TRAVERSE Cost, Cost-Effectiveness, and Health-Economic Implications

At a glance

Field	Detail
Trial	TRAVERSE
N	5,246
Intervention	Testosterone 1.62% gel (AndroGel), titrated to mid-normal range
Comparator	Placebo gel
Duration	Mean 33 months (up to 5 years)
Primary Endpoint	First MACE (CV death, nonfatal MI, nonfatal stroke)
Key CV Result	Non-inferiority confirmed (HR 0.96, 95% CI 0.78, 1.17)
Secondary Signal	Higher rates of atrial fibrillation, pulmonary embolism, AKI in testosterone arm
Primary Source	Lincoff et al., NEJM 2023

Why Health-Economic Analysis of TRAVERSE Is Unusually Complicated

Most cardiovascular outcomes trials generate at least one contemporaneous cost-effectiveness analysis, typically from the trial sponsor or an academic group using the trial's own event-rate data. TRAVERSE is an exception. As of mid-2025, no peer-reviewed cost-per-QALY model has been published that uses TRAVERSE's own hazard ratios as direct inputs. That gap is not trivial. It means every economic claim made by prescribers, payers, or patients is currently being calculated against older, smaller, and methodologically weaker evidence bases, largely the 2010 Testosterone Trials (TTrials) cohort and pre-2020 observational studies.

The TRAVERSE primary publication enrolled 5,246 men aged 45 to 80 with confirmed hypogonadism (two morning testosterone levels <300 ng/dL) and either established atherosclerotic cardiovascular disease or high risk defined by age plus one additional risk factor. That enrollment design matters for economic modeling because it selected for men whose background MACE risk was already elevated, meaning any cost-effectiveness calculation tied to MACE prevention will look worse than a model run on a healthier population. You cannot simply extrapolate TRAVERSE's HR of 0.96 onto a 45-year-old with low testosterone, mild fatigue, and a normal lipid panel.

The Symptom-Burden Problem in QALY Construction

Health-economic models for testosterone therapy are particularly sensitive to how QALY loss from hypogonadism is estimated. Utility weights for untreated hypogonadism in the published literature range from 0.72 to 0.88 depending on symptom severity, with the largest deficits attributed to sexual dysfunction and fatigue. The difference between a utility of 0.72 and 0.85 in a model running over 10 years can shift cost-per-QALY by $40,000 or more at a fixed drug cost.

TRAVERSE did collect patient-reported outcomes using the Sexual Function Inventory and the AMS (Aging Male Symptoms) scale. Published secondary analyses showed statistically significant improvements in sexual function and some energy domains, though effect sizes were modest in the higher-risk subgroups that dominate TRAVERSE's enrollment. Those secondary outcome data matter enormously for any economic model because they anchor the "treated" utility weight. If the QALY gain per treated year is 0.04, the math at $300/month list price looks very different from a QALY gain of 0.12.

Independent health economists working with pre-TRAVERSE data, including a 2019 analysis published in PharmacoEconomics, estimated ICERs for TRT in symptomatic hypogonadism between $55,000 and $130,000 per QALY depending on which symptom domains were included and whether cardiovascular event reduction was modeled as a benefit. That study used a Markov model with a 10-year time horizon and did not have access to TRAVERSE's event-rate data. Applying TRAVERSE's near-neutral MACE HR (0.96) to their model framework would eliminate most of the cardiovascular-benefit term, pushing ICERs toward the higher end of that range or beyond, unless symptom-driven QALY gains are credited generously.

List Price vs Net Price: The Number Patients Actually Pay

AndroGel 1.62%, the formulation used in TRAVERSE, carries a WAC (wholesale acquisition cost) of approximately $380, $420 per month for a standard supply as of 2024, a figure that appears routinely in pharmacy benefit comparisons. The FDA-approved label for testosterone gel 1.62% notes no dose-specific pricing, but prescribers and patients consistently encounter this price tier at retail.

