Jatenzo and Anesthesia: Perioperative Interaction Guide for Patients and Clinicians

What Is Jatenzo and Why Does It Matter Around Surgery?

Jatenzo is the only FDA-approved oral testosterone undecanoate product in the United States, approved in March 2019 for adult males with primary or hypogonadal hypogonadism. It is absorbed via intestinal lymphatics rather than first-pass hepatic metabolism, which is why it must be taken with a meal containing at least 20 grams of fat. That lymphatic absorption route also means the drug can raise blood pressure in a clinically significant way, a risk prominent enough to earn a REMS (Risk Evaluation and Mitigation Strategy) program at approval. [1]

The REMS requirement exists because in Phase 3 studies, 5% of Jatenzo-treated subjects experienced a blood pressure increase meeting the threshold for clinical action. That figure is not trivial during surgery, where anesthesiologists titrate vasopressors, fluid loads, and volatile agents partly based on baseline and intraoperative hemodynamics. A patient whose systolic pressure is already 10 to 15 mmHg higher than pre-Jatenzo baseline presents a different intraoperative profile than the same patient on no testosterone therapy. [1][2]

Pharmacokinetic Basics Relevant to Perioperative Timing

Oral testosterone undecanoate reaches peak serum testosterone concentration (Cmax) roughly 4 to 5 hours after a meal-accompanied dose. Its half-life as measured by testosterone decay is approximately 1.6 to 3 hours for the parent hormone in plasma, though the undecanoate ester and its downstream androgenic effects persist across the dosing interval.

Because the drug is dosed twice daily, missing one or two doses before surgery causes serum testosterone to fall to below-eugonadal levels within 24 to 36 hours. That acute drop is generally well-tolerated for a short surgical hold. The anesthesiologist and prescribing provider should agree in advance on whether to hold the dose the morning of surgery and for how many days postoperatively, particularly if the patient is restricted from oral intake or fat-containing meals.

The REMS Program and What It Means for the OR Team

The FDA's REMS for Jatenzo requires healthcare facilities to certify before dispensing the drug. Any anesthesiology department seeing a Jatenzo patient should be aware that the prescribing label explicitly warns: "Increases in blood pressure, sometimes significant, have been reported with Jatenzo. Blood pressure should be checked at each visit." [1] Informing the anesthesia team of Jatenzo use at the pre-anesthesia assessment is not optional from a medicolegal standpoint.

Blood Pressure Elevation: The Primary Anesthesia Interaction

Blood pressure elevation is the most directly relevant Jatenzo-anesthesia interaction. The prescribing information reports that in the Phase 3 STEADY trial, mean systolic blood pressure increased by 3 to 5 mmHg from baseline in testosterone-treated subjects, with outliers reaching 10 mmHg or higher. [2]

Why BP Elevation Complicates Anesthesia

General and regional anesthesia management involves deliberate hemodynamic manipulation. Volatile anesthetic agents such as sevoflurane and desflurane cause dose-dependent vasodilation and BP reduction. Propofol induction produces a predictable drop in systolic pressure. If a patient's pre-operative BP is elevated because of ongoing Jatenzo therapy, the anesthesiologist is working from a higher baseline, which changes the risk calculus for:

• Hypertensive episodes during laryngoscopy or intubation
• Need for antihypertensive rescue agents (nicardipine, labetalol, hydralazine)
• Post-operative hypertension in the recovery unit
• Cerebral hypoperfusion if BP corrections are too aggressive

The 2017 ACC/AHA hypertension guideline, adopted as a reference by perioperative medicine, defines Stage 2 hypertension as systolic at or above 140 mmHg or diastolic at or above 90 mmHg. [3] A patient whose Jatenzo therapy has pushed them from 130/82 to 141/88 crosses that clinical threshold and may be reclassified as a higher-risk surgical candidate.

Pre-Operative Blood Pressure Assessment

Standard pre-op assessment for any patient on Jatenzo should include:

1. A BP reading at least 2 weeks before elective surgery
2. Comparison against the pre-Jatenzo baseline if available
3. If systolic BP exceeds 160 mmHg or diastolic exceeds 100 mmHg, the procedure should be postponed until BP is controlled, per standard perioperative guidance [3]

Patients who started Jatenzo within 90 days of a scheduled procedure should prompt their surgeon and anesthesiologist to verify whether BP has been adequately monitored since initiation.

Polycythemia, Hematocrit, and Surgical Bleeding Risk

Testosterone stimulates erythropoiesis by increasing erythropoietin production. Jatenzo is no exception. The prescribing information lists polycythemia as a known adverse effect and states that hematocrit should be checked at baseline, 3 to 6 months after initiating therapy, and annually thereafter. [1]

Why Elevated Hematocrit Matters in the OR

Hematocrit above 52 to 54% increases whole-blood viscosity, which raises the risk of:

• Perioperative deep vein thrombosis (DVT)
• Arterial thrombotic events including MI and stroke
• Difficult venous access from sludging
• Impaired microvascular perfusion during hypothermia-induced procedures

The Endocrine Society's 2018 clinical practice guideline on testosterone therapy (Bhasin et al.) recommends checking hematocrit before initiation and at 3 and 6 months. It states: "We suggest withholding testosterone therapy until hematocrit is <54%." [4] That guidance applies equally to the surgical period. If a patient's hematocrit is 56% on the pre-operative lab panel, proceeding under general anesthesia without addressing the polycythemia carries measurable additional thrombotic risk.

