Is oral testosterone undecanoate (Jatenzo) safe for adult men with primary or secondary hypogonadism who have no contraindications?

Is Jatenzo (Oral Testosterone Undecanoate) Safe?

Jatenzo carries a unique cardiovascular risk profile that distinguishes it from other testosterone formulations—specifically, it increases blood pressure by 3-6 mmHg and is FDA-contraindicated in men with age-related hypogonadism due to demonstrated BP elevations and lack of established efficacy in this population. 1

FDA Black Box Warning and Cardiovascular Risk

The FDA mandates a boxed warning for Jatenzo stating that it can cause blood pressure increases that elevate the risk of major adverse cardiovascular events (MACE), including non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death. 1 This risk is amplified in patients with pre-existing cardiovascular risk factors or established cardiovascular disease. 1

Before initiating Jatenzo, you must:

• Assess the patient's baseline cardiovascular risk profile 1
• Ensure blood pressure is adequately controlled at baseline 1
• Confirm the patient has hypogonadism associated with structural or genetic etiologies only—not age-related hypogonadism 1

After starting therapy:

• Monitor blood pressure periodically and treat new-onset hypertension or exacerbations of pre-existing hypertension 1
• Re-evaluate whether benefits outweigh risks if cardiovascular risk factors develop during treatment 1

Clinical trial data demonstrate systolic blood pressure increases of 3-5 mmHg in short-term studies 2 and 3-6 mmHg over 2 years 3, which are statistically significant (p < 0.05). 3

Absolute Contraindications

Jatenzo is absolutely contraindicated in: 1

• Men with carcinoma of the breast or known/suspected prostate cancer 1
• Women who are pregnant (causes virilization of female fetus) 1
• Patients with known hypersensitivity to testosterone undecanoate or its ingredients 1
• Men with age-related hypogonadism or other conditions not associated with structural or genetic etiologies 1

The last contraindication is unique to Jatenzo and reflects the FDA's specific concern about its blood pressure effects in men without clearly defined organic hypogonadism. 1

Hematologic Safety Profile

Jatenzo carries a lower risk of erythrocytosis compared to injectable testosterone. 4 Injectable testosterone causes erythrocytosis in approximately 44% of users, 4 whereas oral formulations produce dose-dependent rates: 3% at low doses (5 mg/day), 11% at moderate doses (50 mg/day), and 18% at high doses (100 mg/day). 4

In the 2-year extension study, hematocrit increased slightly but remained below 48% throughout the entire study period. 3 This represents a significant safety advantage over injectable formulations. 4

Monitoring requirements:

• Check hematocrit at baseline before initiating therapy 4
• Monitor hematocrit periodically during treatment 4
• Withhold treatment if hematocrit exceeds 54% 4
• Consider phlebotomy in high-risk cases with persistent erythrocytosis 4

Hepatic Safety

Unlike older oral testosterone formulations that caused hepatotoxicity, Jatenzo has demonstrated no clinically significant liver toxicity. 2, 3 The 2-year study showed no clinically significant changes from baseline in liver function tests. 3

This safety profile distinguishes Jatenzo from historical oral testosterone products that were associated with hepatotoxicity and led to the long absence of oral testosterone in the United States. 5

Prostate Safety

Prostate-specific antigen (PSA) levels showed no clinically significant changes over 2 years of treatment. 3 However, standard monitoring protocols still apply:

• Perform digital rectal examination at baseline in men over 40 years 4
• Measure baseline PSA level in men over 40 years 4
• Monitor PSA periodically during treatment 4
• Refer for urologic evaluation if PSA increases >1.0 ng/mL in the first 6 months or >0.4 ng/mL per year thereafter 4

Lipid Effects

High-density lipoprotein (HDL) cholesterol decreased by 9.8 ± 0.9 mg/dL from baseline over 2 years (p < 0.0001). 3 This is a typical testosterone-induced change seen with all formulations. 4

Gastrointestinal Tolerability

Jatenzo-treated patients experienced a greater number of mild gastrointestinal adverse effects compared to topical testosterone. 2 These were generally mild and did not lead to significant treatment discontinuation. 2

Cardiovascular Biomarkers

Jatenzo was not associated with elevation in high-sensitivity C-reactive protein or lipoprotein-associated phospholipase A2 (cardiovascular safety biomarkers) after 365 days of therapy. 2 This provides some reassurance regarding inflammatory cardiovascular risk, though the blood pressure effects remain the primary concern. 1, 2

Efficacy Context for Risk-Benefit Assessment

When weighing Jatenzo's risks, consider that testosterone therapy in general produces:

• Small but significant improvements in sexual function and libido (standardized mean difference 0.35) 6, 4
• Little to no effect on physical functioning, energy, vitality, depressive symptoms, or cognition 6, 4

Jatenzo specifically achieved 84-87% of patients reaching eugonadal testosterone levels in phase III trials, 2 with significant improvements in all Psychosexual Daily Questionnaire parameters (p < 0.0001). 2

Clinical Decision Algorithm

Use Jatenzo only when:

1. The patient has confirmed hypogonadism (two morning testosterone measurements <300 ng/dL) with structural or genetic etiology 1
2. Baseline blood pressure is adequately controlled 1
3. No cardiovascular disease or significant cardiovascular risk factors are present 1
4. The patient has no contraindications (prostate cancer, breast cancer, desire for fertility) 1
5. The patient prefers oral administration and understands the blood pressure monitoring requirements 2

Avoid Jatenzo in favor of transdermal testosterone when:

• The patient has pre-existing hypertension or cardiovascular disease 1
• The patient has age-related hypogonadism without structural/genetic etiology 1
• The patient has elevated hematocrit at baseline (>50%) 4

Monitoring schedule:

• Blood pressure at every visit 1
• Testosterone levels 7 days after starting or dose adjustment, then periodically 1
• Hematocrit periodically 4
• PSA in men over 40 years 4
• Lipid panel periodically 3

Common Pitfalls to Avoid

• Do not prescribe Jatenzo for age-related hypogonadism—this is an FDA contraindication specific to this formulation 1
• Do not ignore blood pressure monitoring—the BP increase is the primary safety concern that distinguishes Jatenzo from other formulations 1, 2
• Do not assume Jatenzo will improve energy, vitality, or physical function—evidence shows minimal to no benefit in these domains 6, 4
• Do not use Jatenzo in men desiring fertility—like all testosterone therapy, it suppresses spermatogenesis and causes azoospermia 4