How does testosterone therapy affect patients with hypertension or at risk for hypertension?

Testosterone Therapy and Hypertension

Testosterone therapy is generally associated with a reduction in blood pressure in hypogonadal men, with greater reductions observed in those with higher baseline blood pressure values. 1

Effects of Testosterone on Blood Pressure

Positive Effects

• Testosterone undecanoate therapy has been shown to significantly reduce systolic blood pressure, diastolic blood pressure, and pulse pressure in men with testosterone deficiency 1
• These reductions occur regardless of whether patients are on antihypertensive therapy, though larger reductions are seen with concurrent antihypertensive treatment 1
• In men not receiving antihypertensive agents, median reductions of 12.5 mmHg in systolic BP and 8.0 mmHg in diastolic BP have been observed 1

Potential Risks

• The FDA required a labeling change in 2015 regarding possible increased cardiovascular risks, with injectable testosterone potentially associated with greater cardiovascular risk than gels due to fluctuating levels 2
• Some testosterone preparations' product labels caution about potential association with hypertension 1
• Rare cases of hypertension as a complication of topical testosterone therapy have been reported, with blood pressure returning to normal after discontinuation 3

Recommendations for Patients with Hypertension

Before Starting Therapy

1. Assess all testosterone deficient patients for ASCVD risk factors, both fixed (e.g., older age, male gender) and modifiable (e.g., dyslipidemia, hypertension, diabetes, current cigarette smoking) 4
2. Measure baseline hemoglobin/hematocrit, as increased hematocrit can contribute to hypertension 4
3. Counsel patients that the current scientific literature does not definitively demonstrate that testosterone therapy increases the risk of major adverse cardiovascular events (MACE) 4

During Therapy

1. Adjust testosterone therapy dosing to achieve a total testosterone level in the middle tertile of the normal reference range (450-600 ng/dL) 4, 2
2. Monitor blood pressure regularly, particularly in patients with pre-existing hypertension or cardiovascular risk factors 2
3. Monitor hematocrit, as increases in hematocrit (which commonly occur with testosterone therapy) can potentially affect blood pressure 4, 5
4. If hematocrit exceeds 54%, intervene with dose reduction or temporary discontinuation 4

Special Considerations

• For patients with a history of cardiovascular events, testosterone therapy should not be commenced for a period of three to six months after the most recent cardiac event 4
• Due to sodium and water retention, edema with or without congestive heart failure may be a serious complication in patients with pre-existing cardiac, renal, or hepatic disease 6
• If edema develops, discontinuation of testosterone and diuretic therapy may be required 6

Lifestyle Modifications

Counsel patients with testosterone deficiency about lifestyle modifications:

• Weight loss for overweight or obese patients 4, 2
• Increasing physical activity 4, 2
• These modifications can increase total testosterone levels and/or reduce signs and symptoms associated with testosterone deficiency 4
• High BMI coupled with low testosterone could put patients at risk for cardiovascular events 4

Monitoring Protocol

1. Check testosterone levels 2-3 months after starting therapy 2
2. Monitor hematocrit regularly - discontinue therapy if it exceeds 54% 4
3. For patients with hypertension or cardiovascular risk factors, more frequent monitoring of blood pressure is recommended 2
4. Advise patients to report any cardiovascular symptoms such as chest pain, shortness of breath, dizziness, or transient loss of consciousness 4

Conclusion

While there have been concerns about testosterone therapy potentially increasing cardiovascular risk, recent evidence suggests that testosterone replacement in hypogonadal men may actually have beneficial effects on blood pressure. However, careful patient selection, appropriate dosing, and regular monitoring are essential to minimize risks, particularly in patients with pre-existing hypertension or cardiovascular disease.