News Author: Laurie Barclay, MD
CME Author: Charles Vega, MD, FAAFP
To earn CME credit, read the news brief along with the CME information that follows and answer the test questions.
Release Date: August 28, 2006; Valid for credit through August 28, 2007
Physicians – maximum of 0.25 AMA PRA Category 1 Credit(s)™ for physicians;
Family Physicians – up to 0.25 AAFP Prescribed credit(s) for physicians;
Nurses – 0.3 nursing contact hours (None of these credits is in the area of pharmacology)
August 28, 2006 — Low testosterone levels were linked with an increase in mortality in a cohort of male veterans, according to the results of a study reported in the August 14/28 issue of the Archives of Internal Medicine.
“Low serum testosterone is a common condition in aging associated with decreased muscle mass and insulin resistance,” write Molly M. Shores, MD, from the VA Puget Sound Health Care System in Seattle, Washington, and colleagues. “Testosterone levels also decrease with acute and chronic illnesses and with medications such as glucocorticoids and opiates.”
The investigators used a clinical database to identify men older than 40 years with repeated testosterone levels obtained from October 1, 1994, to December 31, 1999, and without diagnosed prostate cancer. Low testosterone was defined as a total testosterone level of less than 250 ng/dL (< 8.7 nmol/L) or a free testosterone level of less than 0.75 ng/dL (< 0.03 nmol/L). Men were classified as having a low testosterone level (n = 166; 19.3%), an equivocal testosterone level with an equal number of low and normal levels (n = 240; 28.0%), or a normal testosterone level (n = 452; 52.7%). Cox proportional hazards regression models adjusting for demographic and clinical covariates were used to estimate the risk for all-cause mortality during follow-up of up to 8 years.
Mortality was 20.1% in men with normal testosterone levels (95% confidence interval [CI], 16.2% – 24.1%) compared with 24.6% in men with equivocal testosterone levels (95% CI, 19.2% – 30.0%), and 34.9% in men with low testosterone levels (95% CI, 28.5% – 41.4%).
After adjustment for age, medical morbidity, and other clinical covariates, low testosterone levels continued to be associated with increased mortality (hazard ratio, 1.88; 95% CI, 1.34 – 2.63; P < .001). However, after adjustment, equivocal testosterone levels did not differ significantly from normal testosterone levels (hazard ratio, 1.38; 95% CI, 0.99% – 1.92%; P =.06). When men who died within the first year (n = 50; 5.8%) were excluded to minimize the effect of acute illness, low testosterone levels continued to be associated with elevated mortality.
Study limitations include retrospective design, inability to establish causality, lack of systematic assessment of a prospective cohort, lack of data on testosterone treatment, use of platform testosterone assays, and lack of generalizability beyond a Veterans Affairs clinic-based population.
“Low testosterone levels were associated with increased mortality in male veterans,” the authors write. “Further prospective studies are needed to examine the association between low testosterone levels and mortality… The persistence of elevated mortality risk after excluding early deaths suggests that the association between low testosterone and mortality is not simply due to acute illness.”
The Geriatric Research, Education, and Clinical Center; VA Puget Sound Health Care System; and the Royalty Research Fund of the University of Washington supported this study. Some of the authors have disclosed various financial relationships with Solvay Pharmaceuticals Inc., GlaxoSmithKline, Ascend Therapeutics, and GTx Inc.
Arch Intern Med. 2006;166:1660-1665.
Learning Objectives for This Educational Activity
Upon completion of this activity, participants will be able to:
- Describe the epidemiology and consequences of low testosterone levels in older men.
- Compare the risk for mortality among men with low, equivocal, and normal testosterone levels.
Testosterone levels gradually decrease with age in men, falling by approximately 1.5% per year. By the age of 80 years, approximately half of men have a testosterone deficiency. These patients may have reduced muscle mass, lower bone density, increased fat mass, insulin resistance, and dysphoria compared with men with normal levels of testosterone.