Chevy Chase, MD,February 6, 2007 - Widely used assay methods to measure serum testosterone (T) suffer from a lack of accuracy and sensitivity, making it difficult for physicians to appropriately diagnose and treat androgen-related disorders in women, children, and men. To address the severely limited utility of these tests, The Endocrine Society has issued a new position statement that outlines a series of recommendations to physicians ordering and using androgen assays. The statement, published in the February 2007 issue of the Journal of Clinical Endocrinology & Metabolism, calls for standardizing the methods by which these assays are validated.

“There are serious problems with sensitivity and accuracy in testosterone assays, which need to be as accurate and reproducible as possible,” said Dr. William Rosner, professor of medicine, Columbia University College of Physicians and Surgeons, New York City, and member of the Society’s Androgen Assay Working Group, which studied the accuracy of the assays and prepared the Society’s statement. “The diagnosis and management of many serious medical conditions for women and men will depend to a large degree on highly accurate testosterone measurements.”

Testosterone is the primary male sex hormone, but it may also fulfill important functions in women and children, including helping to maintain bone and muscle mass throughout life. In men, insufficient testosterone levels (hypogonadism) have been linked to obesity, low libido, and other serious medical conditions.

To develop its recommendations, the Society working group evaluated existing data on measuring total testosterone (TT) and free testosterone (FT) in women, men, and children. The working group also reviewed proficiency survey data from the College of American Pathologists (CAP), which administers a laboratory quality-control program. According to the working group, the CAP survey revealed an unacceptable reliability for T assays. However, the survey also showed that standardization is achievable by the widespread use of the most accurate assay methods, which are able to identify the chemical structure of the molecule being measured.

Based on these results, the Society working group made the following principal recommendation:

• Laboratory proficiency testing should be based on the ability to accurately and precisely measure a sample containing a known concentration of T and not only on agreement with peers using the same method. When such standardization is in place, normative values for TT and FT should be established taking into account all the appropriate variables, e.g. gender, age, race, stage of puberty, time of day, etc. We believe that this goal can be accomplished. It has been done for cholesterol.

“It is critical for patient health that we reconsider the ways in which we measure testosterone in all ages and across both sexes,” said Rosner. “We have the technology to improve the testosterone assays and must prioritize this over simplicity and economy to take proper care of our patients.”

Until standardization occurs, the Society offers the following nine recommendations to physicians when ordering and using androgen assays:

• Know the type and quality of the assay that is being used and the properly established and validated reference intervals for that assay. Reference intervals should be established by each laboratory in collaboration with endocrinologists, using well-defined and characterized populations.
• In the absence of other information, direct assays (those performed on whole serum) perform poorly at low T concentrations (i.e. in women, children, and hypogonadal men) and should be avoided. Assays after extraction and chromatography, followed by either MS (mass spectrometry) or immunoassay, are likely to furnish more reliable results and are currently preferred. 
• Assays for T may behave differently in controls and affected individuals, perhaps reflecting differences in the endocrine milieu of patients.
• Most assays will distinguish between T concentrations in classic hypogonadism and those in normal men. Serum TT, preferably obtained on more than one morning sampling, is the recommended screening test for hypogonadism.
• Assuming a high-quality assay and well-defined reference intervals, a serum TT, preferably drawn during the early follicular phase of the menstrual cycle, is recommended as the initial test in seeking out androgen-producing tumors in women.
• Calculated FT, using high-quality T and SHBG (sex hormone binding globulin) assays with well-defined reference intervals, is the most useful, clinically sensitive marker of hyperandrogenemia (androgen excess) in women and can be used in concert with clinical end points in the diagnosis and follow-up of such patients.
• In the absence of pituitary insufficiency, the use of T assays in the evaluation of sexual dysfunction or fatigue in adult women is not supported by published evidence and is strongly discouraged.
• In children, reference intervals must be adjusted for gender, age, and stage of adolescent development and must be specific for the assay method, until a universal standard is available.
• FT measurements in children are of limited value. Evaluations of androgen excess, virilization, intersex disorders, or contrasexual maturation are the only indications for T measurement in girls. Several indications exist for T measurements in boys, including assessment of gonadal failure, disorders of sexual development or puberty, and monitoring response to treatment.

Other members of the working group include Dr. Richard J. Auchus, division of endocrinology and metabolism, University of Texas Southwestern Medical Center, Dallas; Dr. Ricardo Azziz, center for androgen related disorders and department of obstetrics/gynecology, Cedars-Sinai Medical Center, and department of obstetrics-gynecology and department of medicine, The David Geffen School of Medicine, University of California, Los Angeles; Dr. Hershel Raff, endocrine research laboratory, Aurora St. Luke’s Medical Center, division of endocrinology, metabolism, and clinical nutrition, Medical College of Wisconsin, Milwaukee; and Dr. Patrick M. Sluss, reproductive endocrinology unit and department of pathology, Massachusetts General Hospital, Boston.

# # #

Founded in 1916, The Endocrine Society is the world's oldest, largest, and most active organization devoted to research on hormones and the clinical practice of endocrinology. Today, The Endocrine Society's membership consists of over 14,000 scientists, physicians, educators, nurses and students in more than 80 countries. Together, these members represent all basic, applied, and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Md. To learn more about the Society, and the field of endocrinology, visit our web site at www.endo-society.org.