Jatenzo Geriatric (65+) Dosing: Oral Testosterone Undecanoate in Older Men

Why Geriatric Dosing of Jatenzo Deserves Separate Attention

Men aged 65 and older account for a growing share of testosterone replacement therapy (TRT) prescriptions, yet age-related physiological changes affect how oral testosterone undecanoate is absorbed, metabolized, and cleared. The FDA-approved prescribing information for Jatenzo does not specify a separate geriatric dose, but that does not mean the drug behaves identically in a 70-year-old and a 40-year-old [1].

Aging reduces hepatic blood flow by roughly 20% to 40% between ages 25 and 65, according to data reviewed by the National Institute on Aging. Because Jatenzo undergoes first-pass intestinal lymphatic absorption rather than conventional hepatic first-pass metabolism, this reduction has a less pronounced effect on bioavailability than it would for standard oral androgens [2]. That distinction is one reason oral testosterone undecanoate received FDA approval while older oral formulations like methyltestosterone fell out of favor due to hepatotoxicity.

Still, the key trial by Swerdloff et al. enrolled patients aged 18 to 65, and the subset of men older than 55 was small [1]. Clinicians prescribing to the 65+ population are extrapolating. The Endocrine Society's 2018 guideline on testosterone therapy in men with hypogonadism recommends that "in older men, clinicians should discuss the potential benefits and risks before starting testosterone therapy" and suggests individualized decision-making rather than blanket treatment [3].

Starting Dose and Titration Protocol

The recommended starting dose is 237 mg taken orally twice daily. This applies to all adult men with confirmed hypogonadism, including those over 65 [2]. Each dose must be taken with a fat-containing meal. Skipping meals or eating low-fat foods significantly reduces absorption and can produce sub-therapeutic testosterone levels.

Titration follows a structured protocol. A serum total testosterone level should be drawn approximately 6 hours after the morning dose, at minimum 1 week after starting therapy. Based on that result:

• If serum T is below 300 ng/dL, increase to 316 mg twice daily
• If serum T is between 300 and 1 to 000 ng/dL, maintain the current dose
• If serum T exceeds 1 to 050 ng/dL, decrease by one capsule strength (e.g., from 237 mg to 198 mg twice daily)
• If serum T exceeds 1 to 050 ng/dL on the lowest dose (158 mg twice daily), discontinue

For geriatric patients, some clinicians prefer to start at 198 mg twice daily and titrate upward, particularly in men with borderline cardiovascular risk or those already on multiple medications. This off-label conservative approach lacks formal trial support but aligns with the general geriatric principle of "start low, go slow" [4].

Pharmacokinetic Considerations in Older Adults

Jatenzo uses a self-emulsifying drug delivery system (SEDDS) that promotes lymphatic absorption, bypassing hepatic first-pass metabolism [2]. This mechanism distinguishes it from older oral testosterone formulations. The drug is absorbed through intestinal lymphatics, converted to testosterone and dihydrotestosterone (DHT) in the systemic circulation.

Age affects this process in several ways. Intestinal motility slows with age, which could prolong absorption time. Reduced gastric acid secretion (common in patients on proton pump inhibitors, which over 30% of adults aged 65+ use according to CDC data) may alter the emulsification environment, though Jatenzo's SEDDS formulation was designed to be relatively pH-independent [5].

Renal function declines predictably after age 40. The average glomerular filtration rate (GFR) drops approximately 1 mL/min/year. Jatenzo's prescribing information does not require dose adjustments for renal impairment because testosterone undecanoate is not primarily renally excreted [2]. Protein binding also shifts: sex hormone-binding globulin (SHBG) rises with age, which means a larger fraction of circulating testosterone is bound and biologically inactive [6]. This makes free testosterone measurement more informative than total testosterone in the 65+ population.

Dr. Ronald Swerdloff, lead investigator of the key Jatenzo trial, noted that "oral testosterone undecanoate offers a delivery route that avoids the skin reactions of gels and the peaks-and-troughs pattern of injections, which can be particularly relevant for older patients managing multiple chronic conditions" [1].

Cardiovascular Risk: The 2024 Boxed Warning

In March 2024, the FDA added a class-wide boxed warning to all testosterone products, including Jatenzo, regarding major adverse cardiovascular events (MACE) [7]. This decision drew on data from the TRAVERSE trial (N=5,204), which randomized men aged 45 to 80 with hypogonadism and established or high cardiovascular risk to transdermal testosterone gel versus placebo [8].

TRAVERSE found a non-inferior but not definitively safe cardiovascular profile: the composite MACE endpoint occurred in 7.0% of the testosterone group versus 7.3% of the placebo group (HR 0.96 to 95% CI 0.78 to 1.17) at a median follow-up of 33 months [8]. The trial was not powered to detect small increases in risk among the oldest participants, and Jatenzo (an oral formulation) was not the product tested.

For geriatric patients, the clinical implication is clear. Baseline cardiovascular assessment before prescribing Jatenzo should include blood pressure measurement, lipid panel, fasting glucose or HbA1c, and a discussion of the TRAVERSE findings. The American Urological Association recommends that "testosterone therapy should not be commenced without a careful cardiovascular risk assessment, especially in men over 65" [9].

Hematocrit monitoring adds another layer. Testosterone stimulates erythropoiesis, and polycythemia (hematocrit above 54%) requires dose reduction or cessation. Older men already have higher baseline cardiovascular risk from elevated hematocrit compared to younger cohorts. In the Swerdloff trial, 4.1% of participants developed hematocrit values exceeding 54%, prompting dose adjustment [1].

