An observational study of some 83,000 men whose low levels of testosterone were either treated or untreated finds that returning those levels to “normal” was associated with a lower risk of death, stroke, or heart attack. The research joins a growing number of studies of the effects of testosterone therapy that, together, constitute a mixed landscape of results. It’s unclear if this release will help readers navigate that landscape with more confidence. There’s nothing sensational or overblown about the description of the study or its findings, and there is substantial detail on the methodology and at least a hint toward limitations. There is some solid, commendable writing here. What we were looking for was a more clear-cut statement regarding what this study can and cannot tell us — specifically that it’s unclear if testosterone treatment or some other factor is responsible for the cardiovascular benefits that were observed by the researchers. We thought that would help clear up what can be a confusing topic for consumers.
“Low-T” has been raised to the level of a health problem in American society, making it important to figure out if the merits of testosterone therapy actually do trump the debits. This large observational study may serve as one important cog in that evaluative process, but patterns that would lead to treatment recommendations remain elusive.
Cost is not mentioned in this document. Generic testosterone is relatively inexpensive, which suggests that if these results reflect a real benefit, the treatment might actually be cost saving.
Although the press release does provide likelihood estimates of illness or death as a result of testosterone treatment, indicating that individuals whose treatment returned their testosterone to normal levels were less likely to suffer a heart attack, a stroke or to die during follow up, it provides no baseline numbers that would permit us to evaluate those ratios. We learn that the differences are statistically significant, but we have no means of determining if they are important. The absolute reductions are not quantified.
The release mentions an FDA advisory about possible increased risk of heart attack and stroke with testosterone therapy. We’ll call this acknowledgment of possible risks good enough for a Satisfactory rating, although many other possible risks exist including exacerbating sleep apnea, skin reactions, and promoting noncancerous growths of the prostate. One of the researchers is quoted as urging individuals to get appropriate screening from a health professional before considering testosterone therapy, but the reader does not learn why this is important. Bottom line: we know the overall mortality was lower in the group that was treated to a normal testosterone level, so serious adverse events , within the time frame of the study, do not appear to outweigh benefits. However, prostate cancer, for instance, is slow growing and might not have manifested within the time frame studied.
The reader will find a lot of methodological detail in this news release, enough to make it clear that this was not a clinical study but, rather, an observational one in which men with low levels of testosterone who had received VA care were divided into groups that reflected either no treatment for the condition or treatment that led to normal levels for some individuals and continued lower levels for others. The narrative indicates that the three groups were “propensity matched” across a range of biological markers, a strategy that is not as good as random assignment to conditions in a true experimental design but that does make comparisons possible. Still, this study can only speak to “association” between testosterone levels and health impacts, and while the wording used in the news release does mostly avoid the “causality” hole, the headline and other statements in the release suggest that the study “found a benefit” from testosterone that can be “maximized” through appropriate dosing and other strategies. As a result, readers may well infer that the testosterone “caused” the benefits and that supplementing testosterone levels is a good idea.
In the end, while it could have been more clearly stated that cohort studies such as this are not the last word, we think the overall discussion of evidence was sufficient for a Satisfactory rating. This was a fairly strong research design and would be rated pretty highly for an observational study — though not as good as a randomized controlled trial.
We are of two minds on this criterion. The news release leads the reader to infer that low testosterone levels are a health problem, but the existing research in this area offers only mixed support for that. If testosterone levels indeed are causally related to heart attacks and strokes, then this study has identified a substantive health issue. But it is not clear that existing research makes that conclusion possible.
To the release’s credit, it does specifically warn that doctors should not write a prescription simply because an older man is complaining of symptoms such as low energy and low sex drive. In this sense, it does push back to some extent against drug company promotional efforts surrounding “low T,” which we’ve previously flagged for disease-mongering.
Although the study itself offers full disclosure regarding funding and conflicts of interest (the investigators assert no such conflicts), none of this finds its way into the news release.
Information about other ways to reduce mortality from heart attacks or stroke — whether lifestyle changes or other types of drugs — is not mentioned.
It is clear that testosterone therapy is available to patients. The narrative does go to the trouble of noting that “off-label” use of testosterone is a no-no.
The reader will find a reasonable contextual discussion of research on the impacts of low testosterone, which suggests that the proposed health link is not new and that outcomes of testosterone therapy remain mixed in the research literature. The news release makes a pitch for the novelty of this particular study “because of its large size and relatively long follow-up period.”
While we felt that the news release worked hard to push the argument that testosterone therapy that returns the level of the hormone to “normal” offers a health benefit, the careful reader will find cautionary information that tempers that claim.