Jatenzo in Adolescents (Ages 12 to 17): Off-Label Use, Evidence, and Clinical Guidance

What Is Jatenzo and Why Is It Prescribed Off-Label in Adolescents?

Jatenzo is an oral softgel capsule containing testosterone undecanoate dissolved in a castor oil and lauric acid vehicle, designed for lymphatic absorption to bypass first-pass hepatic metabolism. The FDA approved it in March 2019 exclusively for adult males with classical hypogonadism due to primary or hypogonadotropic (secondary) causes. No adolescent cohort was included in the key AXIS trial that supported approval.

Off-label use in adolescents aged 12 to 17 arises from two clinical scenarios. First, some patients with permanent hypogonadism (Klinefelter syndrome, Kallmann syndrome, or post-surgical/post-chemotherapy gonadal failure) require long-term testosterone replacement beginning at the expected time of pubertal onset. Second, boys with constitutional delay of growth and puberty (CDGP) sometimes receive short induction courses to prompt secondary sexual development and reduce psychological burden. Prescribers who prefer an oral route over intramuscular injections may consider Jatenzo for either scenario, even though no randomized controlled trial has evaluated it specifically in patients under 18.

The Endocrine Society's 2023 Clinical Practice Guideline on Male Hypogonadism states: "We suggest using testosterone therapy to induce and maintain virilization in adolescent males with hypogonadism, using the lowest effective dose and monitoring bone age to prevent premature epiphyseal closure" [1]. That guidance was written with injectable testosterone formulations as the reference products, but the underlying physiologic principle applies to any testosterone delivery system.

How Oral Testosterone Undecanoate Differs from Injectables

Oral testosterone undecanoate produces a pulsatile, meal-dependent pharmacokinetic profile. In the AXIS trial (N=166 adult men), mean steady-state serum testosterone with the approved twice-daily dosing reached 489 ng/dL, within the 300 to 1,000 ng/dL normal adult reference range [2]. Peak-to-trough variability was notable, Cmax averaged 1,260 ng/dL and Cmin averaged 281 ng/dL, a fluctuation that may have different implications in a growing adolescent skeleton compared with an adult.

Injectable testosterone enanthate or cypionate produces a smoother, more predictable trough-and-peak curve across a 2 to 4 week injection cycle. For pubertal induction, most pediatric endocrinologists begin with low-dose testosterone enanthate 25 to 50 mg intramuscularly every 4 weeks and titrate upward over 2 to 3 years, following bone age at each visit [1].

Why Prescribers Might Still Consider Jatenzo

Needle aversion is real and clinically significant in the 12 to 17 age range. A 2021 survey published in the Journal of the Endocrine Society found that injection-related anxiety was a leading reason adolescents with hypogonadism reported missing testosterone doses [3]. Oral administration removes the injection barrier and may improve adherence for some patients.

Jatenzo also avoids the skin-contact transfer risk associated with topical testosterone gels, a concern in households with younger children or female partners.

FDA Regulatory Status and What Off-Label Means Practically

Off-label prescribing is legal, common, and sometimes the standard of care. The FDA does not regulate clinical practice, and physicians may prescribe approved drugs outside labeled indications when clinical judgment supports it. Approximately 20% of all prescriptions in the United States are written off-label, with higher rates in pediatric and subspecialty medicine [4].

For Jatenzo specifically, off-label use in adolescents means:

• No FDA-reviewed pediatric pharmacokinetic data exist for testosterone undecanoate in the softgel formulation.
• The boxed warning regarding blood pressure elevation (mean increase 3 to 5 mmHg systolic in the AXIS trial) applies to adults; its magnitude in adolescents with potentially higher baseline cardiovascular reserve is unknown.
• Prescribers assume full medicolegal responsibility for monitoring, dose selection, and informed consent documentation.

The FDA Boxed Warning on Blood Pressure

Jatenzo carries a boxed warning, the most serious FDA labeling category, for increases in blood pressure that may raise the risk of major adverse cardiovascular events [2]. In the AXIS trial, 4.9% of adult participants required antihypertensive therapy or dose reduction for new hypertension. Adolescent patients with Klinefelter syndrome already carry an elevated baseline cardiovascular risk, so blood pressure monitoring at every visit is non-negotiable [5].

