Why did we see a massive drop in the number of Testosterone Prescriptions between 2014 and 2016 ?

Why did we see a massive drop in the number of Testosterone Prescriptions between 2014 and 2016 ?

In 2018 a study was published that showed the number of testosterone prescriptions in the USA fell by as much as 48{4810c8228756a9189e64fcffe2b64504834fd1a9aa1761a0e9a85eac56097be8} in established users and 62 percent in new users in between 2014 and 2016.

Why ?

Simple hysterics.

In early 2014 studies where published suggesting increased cardiovascular risks with testosterone therapy that generated enormous media attention, even lead to an FDA safety notice being issued.

Its is important to note that the study by Baillargeon et al was based on insurance claims and, therefore did not capture self-pay prescriptions or self administration ( our tribe )

Following the media hysteria that followed insurance companies began instituting rigorous approval criteria for testosterone prescriptions, causing physicians and their patients to increasingly turn to treatment with the relatively inexpensive short-acting testosterone esters, cypionate and enanthate, for patients with testosterone deficiency who were no longer covered by insurance and needed to pay for these medications themselves.

Although the major decline is prescriptions written is consistent with an abrupt increase in physician concerns regarding testosterone therapy at that time, any subsequent recovery in pre- scriptions owing to prescriptions purchased without insurance would not have been cap tured in the insurance-based data reported by Baillargeon and colleagues.

Regardless, the substantial costs involved in prescribing testosterone have shifted from insurance companies to patients. Given the substantial symptomatic and general health benefits provided by testosterone therapy, this shift contributes to increased disparity in health care between those with financial means and those without.

For 20 years, evidence had accumulated that low testosterone concentrations were associated with cardiovascular risk and mortality, and testosterone therapy seemed to be protective.

This view changed precipitously in November 2013 with publication of the Vigen study in JAMA. This observational study reported combined rates of myocardial infarction, stroke, and death in 8,701 men in the Veteran’s Affairs system with testosterone levels <300 ng/dl who underwent coronary angiography, some of whom were later prescribed testosterone therapy. Men who received a testosterone prescription were reported to have experienced an increased absolute rate of events at 3 years compared with untreated men (25.7 percent versus 19.9 percent ) , which seemed to be subsequently confirmed.

This unexpected risk with testosterone therapy was reported on news media as a major health event, accompanied by provocative editorials that criticized physicians for prescribing testosterone.

However, the Vigen study was subsequently shown to have misreported its original results, with the absolute rate of events in the testosterone-treated group actually being half of the rate in the untreated group (10.1 percent versus 21.2 percent )

Subsequently, JAMA issued a correction that showed that nearly 10 percent of the all-male population was female !

JAMA was petitioned to retract the study by 29 medical societies asserting the results were no longer credible, but it declined to do so without explanation and these disqualifying flaws in the study were not reported in the media

Since then what evidence do we have ?

In a review of 23 studies investigating testosterone therapy published since the FDA warning in 2015, not one has provided evidence of increased cardiovascular events with testosterone therapy.

Conversely, several showed substantially decreased cardiovascular risk

Concerns regarding cardiovascular risks with testosterone therapy have resulted in a variety of criticisms forming a popular narrative that testosterone therapy is being improperly administered.

One  criticism is that testosterone is overprescribed, as the number of men with hypogonadism is unlikely to have increased while prescrip- tions tripled from 2001 to 2011. However, as late as 2007, the FDA asserted that only 5 percent of men with hypogonadism were receiving treatment. Thus, a tripling of prescriptions would still mean substantial undertreatment.

A frequently cited statistic that seems to support inappropriate prescribing is that studies of computerized health records show that approximately one-quarter of men receiving a testosterone prescription did not have a documented previous testosterone level.  However, this rate was nearly 20 percent among men seen by endocrinologists. This finding should lead one to question the completeness of computerized health data in these studies, as it is not credible that any endocrinologist would treat without obtaining at least one baseline serum testosterone concentration.

Another  criticism  holds  pharmaceutical marketing responsible for the dramatic rise in prescriptions. However, prescription rates rose simultaneously in many countries where pharmaceutical advertising is illegal. My view as a clinician and educator in this space is that prescription rates rose as physicians became aware of studies demonstrating beneficial effects and as the fear declined that testosterone therapy caused prostate cancer

Testosterone therapy seems to offer cardio- vascular benefits, not harms. Recognizing the effect of the media on medical decision-making is important. At a time when most clinicians struggle to find the time to read journal articles, we increasingly learn about the latest medical news from the media. What is inadequately appreciated is how journals and the media work together to select the most newsworthy study results among the hundreds published daily. Unexpected serious risks of a popular treatment qualify as newsworthy. Media companies compete for clicks, journals for impact factor. The reader is, therefore, provided with a highly selected set of results, without opportunity to vet their reliability.

Notably, none of the important criticisms regarding the Vigen study received media attention, nor did the correction, nor did subsequent studies revealing cardiovascular benefits associated with testosterone therapy. Unsurprisingly reassuring results are not nearly as newsworthy as unexpected risks.

Testosterone deficiency is a real condition affecting real men.

Testosterone therapy in these men is effective and supported by level 1 evidence. Indeed, every clinician experienced with testosterone therapy has had the remarkable experience of having a treated patient sincerely thank them. The testosterone therapy controversies have distracted us from one of the most exciting stories in all of medicine — the powerful potential of testosterone therapy to improve quality of life and general health

References 

Traish, A. , Vance, J. C. & Morgentaler, A. Overselling hysteria: the role of the media and medical journals in promoting questionable risks-a case study of the testosterone controversy. EMBO Rep. 18, 11–17  (2017).

Vigen, R. et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA 310, 1829–1836 (2013); erratum 311, 967 (2014).

Baillargeon, J. et al. Testosterone prescribing in the United States, 2002-2016. JAMA. 320, 200–202 (2018).

Morgentaler, A. et al. Testosterone therapy and cardiovascular risk: advances and controversies. Mayo Clin. Proc. 90, 224–251 (2015).

Traish, A. , Guay, A. T. & Morgentaler, A. Death by testosterone? We think not! J. Sex. Med. 11, 624–629 (2014).

Morgentaler, A. & Lunenfeld, B. Testosterone and cardiovascular risk: world’s experts take unprecedented action to correct misinf Aging Male 17, 63–65 (2014).

Miner, M. et al. The state of testosterone therapy since the FDA’s 2015 labelling changes: indications and cardiovascular risk. Clin. Endocrinol. (Oxf.). 89, 3–10 (2018).

US Food and Drug Administration. http://www.fda. gov/fdac/departs/196_html (Accessed 6 March 2007).

Baillargeon, et al. Screening and monitoring in men prescribed testosterone therapy in the U. S., 2001–2010. Publ. Health Rep. 130, 143–152 (2015).

Morgentaler, A. et al. Fundamental concepts regarding testosterone deficiency and treatment: international expert consensus resolutions. Mayo Clin. Proc. 9, 881–896 (2016).