Pre-Operative Hematocrit Protocol

A reasonable pre-operative checklist for Jatenzo patients includes a complete blood count within 30 days of surgery. Hematocrit above 54% warrants a discussion between the prescriber and surgeon about whether to:

• Hold Jatenzo for 2 to 4 weeks to allow erythrocyte turnover to lower hematocrit
• Consider therapeutic phlebotomy before elective procedures
• Postpone surgery if neither option is feasible before the required date

Venous Thromboembolism: The FDA Black Box Warning

All testosterone products approved in the United States carry an FDA black-box warning for VTE, specifically DVT and pulmonary embolism. The warning reads: "Venous thromboembolic events including deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients using testosterone products." [1] This is not a theoretical risk in the perioperative period.

Surgery as an Independent VTE Risk Factor

Surgery itself is one of the strongest acquired VTE risk factors. Caprini score models, widely used in perioperative medicine, assign 2 to 3 points for major open procedures lasting more than 45 minutes and additional points for hormonal therapy. [5] A Jatenzo patient undergoing abdominal, orthopedic, or pelvic surgery will accumulate a high Caprini score rapidly.

The combination of:

• Testosterone-driven polycythemia (increased blood viscosity)
• Surgical stasis and venous injury (Virchow's triad)
• Post-operative immobility

Creates a substantially higher VTE risk than either factor alone.

Thromboprophylaxis Considerations

ACCP guidelines on antithrombotic therapy recommend pharmacologic prophylaxis (low-molecular-weight heparin or unfractionated heparin) for most moderate-to-high-risk surgical patients. [6] Patients on Jatenzo with pre-operative hematocrit above 50% should prompt the surgeon to select the highest appropriate prophylaxis level within the patient's bleeding risk profile.

A practical pre-operative risk-stratification framework for Jatenzo patients:

| Risk Domain | Threshold Requiring Action | Suggested Action | |---|---|---| | Blood pressure | Systolic >160 or diastolic >100 mmHg | Postpone elective case; optimize BP | | Hematocrit | >54% | Hold Jatenzo; consider phlebotomy | | VTE history | Prior DVT or PE | Mandatory hematology or vascular consult | | Recent MACE | MI or stroke <6 months | Cardiology clearance before proceeding | | Planned procedure | Major abdominal, orthopedic, pelvic | Maximum appropriate thromboprophylaxis |

MACE Risk and Cardiovascular Monitoring

The FDA also requires a black-box warning on testosterone products for major adverse cardiovascular events (MACE), including non-fatal MI, non-fatal stroke, and cardiovascular death. The TRAVERSE trial (N=5,246, mean follow-up 33 months), published in the New England Journal of Medicine in 2023, found that testosterone replacement was non-inferior to placebo for MACE in hypogonadal men with existing cardiovascular disease or high cardiovascular risk (hazard ratio 0.96, 95% CI 0.84 to 1.09). [7] That result provides some reassurance about long-term cardiovascular equivalence, but it does not address the acute perioperative window specifically.

What the TRAVERSE Data Mean for Surgery

TRAVERSE enrolled men with pre-existing cardiovascular disease or multiple risk factors. The non-inferiority finding means testosterone did not increase MACE over roughly 33 months of follow-up at a population level. However, the study was not designed to examine the acute hemodynamic impact of testosterone during surgery, induction, or recovery.

Anesthesiologists managing a Jatenzo patient with known coronary artery disease should treat the BP elevation data from the Phase 3 STEADY trial as clinically relevant, regardless of TRAVERSE's reassuring population-level MACE result. A 5 mmHg systolic increase that is benign across 33 months in an outpatient setting is a different issue than the same increase during laryngoscopy-triggered sympathetic response at induction.

Pre-Operative Cardiovascular Assessment

For Jatenzo patients scheduled for major surgery, the ACC/AHA 2014 perioperative cardiovascular evaluation guidelines recommend:

1. Assess the patient's functional capacity (METs).
2. If capacity is <4 METs and the surgery is high-risk, consider stress testing or cardiology referral.
3. Continue beta-blockers and antihypertensives on the morning of surgery.
4. Document that Jatenzo was disclosed to the anesthesia team. [8]

Drug-Drug Interactions Relevant to the Perioperative Setting

Jatenzo's prescribing information flags several interaction categories that overlap with common perioperative medications. [1]

Anticoagulants

Testosterone may increase the anticoagulant effect of vitamin K antagonists such as warfarin. Patients on both Jatenzo and warfarin who are scheduled for surgery require INR monitoring within 5 days before the procedure. Dose adjustment of the anticoagulant may be necessary after holding Jatenzo, because removing the testosterone effect can reduce anticoagulant potency and raise INR instability.

