Key Facts
- Study population
- 113,554 men with hypogonadism and 113,554 men without hypogonadism, all prescribed testosterone
- Primary outcome
- Major adverse cardiovascular events (composite of myocardial infarction, ischemic stroke, cardiac arrest, all-cause mortality)
- Risk increase
- 49% higher risk for CV events in men without hypogonadism (HR = 1.51)
- Highest risk subgroup
- Asian men without hypogonadism (HR = 2.39 for CV events, HR = 2.98 for mortality)
- Lowest risk subgroup
- Black men without hypogonadism (HR = 1.31 for CV events, HR = 1.51 for mortality)
- Study lead
- Hatim Kerniss, MD, University Hospital Frankfurt, Germany
Background
A new analysis of data from the TriNetX global collaborative network, published in eBioMedicine, suggests that men prescribed testosterone therapy without hypogonadism face higher risks for major adverse cardiovascular events and all-cause mortality compared with men with hypogonadism using the therapy.
The study, led by Hatim Kerniss, MD, a physician and researcher at University Hospital Frankfurt in Germany, underscores the importance of screening for hypogonadism before prescribing testosterone. Kerniss emphasized that testosterone treatment should not be viewed as a general intervention for aging-related symptoms, fatigue, reduced vitality, or physical performance without adequate diagnostic evaluation.
Current Situation
Researchers conducted a retrospective cohort study of men aged 30 to 75 years who were prescribed testosterone therapy beginning in 2006. Hypogonadism was defined as having at least one symptom of testicular hypofunction, total testosterone concentration of 300 ng/dL or less, or free testosterone of 60 pg/mL or lower.
Using propensity score matching, they paired 113,554 men with hypogonadism using testosterone with 113,554 men prescribed testosterone without hypogonadism. The primary outcome was major adverse cardiovascular events, a composite of myocardial infarction, ischemic stroke, cardiac arrest, and all-cause mortality.
Men without hypogonadism had a higher risk for major adverse cardiovascular events (HR = 1.51; 95% CI, 1.46-1.56; P < .001) and also showed increased risks for all-cause mortality (HR = 1.9; 95% CI, 1.8-2; P < .001), ischemic stroke (HR = 1.23; 95% CI, 1.14-1.33; P < .001), myocardial infarction (HR = 1.1; 95% CI, 1.02-1.17; P = .008), cardiac arrest (HR = 1.41; 95% CI, 1.23-1.61; P < .001), heart failure (HR = 1.32; 95% CI, 1.26-1.39; P < .001), and pulmonary embolism (HR = 1.15; 95% CI, 1.05-1.25; P = .002).
| Outcome | Hazard Ratio | 95% CI | P value |
|---|---|---|---|
| Major adverse CV events | 1.51 | 1.46-1.56 | < .001 |
| All-cause mortality | 1.9 | 1.8-2 | < .001 |
| Ischemic stroke | 1.23 | 1.14-1.33 | < .001 |
| Myocardial infarction | 1.1 | 1.02-1.17 | .008 |
| Cardiac arrest | 1.41 | 1.23-1.61 | < .001 |
| Heart failure | 1.32 | 1.26-1.39 | < .001 |
| Pulmonary embolism | 1.15 | 1.05-1.25 | .002 |
Impacts
The findings indicate that men without hypogonadism who are prescribed testosterone may face a significantly higher risk of cardiovascular events and death. This could affect clinical decision-making, prompting physicians to screen more carefully for hypogonadism before prescribing testosterone and to optimize cardiovascular risk factors before treatment.
Racial and ethnic differences were observed. Asian men without hypogonadism had the highest increased risk for major adverse cardiovascular events (HR = 2.39) and all-cause mortality (HR = 2.98) compared with those with hypogonadism. Black men without hypogonadism had the lowest increased risk for major adverse cardiovascular events (HR = 1.31) and all-cause mortality (HR = 1.51) than those with hypogonadism (log-rank P for all < .0001).
Kerniss noted that it was surprising to see Asian men having the highest risk for both outcomes, raising questions about biological susceptibility, body composition, pharmacokinetics, prescribing patterns, or residual confounding. He called for dedicated studies involving Asian populations to confirm these findings.
Future Outlook
Scenario analysis: The possibilities below are not certain predictions.
Kerniss suggested that large prospective registry studies and real-world target-trial emulations should be conducted to confirm the findings and allow more detailed analysis. Particular attention should be paid to treatment dose and formulation, achieved testosterone levels, hematocrit changes, duration of exposure, and cardiovascular risk profiles.
If confirmed, these findings could lead to stricter guidelines for testosterone prescribing, emphasizing the need for diagnostic evaluation and cardiovascular risk assessment before initiation. The pronounced signals observed in Asian men may also prompt further research into whether they reflect biological susceptibility, treatment patterns, or residual confounding.
However, the study's retrospective design and potential residual confounding mean that causality cannot be established. Future prospective studies may provide clearer evidence, but until then, clinicians should weigh the potential cardiovascular risks when considering testosterone therapy for men without hypogonadism.
Source: healio.com
खबर को बेहतर समझें
आंकड़े, तुलना और घटनाक्रम—एक ही जगह, बिना अनुमान के
Hazard Ratios for Cardiovascular Outcomes in Men Without Hypogonadism vs. With Hypogonadism
Pulmonary embolism1.15
सटीक आंकड़े देखें
| श्रेणी | Hazard Ratio |
|---|---|
| Major adverse CV events | 1.51 |
| All-cause mortality | 1.9 |
| Ischemic stroke | 1.23 |
| Myocardial infarction | 1.1 |
| Cardiac arrest | 1.41 |
| Heart failure | 1.32 |
| Pulmonary embolism | 1.15 |
स्रोत:healio.com स्रोत-समर्थित