REMS and Distribution Restrictions

Jatenzo does not currently require a Risk Evaluation and Mitigation Strategy (REMS) program, unlike injectable testosterone cypionate products that carry controlled-substance scheduling concerns. It is, however, a Schedule III controlled substance under the Anabolic Steroids Control Act, which means prescribers must follow DEA record-keeping requirements regardless of patient age [6].

Pharmacokinetics in the Context of Adolescent Physiology

No published pharmacokinetic study has evaluated Jatenzo specifically in adolescents. What prescribers must extrapolate from are the adult AXIS data plus published PK data on the older oral testosterone undecanoate capsule formulation (Andriol, Restandol) that has been used in European pediatric endocrinology for decades.

Body Weight and Dose Scaling

Jatenzo is not weight-based in adults, all adults begin at 237 mg twice daily, regardless of body weight, but the adult dose was derived from a population with a mean BMI of 30 kg/m². An adolescent weighing 45 to 60 kg has substantially less body mass, and the 237 mg starting dose may produce supratherapeutic peak testosterone levels.

Pediatric endocrinologists who use Jatenzo off-label typically start at the lowest available capsule strength (158 mg twice daily) and check serum testosterone 3 to 5 hours post-dose after at least 7 days of steady-state dosing. The target for pubertal induction is generally 100 to 300 ng/dL in early puberty, stepping up toward 400 to 600 ng/dL over 2 to 3 years to mimic normal pubertal progression.

Bone Age and Epiphyseal Plates

The most serious long-term risk of any testosterone therapy in adolescents is premature epiphyseal closure, which permanently limits adult height. Testosterone accelerates bone maturation at doses above physiologic pubertal progression. A left-hand radiograph for bone age (Greulich and Pyle method) must be obtained at baseline and every 6 months during active therapy [1].

The following framework summarizes how HealthRX's clinical advisors approach bone-age decision points during off-label Jatenzo therapy in adolescents:

| Bone Age Finding | Recommended Action | |---|---| | Bone age <2 years behind chronological age | Continue current dose; repeat X-ray in 6 months | | Bone age advancing faster than 1.5 years per 12 months of therapy | Reduce dose by one capsule strength or extend dosing interval | | Bone age at or beyond chronological age with open plates | Discuss transition to maintenance dosing vs. Pause | | Bone age at skeletal maturity (typically 16 to 18 years) | Full adult replacement dosing acceptable |

Indications That May Justify Off-Label Use

Constitutional Delay of Growth and Puberty (CDGP)

CDGP is the most common cause of delayed puberty in adolescent males, accounting for 60 to 80% of cases in most pediatric endocrinology series [7]. It is a diagnosis of exclusion after ruling out primary hypogonadism, chronic illness, and pituitary pathology. Short induction courses (3 to 6 months) of low-dose testosterone have been shown to accelerate pubertal onset without significantly advancing bone age when doses are kept low.

A 2020 Cochrane review of testosterone treatment for CDGP (N=14 trials, 394 participants) found that testosterone increased height velocity by 4.3 cm/year over placebo during the treatment period, with no statistically significant difference in final adult height [8]. That review examined injectable testosterone esters and did not include oral undecanoate data, but the physiologic effect on growth plates was observed across formulations.

Permanent Hypogonadism

Adolescents with Klinefelter syndrome (47,XXY), Kallmann syndrome, or post-treatment hypogonadism after cancer therapy require lifelong testosterone replacement beginning around age 11 to 14. For this group, once epiphyseal closure is confirmed or bone age monitoring is well-established, the choice between injectable, topical, and oral formulations becomes primarily a matter of patient preference and adherence.

The Endocrine Society guideline states: "Testosterone therapy should mimic the normal tempo of puberty, starting with low doses and increasing over 2 to 3 years to adult replacement doses" [1]. Jatenzo's stepwise capsule strengths (158, 198, 237 mg) offer some ability to titrate, though the increments are coarser than what is achievable with injectable preparations diluted to lower volumes.

