You might have been alarmed by recent television commercials by law firms soliciting patients that have taken testosterone and suffered a heart attack. Unfortunately, these campaigns have been influenced by one or two negative observational studies of weak power and poor design.
Fortunately, there is over 40 years of well-designed, randomized controlled trials and laboratory research that support the safety and efficacy of testosterone administration. The most recent negative observation, which reported an association between the use of testosterone therapy and increased risk of death and heart attacks, appeared in the Journal of the American Medical Association (JAMA), causing legal zealots to jump on the bandwagon to condemn all physicians – and patients – taking prescribed testosterone.
I do not change my prescribed therapy based on any study of weak data and design that goes against a plethora of data showing safety and benefit. I base my therapy on a composite of many studies over several decades of research.
It helps to understand the difference between a randomized controlled study (RCTs) and an observational study. In an RCT, subjects are screened to remove those that might influence the data, and groups are given different interventions to study outcome. To simplify, there is a treated and a placebo group. In observational studies, existing studies and reports (which may or may not be RCTs) are selectively reviewed. Reviewers pick and choose from the studies without randomization or control from other influencing factors.
A post by three professional medical societies, along with an international group of 130 scientists and physicians, have petitioned JAMA to retract this recent article (JAMA 2013; 310:1829-36). In a letter addressed to JAMA editors, the newly formed Androgen Study Group cites “gross data mismanagement thereby rendering the article no longer credible.” The article was one of two studies that prompted the FDA to issue a safety bulletin on the use of testosterone products. However, this warning from the FDA is only an advisory as the FDA has cautioned both patients and physicians not to stop testosterone therapy.
This article has already undergone two published corrections. The first was published in January due to misreporting of primary results. A second correction published in March revealed what the group called “major errors” in the article’s text and figures. Translation: the statistical analysis utilized was not appropriate and other statistical methods actually show opposite (beneficial) results. Also, the numbers used for the statistical analysis were different from the numbers published in their tables. The raw numbers in their tables actually proved protection against myocardial infarction (heart attack) and not an increase. It is not until their data is plugged into a complex analytical scheme that it shows harm, and thus the insistence that the study be recalled by JAMA. The letter was signed by the International Society for Sexual Medicine, the Sexual Medicine Society of North America, and the International Society for the Study of the Aging Male, along with more than 125 scientists and physicians (of which I am one).
“This is an extraordinary event,” said Abraham Morgentaler, MD, of Harvard University who is chairman of the Androgen Study Group. “In my 25 years in academic medicine, I have never witnessed anything like this response to a journal article.” He adds that the call for retraction of an article is exceedingly rare. “To have several professional societies and so many of the most accomplished experts in the field unite in this action indicates the seriousness of the article’s errors, and the magnitude of damage this article has caused to the public’s perception of testosterone therapy.”
He goes on to say that, “Lost in the media frenzy that followed this article’s publication is the fact that substantial evidence accumulated over 30 years has repeatedly shown that higher testosterone levels are associated with better cardiovascular outcomes. In the interests of medical science and the public good, JAMA should do the right thing and retract the article.”
Many of my patients stopped taking testosterone because of the JAMA article, even those who had experienced substantial benefits. And now we find out it was all based on nothing but sloppy science. We are talking about real consequences on individuals’ health and quality of life. The Androgen Study Group says it is dedicated to education and accurate reporting on the science of testosterone deficiency and treatment in men. It was organized specifically to respond to the “recent unwarranted, unscientific attacks” on testosterone therapy in the medical and public media.
I cannot emphasize the importance of realizing that one or two weak and negative studies do not negate 40 years of positive, beneficial studies. RCTs have more power and predictive value. A recent statement from the American Academy of Clinical Endocrinologists supports these facts suggesting that physicians and patients not jump to conclusions and stop their testosterone prescription based on one poorly done study. Patients should continue taking testosterone until further evaluation and review is complete. The FDA, knowing the history of 40 years of positive studies demonstrating protection against heart disease, has also recommended that men not stop their testosterone prescriptions based on just two poorly done studies.
The facts, according to 40 years of studies, state that not only is there no risk in men with testosterone replacement therapy, but that there is significant benefit. Many of these studies support that low endogenous levels of testosterone may be positively associated with cardiovascular disease and heart attacks. Testosterone has been shown to prevent plaque deposition (atherosclerosis), which is the primary cause of heart attacks. Our goal should be preventing the plaque from forming in the first place.
Despite the negative press seen on television, science and the experts recommend testosterone for cardiovascular protection, as well as for quality of life benefits as demonstrated in 40 years of solid research. I agree.
Dr. Neal Rouzier is a physician specializing in bio-identical hormone replacement therapy, and the Medical Director of the Preventive Medicine Clinic of the Desert. He can be reached at (760) 320.4292.