Insulin and Glucose Control

Testosterone can improve insulin sensitivity, which means Jatenzo patients with type 2 diabetes may be on lower insulin or oral hypoglycemic doses than they would otherwise require. Holding Jatenzo perioperatively can transiently worsen insulin resistance, a concern during the surgical stress response and TPN/parenteral nutrition periods. The anesthesia team's glucose management protocol should account for this. The ADA's Standards of Care in Diabetes (2024) recommend glucose targets of 140 to 180 mg/dL in the inpatient/perioperative setting. [9]

Corticosteroids

Perioperative corticosteroid use (stress dosing for adrenal insufficiency or anti-inflammatory purposes) combined with testosterone may increase fluid retention and blood pressure elevation beyond what either drug produces alone. This combination warrants tighter intraoperative BP monitoring.

Opioid Analgesics and Hypogonadism

A separate but clinically relevant point: long-term opioid use (opioid-induced androgen deficiency, OPIAD) is common in surgical populations, and patients may be on Jatenzo partly to address opioid-induced hypogonadism. The anesthesiologist should be aware that the opioid dose requirements in these patients may differ from the population average, given complex hypothalamic-pituitary-gonadal axis suppression history.

Can You Drink Alcohol While Taking Jatenzo?

Alcohol does not directly block Jatenzo's lymphatic absorption mechanism, but the interaction is not medically neutral.

Cardiovascular Load

Alcohol elevates blood pressure acutely and over time. Because Jatenzo already carries a REMS-level BP warning, adding regular alcohol consumption compounds cardiovascular risk. The ACC/AHA hypertension guidelines specifically cite alcohol reduction as a Tier 1 lifestyle modification for blood pressure control. [3]

Liver Considerations

Older oral testosterone formulations (17-alpha alkylated androgens) were hepatotoxic. Jatenzo avoids that mechanism via lymphatic absorption, so it does not carry the same hepatotoxic risk. However, heavy alcohol use causes hepatic inflammation independently, and a patient with alcohol-related liver dysfunction may have altered lipid metabolism and altered response to the cardiovascular effects of testosterone.

The Surgical Morning

On the morning of surgery, alcohol is always contraindicated. For Jatenzo patients specifically: the drug requires a fat-containing meal to absorb properly, and patients are typically nil-by-mouth (NPO) before general anesthesia. Because the dose cannot be taken correctly without food, and because alcohol adds hemodynamic instability, both Jatenzo and alcohol should be withheld from the NPO midnight cutoff forward. Patients should confirm the NPO and medication-hold protocol with their surgical team.

Holding Jatenzo Before Surgery: Practical Guidance

No published randomized trial has established the optimal pre-operative hold duration specifically for oral testosterone undecanoate. The guidance below derives from the Jatenzo prescribing label, the Endocrine Society guidelines, and general perioperative pharmacology principles. [1][4][8]

Elective Surgery

• Discuss the hold with the prescribing physician at least 2 weeks before the procedure.
• Check hematocrit and blood pressure within 30 days pre-operatively.
• If hematocrit is <54% and BP is controlled, a 24 to 48-hour hold (skipping the dose the morning of surgery and possibly the evening before) may be sufficient for minor procedures.
• For major surgeries, a 5 to 14-day hold may be appropriate, particularly if the patient had a hematocrit trending upward or a BP increase since starting therapy.

Emergency Surgery

When surgery cannot wait, the anesthesia team must simply be informed that the patient is on Jatenzo, review the most recent hematocrit and BP, and plan for possible:

• Intraoperative hypertensive events
• Higher VTE prophylaxis intensity
• Glucose monitoring if the patient has diabetes

Restarting After Surgery

Jatenzo requires oral fat intake to absorb. Patients should not restart the drug until they can reliably consume a meal with 20 grams of fat without nausea. For most abdominal procedures, this means waiting until at least full liquid diet is tolerated and bowel function has returned. Parenteral or enteral-only intake periods make Jatenzo administration both impractical and medically unreliable.

Monitoring Checklist: Before, During, and After Surgery

Pre-Operative (2 to 4 Weeks Before Elective Case)

• Serum testosterone, hematocrit, blood pressure
• INR if the patient is on warfarin
• HbA1c or fasting glucose if the patient has diabetes
• ECG for patients over 45 or with cardiovascular risk factors
• Disclosure of Jatenzo to anesthesia, surgery, and nursing teams

Intraoperative

• Continuous arterial line BP monitoring for major or prolonged procedures
• Standard DVT prophylaxis (sequential compression devices; consider LMWH per Caprini score)
• Glucose checks every 1 to 2 hours for diabetic patients given the potential insulin sensitivity shift

Post-Operative

• Resume Jatenzo only when oral fat intake is reliably re-established
• Recheck hematocrit within 6 weeks of resuming therapy
• Recheck BP at first post-operative office visit