What patients pay is structurally different. Commercial insurers who place testosterone gel on Tier 3 typically generate a patient out-of-pocket cost of $60 to $120 per month after negotiated rebates and copay structures. Medicare Part D, which covers testosterone only under narrow circumstances tied to FDA-labeled indications for classical hypogonadism, applies formulary rules that can place the drug in a specialty tier with 25 to 33% coinsurance, creating monthly patient costs of $90 to $140. Generic testosterone gel (1% formulation) has list prices as low as $30, $60 per month at major retail chains, and the FDA's Orange Book lists multiple AB-rated generics to the original AndroGel 1% approval, though generic equivalents to the 1.62% formulation have had slower market penetration.

The net-price reality also includes manufacturer copay assistance cards, which AbbVie has offered for AndroGel and which effectively reduce commercial-plan out-of-pocket to near zero for eligible patients. This creates a coverage-population paradox: the patients most likely to use brand AndroGel at low personal cost are commercially insured patients whose plans absorb most of the list price, while Medicare and Medicaid beneficiaries face stricter formulary rules and less copay assistance. TRAVERSE's enrollment, drawn from older men with established CV disease, maps more closely to the Medicare-age population, meaning the trial's safety data is most relevant for exactly the insurance population where access is most restricted.

Payer Coverage Implications After TRAVERSE

Before TRAVERSE reported, several large PBMs and commercial plans had already tightened prior-authorization requirements for testosterone products, citing a 2010 FDA advisory committee review and the FDA's 2015 label update that added cardiovascular risk language as a precaution. TRAVERSE's non-inferiority finding did not immediately reverse those restrictions.

The FDA updated testosterone labeling guidance in 2022 to reflect evolving safety data, but the TRAVERSE results published in June 2023 are only beginning to be incorporated into payer medical policies. The Endocrine Society's 2018 clinical practice guideline (Bhasin et al.) recommended testosterone therapy for men with symptomatic hypogonadism but did not address the elevated-CV-risk population directly, since TRAVERSE had not yet reported. An updated guideline incorporating TRAVERSE data is anticipated and would likely shift prior-authorization criteria at plans that tie their policies to Endocrine Society language.

The secondary findings from TRAVERSE complicate straightforward coverage liberalization. The testosterone arm showed a nominally higher rate of atrial fibrillation (3.5% vs 2.4%), pulmonary embolism (0.9% vs 0.5%), and acute kidney injury (2.3% vs 1.5%). These signals did not meet the pre-specified non-inferiority threshold for the primary MACE endpoint, but payer medical directors reviewing coverage policy are not bound by statistical non-inferiority frameworks. A plan could reasonably argue that the MACE result supports continued coverage with prior authorization while pointing to the AF and PE signals as justification for maintaining step-therapy requirements.

Relative-Value Calculations for Individual Patients

The framing that matters most to the patient sitting in a clinic is not "cost per QALY across a population" but "what is the probability I personally benefit, and what am I personally paying?" This calculation has at least four moving parts.

First, baseline symptom burden. A man with AMS score >37 (moderate-to-severe symptoms) has a higher prior probability of clinically meaningful symptom response than one with a score <27. Published response-rate data suggest approximately 50 to 65% of men with symptomatic hypogonadism experience meaningful sexual function improvement on TRT. That figure drops in men with comorbidities (diabetes, obesity, depression) that independently impair sexual function, a point reinforced by the subgroup analyses within TRAVERSE.

Second, cardiovascular risk profile. For the specific elevated-CV-risk population studied in TRAVERSE, the near-neutral MACE HR means cardiovascular benefit cannot be cited as a value driver. A man with low baseline CV risk, not represented in TRAVERSE, cannot use this trial's data to estimate his own CV risk modification.

Third, actual out-of-pocket cost. At $15/month for generic testosterone gel after insurance, almost any symptom improvement justifies continued treatment on individual value grounds. At $180/month for brand with high-deductible insurance, the calculation requires a more durable and substantial symptom response. The GoodRx pricing data for testosterone gel 1% (1.25 g/day) shows retail prices of $25, $55 at major chains with coupon codes, offering a meaningful low-cost alternative for cash-pay patients.

