Testosterone therapy reduces CV events, death in men with hypogonadism
NEW ORLEANS — Low testosterone is associated with increased all-cause and cardiovascular mortality, and testosterone replacement therapy in men with a confirmed diagnosis of hypogonadism is associated with reduced CV events and CV death, according to a speaker at the Androgen Society 2nd Annual Meeting.
“Testosterone deficiency is a risk factor for cardiovascular events and death,” T. Hugh Jones, MBChB, MD, FRCP, honorary professor of andrology in the department of human metabolism the University of Sheffield Medical School, United Kingdom, and consultant endocrinologist at the Royal Hallamshire Hospital in Sheffield, told Endocrine Today. “If you normalize the circulating testosterone level with replacement therapy and monitor the patient, then that ultimately reduces the risk for CV death and events, especially in the diabetes population, for which we have produced evidence. Three other studies have confirmed this. It is important to make a careful, correct diagnosis of hypogonadism and replace the testosterone to a normal level.”
The weight of medical evidence from well-performed studies now supports the idea that testosterone, when replaced to adequate, normal-range levels, has no overall adverse effects on the CV system, and has shown benefit, Jones said during a presentation. Evidence that testosterone protects against ectopic lipid deposition and may modulate the inflammatory response within atherosclerotic plaque is key to researchers’ understanding of how testosterone works.
“I’ve been working in research in testosterone and cardiovascular disease since 1996, and I have treated a large number of men with cardiovascular disease,” Jones said. “We recently did an audit of 505 men, of which one-third had CVD. Over a follow-up of 2,500 patient-years, there was only one CV death and 17 CV events, all of which occurred in people with pre-existing heart disease.”
Jones cited several studies, including an analysis of 3,690 men aged 70 to 89 years published in The Journal of Clinical Endocrinology & Metabolism in 2014. Bu Beng Yeap, MBBS, FRACP, PhD, a professor at the University of Western Australia Medical School and endocrinologist at Fiona Stanley Hospital in Perth, Western Australia, and colleagues measured plasma total testosterone, dihydrotestosterone and estradiol, assayed using liquid chromatography-tandem mass spectrometry, in early morning samples collected from 2001 to 2004, and accessed deaths through 2010 (n = 974). The researchers found that optimal androgen levels are a biomarker for survival. Older men with midrange levels of testosterone and dihydrotestosterone had the lowest death rates from any cause, Jones said, whereas those with higher dihydrotestosterone had lower ischemic heart disease mortality.
“Testosterone replacement therapy improves cardiac ischemia, some CV risk factors and is beneficial in chronic heart failure,” Jones said.
In addition, new techniques for assessing in vivo plaque content, such as intravascular ultrasound with virtual histology, will likely contribute to the understanding of testosterone’s effect on the vasculature in future studies, Jones said.
There are several “points” along the process, from a healthy artery to atherosclerotic artery, where testosterone may have beneficial effects, Jones said. Research in humans and mice suggests that testosterone suppresses pro-inflammatory cytokines, improves insulin resistance, improves the anti-inflammatory cytokine response, reduces adhesion molecule expression and improves vascular reactivity and LDL cholesterol, Jones said — all potential mechanisms by which testosterone may regulate plaque development.
An ongoing, 5-year CV outcomes trial may soon provide more answers for researchers, Jones said. The trial, the Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE ), is assessing time to first major adverse CV event as a primary outcome in 6,000 men with symptomatic hypogonadism randomly assigned to topical testosterone or placebo. The estimated study completion date is June 2022.
“At the moment, we don’t have the 5-year outcome study, but the adverse evidence published between 2010 and 2014 were not very well-performed,” Jones said in an interview after his presentation. “Since then, other studies that have confirmed that the appropriate patients that were treated with testosterone showed this CV benefit.” – by Regina Schaffer
Jones TH. Might T therapy offer CV benefits rather than risk? Presented at: The Androgen Society 2nd Annual Meeting; March 21-22, 2019; New Orleans.
Yeap BB, et al. J Clin Endocrinol Metab. 2014;doi:10.1210/jc.2013-3272.
Disclosure: Jones reports he has received research grants and fees for nonpromotional education lectures from Bayer and Besins Healthcare, served on an advisory board for Ferring and received consultant fees from Mereo BioPharma.