Testosterone Prescriptions Plunge After CVD Signals, FDA Alert

Marlene Busko

July 10, 2018

After a decade of steadily increasing insurance claims for testosterone therapy in a large US database, the number of prescriptions for testosterone plummeted in 2013.

The sharp decline coincided with the publication of two articles linking testosterone therapy with stroke and myocardial infarction (MI) (JAMA. 2013;310:1829-1836; PLoS One. 2014;9:e85805), which prompted the US Food and Drug Administration (FDA) to issue a safety communication and a requirement for a warning on the product label.    

Jacques Baillargeon, PhD, from the Department of Preventive Medicine and Community Health at the University of Texas in Galveston, and colleagues traced the rise and fall of testosterone prescriptions from 2002 to 2016 among employed American men covered by a large US insurer.

The findings were published in a research letter in the July 10 issue of JAMA.

Notably, "between 2013 and 2016, new testosterone use decreased by 62% and established use decreased by 48%," Baillargeon pointed out to Medscape Medical News.

The "very dramatic drops" coincided with the publication of the two articles, which generated a lot of publicity and the issuance of the FDA communication.

In earlier work, researchers found a quarter of the men who received a new prescription for testosterone had not had a blood test to determine serum levels (JAMA Intern Med. 2013;173:1465-1466).

When there was a striking increase in testosterone prescriptions in the previous decade, "we were alerted about possible overtreatment," Baillargeon said.

Similarly, "I think a dramatic decline should alert us to the possibility that some men who are hypogonadal may not be receiving adequate treatment."

Men with hypogonadism who discontinue testosterone therapy, "could develop osteoporosis, a real loss of muscle mass, increase in [central] adiposity, increase in metabolic syndrome, reduced physical activity, depression, [and] fatigue," he warned, and some of these symptoms could put them at increased risk of cardiovascular disease.

Tripling of Testosterone Prescriptions

Testosterone use in the United States tripled from 2001 through 2011, the researchers report, and many men did not have a clear indication for the therapy, such as low serum testosterone plus symptoms such as erectile dysfunction.

But the surge in prescriptions stopped in late 2013/early 2014.

Baillargeon and colleagues examined total and new testosterone prescriptions from 2002 through 2016 using figures from Clinformatics Data Mart.

They identified 9,962,538 employed men who were 30 to 64 years old and lived in the US Northeast, Midwest, South, and West.

The men were a median age of 46 years in 2002 and 53 years in 2016.

Overall, 0.52% of the men used testosterone in 2002, and by 2013, 3.20% of the men had used it.

However, after 2013, testosterone use dropped steeply, and by 2016, only 1.67% of the men were still using it.

Similarly, in 2002, 0.28% of the men were newly prescribed testosterone, and by 2013, 1.26% of the men were newly prescribed the drug.

However, new prescriptions fell sharply starting in 2013, and by 2016, only 0.48% of the men received a new prescription for testosterone.

Researchers identified five key times when rates of new and total testosterone prescribing changed:

  • November 6, 2013: Article by Vigen and colleagues published (JAMA. 2013;310:1829-1836).

  • January 29, 2014: Article by Finkle and colleagues published (PLoS One. 2014;9:e85805).

  • January 31, 2014: FDA issued a safety communication on testosterone therapy.

  • September 17, 2014: An FDA advisory committee met to discuss possible cardiovascular risks associated with testosterone therapy.

  • March 3, 2015: FDA required a testosterone label change indicating possible increased risk of MI and stroke.

There was a steep 22% drop in new testosterone users from October 2013 to December 2013 following the publication of the article by Vigen and colleagues that linked testosterone to adverse cardiovascular events.

An additional 50% decrease in new testosterone users occurred during the next 8 months subsequent to the findings by Finkle and colleagues and the FDA communication.

"Who Are These Men Who Discontinue?"

The group is continuing to look into which type of men discontinued testosterone therapy and the clinical implications.

"What we really want to know is how this big decrease is affecting men in the United States," said Baillargeon.

"Who are the men who are discontinuing their treatment, or not even starting treatment? What percentage of men have very clinically significant and highly symptomatic hypogonadism?"

It is likely that some men who discontinued testosterone had clinically significant hypogonadism and others probably should never have received the therapy, he believes.

But the researchers lacked information about the indications for testosterone therapy and whether insurance reimbursement policies changed.

"Given the debate that has surrounded this issue," for example, a meta-analysis did not find an increased risk of stroke or MI with testosterone therapy (Am J Med. 2017;130:293-305), "continued monitoring of testosterone prescribing trends will be important," the researchers conclude, as it affects the health of many men.

The study was supported by grants from the National Institutes of Health. Baillargeon reported receiving fees from AbbVie, Endo Pharmaceuticals, Auxilium Pharmaceuticals, and GlaxoSmithKline.  

JAMA. 2018;320:200-202. Research Letter

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