IMPORTANCE Controversy exists regarding the safety of testosterone replacement therapy (TRT) following recent reports of an increased risk of adverse cardiovascular events.OBJECTIVE To investigate the association between TRT and cardiovascular outcomes in men with androgen deficiency. DESIGN, SETTING, AND PARTICIPANTSA retrospective cohort study was conducted within an integrated health care delivery system. Men at least 40 years old with evidence of androgen deficiency either by a coded diagnosis and/or a morning serum total testosterone level of less than 300 ng/dL were included. The eligibility window was January 1, 1999, to December 31, 2010, with follow-up through December 31, 2012.EXPOSURES Any prescribed TRT given by injection, orally, or topically. MAIN OUTCOMES AND MEASURESThe primary outcome was a composite of cardiovascular end points that included acute myocardial infarction (AMI), coronary revascularization, unstable angina, stroke, transient ischemic attack (TIA), and sudden cardiac death (SCD). Multivariable Cox proportional hazards models were used to investigate the association between TRT and cardiovascular outcomes. An inverse probability of treatment weight, propensity score methodology, was used to balance baseline characteristics. RESULTSThe cohorts consisted of 8808 men (19.8%) ever dispensed testosterone (ever-TRT) (mean age, 58.4 years; 1.4% with prior cardiovascular events) and 35 527 men (80.2%) never dispensed testosterone (never-TRT) (mean age, 59.8 years; 2.0% with prior cardiovascular events). Median follow was 3.2 years (interquartile range [IQR], 1.7-6.6 years) in the never-TRT group vs 4.2 (IQR, 2.1-7.8) years in the ever-TRT group. The rates of the composite cardiovascular end point were 23.9 vs 16.9 per 1000 person-years in the never-TRT and ever-TRT groups, respectively. The adjusted hazard ratio (HR) for the composite cardiovascular end point in the ever-TRT group was 0.67 (95% CI, 0.62-0.73. Similar results were seen when the outcome was restricted to combined stroke events (stroke and TIA) (HR, 0.72; 95% CI, 0.62-0.84) and combined cardiac events (AMI, SCD, unstable angina, revascularization procedures) (HR, 0.66; 95% CI, 0.60-0.72).CONCLUSIONS AND RELEVANCE Among men with androgen deficiency, dispensed testosterone prescriptions were associated with a lower risk of cardiovascular outcomes over a median follow-up of 3.4 years.

During nearly 5 years of follow-up, 28.9% of patients with diabetes were nonadherent to the retinal screening guidelines. Future research should focus on the development of interventions to address modifiable factors associated with nonadherence.

Adherence to medications for DM and HTN were differed and higher MMA reduced microvascular or macrovascular complications when controlling for endogeneity bias.