COMMENTARY

Treating Low T: Are the Benefits Worth the Risks?

Sandra Adamson Fryhofer, MD

Disclosures

October 08, 2014

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Hello. I'm Dr Sandra Fryhofer. Welcome to Medicine Matters. The topic: low T. Are the benefits of treating worth the risk? A new commentary in the Lancet sheds light on what we don't know.[1] Here is why it matters.

Low T. We have all seen the commercials: a handsome older man with a gorgeous younger woman at his side. Some clinicians say that low T is an invented condition and there is really no such disease. One thing is for sure: Testosterone is a billion-dollar industry. The number of testosterone prescriptions has skyrocketed—a fivefold increase over the past 10 years; 5.3 million prescriptions in 2011.

But two recent observational studies, one by Vigen and colleagues[2] and the other by Finkle and colleagues,[3] have raised concerns about the safety of testosterone therapy. The Vigen study, published in JAMA, looked at 8000 male veterans with low T, a total testosterone < 300 ng/dL, mean age 63 years. They found an association between testosterone therapy, heart attack, and stroke.However, this editorial points out that before the raw data were adjusted for 50-plus variables, 10% in the testosterone-treated group (vs 20% in the untreated group) had a cardiovascular event.

The Finkle study, published in PLOS ONE, used a large healthcare database and looked at the risk for myocardial infarction (MI) in the initial 90 days after initial testosterone prescription compared with the year prior to receiving the prescription. They linked testosterone therapy to increased heart attack risk in younger and in older men with preexisting heart disease.

An earlier study by Shores and colleagues,[4] also looking at veterans, found just the opposite—a decrease in mortality in those taking testosterone, even those with preexisting heart disease.

So what about clinical trials? The longest clinical trial is the TOM trial, the testosterone trial in older men published in the New England Journal of Medicine.[5] It lasted only 3 years and looked at the effects of high-dose testosterone therapy on frail, older men and was stopped owing to increased cardiovascular events in the testosterone-treated group.

Stephanie Page, who wrote the Lancet editorial,[1] calls for well-designed, randomized clinical trials and reminds us what the Women's Health Initiative revealed about hormone replacement therapy. She also mentioned the debate about testosterone therapy and prostate cancer and the scarcity of long-term randomized trial data.

Here is what testosterone therapy can do. It can boost energy and sex drive. It improves bone mineral density. It increases lean body mass and strength. It improves lipid profiles, although it does lower high-density lipoprotein (HDL) cholesterol. It also improves insulin resistance.

There are downsides that could increase cardiac risk. It increases platelet thromboxane A2 and platelet aggregation. Testosterone metabolites increase smooth-muscle proliferation and enhanced monocyte activation in the endothelium. It also worsens sleep apnea, a risk factor for atherosclerosis.

The Endocrine Society recommends testosterone therapy only in men with unequivocally low testosterone levels.[6] Patients with low T who are receiving therapy must be informed of the risk and benefits of testosterone therapy—but, as this editorial says, we should also admit to patients that there is still a lot we just don't know. We need good, evidence-based clinical trials in order to have good evidence-based guidelines for prescribing testosterone therapy.

Meanwhile, the US Food and Drug Administration (FDA) announced it will be taking a closer look at risk for heart attack, stroke, and death in men taking FDA-approved testosterone products.[7]

For Medicine Matters, I'm Dr Sandra Fryhofer.

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