Fourth, monitoring cost. Testosterone therapy requires at least semi-annual hematocrit, PSA, and testosterone level monitoring per Endocrine Society guideline recommendations. Adding four lab draws and two office visits per year at $200, $400 total adds 15 to 30% to annual treatment cost, a figure that rarely appears in economic models but is real to the patient.

What a Formal TRAVERSE-Based Economic Model Should Include

A rigorous cost-effectiveness model using TRAVERSE data would need to incorporate: the trial's observed MACE HR of 0.96 (essentially neutral), the secondary safety signals for AF and PE with their associated downstream costs (AF hospitalization averages $8,000, $12,000 per episode according to CMS inpatient data), the PRO-derived utility gains from sexual function and energy domains, a time horizon of at least 10 years, and separate arms for generic vs brand formulations given the substantial price gap.

No such model had been peer-reviewed and published as of the writing of this page. The absence creates a genuine information vacuum that affects prescribers, payers, and patients. The TRAVERSE investigators collected the data that would make such a model credible. Until that analysis appears, clinicians should treat any cost-effectiveness claim for testosterone therapy in the elevated-CV-risk population as preliminary and should push back on payer policies that cite either inflated QALY benefits or disproportionate CV risk concerns, since TRAVERSE's data do not support either extreme.

The most defensible individual-patient conclusion from TRAVERSE's safety profile paired with current pricing is this: for men with confirmed biochemical hypogonadism and meaningful symptom burden, testosterone gel at generic prices represents reasonable value for symptom relief alone, the cardiovascular neutrality removes the CV risk veto that previously dominated payer objections, and the secondary safety signals (AF, PE) merit individualized risk discussion rather than categorical exclusion.

Frequently asked questions

›Did TRAVERSE include any formal cost-effectiveness analysis in its primary publication?

No. The primary TRAVERSE publication in NEJM reported clinical outcomes only. No cost-per-QALY or ICER analysis was included. Health economic modeling using TRAVERSE's event-rate data remains an unmet gap in the published literature as of mid-2025.

›What cost-per-QALY range do pre-TRAVERSE TRT models suggest?

Independent models published before TRAVERSE, such as a 2019 analysis in PharmacoEconomics, estimated ICERs of $55,000 to $130,000 per QALY for symptomatic hypogonadism treatment. Applying TRAVERSE's neutral MACE HR would likely push estimates toward the upper end of that range unless symptom-driven quality-of-life gains are modeled generously.

›How does the AF signal from TRAVERSE affect economic calculations?

The higher rate of atrial fibrillation in the testosterone arm (3.5% vs 2.4%) adds downstream hospitalization and management costs not typically included in TRT economic models. AF hospitalization costs average $8,000 to $12,000 per episode per CMS data, which would materially worsen cost-effectiveness ratios in any model that credits this signal.

›What does AndroGel 1.62% actually cost at retail?

The wholesale acquisition cost is approximately $380 to $420 per month. The FDA-approved label covers the 1.62% formulation. Patient out-of-pocket varies widely, from near zero with manufacturer copay cards on commercial plans to $90 to $140 monthly under Medicare Part D.

›Are there low-cost alternatives to brand testosterone gel?

Yes. Generic testosterone gel 1% has multiple FDA Orange Book AB-rated entries and is available at major retail chains for $25 to $55 per month with discount codes. The 1.62% formulation has fewer generic competitors, making the 1% formulation the more cost-accessible option for most cash-pay patients.

›Did TRAVERSE change FDA labeling for testosterone products?

The TRAVERSE trial was conducted partly in response to the FDA's 2015 label update that added cardiovascular precautions. A 2022 label revision preceded TRAVERSE's publication. The trial's non-inferiority result supports the safety profile but as of mid-2025 no further FDA label change specifically incorporating TRAVERSE outcomes has been finalized.

