TRT, blood clot risk evaluated in large analysis

Middle-aged and older men undergoing testosterone replacement therapy aren’t at increased risk of venous thromboembolism (VTE), the results of a large comparative case-control analysis published online in Mayo Clinic Proceedings (July 15, 2015) suggest.

A leading sexual dysfunction expert praised the researchers’ efforts but noted that a prospective long-term clinical trial would be most effective at determining the risk.

Researchers studied 30,572 men 40 years of age and older who were enrolled in one of the country’s largest commercial insurance programs between Jan. 1, 2007 and Dec. 31, 2012. They identified 7,643 cases, defined as men diagnosed with VTE (deep vein thrombosis or pulmonary embolism) at any time during the study period who received at least one prescription for an anticoagulant or had an intravascular vena cava filter inserted within 60 days after the VTE diagnosis.

Read: What do you think of new warning labels on TRT products?

Cases were matched with three control subjects on event/index month, age, geographic region, diagnosis of hypogonadism, and diagnosis of any underlying prothrombic condition. The analysis adjusted for potential confounding factors, including age, geographic region, calendar year, underlying medical conditions, and medications.

Exposure to testosterone therapy within 15 days of the event/index date wasn’t associated with increased risk of VTE (adjusted odds ratio, 0.90), nor were any of the routes of administration that the authors examined-topical, transdermal, or intramuscular. The finding extended to men who received therapy 30 or 60 days before the VTE diagnosis.

NEXT: “These findings may provide clinically relevant information about the benefit-risk assessment for men with testosterone deficiency considering treatment."

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“These findings may provide clinically relevant information about the benefit-risk assessment for men with testosterone deficiency considering treatment. This investigation is the first comparative study to evaluate a possible link between testosterone therapy and VTE and addresses widespread international concern about this issue,” wrote the authors, led by Jacques G. Baillargeon, PhD, of the University of Texas Medical Branch at Galveston.

Faced with conflicting evidence about the relationship between testosterone therapy and VTE, the FDA mandated in 2014 that a warning about potential risks be added to the labeling of all approved testosterone products.

The possible risk of VTE raised concern about testosterone prescriptions among both patients and physicians, the authors note.

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“It is important to acknowledge, for a man who has medically diagnosed low testosterone, that there are clear risks to not receiving testosterone therapy, including osteoporosis, sexual dysfunction, increased amounts of fat tissue, decreased lean muscle mass, possible metabolic syndrome, and cardiovascular disease. It’s also important to note that further research needs to be conducted to rigorously assess the long-term risks of testosterone therapy,” said Dr. Baillargeon in a press release from the University of Texas Medical Branch.

While acknowledging several limitations of their study, the authors highlight its strengths, namely a large representative patient sample, matching based on sociodemographic and disease risk factors, simultaneous adjustment for potentially confounding medications and medical conditions, and evaluation of several windows of testosterone exposure (15, 30, and 60 days). The findings are generally consistent with two previous population-based studies, they point out.

NEXT: Arthur L. Burnett, II, MD, MBA, discusses findings

Urology Times Editorial Council member Arthur L. Burnett, II, MD, MBA, commented on the study’s results.

“The work is important in addressing a major cardiovascular comorbidity that would be concerning with testosterone therapy,” said Dr. Burnett, who was not involved with the research. "The study is a very large, well-done investigation using a case-control study design.

“It offers good insight about the risk of VTE associated with testosterone therapy, although a large, prospective long-term clinical trial would be most definitive to establish the determination of risk. Such further study would best serve to meet the bar the FDA has set. The FDA may still feel justified in requesting continued warnings at this time. However, it adds to our understanding and may help guide practitioners in discussions with patients.”

The study was supported by the National Institutes of Health.

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