In 2010, the FDA's Division of Reproductive and Urologic Products (now the Division of Bone, Reproductive and Urologic Products) (DBRUP) opened a Tracked Safety Issue (TSI) beginning a review of the safety of testosterone replacement therapy products. The safety review was initiated because a clinical trial was stopped early due to an issue with disproportionate cardiovascular-related adverse events among those taking TRT versus those taking a placebo. After conducting a review of existing medical literature and weighing all available evidence, the FDA closed the TSI citing insufficient evidence of cardiovascular risk of adverse associated with testosterone replacement therapy to warrant regulatory action.
In December 2013, the FDA reopened the TSI after the publication of the Vigen Study reporting an increase of adverse cardiovascular events associated with testosterone therapy. This was followed by another study published in January 2014 reporting an increased risk of non-fatal heart attacks in men who used testosterone replacement therapy. In addition, a meta-analysis, or study that analyzes the results of several studies, also published in December 2013 reported that testosterone therapy was associated with an increased risk of adverse cardiovascular events. Following the publication of these studies, on January 31, 2014, the FDA released a Drug Safety Communication stating it was investigating the risk of stroke, heart attack and death in men taking FDA-approved testosterone products.
On September 17, 2014, the FDA convened an advisory committee meeting to discuss two controversial issues with testosterone replacement therapy: (1) The appropriate indicated population for testosterone replacement therapy; and (2) The potential for adverse cardiovascular outcomes associated with use of TRT. The panel also voted on two questions: (1) Should the FDA revise the current label for testosterone therapy; and (2) Should the FDA require manufacturers of testosterone products to conduct a study to further assess a potential cardiovascular risk with the use of testosterone therapy.
The panel voted overwhelmingly in favor of changing the label and requiring the industry to conduct a study. The panel advised narrowing the set of indicators for use in the label to distinguish classic hypogonadism, such as pituitary disease, from hypogonadism due to old age. Results are expected from a multicenter study of seven coordinated randomized trials conducted by Dr. Peter J. Snyder at the University of Pennsylvania as well as several industry trials by mid-2015.