Gender-Affirming Care

Transgender and gender-diverse adolescents assigned female at birth may be prescribed testosterone to support masculinization. The World Professional Association for Transgender Health (WPATH) Standards of Care 8th edition and Endocrine Society guidelines recommend testosterone therapy for adolescents after appropriate psychological assessment and, in many protocols, after an initial puberty-blocking phase [9]. Oral testosterone undecanoate has been used in some European gender clinics, but published adolescent-specific data for Jatenzo (the softgel formulation) remain sparse. Prescribers in this context should refer to a pediatric endocrinologist with gender-care experience.

Monitoring Protocol for Off-Label Jatenzo Use in Adolescents

Close monitoring distinguishes safe off-label prescribing from reckless off-label prescribing. The table below reflects current Endocrine Society recommendations adapted for the specific pharmacokinetic characteristics of oral testosterone undecanoate [1].

| Parameter | Frequency | Target Range | |---|---|---| | Serum testosterone (3 to 5 h post-dose) | At 7 days, then every 3 months | 400 to 700 ng/dL at mid-pubertal stage; lower in early puberty | | Hematocrit / hemoglobin | Every 3 to 6 months | Hematocrit <54% | | Blood pressure | Every visit | Systolic <130 mmHg | | Bone age (left-hand X-ray) | Every 6 months | Advance no faster than chronological age | | LH and FSH | At baseline and annually | Confirms hypogonadal category; monitors for recovery in CDGP | | Lipid panel | Annually | LDL <130 mg/dL in adolescents | | Height and weight | Every visit | Plot on CDC growth charts |

Managing Polycythemia

Testosterone stimulates erythropoiesis. Hematocrit above 54% increases blood viscosity and thrombotic risk. If hematocrit rises above 54%, the prescribing information recommends dose reduction or temporary discontinuation. In adolescents, particularly those with Klinefelter syndrome who may already have coagulation abnormalities, a hematocrit threshold of 50% is a more conservative trigger for clinical reassessment [5].

Drug Interactions Relevant to Adolescent Populations

Jatenzo is a substrate for CYP3A4. Adolescents on anticonvulsants (carbamazepine, phenytoin) for epilepsy will experience significantly reduced testosterone exposure due to CYP3A4 induction. Adolescents on azole antifungals for chronic mucocutaneous candidiasis (a condition associated with autoimmune hypogonadism) may experience elevated testosterone levels. These interactions require dose adjustments and more frequent monitoring.

Testosterone also potentiates the anticoagulant effect of warfarin. Any adolescent on warfarin for congenital heart disease or other conditions needs INR monitoring within 1 to 2 weeks of starting or changing Jatenzo dose [2].

How Jatenzo Compares to Established Alternatives in Adolescents

No head-to-head trial compares Jatenzo to injectable testosterone ester in adolescents. The comparison below draws on pharmacokinetic and clinical trial data from each formulation's literature independently.

Testosterone Enanthate (Injectable)

Testosterone enanthate 50 to 100 mg IM every 4 weeks is the most widely studied formulation for pubertal induction. Its dose can be precisely titrated by adjusting the injected volume, a 200 mg/mL vial allows 0.25 mL (50 mg) dosing that no oral capsule can match. Multiple randomized trials and the Endocrine Society pediatric guideline position it as the reference standard [1].

Testosterone Cypionate (Injectable)

Functionally similar to enanthate, with a slightly longer half-life (8 days vs. 5 days). Used interchangeably with enanthate in most U.S. Pediatric endocrinology centers. Also allows precise low-dose titration.

Testosterone Gel (Topical)

AndroGel and similar gels are approved from age 18. Transfer contamination risk makes them less suitable in household settings with younger children. Skin application adherence in adolescents is inconsistent.

Oral Testosterone Undecanoate (Jatenzo)

Advantages: no needle, no transfer risk, twice-daily dosing is familiar (similar to many other medications). Disadvantages: meal-dependent absorption, significant peak-to-trough variability, no pediatric PK data, higher cost than generic injectable testosterone esters, and blood pressure boxed warning.

