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Testosterone therapy duration associated with mortality, CV events
Short-duration testosterone replacement therapy in older men was associated with increased risks for mortality and cardiovascular events, whereas longer duration therapy was associated with reduced mortality and cardiovascular events vs. matched controls, according to recent study findings.
“This study resolves the controversy of testosterone replacement therapy,” Robert Nam, MD, FRCSC, chair in urologic oncology and professor of surgery at the University of Toronto, told Endocrine Today. “Short-term intake is associated with higher mortality and CV rates because patients are still suffering from testosterone deficiency. When taken for longer, the protective effect is realized.”
Robert Nam
In a retrospective, population-based, matched-cohort study, Nam, Christopher J.D. Wallis, MD, of the division of urology at Sunnybrook Health Sciences Centre at the University of Toronto, and colleagues analyzed data from 10,311 men aged at least 66 years receiving at least one prescription for testosterone replacement therapy, identified through the Ontario Drug Benefit database. Men were matched with up to three men from the general population (n = 28,029) who had no prescription for testosterone therapy to serve as controls, matched for age, region of residence, comorbidities, diabetes status and index year (between 2007 and 2012). Researchers followed patients from index date (date of first prescription for testosterone replacement therapy) until the death, development of a CV outcome, prostate cancer diagnosis or March 31, 2013.
Researchers linked the Ontario Drug Benefit database, the Canadian Institute for Health Information (CIHI) Discharge Abstract Database, the CIHI National Ambulatory Care Reporting System, the Ontario Health Insurance Plan database, the Ontario Myocardial Infarction Database, the Ontario Diabetes Database, the Ontario Cancer Registry, and the Registered Persons Database.
Median follow-up was 5.3 years in the testosterone therapy group and 5.1 years in the control group. Researchers also assessed the association between testosterone replacement therapy based on cumulative dose exposure and outcomes; median duration in the lowest tertile was 2 months; median duration in the middle tertile was 9 months; median duration in the highest tertile was 35 months.
During follow-up, patients treated with testosterone replacement therapy had lower mortality vs. controls (HR = 0.88; 95% CI, 0.84-0.93). Patients in the lowest tertile of testosterone exposure had increased risks for mortality (HR = 1.11; 95% CI, 1.03-1.2) and CV events (HR = 1.26; 95% CI, 1.09-1.46) vs. controls; however, patients in the highest tertile of testosterone exposure had decreased risks for mortality (HR = 0.67; 95% CI, 0.62-0.73) and CV events (HR = 0.84; 95% CI, 0.72-0.98) vs. controls, with a trend observed across tertiles (P < .0001).
Researchers found a decreased risk for prostate cancer diagnosis for patients only in the highest tertile of exposure (HR = 0.6; 95% CI, 0.45-0.8) vs. controls.
“As a result of this approach, we were able to account for the previous conflicting findings of the effect of testosterone replacement therapy on [CV] events and mortality,” the researchers wrote. “With a large sample size and long duration of follow-up, we identified a beneficial association of long-term testosterone replacement therapy, but also showed that short-term durations of therapy might be associated with harm.”
In commentary accompanying the study, Michael S. Lauer, MD, of the Office of Extramural Research at the NIH, noted that the researchers took an important step in focusing only on men whose physicians gave them new prescriptions for testosterone, using the date of first prescription as the index date of observation and the corresponding date for controls.
“Using this study design, the investigators were able to identify a nuanced association between testosterone exposure and outcomes,” Lauer wrote. “This intention-to-treat design suggests that the effects of testosterone on health are unlikely to be simple and monotonic.” – by Regina Schaffer
For more information:
Robert Nam, MD, FRCSC, can be reached at the Odette Cancer Center, Sunnybrook Health Sciences Center, 2075 Bayview Ave., Room MG-406, Toronto, Ontario, M4N 3M5; email: Robert.nam@utoronto.ca.
Disclosure: The researchers report no relevant financial disclosures. Lauer reports no relevant financial disclosures.