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Cardiovascular disease and T therapy: Dangerous or protective?
There are extensive epidemiological data on hypogonadism, and a growing number of studies are investigating the effects of testosterone therapy on cardiovascular outcomes. In the MrOS (Osteoporotic Fractures in Men) Study, high testosterone levels were associated with a reduced risk of cardiovascular events in elderly men.1 Notably, men with the highest testosterone levels (≥19.1 nmol/L or ≥550 ng/dL) had a 30% lower risk (hazard ratio: 0.70) of cardiovascular events compared to men with lower testosterone levels. This association remained after adjustment for traditional cardiovascular risk factors.1
The Registry of Hypogonadism in Men (RHYME) study investigated the cardiovascular safety of testosterone therapy in a large, diverse multi-national cohort of European men with hypogonadism.2 Of 999 patients enrolled with clinically diagnosed hypogonadism, 750 (75%) initiated some form of testosterone therapy. It was found that cardiovascular event rates for men receiving testosterone therapy were not statistically different from untreated men. It was concluded that age and prior cardiovascular history, not testosterone therapy, were predictors of new-onset cardiovascular events.2
A registry “real-life” study, investigated the long-term effects and safety of testosterone therapy for up to 8 years in hypogonadal men attending a urological office.3 Differences in cardiovascular risk factors and mortality were compared to those seen in hypogonadal men attending the same urological office but not receiving testosterone therapy. The results confirmed the well documented improvements in lipid profile, especially reduction in non-HDL levels, and glycemic control (marked reduction in HbA1c from diabetic to normal glycemia). Importantly, it was found that long-term testosterone therapy for 8 years in obese men with testosterone deficiency reduced death, non-fatal heart attack and stroke, compared to men not receiving testosterone therapy.3 The testosterone-group had an estimated reduction in mortality between 66% and 92% compared to non-treated men. Being conducted in a real-life setting – as opposed to a controlled study environment – this study provides evidence that long-term testosterone therapy is both effective, safe and feasible in clinical practice, and importantly, results in a reduction in "hard clinical endpoints".3
Out of 11 meta-analyses, only 1 suggested an increased cardiovascular disease risk. Hence, there is overwhelming evidence supporting the standpoint that testosterone therapy is safe and does not increase cardiovascular disease risk. In summary, testosterone therapy in the physiological range in men with hypogonadism improved cardiovascular risk factors and may be protective against cardiovascular disease.
Abdulmaged Traish, PhD Boston University School of Medicine
Ohlsson C, Barrett-Connor E, Bhasin S, Orwoll E, Labrie F, Karlsson MK, Ljunggren O, Vandenput L, Mellström D, Tivesten A. High serum testosterone is associated with reduced risk of cardiovascular events in elderly men. The MrOS (Osteoporotic Fractures in Men) study in Sweden. J Am Coll Cardiol. 2011 Oct 11;58(16):1674-81Return to content
Maggi M, Wu FC, Jones TH, Jackson G, Behre HM, Hackett G, Martin-Morales A, Balercia G, Dobs AS, Arver ST, Maggio M, Cunningham GR, Isidori AM, Quinton R, Wheaton OA, Siami FS, Rosen RC; RHYME Investigators. Testosterone treatment is not associated with increased risk of adverse cardiovascular events: results from the Registry of Hypogonadism in Men (RHYME). Int J Clin Pract. 2016 Oct;70(10):843-852.Return to content
Traish AM, Haider A, Haider KS, Doros G, Saad F. Long-Term Testosterone Therapy Improves Cardiometabolic Function and Reduces Risk of Cardiovascular Disease in Men with Hypogonadism: A Real-Life Observational Registry Study Setting Comparing Treated and Untreated (Control) Groups. J Cardiovasc Pharmacol Ther. 2017 Sep;22(5):414-433Return to content