Wide Variations in Use of Testosterone Therapy Among VHA Facilities
Published Online: October 02, 2013
Guneet K. Jasuja, PhD; Shalender Bhasin, MD; Joel I. Reisman, AB; and Adam J. Rose, MD, MSc
An expert panel of the Endocrine Society defi ned hypogonadism as “a clinical syndrome that results from failure of the testis to produce physiological levels of testosterone (androgen deficiency) and a normal number of spermatozoa due to disruption of one or more levels of the hypothalamic-pituitary-testicular axis” and recommended that a diagnosis of androgen deficiency should be made “only in men with consistent symptoms and signs and unequivocally low serum testosterone levels.”1 Testosterone therapy is indicated for the treatment of men with hypogonadism1,2 and is associated with a favorable risk/benefit ratio.1-5 The exact prevalence and incidence of hypogonadism are not known.1
The sales of testosterone and other androgenic products have had explosive growth during the past decade in the setting of strong promotion by the pharmaceutical industry; the retail sales exceeded $1.6 billion in 2011 (IMS Inc; data courtesy of Dr Michael Miller, Abbott Laboratories). In the United States, the prescription sales of testosterone grew by 25% to 30% annually between 1993 and 2002.6 Although the exact distribution of the indications for which testosterone therapy is prescribed in the United States is not known, it has been suspected that a sizable proportion of testosterone use is for conditions such as the age-related decline in testosterone, for which testosterone therapy is currently not approved or recommended.
Total testosterone levels in men decline progressively with age at an average rate of 1.5% per year.7-10 This agerelated decline in testosterone levels has been associated with adverse cardiometabolic, physical function, and mobility outcomes in older men.11-20 However, neither the clinical benefi ts nor the long-term risks of testosterone therapy have been established in adequately powered randomized trials in older men with age-related decline in testosterone levels.6 Testosterone therapy currently is not approved for treatment of age-related decline in testosterone levels. The growing use of testosterone in men, particularly older men, without a clear understanding of its benefits or long-term risks, has raised concern among regulatory agencies.
For many years, injectable testosterone esters have been the most frequently used treatment modality for male hypogonadism.21 Recently, newer treatment modalities have been introduced, including transdermal patches and gels. These new forms, which may be more acceptable to patients, will provide additional options and convenience, and may further contribute to increasing demand for exogenous testosterone therapy.
There have been few systematic investigations of the overall rate of use for exogenous testosterone therapy. The variability in this rate of testosterone use among sites of care or providers is largely unknown. Thus, our first objective was to examine variation in age-adjusted rates of exogenous testosterone administration among sites of care in the Veterans Health Administration (VHA), the nation’s largest integrated healthcare system. Our second objective was to explore the cost implications of the variation in rates of prescription among sites. We expected to find that VHA sites would vary widely in rates of prescription of exogenous testosterone therapy to male veterans, even after adjusting for the age profi le at each site. Greater understanding of the site-level variation in testosterone prescribing will be an important fi rst step to understanding the site-level and patient-level predictors of testosterone utilization in the VHA system. It is likely that testosterone is overused at some sites, and in fact it may be underused at other sites. This study will constitute an important fi rst step to promoting a more consistently evidence-based and rational approach to prescribing exogenous testosterone.
The database for this study comprised prescription, demographic, diagnostic, and care delivery data for patients receiving care in VHA. The data set encompassed a 1-year period from October 1, 2010, to September 30, 2011 (fiscal year 2011 [FY11]). The study was approved by the institutional review board of the Bedford VHA Medical Center.
The study population consisted of all patients who had at least 1 outpatient visit or hospitalization during the study period, were male, and did not test positive for the human immunodefi ciency virus (HIV) (N = 5,196,156). The mean age of the sample was 62.4 years (range, 20-105 years; standard deviation, 15.8 years). Exogenous administration of testosterone to patients with HIV is a different issue from its use in the general population.22-25 Patients’ HIV status was determined according to VHA data. Any positive HIV antibody result or nonzero HIV viral load was taken to indicate that the patient was HIV positive. Among males in the study population, 2.0% were deemed to be HIV positive and were therefore excluded.
VHA healthcare facilities are organized into sites, typically consisting of a main hospital and several satellite clinics. There were 129 sites in the study. About 90% of VHA patients receive all their care at 1 site. When a patient received care at multiple sites, most often this was attributable to the patient relocating. For the present analysis, patients were assigned to the site at which they had the most encounters (outpatient and inpatient); in the event of a tie, they were assigned to the site at which they had most recently received care.
Exogenous Testosterone Administration Characteristics
Testosterone prescription fills were counted if they were issued in the outpatient setting. The indicated days of supply of a fill were assumed to represent the quantity of medication dispensed in a way that would allow comparison among the different routes of administration. The measure of total cost of a fill represented the combined costs of the medication and the labor and materials used in dispensing it. It does not, however, include the cost of nursing staff effort to administer intramuscular injections.
Site Proportion on Testosterone
Patients were considered to be “on testosterone” if they received any form of testosterone from an outpatient VHA pharmacy during the 1-year study period. We examined both the actual proportion of patients at a site who received testosterone and the age-standardized proportion. In the age-standardized analysis, every site was treated as though it had the same age distribution as the overall VHA population.
Statistical Assessment of Site-Level Variation in Testosterone Prescribing
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