Testosterone for diabetes may be new market for Lilly, others

When Gary Wittert began looking for overweight male baby boomers to take part in a clinical trial last month, he got 800 volunteers in one day. The draw: free testosterone injections.

Wittert, a professor of medicine at the University of Adelaide in Australia, and his colleagues suspect the sex hormone known to increase libido and musculature could also play a role in preventing a form of diabetes that tends to strike later in life and afflicts more than 330 million people worldwide.

The steroid, which cyclist Lance Armstrong admitted to using in winning seven Tour de France titles, could go from being popular among men “looking to spice up their sex lives” to becoming a mainstream therapy if the trial, the largest test of testosterone’s potential to fight diabetes, shows positive results, said Stuart Roberts, a health-care analyst with Bell Potter Securities Ltd. in Sydney.

“The Wittert study will be the real kicker here,” Roberts said. “This is what gets you away from the ‘snigger factor’ with testosterone. And, because testosterone is cheap and easy to make, it won’t be an impost to the health-care system.”

The study was discussed Saturday at the 10th International Congress of Andrology, which runs Feb. 23 to 26 in Melbourne.

Testosterone, most of which is produced in men’s testes or replicated chemically by companies including Indianapolis-based Eli Lilly and Co., Bayer AG and AbbVie Inc., is already in demand.

Revenue from prescription sales in the United States has grown tenfold, to $2.2 billion, since 2001. Newer topical gel formulations are spurring 20-percent-a-year growth in the market, which will reach $5 billion by 2017, Global Industry Analyst Inc., a San Jose, Calif.-based research firm, said last April.

Lilly's testosterone roll-on underarm gel, Axiron, launched in 2010, had sales of $48 million in 2011.
In Australia, where testosterone prescriptions are also climbing, demand is spurred by what David Handelsman, a professor of medicine at the University of Sydney, describes as an “anti-aging racket” targeting gullible men.

“They think testosterone is the essence of manhood and it will prolong their youthful vigor forever,” said Handelsman, whose research focuses on male reproductive health. “They’re persuaded because sex sells and anything to do with sex and reproduction is easy to market.”

About 5 million American men don’t produce enough of the hormone, according to the National Institutes of Health. A study in Europe published a decade ago found one in five men over 50 has moderate-to-severe symptoms of testosterone deficiency. Fewer than 2 percent of cases outside the U.S. get treated, Malcolm Carruthers at London’s Centre for Men’s Health, wrote in a paper published in 2009.

“Like global warming, awareness of the effects of testosterone deficiency is also increasing as the general public surf the oceans of information available on the Internet, but still the condition remains largely unrecognized and untreated,” Carruthers wrote.
Replacement therapy has been used since the 1930s to treat men with medical conditions, such as Klinefelter’s syndrome, that cause testosterone deficiencies leading to low energy, poor concentration, reduced sex drive, loss of muscle strength, and increased risk of osteoporosis.

Athletes, especially sports amateurs, have used testosterone to boost muscle growth since the 1950s, and cyclist Armstrong said last month he took the banned performance-enhancing hormone alongside erythropoietin and blood transfusions. The hormone can be administered via injections, gels, patches, pills and gum tablets known as troches.

“It’s very popular,” Handelsman said. “Nobody dislikes being on testosterone. It’s mood-elevating.”
It does pose potential health risks. In men, high levels can cause symptoms such as acne, aggression, impotence, liver dysfunction, testicular atrophy and sperm reduction, breast enlargement and baldness.

A study of testosterone use in elderly males, funded by the U.S. National Institute on Aging and run by Shalender Bhasin at Boston Medical Center, was stopped in 2009 because an audit found it caused more heart attacks and hypertension.

“People who use it at very high doses can become manic and can fly off the handle and become dangerous,” Handelsman said.

Testosterone levels can vary depending on the time of day, the test used, the age of men sampled and their health, according to Carolyn Allan, a medical adviser to Andrology Australia, a government-funded research and education center in Melbourne.
A normal range for healthy, young adult men is 8 to 27 nanomolars per liter. Levels typically fall by 1 to 2 percent a year from about age 30, Allan says.

There’s some controversy about whether a drop in testosterone is due simply to age or medical conditions that occur more frequently in older age, said Ronald Swerdloff, professor of medicine and chief of endocrinology at Harbor-UCLA Medical Center in Los Angeles.

Testosterone should be kept above 8 nanomolars to avoid erectile dysfunction and above 10 to prevent bone loss, Allan said. Levels above 15 will help protect against increased accumulation of body fat and a flagging libido.

The findings of a study in Germany presented at a medical meeting in June showed the hormone helped obese men with low testosterone levels lose weight and keep it off. The study followed 214 men for at least two years and 115 for at least five. Their cholesterol, blood-sugar and blood pressure also improved with the treatment.

Australia’s National Health and Medical Research Council is committing $4.6 million to a study seeking to establish whether testosterone is a safe and effective tool that can be used with diet to mitigate diabetes risk in older men.

Current recommendations to prevent or delay type 2 diabetes focus on reducing body fat and exercising — a strategy that fails to stop as much as 30 percent of those at risk of the obesity-linked condition developing it within five years. The International Diabetes Federation says fighting the disease costs $471 billion to treat worldwide.

Wittert, who is leading the testosterone study that started recruiting patients last month, and his colleagues found in addition to the 800 men who signed up on the first day, another 3,200 had clicked on a Web link calling for participants.

The scientists aim to recruit 1,500 pre-diabetic men ages 50 to 74 years with relatively low testosterone and waist circumference of 95 centimeters (37 inches) or more. Participants will receive free access to a weight-loss program provided by Weight Watchers International Inc. and treatment with either testosterone or a placebo.
Those receiving the hormone will get it in the form of 1,000 milligrams of Bayer AG’s long-acting Nebido, sold as Reandron in Australia, on entering the trial, after six weeks, and every three months for about two years. Men with prostate cancer and cardiovascular conditions are ineligible for study, which is also being supported by Lilly, Sanofi and Becton Dickinson & Co.

The trial is an investigator-led study and Bayer is only providing the testosterone medicine, said Astrid Kranz, a spokeswoman for the Leverkusen, Germany-based company.

Although diabetes and obesity are linked to testosterone deficiency, scientists don’t know what effect testosterone has on diabetes risk for men whose waning sensitivity to insulin makes them pre-diabetic.

Trial participants will be monitored for blood-sugar, muscle strength, body composition, and their motivation to stick with a lifestyle program, Wittert said. An independent data safety monitoring board will watch for signs that the treatment is causing harm.

“It’s going to be big undertaking, but we will get an answer,” said the University of Sydney’s Handelsman, whose ANZAC Research Institute is one of six sites in Australia involved in the research. “No other study of that scale and ambition is underway anywhere in the world to my knowledge.”

Use of testosterone in older men for purported benefits to physical health and quality of life is a contentious area, according to Andrology Australia. Until the findings from large research trials are known, the group recommends testosterone in men of all age groups be used “judiciously.”

Any potential benefit from testosterone beyond current guidelines needs to be weighed carefully against the risks, the University of Sydney’s Handelsman said. Hormone replacement therapy was used routinely for symptom relief in menopausal women for three decades before large-scale clinical data showed it increased heart attacks and strokes, he said.

Without proper research, the same mistakes could be made with testosterone, Handelsman said. “I suspect, unfortunately, we are sliding down that pathway,” he said.