Normalization of Testosterone Levels After Testosterone Replacement Therapy Is Associated With Decreased Incidence of Atrial Fibrillation

Abstract

BackgroundAtrial fibrillation (AF) is the most common cardiac dysrhythmia associated with significant morbidity and mortality. Several small studies have reported that low serum total testosterone (TT) levels were associated with a higher incidence of AF. In contrast, it is also reported that anabolic steroid use is associated with an increase in the risk of AF. To date, no study has explored the effect of testosterone normalization on new incidence of AF after testosterone replacement therapy (TRT) in patients with low testosterone.Methods and ResultsUsing data from the Veterans Administrations Corporate Data Warehouse, we identified a national cohort of 76 639 veterans with low TT levels and divided them into 3 groups. Group 1 had TRT resulting in normalization of TT levels (normalized TRT), group 2 had TRT without normalization of TT levels (nonnormalized TRT), and group 3 did not receive TRT (no TRT). Propensity score–weighted stabilized inverse probability of treatment weighting Cox proportional hazard methods were used for analysis of the data from these groups to determine the association between post‐TRT levels of TT and the incidence of AF. Group 1 (40 856 patients, median age 66 years) had significantly lower risk of AF than group 2 (23 939 patients, median age 65 years; hazard ratio 0.90, 95% CI 0.81–0.99, P=0.0255) and group 3 (11 853 patients, median age 67 years; hazard ratio 0.79, 95% CI 0.70–0.89, P=0.0001). There was no statistical difference between groups 2 and 3 (hazard ratio 0.89, 95% CI 0.78– 1.0009, P=0.0675) in incidence of AF.ConclusionsThese novel results suggest that normalization of TT levels after TRT is associated with a significant decrease in the incidence of AF.

The state of testosterone therapy since the FDA's 2015 labelling changes: Indications and cardiovascular risk

“…Risks of adverse CV events were similar for untreated men and treated men without T normalization. This same group found that normalization of testosterone levels is associated with a decreased incidence of atrial fibrillation, a condition often associated with increased risk of stroke …”

“…Since the FDA advisory committee meeting in September 2014, 23 new studies published addressing CV risks of TTh. This includes 12 clinical trials and 11 observational data analyses . Five of these studies comprise the T Trials .…”

“…A 3‐year placebo‐controlled trial showed no difference in progression of carotid atherosclerosis . Two observational studies showed reduced hazard ratio of MACE for men whose T levels normalized with treatment compared with those whose T levels failed to normalize, indicating suboptimal treatment may increase CV risk . Further, one study showed that longer duration of treatment was associated with reduced CV events .…”

Emerging Evidences in the Long Standing Controversy Regarding Testosterone Replacement Therapy and Cardiovascular Events

“…There are few studies that have investigated the effect of TTh on arrhythmias. Sharma et al [ 45 ] studied whether normalization of serum T levels after TTh has an impact on the incidence of atrial fibrillation (Afib). They retrospectively compared patients at the US VA who received TTh and resulted in normalization of serum T (n=40,856), patients who received TTh without normalization of serum T (n=23,930), and those who did not receive TTh and continued to have low serum T (n=11,853).…”

“…Sharma et al [ 45 ] highlighted that normalization of T levels is associated with a lower incidence of Afib in men with LOH. Although the mechanism by which normal T levels reduce the risk of Afib is still unclear, their study suggested that TTh may have antiarrhythmogenic properties.…”