Can testosterone therapy cause hypertension?

Testosterone and Blood Pressure: Evidence-Based Answer

Testosterone therapy at physiologic replacement doses does not typically cause clinically significant hypertension, though oral formulations may produce small blood pressure increases that warrant monitoring. 1

Key Evidence on Blood Pressure Effects

Physiologic Replacement Doses (Intramuscular/Transdermal)

• Studies of testosterone replacement therapy have not demonstrated increased cardiovascular disease or events including hypertension at physiologic doses. 1

• The New England Journal of Medicine guidelines indicate that existing evidence suggests a neutral or possible beneficial effect on cardiovascular disease risk with standard testosterone replacement. 1

• Fluid retention is listed as a potential risk but is "rarely of clinical significance" in clinical practice. 1

• Long-term data with testosterone undecanoate (intramuscular) showed significant reductions in systolic and diastolic blood pressure over time, with median decreases of -12.5 mmHg systolic and -8.0 mmHg diastolic in men not on antihypertensives. 2

Oral Testosterone Formulations: Important Exception

• The FDA specifically contraindicated oral testosterone undecanoate for age-related hypogonadism, citing demonstrated increases in blood pressure. 1

• Oral testosterone undecanoate produces small but consistent blood pressure increases: mean 24-hour ambulatory systolic BP increased 1.7-3.8 mmHg at 4-6 months. 3, 4

• Men on antihypertensive therapy experienced greater BP increases (3.1-3.4 mmHg) compared to those not on antihypertensives (0.7-1.0 mmHg). 3

• The top quartile of hematocrit increases (6-14%) correlated with the largest BP elevations (mean 8.3 mmHg), suggesting hematocrit monitoring can predict BP risk. 4

Formulation-Specific Considerations

• Transdermal and intramuscular testosterone at physiologic doses show minimal to no clinically significant BP effects. 1

• A systematic review of transgender men on testosterone found that only 3 of 7 studies detected modest increases or clinically irrelevant changes in blood pressure, though two isolated cases developed hypertension that resolved with cessation. 5

• One case report documented hypertension developing with topical testosterone gel that resolved upon discontinuation, linked to increased hematocrit. 6

Clinical Monitoring Algorithm

For patients starting testosterone therapy:

1. Baseline assessment: Measure blood pressure and hematocrit before initiating therapy 7, 4

2. Avoid oral formulations in men with pre-existing hypertension or cardiovascular risk factors 1

3. Monitor hematocrit closely: Increases >6% predict greater BP elevations and may require dose adjustment 4

4. Check BP at follow-up visits: Particularly in the first 4-6 months when oral formulations show peak effects 3, 4

5. Consider dose reduction or formulation change if BP increases >5-10 mmHg or hematocrit rises significantly 4, 5

Important Caveats

• Pre-existing cardiac, renal, or hepatic disease increases risk for edema and potential BP complications with testosterone therapy. 7

• The mechanism of BP increase appears related to erythrocytosis (increased red blood cell production), not direct vascular effects. 1, 4

• Supraphysiologic doses (such as those used for performance enhancement) carry different and potentially greater cardiovascular risks than replacement therapy. 1, 7

• Men with higher baseline blood pressure may experience greater reductions with intramuscular testosterone undecanoate, suggesting potential benefit in some populations. 2