What is the relationship between testosterone replacement therapy (TRT) and hypertension?

From the Guidelines

Testosterone replacement therapy (TRT) may have a neutral effect on cardiovascular risk, including hypertension, according to the most recent and highest quality study 1. The relationship between TRT and hypertension is complex, and the effect on blood pressure varies between individuals. Some men may experience no change, while others may see increases of 5-10 mmHg in systolic pressure. This occurs because testosterone can increase red blood cell production (erythrocytosis), increase sodium and water retention, and potentially reduce nitric oxide production, all of which can elevate blood pressure. Men starting TRT should have their blood pressure checked before beginning treatment, then at 3-6 month intervals during the first year, and annually thereafter. If blood pressure rises above 130/80 mmHg during treatment, more frequent monitoring is recommended. Key considerations for managing hypertension in men on TRT include:

• Ensuring well-controlled blood pressure before starting TRT
• Adjusting antihypertensive medications as needed
• Considering lifestyle modifications, such as reduced sodium intake, regular exercise, weight management, and limited alcohol consumption
• Monitoring for erythrocytosis and considering hematocrit reduction through therapeutic phlebotomy if necessary The most recent guideline recommends counseling patients that the current scientific literature does not definitively demonstrate that testosterone therapy increases the risk of major adverse cardiovascular events (MACE) 1. However, it is essential to continue monitoring and adjusting treatment as needed to minimize potential risks and optimize outcomes.

From the FDA Drug Label

Due to sodium and water retention, edema with or without congestive heart failure may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease Long term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men The relationship between testosterone replacement therapy (TRT) and hypertension is not directly addressed in the label. However, it is mentioned that sodium and water retention can lead to edema and potentially congestive heart failure in patients with preexisting conditions, which may be related to blood pressure regulation.

• The label does not provide a clear answer to the question of the relationship between TRT and hypertension.
• It is recommended to exercise caution when prescribing TRT to patients with preexisting cardiac or renal disease. 2

From the Research

Relationship Between Testosterone Replacement Therapy (TRT) and Hypertension

• The relationship between TRT and hypertension is complex and has been studied in various research papers 3, 4, 5, 6, 7.
• Some studies suggest that TRT may increase the risk of cardiovascular disease, including hypertension 3, 4.
• However, other studies have found that TRT may actually lower blood pressure in men with hypogonadism 5.
• A meta-analysis of randomized controlled studies found that TRT had no effect on systolic or diastolic blood pressure in men with heart failure 7.
• Another study found that testosterone replacement therapy was associated with significant reductions in systolic, diastolic blood pressure, and pulse pressure, regardless of antihypertensive therapy 5.

Factors Influencing the Relationship Between TRT and Hypertension

• Baseline blood pressure values may be inversely associated with changes in blood pressure after TRT 5.
• Antihypertensive therapy may also influence the relationship between TRT and hypertension, with larger reductions in blood pressure seen in men receiving concurrent antihypertensive therapy 5.
• The effects of TRT on blood pressure may also depend on the specific population being studied, such as men with hypogonadism or heart failure 5, 7.

Limitations and Controversies

• The evidence on the relationship between TRT and hypertension is not uniform, and more research is needed to fully understand the effects of TRT on cardiovascular health 3, 4, 6.
• The FDA has released a warning statement about the potential cardiovascular risks of testosterone replacement therapy, but the cardiovascular safety of this therapy remains unclear 3.