What are the considerations for administering testosterone injections to a patient with hypertension?

Testosterone Injections and Hypertension

Testosterone therapy, including injections, can be safely administered to patients with hypertension, but requires careful cardiovascular risk assessment, blood pressure monitoring, and consideration of transdermal formulations over injections in high-risk patients. 1

Pre-Treatment Cardiovascular Assessment

Before initiating testosterone therapy in any patient, clinicians must measure hemoglobin and assess all patients for atherosclerotic cardiovascular disease (ASCVD) risk factors, including both fixed factors (older age, male gender) and modifiable factors such as dyslipidemia, hypertension, diabetes, and current cigarette smoking. 1 This comprehensive cardiovascular risk stratification is mandatory and should guide formulation selection.

Hypertension Risk: Conflicting Evidence

The relationship between testosterone therapy and hypertension shows contradictory findings across different study types:

Evidence Suggesting Increased Risk

• The FDA required labeling changes in 2015 warning of possible increased risk of heart attack and stroke with testosterone preparations. 1
• Injectable testosterone formulations are associated with greater risk of cardiovascular events, hospitalizations, and deaths compared with gels. 1
• One case report documented new-onset hypertension following topical testosterone gel use, which resolved upon discontinuation. 2
• A UK cohort study found higher rates of hypertension with injectable testosterone (14.4/1000 person-years) compared to oral preparations (12.3/1000 person-years), though the adjusted relative risk was not statistically significant. 3

Evidence Suggesting Benefit or Neutral Effect

• A 2024 study of 737 men treated with testosterone undecanoate showed significant reductions in systolic blood pressure (median -12.5 mmHg), diastolic blood pressure (-8.0 mmHg), and pulse pressure (-6.0 mmHg) in men never on antihypertensive agents. 4
• Only 1 of 152 men not on antihypertensives at baseline required new antihypertensive therapy during follow-up, while 33 of 202 men on antihypertensives had their medications discontinued. 4
• A 2018 meta-analysis of randomized controlled trials found no clear effect of testosterone therapy, either beneficial or detrimental, on cardiovascular events overall. 5

Formulation Selection in Hypertensive Patients

For patients with hypertension or elevated cardiovascular risk, transdermal testosterone preparations (gels, patches) are preferred over injectable formulations. 1 The rationale includes:

• Injectable testosterone causes fluctuating serum levels with peaks and valleys, resulting in increased time spent in both supratherapeutic and subtherapeutic ranges. 1
• These fluctuations may contribute to the higher cardiovascular event rates observed with injections. 1
• Transdermal preparations provide more stable testosterone levels throughout the day. 1

For patients over 70 years or those with chronic illness (including poorly controlled hypertension), use easily titratable testosterone formulations such as gel, spray, or patch rather than intermediate or long-acting injectable formulations. 1

Special Considerations for High-Risk Patients

Testosterone therapy should be used cautiously in men with congestive heart failure or renal insufficiency due to potential fluid retention, though this complication is generally uncommon and mild. 1 Hypertension is rarely reported as a direct adverse effect in clinical guidelines. 1

When testosterone therapy is deemed necessary in hypertensive patients:

• Target mid-normal testosterone levels (500-600 ng/dL) rather than higher ranges. 1, 6
• In patients with history of congestive heart failure, repletion goals should be in the middle range (350-600 ng/dL). 1
• Consider a 4-6 month trial in symptomatic men with borderline testosterone levels (231-346 ng/dL), continuing only if clinical benefit is demonstrated. 1

Monitoring Protocol

Baseline Assessment

Prior to initiating therapy, measure: 1

• Hemoglobin/hematocrit (withhold if Hct >50% until etiology investigated)
• PSA in men over 40 years
• Blood pressure and cardiovascular risk factors

Follow-Up Monitoring

• First visit at 1-2 months to assess efficacy and tolerability. 1
• Subsequent visits at 3-6 month intervals for the first year, then yearly. 1
• At each visit, assess blood pressure, voiding symptoms, and sleep apnea symptoms. 1
• Monitor hematocrit (intervention warranted if >54% on treatment). 1
• For injectable testosterone, measure levels midway between injections targeting 500-600 ng/dL. 1
• For transdermal preparations, levels can be measured at any convenient time. 6

Critical Clinical Pitfalls

The most important pitfall is prescribing high-dose or supraphysiologic testosterone to frail, elderly men with multiple cardiovascular risk factors. A 2010 trial was terminated early due to significantly higher cardiovascular events in older men (mean age 74) with mobility limitations and high prevalence of hypertension, diabetes, and hyperlipidemia. 7 This population had 23 cardiovascular events in the testosterone group versus 5 in placebo. 7

Avoid testosterone therapy or use extreme caution in:

• Men with uncontrolled hypertension until blood pressure is optimized
• Elderly patients with multiple cardiovascular comorbidities
• Patients with recent cardiovascular events (contraindicated with recent stroke or myocardial infarction) 1

Lifestyle Optimization

All patients with hypertension receiving testosterone should receive concurrent lifestyle counseling, as lifestyle modifications reduce cardiovascular risk and may improve erectile function: 1

• Smoking cessation
• Regular dynamic exercise
• Weight loss
• Mediterranean diet emphasizing fruits, vegetables, whole grains, nuts, fish
• Moderate alcohol consumption