FDA testosterone alert

here is the Jan 31 FDA alert about testosterone (also see link: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm384225.htm):

AUDIENCE: Cardiology, Urology, Family Practice

ISSUE: FDA is investigating the risk of stroke, heart attack, and death in men taking FDA-approved testosterone products. We have been monitoring this risk and decided to reassess this safety issue based on the recent publication of two separate studies that each suggested an increased risk of cardiovascular events among groups of men prescribed testosterone therapy. FDA is providing this alert while it continues to evaluate the information from these studies and other available data. FDA will communicate final conclusions and recommendations when the evaluation is complete.

BACKGROUND: Testosterone is a hormone essential to the development of male growth and masculine characteristics. Testosterone products are FDA-approved only for use in men who lack or have low testosterone levels in conjunction with an associated medical condition.

RECOMMENDATION: At this time, FDA has not concluded that FDA-approved testosterone treatment increases the risk of stroke, heart attack, or death. Patients should not stop taking prescribed testosterone products without first discussing any questions or concerns with their health care professionals. Health care professionals should consider whether the benefits of FDA-approved testosterone treatment is likely to exceed the potential risks of treatment. The prescribing information in the drug labels of FDA-approved testosterone products should be followed.

i just sent out one of the studies (from PLoS) last week, the other one being a recent one in JAMA (see testosterone and mortality jama 2013, or doi:10.1001/jama.2013.280386). in the jama study they looked retrospectively of 8700 men in the VA with low testosterone levels (<300 ng/dL) who had coronary angiography in the years 2005-2011. findings:

--1223 of these men started testosterone an average of 531 days after cath (20% with prior hx MI, 50% with diabetes, 80% with known CAD). those on testosterone tended to be younger and have fewer comorbidities. the testosterone levels were also lower (176) in those put on testosterone therapy vs those not (207)

--after 3 years, those who were on testosterone: 25.7% had an event (all-cause mortality, MI, or stroke) vs 19.9% not on testosterone, finding a 29% increase in events in those on testosterone. no relation between those with or without coronary artery disease. (unlike some prior studies, the increase in events did not happen soon after starting testosterone, but after 3 years). no diff in the VA group with baseline cardiovasc risk factors in those who had/did not have events.

speculated mechanisms for testosterone and cardiovasc disease: testosterone increases platelet thromboxane A2 receptor density and platelet aggregation; dihydrotestosterone (a metabolite) increases smooth muscle proliferation and expression of vascular cell adhesion molecule 1; testosterone worsens sleep disordered breathing in those with OSA. (all of these are potentially directly assoc with cardiovasc dz)

so, nothing definitive, and the FDA alert is an alert, albeit a lukewarm one. but my sense is that there are enough data to reinforce being wary, at least only prescribing testosterone if there is a clear clinical indication, and letting patients know that there is a potential link.