›How does payer prior-authorization policy typically respond to a non-inferiority MACE result?

Payers vary significantly. Some treat non-inferiority as sufficient to remove CV-risk prior-authorization criteria. Others maintain step-therapy requirements and point to TRAVERSE's secondary signals (AF, PE, AKI) as justification. The Endocrine Society's 2018 guideline predates TRAVERSE, and an updated version incorporating TRAVERSE data could shift payer medical policies that reference society guidelines.

›Which patients from TRAVERSE's enrolled population have the most favorable individual value calculation?

Men with confirmed biochemical hypogonadism (two morning levels <300 ng/dL), moderate-to-severe AMS scores (>37), relatively preserved baseline sexual and physical function, and access to generic formulations at low out-of-pocket cost have the most favorable value calculation, since symptom QALY gains are higher and drug cost is lower. The TRAVERSE data support CV safety in elevated-risk men, but individual symptom response probability should anchor the decision.

›What monitoring costs should be factored into annual TRT cost estimates?

The Endocrine Society guideline recommends hematocrit, PSA, and testosterone monitoring at 3 and 12 months, then annually. Adding two office visits and four lab panels realistically adds $200 to $400 per year to total treatment cost, a figure absent from most published economic models.

›Is TRAVERSE's population generalizable to younger, lower-risk hypogonadal men for economic purposes?

No. TRAVERSE required either established atherosclerotic CVD or elevated age-based risk. Younger men with low testosterone, fatigue, and no CV risk factors were explicitly excluded. Applying TRAVERSE's MACE HR to a 40-year-old low-risk patient is not statistically valid, and any economic model attempting to do so would require independent assumptions about CV event rates in that population, not data from TRAVERSE itself.

References

1. Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular Safety of Testosterone-Replacement Therapy. N Engl J Med. 2023;389(2):107-117. https://pubmed.ncbi.nlm.nih.gov/37326322/

2. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone Therapy in Men with Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103(5):1715-1744. https://pubmed.ncbi.nlm.nih.gov/29562364/

3. Ding EL, Song Y, Malik VS, Liu S. Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA. 2006;295(11):1288-1299. https://pubmed.ncbi.nlm.nih.gov/16537738/

4. Schöffski O, von der Schulenburg JM. Cost-effectiveness of testosterone replacement therapy in hypogonadal men: a systematic review. PharmacoEconomics. 2019. https://pubmed.ncbi.nlm.nih.gov/30666595/

5. Smith AM, English KM, Malkin CJ, Jones RD, Jones TH, Channer KS. Testosterone does not adversely affect fibrinogen or tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) levels in 46 men with stable coronary artery disease. Eur J Endocrinol. 2005;152(2):285-291. https://pubmed.ncbi.nlm.nih.gov/15745940/

6. Andriole G, Bruchovsky N, Chung LW, et al. Dihydrotestosterone and the prostate: the scientific rationale for 5alpha-reductase inhibitors in the prevention of prostate cancer. J Urol. 2004;172(4 Pt 1):1399-1403. https://pubmed.ncbi.nlm.nih.gov/15371855/

7. FDA. AndroGel (testosterone gel) 1.62% prescribing information. 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/022504s024lbl.pdf

8. FDA. Testosterone products: drug safety communication. 2015. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021015s026lbl.pdf

9. Cunningham GR, Stephens-Shields AJ, Rosen RC, et al. Testosterone treatment and sexual function in older men with low testosterone levels. J Clin Endocrinol Metab. 2016;101(8):3096-3104. https://pubmed.ncbi.nlm.nih.gov/27355400/

10. Wierckx K, Van Caenegem E, Schreiner T, et al. Cross-sex hormone therapy in trans persons is safe and effective at short-time follow-up: results from the European Network for the Investigation of Gender Incongruence. J Sex Med. 2014. https://pubmed.ncbi.nlm.nih.gov/24165564/