Drug Interactions in the Polypharmacy Setting

Older adults take a median of 5 prescription medications, and roughly 40% of adults aged 65 and older meet the definition of polypharmacy (5 or more concurrent medications) according to the CDC's National Health Interview Survey [10]. Jatenzo's interaction profile matters more in this population than in younger men on monotherapy.

Testosterone undecanoate is metabolized in part by CYP3A4 enzymes. Strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, clarithromycin) can increase testosterone exposure, raising the risk of polycythemia, edema, and mood changes. Strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin) can reduce efficacy [2].

Specific interactions relevant to geriatric practice:

Warfarin and anticoagulants. Testosterone may enhance the anticoagulant effect of warfarin and other vitamin K antagonists. INR should be monitored more frequently during the first month of concurrent use and after any Jatenzo dose change [2].

Insulin and oral hypoglycemics. Testosterone can improve insulin sensitivity, potentially requiring downward adjustment of diabetes medications. In a study of hypogonadal men with type 2 diabetes, testosterone therapy reduced HbA1c by 0.94% over 12 months compared to placebo (P<0.001) [11].

Corticosteroids. Concurrent corticosteroid use increases the risk of edema. Both drug classes promote sodium retention. This combination is relatively common in older men with inflammatory conditions.

Statins. No direct pharmacokinetic interaction, but both testosterone and statins affect lipid profiles. Monitor LDL and HDL at 3 and 6 months after initiating Jatenzo in statin-treated patients.

Falls, Frailty, and the Functional Benefit Question

One argument for TRT in older men is the potential for improved physical function, muscle mass, and bone density. The Testosterone Trials (TTrials), a coordinated set of seven trials in 790 men aged 65 and older with serum testosterone below 275 ng/dL, provide the most relevant data [12].

TTrials used transdermal testosterone gel, not Jatenzo. The physical function trial found a modest but statistically significant improvement in the 6-minute walk test: 14.3 meters more than placebo at 12 months [12]. The bone density trial showed significant increases in volumetric bone mineral density of the spine (7.5% vs. 0.8%, P<0.001) and hip trabecular bone [13].

These results are encouraging, but they do not directly apply to oral testosterone undecanoate. No published trial has specifically evaluated Jatenzo's effects on physical function or fall risk in men over 65. Clinicians who prescribe Jatenzo for functional outcomes in this age group are making a class-effect inference.

The Endocrine Society guideline states: "We suggest that clinicians offer testosterone therapy on an individualized basis to men >65 years of age who have symptoms and signs of testosterone deficiency and consistently and unequivocally low morning testosterone levels" [3]. The wording ("suggest" rather than "recommend") reflects the lower certainty of evidence in this age group.

Prostate Safety and PSA Monitoring

The relationship between testosterone therapy and prostate cancer risk has been debated for decades. Current evidence does not support the historical assumption that TRT causes prostate cancer [14]. A meta-analysis of 22 randomized controlled trials (N=2,351) published in BJU International found no significant increase in prostate cancer incidence with testosterone therapy (RR 0.87 to 95% CI 0.30 to 2.50) [14].

For geriatric patients starting Jatenzo, baseline evaluation should include a digital rectal examination and PSA measurement. Follow-up PSA should be checked at 3 months, 6 months, and then annually. A PSA increase of more than 1.4 ng/mL within 12 months, or a total PSA exceeding 4.0 ng/mL, warrants urological referral [3].

Jatenzo is contraindicated in men with known or suspected breast or prostate cancer [2]. Benign prostatic hyperplasia (BPH) is not a contraindication, but men with severe lower urinary tract symptoms (International Prostate Symptom Score above 19) should have those symptoms managed before initiating TRT.

Monitoring Schedule for Men 65 and Older

A structured monitoring protocol for geriatric patients on Jatenzo should include:

Before starting therapy: Confirm hypogonadism with two morning total testosterone values below 300 ng/dL drawn before 10 AM. Obtain baseline hematocrit, lipid panel, PSA, hepatic function panel, fasting glucose, and blood pressure. Review the complete medication list for CYP3A4 interactions.

At 1 month: Serum total testosterone (drawn 6 hours post-morning dose), hematocrit, and blood pressure. Assess for edema, sleep apnea symptoms, and mood changes.

At 3 months: Repeat testosterone, hematocrit, PSA, and lipid panel. This is the titration decision point. In the Swerdloff trial, 87% of patients had achieved serum testosterone in the normal range by this visit [1].

At 6 months and annually: Full panel including testosterone, free testosterone, hematocrit, PSA, lipid panel, fasting glucose, and hepatic function. Digital rectal examination annually. Reassess treatment goals and consider deprescribing if the patient's clinical status has changed (e.g., new heart failure diagnosis, uncontrolled polycythemia, progression of frailty beyond what TRT can address).

When to Consider Deprescribing Jatenzo

Not every 65-year-old who starts TRT should remain on it indefinitely. Deprescribing testosterone is appropriate when hematocrit repeatedly exceeds 54% despite dose reduction, when new cardiovascular events occur, when prostate cancer is diagnosed, or when the patient no longer meets the clinical criteria for hypogonadism.

The withdrawal process should be gradual. Abrupt cessation can produce fatigue, depressed mood, and loss of libido. A reasonable approach: reduce to 158 mg twice daily for 4 weeks, then discontinue. Recheck serum testosterone 4 to 6 weeks after stopping to confirm whether endogenous production recovers.

For men aged 75 and older, annual reassessment of whether TRT still aligns with the patient's overall treatment goals is appropriate. The benefit-risk ratio shifts as comorbidities accumulate and life expectancy considerations change.

Prescribers should document the rationale for continuing testosterone therapy at each annual visit, including symptom response, lab values, and the patient's informed preference.