Testosterone treatment in older men reduced anemia but did not improve cognitive function, and was associated with a significant increase in arterial plaque, according to recent Northwestern Medicine studies published in the Journal of the American Medical Association (JAMA) and JAMA Internal Medicine journals.

Mark Molitch, MD, Martha Leland Sherwin Professor of Medicine in the Division of Endocrinology, Metabolism and Molecular Medicine, and David Cella, PhD, Ralph Seal Paffenbarger Professor and chair of Medical Social Sciences, were co–authors on the papers, which come from the Testosterone Trials, a set of seven controlled clinical trials conducted between 2010 and 2014 at U.S. academic medical centers, including Northwestern Memorial Hospital.

The Testosterone Trials were designed in response to a 2003 Institute of Medicine panel, which concluded there was insufficient evidence for testosterone treatment in older men and called for a coordinated set of clinical trials to investigate potential benefits and risks.

The trials, supported by the National Institutes of Health (NIH), looked at the effects of 12 months of treatment with testosterone gel in 788 men age 65 and older with low levels of testosterone.

The first results from the trials, which found testosterone treatment improved sexual function, were published last year in the New England Journal of Medicine, and were also co–authored by Molitch and Cella.

In the current studies, the investigators looked at the association between testosterone treatment and measures of anemia, cognitive function and coronary artery plaque.

In the JAMA Internal Medicine study, the treatment significantly increased hemoglobin levels in 54 percent of men with unexplained anemia and 52 percent with anemia from known causes, compared to just 15 percent and 12 percent from the control group.

However, treatment did not lead to improved memory or other cognitive functions in older men with age–associated memory impairments, compared to a placebo. Further, treatment with the gel was associated with a significant increase in the volume of noncalcified coronary artery plaque. Both of those studies were published in JAMA journal.

Still, as reported in the primary paper published last year in the New England Journal of Medicine, there was no increase in cardiovascular clinical events in those treated with testosterone compared to those treated with placebo for the year of treatment and for one year following treatment.

A fourth recent paper from the trials, published in JAMA Internal Medicine journal but not co–authored by Northwestern Medicine investigators, also found that the treatment improved bone density in study participants.

“These studies show that the use of testosterone in men over 65 has mixed effects, both positive and negative,” said Cella, also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “Testosterone replacement can indeed be beneficial for some; for others it may do more harm than good. We hope these studies help doctors and patients have the necessary highly–individualized discussions to make the right choice.”