With nearly 3% of American men over 40 boosting their testosterone levels with a prescription supplement, the financial and public health stakes couldn't be higher. But in increasing numbers, physicians are complaining that research on the safety of testosterone patches, creams and emollients is anything but conclusive, leaving doctors and patients alike uncertain about how and whether to treat a condition newly branded as "low T."

In the wake of studies linking testosterone supplementation to increased heart attack and stroke risk, a physician writing in the respected British journal Lancet Endocrinology weighed in on the testosterone debate urging caution and more - and better - research.

"What, then, can older patients be told about the risks associated with testosterone?" asked University of Washington endocrinologist Dr. Stephanie T. Page. "Physicians need to admit they simply do not know and use conservative treatment guidelines to guide therapeutic decisions."

Given the design of testosterone safety studies conducted to date, which have yielded a range of conflicting conclusions, "causality can only be inferred, and not proven," Page wrote. Despite the advertising blitzes for testosterone products and "undoubtedly, some degree of overprescription," Page wrote that researchers must launch large, randomized clinical trials in which similar groups of men are assigned to get either testosterone or a placebo, and then followed for several years.

Over recent weeks, a group of physicians and medical organizations has called on the Journal of the American Medical Assn. to retract one of the studies that sounded alarms about testosterone treatment, charging that the authors' conclusions were undermined by "gross data mismanagement."

That study, published in JAMA in November, suggested that men who underwent an artery-clearing procedure and then took prescription testosterone medication were 30% more likely to suffer a heart attack, stroke or death from any cause than were similar patients who did not take testosterone.

In recent months, however, JAMA has published clarifications from the authors. Those have revealed that the study population was much smaller than that reported; and they acknowledged that the calculations of increased risk were based on statistically derived estimates, and not raw data. The raw data, in fact, suggested that those in the testosterone group actually were less likely to suffer a cardiovascular "event" than those who did not take testosterone.

A group of physicians and researchers in men's health, convened under the umbrella of "Androgen Study Group," charged that the authors raised alarm bells about testosterone's safety based on "absurdly complicated statistical manipulations of the data." And they have called on JAMA to retract the study.

The new calls come against the backdrop of testosterone's meteoric rise in the United States, spurred by an aggressive "disease awareness" campaign to alert men to the diffuse symptoms of "low T" (weight gain, low energy, flagging sex drive) and by relentless marketing of prescription testosterone products. Between 2000 and 2011, prescriptions for testosterone supplementation have grown fivefold in the United States, netting the makers of the products $1.6 billion annually.

In the wake of two studies suggesting such supplementation might carry risks, however, advertising for testosterone medication has met its match. Attorneys have begun running advertisements in a bid to recruit clients for liability suits against the manufacturers of prescription testosterone supplements such as Axiron and AndroGel.