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Kaiser Permanente Study Finds Men Taking Long-Acting Chronic Pain Medications Five Times more Likely to have Low Testosterone Levels

The study is the first to show a significant difference in risk between short-acting and long-acting opioids.

January 31, 2013



OAKLAND, Calif. — Low testosterone levels occur five times more often among men who take long-acting instead of short-acting opioids for chronic pain, according to a new Kaiser Permanente study published in The Clinical Journal of Pain.

Kaiser Permanente Division of Research

While it has been known that opioids cause low testosterone in men, this study is the first to show a significant difference in risk between short-acting (immediate release) and long-acting opioids.

The 81 men in the retrospective study were between 26 and 79 years old (median age 51) and were seen in the chronic-pain clinic at Kaiser Permanente’s Santa Rosa Medical Center (Calif.) between January 2009 and June 2010. All of the participants had been on a stable dose of an opioid for at least three months, and none had a previous diagnosis of low testosterone. A larger retrospective study of more than 1,500 male pain patients is currently under way.

“There’s a large gap in the evidence base with regard to opioids,” said Andrea Rubinstein, MD, of the Departments of Chronic Pain and Anesthesiology, Kaiser Permanente Santa Rosa Medical Center. “More safety and efficacy studies are needed. We need to know how we can prescribe these very useful medications in a way that brings the greatest benefits to our patients, without introducing additional risks.”

Once prescribed primarily to cancer patients, the use of opioid-based medications such as oxycodone (Oxycontin) and hydrocodone (Vicodin) for treating chronic, non-cancer pain has increased dramatically in recent decades. An estimated 4.3 million Americans use opioids on a daily basis for pain.

“For years, doctors have been encouraged to prescribe long-acting opioids rather than short-acting opioids because we believed they were safer, had less abuse potential, and offered more consistent pain control, but no study has ever been able to support this practice,” Dr. Rubinstein said.

The study compared the use of short-acting opioids, which immediately release the pain medication and are taken every four to six hours, and long-acting opioids, which slowly release the pain medication and are taken every eight to 12 hours.

A healthy young man should have testosterone levels between 300 and 800 nanograms per deciliter (ng/dL); in this study, low testosterone, also known as hypogonadism, was defined as less than 250 ng/dL. Low testosterone levels have been associated with decreases in muscle mass, bone density (osteoporosis or osteopenia), cognition, mood, libido (sex drive) and general quality of life.

Seventy-four percent of the men on long-acting opioids had low testosterone levels, compared with 34 percent of the men using short-acting opioids. After controlling for daily dosage and body mass index, the study found that the odds of having low testosterone were 4.78 times greater for men taking a long-acting opioid than a short-acting opioid. Dose was not associated with an increased risk of low testosterone.

“These medications work well for short-term, acute pain,” said Dr. Rubinstein. “It has long been extrapolated that they can also be used safely long-term to control chronic pain. We are now finding that the long-term use of opioids may have important unintended health consequences.”

Co-authors of the study were Diane M. Carpenter, MPH, Kaiser Permanente Division of Research; and Jerome R. Minkoff, MD, Kaiser Permanente Department of Endocrinology, Santa Rosa Medical Center.

The Clinical Journal of Pain is the official journal of the Eastern Pain Association.


About Kaiser Permanente

About Kaiser Permanente Kaiser Permanente is committed to helping shape the future of health care. We are recognized as one of America’s leading health care providers and not-for-profit health plans. Founded in 1945, our mission is to provide high-quality, affordable health care services and to improve the health of our members and the communities we serve. We currently serve 8.6 million members in nine states and the District of Columbia. Care for members and patients is focused on their total health and guided by their personal physicians, specialists and team of caregivers. Our expert and caring medical teams are empowered and supported by industry-leading technology advances and tools for health promotion, disease prevention, state-of-the art care delivery and world-class chronic disease management. Kaiser Permanente is dedicated to care innovations, clinical research, health education and the support of community health. For more information, go to: www.kp.org/newscenter.


About the Kaiser Permanente Division of Research

About the Kaiser Permanente Division of Research The Kaiser Permanente Division of Research conducts, publishes, and disseminates epidemiologic and health services research to improve the health and medical care of Kaiser Permanente members and the society at large. It seeks to understand the determinants of illness and well-being and to improve the quality and cost-effectiveness of health care. Currently, the center's 400-plus staff is working on more than 250 epidemiological and health services research projects. About Kaiser Permanente Research Kaiser Permanente's eight research centers comprise one of the largest research programs in the U.S. and engage in work designed to improve the health of individuals everywhere. KP HealthConnect™, Kaiser Permanente's electronic health record, and other resources provide population data for research, and in turn, research findings are fed into KP HealthConnect to arm physicians with research and clinical data. Kaiser Permanente's research program works with national and local health agencies and community organizations to share and widely disseminate its research data. Kaiser Permanente's research program is funded in part by Kaiser Permanente's Community Benefit division, which in 2007 directed more than $1 billion in health services, technology, and funding toward total community health. About Kaiser Permanente Kaiser Permanente is America's leading integrated health plan. Founded in 1945, the program is headquartered in Oakland, Calif. Kaiser Permanente serves 8.7 million members in nine states and the District of Columbia. Today it encompasses Kaiser Foundation Health Plan, Inc., Kaiser Foundation Hospitals and their subsidiaries, and the Permanente Medical Groups. Nationwide, Kaiser Permanente includes approximately 159,000 technical, administrative and clerical employees and caregivers, and 14,000 physicians representing all specialties. The organization’s Labor Management Partnership is the largest health care partnership in the United States. It governs how more than 130,000 workers, managers, physicians and dentists work together to make Kaiser Permanente the best place to receive care, and the best place to work. For more Kaiser Permanente news, visit the KP News Center at: http://xnet.kp.org/newscenter