change to inform of possible increased risk of heart attack and stroke with use. (March 3, 2015). Accessed March 4, 2015 ↩
Food and Drug Administration Center for Drug Evaluation and Research Summary Minutes of the Joint Meeting of the Bone, Reproductive and urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee September 17, 2014. ↩
University Compounding Pharmacy. University Compounding Pharmacy Initiates a Nationwide Voluntary Recall of Certain Pharmacy Products due to Lack of Assurance of Sterility Concerns. (September 6, 2013). FDA.gov. Accessed July 28, 2014. ↩
Main Street Family Pharmacy, LLC. Main Street Family Pharmacy, LLC Issues Voluntary Nationwide Recall of All Sterile Compounded Products. (May 28, 2013). FDA.gov. Accessed July 28, 2014. ↩
Pallimed Solutions, Inc. Pallimed Solutions, Inc. Announces Voluntary Nationwide Recall of All Sterile Compounded Products Dispensed Since January 1, 2013 Due to Possible Filament Contamination. (March 25, 2013) FDA.gov. Accessed July 28, 2014. ↩
Medaus Pharmacy. Medaus Pharmacy Initiates a Nationwide Recall of Certain Pharmacy Products due to Questions Surrounding an Independent Third Party’s Sterility Testing. (Sept. 4, 2013). FDA.gov. Accessed July 28, 2014. ↩
Park Compounding. Park Compounding: Sterile Medication Recall – Concerns of Sterility Assurance at Testing Vendor. (Sept. 10, 2013). FDA.gov. Accessed July 28, 2014. ↩