NCHR Testimony at the FDA Joint Meeting for Bone, Reproductive and Urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee

Good afternoon. My name is Paul Brown. I am testifying on behalf of the National Center for Health Research. Our non-profit research center conducts research and evaluates scientific and medical data so that we can provide objective health information to patients, providers and policy makers. Our president is on the Board of Directors of two non-profit organizations dedicated to providing scientific resources to the FDA.  Our organization does not accept funding from drug companies, and therefore I have no conflicts of interest.

From 2010 to 2013, the number of patients receiving testosterone prescriptions increased from 1.3 million to 2.3 million.[1]  That means a large and growing number of patients may be at-risk for major adverse events due to TRT.   At the same time, it is not clear what percentage of the men taking TRT actually need it for medical reasons.

In the “Topics for Discussion,” I am addressing question 2—whether the data indicates a cardiovascular safety signal associated with the use of testosterone therapy.  The topic covers four issues:

Signal Strength

Three studies have shown evidence for cardiovascular safety signals associated with TRT: The 2014 cohort study by Finkle,[2] the 2013 meta-analysis by Xu[3] [pronounced Shoe] and the 2010 randomized, placebo-controlled trial by Basaria.[4]

In the Basaria, study cardiovascular adverse events were statistically significant after adjusting for age and baseline cardiovascular risk factors, as Dr. Carome pointed out.  It would therefore be inappropriate to assume they happened by chance.

Biological Plausibility Of the Signal

The link between TRT and CV adverse events makes sense biologically, including increased blood viscosity, increased micro-viscosity of red blood cells (which could impair their motion in blood capillaries) and decreased levels of the good cholesterol—HDL.

The Signal Should Apply To All Users

Although data suggest that older men and men with a history of heart disease may be at greatest risk for cardiovascular events from TRT, there are not enough data to conclude that those are the only men at risk.  Having warnings only for older men and men with a history of heart disease will give other TRT patients a false sense of safety.

Adverse Events Warrant Those Warnings On Labels

FDA recently required all testosterone product labels to include a warning about the risk of blood clots. The same processes that place men at risk for blood clots are likely to contribute to the increased risk of adverse cardiovascular events due to TRT. FDA should be consistent with its label warnings and include them for both blood clots and cardiovascular events for all populations that use TRT.


In its August 12, 2014 memorandum, FDA reviewers stated, “the uncertainty around important factors leading to the use of TRT and the association of testosterone level with CV risk are difficult to assess.”1

FDA reviewers have also stated that available data do “not provide conclusive evidence of a causal association between testosterone therapy and [cardiovascular] events.”1 The evidence may not be conclusive but it certainly is substantial.  These products are already on the market and weren’t adequately tested for safety BEFORE FDA granted approval.  The FDA should now be more cautious and provide these potentially life-saving warnings to the millions of patients using TRT.  Therefore, the FDA should include cardiovascular risk information in testosterone product labels for all populations.

  2. PLoS One. 9(1):e85805. doi:10.1371/journal.pone.0085805.
  3. Testosterone therapy and cardiovascular events among men: A systematic review and meta-analysis of placebo-controlled trials. BMC Medicine
  4. Adverse events associated with testosterone administration. N Engl J Med. 363(2):109-122.