Pushing Testosterone, a $2 Billion Drug
Written by Editor   
Thursday, November 26, 2015 12:29 PM

Testosterone has been on the pharmaceutical market for decades, but until 2000 it was primarily used to treat hypogonadism, a relatively rare condition defined as abnormally low testosterone due to a medical condition, such as genetic problems or damage to the testicles.  

But drug companies have exploited a broader definition that includes low testosterone levels that occur due to the natural aging process. A common theme: millions of middle-aged and older men suffer from untreated low testosterone, leading to a lack of sexual function, energy, mood, and libido, as well as obesity, heart disease, cognitive decline, and even premature death.  The FDA's approval of the drug, however, was not based on the products showing proven benefit in treating cardiovascular disease, cognitive decline, or other conditions related to aging.  Rather, the drugs were approved because they do one thing: boost testosterone to levels found in healthy young men.

In 2000, just under 1 million prescriptions were written for testosterone products. That reached 3.3 million in 2008 and 6.5 million last year -- a more than six-fold increase in prescriptions over the 15-year period.  

In 2012, a faculty member at a CME activity funded by the company that marketed the nation's top-selling testosterone product told physicians they could safely prescribe testosterone to men with prostate cancer.  This advice was offered despite treatment guidelines -- and the product label itself -- warning that testosterone should not be given to men with prostate cancer.  The same physician who led the online course has participated in at least 19 CME activities since 2010, part of a wave of courses touting the dubious virtues of testosterone treatment -- all bankrolled by companies that manufacture the products.

Pharmaceutical and device-maker support of CME programs has ebbed and flowed for the last 40 years beginning with a significant pull-back following Congressional investigations of industry sponsored symposia that were often described as junkets, and again in 2007 and 2009 when a new series of investigations raised questions about aggressive promotion of off-label use under the guise of education.

The CME industry and its certifying body, the Accreditation Council for Continuing Medical Education (ACCME), did initiate a number of reforms, but today about a quarter of CME income -- $676 million -- comes from industry, with most of that support paid to the medical education companies that create the course curricula, hire the faculty, promote the programs, and track the "learners."

Payments to physicians -- and academic institutions -- are made by those companies, a process that effectively works as an end run that shields those payments from the federally-mandated Open Payments system, which reports pharma payments to physicians.

A review of 75 drug industry-funded courses involving testosterone found that the majority of the faculty experts already were on the payroll of drug companies as speakers, consultants, and advisors.  All told, 65 of the courses examined had at least one faculty member who already had worked for the drug company that funded the course or a company that makes or markets testosterone products.

The courses are part of a massive drug-company push over the past 10 years to make testosterone products, which reached $2.1 billion in sales in 2014, a central part of men's health. 

Since 2010, testosterone products have been linked to more than 3,900 serious complications. Nearly a quarter of those reports involved cardiovascular problems such as heart attacks or blood clots.  The reports include 150 deaths and nearly 2,000 hospitalizations.

In March, the FDA said it was requiring drug companies to change the labels of testosterone products to warn that they are not approved for men with low testosterone due to aging, but since the products are clinically available, doctors are prescribing off-label.

The review of the testosterone courses show many have downplayed risks, such as heart attacks, clots, and potential prostate cancer risk.

Yet, the medical literature continues to raise concerns.

  • In 2010, a study in The New England Journal of Medicine involving more than 200 men ages 65 and older was stopped early because of a higher number cardiovascular events, such as heart attacks and chest pain in those getting testosterone, though the number of events was small and may have been due to chance, the authors said.

  • A 2014 study in the journal PLoS One looked at a database of 55,000 men ages 65 and older and the rate of nonfatal heart attacks within 90 days of getting a prescription for testosterone therapy. It was more than double what was found in the year prior to the prescription.

Meanwhile, in August a 3-year study in the Journal of the American Medical Association compared testosterone to a placebo in more than 300 men in their 60s with low to low-normal testosterone levels. It found no improvement in sexual function or health-related quality of life.

The FDA has allowed the new testosterone products on the market based on a short-term surrogate measure, the increase in testosterone levels, rather than the gold standard of a proven clinical measure, such as reduced heart attacks or strokes.  That runs contrary to the approach used with other drugs that are billed as potentially reducing the risk of cardiovascular disease. Drugs that affect such things as blood sugar levels, blood pressure, and cholesterol all have been tested in thousands of people.  In August, citing concerns about cardiovascular safety, the FDA said it would require companies that make testosterone products to conduct a controlled clinical trial.

Such a trial may take years and require 10,000 men, said Steven Nissen, MD, but these drugs bring in billions of dollars.

He and others point to the case of hormone replacement therapy for women.  Twenty-five years ago, it was thought the treatment would help women ward off cardiovascular disease and other conditions related to aging.  Then a medical bombshell: in the Women's Health Initiative , a study involving 16,000 middle-aged and older women was halted when it showed that hormones actually increased the risk of a heart attack, stroke, dementia, and breast cancer.

Said Nissen of testosterone products: "This is a great experiment with American men as the guinea pigs."

Over the past 3 years, more than 2,500 federal lawsuits have been filed against companies that market testosterone products.  The cases, which have been consolidated in U.S. District Court in Chicago, allege that drug companies knowingly promoted the drugs for unapproved off-label uses.

Mark Hoffman, MD, JD, a Philadelphia attorney and physician who is working on the lawsuits, said the industry-funded testosterone courses are part of an effort to turn a normal physiological process into a medical condition needing treatment.

"They go to physicians and try to set a standard of care that's so far outside the realities of what testosterone is actually about," said Hoffman. "In my view as a physician, it's absolutely egregious."

The various testosterone lawsuits allege that pharma "funneled" money into continuing medical education efforts and claim the company controlled the content of the programs.  Those suits claim the money was "disguised" as educational grants in order to hide pharma's role and its payments to physician lecturers.

The industry was tarnished in 2007 and 2009, following two U.S. Senate investigations into the practice of drug company funding of continuing medical education courses.

In 2007, a U.S. Senate Finance Committee investigation found that pharmaceutical firms had taken control of the programs to get favorable presentations of their products, grab market share for expensive brand-name drugs, and encourage doctors to write prescriptions for off-label uses.

In a 2009 hearing before the U.S. Senate Committee on Aging, several experts testified that drug company-funded continuing education was being used by the firms to aggressively market their products and contributing to the enormous health care costs in the United States.

At the hearing, a Department of Health and Human Services official testified that every $1 spent on doctor education generated $3.56 in increased revenue for the drug companies.

Source: http://www.medpagetoday.com/special-reports/slipperyslope/54156