Testosterone treatment is not associated with increased risk of adverse cardiovascular events: results from the Registry of Hypogonadism in Men (RHYME)

Abstract

SummaryAims: The aim of this study was to assess cardiovascular (CV) safety of testosterone replacement therapy (TRT) in a large, diverse cohort of European men with hypogonadism (HG). Methods:The Registry of Hypogonadism in Men (RHYME) was designed as a multinational, longitudinal disease registry of men diagnosed with hypogonadism (HG) at 25 clinical sites in six European countries. Data collection included a complete medical history, physical examination, blood sampling and patient questionnaires at multiple study visits over 2-3 years. Independent adjudication was performed on all mortalities and CV outcomes. Results:Of 999 patients enrolled with clinically diagnosed HG, 750 (75%) initiated some form of TRT. Registry participants, including both treated and untreated patients, contributed 23 900 person-months (99.6% of the targeted) follow-up time. A total of 55 reported CV events occurred in 41 patients. Overall, five patients died of CV-related causes (3 on TRT, 2 untreated) and none of the deaths were adjudicated as treatment-related. The overall CV incidence rate was 1522 per 100 000 person-years.CV event rates for men receiving TRT were not statistically different from untreated men (P=.70). Regardless of treatment assignment, CV event rates were higher in older men and in those with increased CV risk factors or a prior history of CV events. Conclusions:Age and prior CV history, not TRT use, were predictors of new-onset CV events in this multi-national, prospective hypogonadism registry.

Quality of Life and Sexual Function Benefits of Long-Term Testosterone Treatment: Longitudinal Results From the Registry of Hypogonadism in Men (RHYME)

“…prostate safety and cardiovascular events and mortality; these results have been reported elsewhere [19,20]. We now present the secondary outcomes of RHYME on sexual function and QOL symptoms which were assessed by means of validated and widely used symptom scales and were analyzed as secondary outcomes [18].…”

Testosterone and Cardiovascular Health

“…The RHYME (Registry of Hypogonadism in Men) trial 35 found no evidence of increased mortality or CVD events in hypogonadal men receiving testosterone therapy compared with those untreated. The lack of an association persisted between older and younger patients, primary and secondary hypogonadism, and injectable and topical modes of testosterone therapy.…”

The great opportunity of the andrological patient: cardiovascular and metabolic risk assessment and prevention

“…Indeed, androgen deficiency has emerged as a predictor of CV events, as well as of all-cause and CV mortality, both in the general population and in patients with CV risk factors, hypertension, established CVD, and with ED (Corona et al, 2011b). However, recently, well-conducted, prospective large studies support accumulating evidence of the benefit of restoring T levels in hypogonadal men (Muraleedharan et al, 2013;Albert & Morley, 2016;Hackett et al, 2014;Maggi et al, 2016) and the European Medicines Agency (EMA) found no consistent evidence of an increased risk of heart problems with TRT administration (European Medicines Agency 2014). The possibility that low testosterone may be an epiphenomenon, marking poor general health rather than modulating CVD risk per se has to be explored.…”

“…Some controversial reports have been published in last years suggesting possible negative effects of testosterone replacement therapy (TRT) on CV safety (Basaria et al, 2010;Vigen et al, 2013;Finkle et al, 2014). However, recently, well-conducted, prospective large studies support accumulating evidence of the benefit of restoring T levels in hypogonadal men (Muraleedharan et al, 2013;Albert & Morley, 2016;Hackett et al, 2014;Maggi et al, 2016) and the European Medicines Agency (EMA) found no consistent evidence of an increased risk of heart problems with TRT administration (European Medicines Agency 2014). Many scientific societies (European Association of Urology, American Association of Clinical Endocrinologists and American College of Endocrinology, Italian Society of Endocrinology, European Menopause Andropause Society) (Dohle et al, 2015;Goodman et al, 2015;Isidori et al, 2015;Dimopoulou et al, 2016) indeed support the ability of T therapy to improve cardiometabolic risk factors and mortality in hypogonadal men.…”