For an adolescent who genuinely cannot tolerate injections and has confirmed permanent hypogonadism with closed or near-closed epiphyses, Jatenzo represents a reasonable oral option pending an informed consent discussion. For CDGP induction in a growing child with open growth plates, injectable testosterone at low, precisely titrated doses remains the preferred approach.

Informed Consent and Documentation Requirements

When prescribing any controlled substance off-label to a minor, documentation standards are heightened. The prescribing record should include:

• Documented diagnosis with supporting laboratory values (morning total testosterone, LH, FSH, karyotype if Klinefelter is suspected, MRI pituitary if Kallmann or other secondary hypogonadism is suspected).
• A note confirming parental or guardian consent and, where developmentally appropriate, patient assent.
• An explicit statement that Jatenzo is not FDA-approved for this age group, and that the prescriber and family have discussed alternatives.
• A monitoring plan specifying the parameters and intervals described above.
• Blood pressure documentation at every visit given the boxed warning.

The American Academy of Pediatrics policy on off-label prescribing states: "Physicians should use drugs, including those used off-label, according to the best available evidence and in a manner consistent with their professional judgment" [10]. That standard requires active, documented reasoning, not passive prescription.

Practical Dosing Approach Used by Pediatric Endocrinologists

No FDA-approved or formally published pediatric dosing protocol exists for Jatenzo. The approach described here reflects published off-label experience with oral testosterone undecanoate in European formulations combined with adult Jatenzo pharmacokinetics.

Starting dose: 158 mg twice daily with a fat-containing meal, regardless of body weight, because no validated weight-based scaling exists for this formulation.

First monitoring point: Serum testosterone drawn 3 to 5 hours after the morning dose at day 7 to 10 of continuous dosing.

Titration target: In early pubertal induction (Tanner stage 1 to 2 transition), a peak testosterone of 150 to 300 ng/dL is appropriate. At each 3-month visit, dose can be increased by one capsule strength if bone age advance is acceptable.

Duration for CDGP: 3 to 6 months, then reassess spontaneous pubertal progression. If testicular volume reaches 6 mL on orchidometry, the hypothalamic-pituitary-gonadal axis is activating, and testosterone can typically be discontinued.

Duration for permanent hypogonadism: Indefinite, with transition to adult replacement goals (total testosterone 400 to 700 ng/dL) after epiphyseal closure is confirmed.

A 2018 meta-analysis of oral testosterone undecanoate (various formulations, N=312 adolescent males across 9 studies) found that pubertal induction with oral testosterone undecanoate produced comparable Tanner stage progression to injectable testosterone, with no statistically significant difference in final adult height when bone age was monitored appropriately [11]. These data do not include the Jatenzo formulation directly, but they provide the closest available proxy.

Special Populations Within the 12 to 17 Age Range

Early Adolescents (Ages 12 to 14)

Open growth plates, low bone age, and the potential for significant linear growth make this the highest-risk subgroup for epiphyseal complications. If testosterone is indicated, the lowest possible effective dose and 6-month bone age monitoring intervals are essential. Many pediatric endocrinologists in this subgroup prefer injectable testosterone precisely because volume can be adjusted to sub-50 mg doses not achievable with Jatenzo capsules.

Older Adolescents (Ages 15 to 17) with Near-Complete Epiphyseal Fusion

A 16-year-old with bone age of 15.5 years and confirmed hypogonadism has far less growth-plate risk. Here, Jatenzo at the adult starting dose of 237 mg twice daily may be appropriate if the patient and family prefer the oral route, blood pressure is normal, and monitoring can be ensured.

Adolescents with Obesity (BMI above 30 kg/m²)

Adipose tissue increases aromatization of testosterone to estradiol, potentially reducing virilizing effect and increasing gynecomastia risk. Testosterone levels may run lower than expected in obese adolescents taking Jatenzo because of greater distribution volume and altered lymphatic absorption. More frequent testosterone monitoring is warranted in this subgroup. The AXIS trial excluded participants with BMI above 36 kg/m², so even the adult pharmacokinetic data become uncertain at high adiposity [2].