This article is more than 5 years old. Information may no longer be current.
Normalization of testosterone levels with replacement therapy lowers mortality risk in men with prior MI
Testosterone replacement therapy in male veterans with prior MI was not associated with an increased risk for recurrent MI and was found to decrease all-cause mortality in those whose total testosterone levels returned to normal, according to data published in the American Journal of Cardiology.
Normalization of total testosterone levels in male veterans with hypogonadism and previous MI using testosterone replacement therapy associated with decreased risk for all-cause mortality compared with those whose levels did not normalize or those who did not receive testosterone replacement therapy.
Additionally, researchers found no significant rise in recurrent MI after the hypogonadal men received testosterone replacement therapy, despite whether they achieved normalized testosterone levels or did not.
“The lack of reduction in MI after [testosterone replacement therapy] in patients with prior MI suggests normalization of [total testosterone] alone may not be sufficient to reduce MI events in this high-risk population,” the authors wrote. “Given the multifactorial nature of atherosclerotic CAD and complex pathophysiology of ACS, a comprehensive risk factor reduction strategy is needed to reduce the risk of recurrent MI.”
Cardiology Today corresponded with Rajat S. Barua, MD, PhD, FACC, FSCAI, chief of cardiology at Kansas City VA Medical Center, regarding the implications of this study.
“This study, taken together with our previous study in patients without previous MI or stroke (Sharma R, et al. Eur Heart J. 2015;doi:10.1093/eurheartj/ehv346), we can infer two things: [In] truly hypogonadal patients, total testosterone normalization through testosterone replacement therapy is likely to benefit patients in terms of all-cause-mortality. In patients without previous MI and stroke, appropriate testosterone replacement therapy is likely to benefit patients in terms of CV events,” Barua said. “[Secondly], in patients with previous MI, we did not see increased harm and also we did not see a reduction in MI event, thus, suggesting a possible neutral effect of testosterone replacement therapy in terms of CV events in this patient population.”
In this retrospective study, researchers analyzed the patient data of 1,470 male veterans with prior MI and documented low total testosterone. Patients were divided into three groups: patients who received testosterone replacement therapy and had normalization of total testosterone levels (n = 755); patients who received testosterone replacement therapy without normalization of total testosterone levels (n = 542); and patients with low total testosterone and received no testosterone replacement therapy (n = 173).
Researchers found that all-cause mortality was lower in those who received therapy and had normalized total testosterone vs. those whose values did not normalize (HR = 0.76; 95% CI, 0.64-0.9), and also when compared with those who received no testosterone replacement therapy (HR = 0.76; 95% CI, 0.6-0.98). The researchers found no difference in mortality risk when they compared the group that received therapy but did not have normalized testosterone and the group that did not receive therapy (HR = 0.97; 95% CI, 0.76-1.24).
According to the study, there was no significant differences in the risk of recurrent MI between each of three groups.
“As clinicians, we should have an honest discussion with our patients and individualize our care,” Barua told Cardiology Today. “Population studies suggest that low serum levels of endogenous testosterone are a risk factor for CV events. But the role of testosterone replacement therapy and its effects on CVD remains controversial. Randomized clinical trials examining the effects of testosterone replacement therapy historically have been small and underpowered to provide conclusive evidence on the risk of adverse CV events. Our current study suggests in truly hypogonadal patients — we had two separate measurements of TT levels — with previous MI , normalization of the total testosterone level was associated with a decrease in all-cause-mortality and there was no increase in CV events in relation to testosterone replacement therapy.”
Barua also said “indiscriminate and inappropriate use of testosterone remains a concern. Testosterone therapy is not a fountain of youth. Like any other medication it has its benefits, side effects and toxicity. [This] study and the previous studies by our group add that simply prescribing testosterone replacement therapy is not good enough. To achieve mortality benefit and CV benefits, the prescribing physician needs to ensure that patients’ testosterone levels achieve a normal therapeutic range. I also propose that risks and benefits of testosterone replacement therapy depend on the risk profile of the patient rather than the therapy itself. To maximize the benefit of testosterone replacement therapy, physicians need to appropriately screen, select, dose and follow up with individual patients.”
The researchers stated that, while further research is needed, there still may be a role for testosterone replacement therapy in carefully selected patients with CVD and hypogonadism.
One example, Barua said, is the randomized TRAVERSE trial, which started in 2018.
“TRAVERSE is the first trial of testosterone therapy that is adequately powered to assess CV events. But outcomes of this trial may take an additional 5 to 10 years to become available,” Barua said. “Personally, I believe there is a U-shaped curve in relation to testosterone level/therapy (i.e., higher events in sub- as well as supra-physiological levels of testosterone) so we are doing some bench research related to that as well to understand the mechanism(s).” – by Scott Buzby
For more information:
Rajat S. Barua, MD, PhD, FACC, FSCAI , can be reached at the Kansas City Veterans Affairs Medical Center, 4801 E. Linwood Blvd, Kansas City, MO 64128; email: rajat.barua@va.gov.
Disclosures: Barua reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.