What is the recommended approach to monitoring blood pressure during testosterone replacement therapy?

Blood Pressure Monitoring During Testosterone Replacement Therapy

Yes, blood pressure monitoring is essential during testosterone replacement therapy, though the evidence shows modest and variable effects—you should check BP at baseline, at 3-4 months after initiation, and then every 6-12 months alongside routine monitoring, with closer surveillance in men already on antihypertensive medications.

Baseline Assessment and Initial Monitoring

• Obtain baseline blood pressure before initiating testosterone therapy, as this predicts the magnitude of BP changes during treatment 1, 2.
• Recheck blood pressure at 3-4 months after starting therapy or after any dose adjustment, as this is when initial BP effects become apparent 1, 2.
• Men with higher baseline BP experience greater increases on testosterone therapy, making baseline measurement particularly important for risk stratification 3.

Expected Blood Pressure Changes

The evidence on BP effects is mixed and depends on formulation, baseline characteristics, and concurrent antihypertensive use:

Oral Testosterone Undecanoate (Newer Formulations)

• Oral testosterone undecanoate causes small increases in 24-hour ambulatory systolic BP of approximately 1.7-3.8 mmHg after 4 months of therapy 1, 2.
• Men already on antihypertensive medications experience larger BP increases (3.1-3.4 mmHg) compared to those not on antihypertensives (0.7-1.0 mmHg) 2.
• Diastolic BP changes are minimal, typically less than 2 mmHg 1, 2.

Injectable Testosterone (Traditional Formulations)

• A large observational registry study of testosterone undecanoate injections showed significant reductions in systolic BP (median -12.5 mmHg), diastolic BP (-8.0 mmHg), and pulse pressure (-6.0 mmHg) in men not on antihypertensive therapy 3.
• Greater BP reductions occurred in men with higher baseline BP values 3.
• Only 1 of 152 men (0.7%) required initiation of antihypertensive therapy during follow-up, while 33 of 202 men (16.3%) on antihypertensives had their medications discontinued 3.

Meta-Analysis Evidence

• A comprehensive 2024 systematic review and individual participant data meta-analysis found no adverse effects of testosterone replacement therapy on blood pressure overall 4.
• Testosterone therapy improved quality of life and sexual function without negatively impacting BP, serum lipids, or glycemic markers 4.

The Hematocrit-Blood Pressure Connection

This is a critical pitfall to understand: The relationship between hematocrit elevation and BP increase is clinically significant.

• Men whose hematocrit rises by more than 6% experience the largest BP increases (mean 8.3 mmHg systolic), while those with smaller hematocrit changes show minimal BP effects (1.9-3.3 mmHg) 1.
• Monitor hematocrit at each visit; if hematocrit exceeds 52%, consider dose reduction, temporary discontinuation, or therapeutic phlebotomy 5.
• Erythrocytosis occurs in 43.8% of patients on intramuscular injections versus only 15.4% with transdermal preparations, which may explain differential BP effects 5.

Ongoing Monitoring Protocol

• Once stable testosterone levels are confirmed, monitor BP every 6-12 months as part of routine follow-up 6.
• Men should be advised to report cardiovascular symptoms (chest pain, shortness of breath, palpitations) during routine follow-up 7.
• Counsel overweight/obese patients regarding weight loss programs concurrent with testosterone therapy, as high BMI coupled with low testosterone increases cardiovascular event risk 7.

Formulation-Specific Considerations

• Transdermal testosterone preparations (gels, patches) produce more stable testosterone levels and may have more neutral BP effects compared to injectable formulations that cause supraphysiologic peaks 6, 5.
• The FDA required labeling changes in 2015 to inform healthcare professionals and patients of possible increased cardiovascular risk, though this remains controversial and may relate to high-risk patient populations rather than the therapy itself 6.
• Some evidence suggests testosterone injections are associated with greater cardiovascular risk compared to gels, potentially related to time spent in both supratherapeutic and subtherapeutic ranges 6.

Critical Caveats

• Do not commence testosterone therapy for 3-6 months in patients with recent cardiovascular events 7.
• The magnitude of BP changes is generally small and clinically insignificant in most patients, particularly those not on antihypertensive therapy 2, 4.
• Baseline BP and concurrent antihypertensive therapy are the strongest predictors of BP changes during testosterone therapy 2.
• Despite FDA warnings in product labeling, long-term observational data provide reassurance that testosterone therapy does not adversely affect BP in most men and may actually lower BP in some populations 3.