TRT After 65: What the Testosterone Trials and TRAVERSE Subgroup Data Show About Older Men

The bottom line in one paragraph

TRT for older men is not the slam-dunk anti-aging therapy direct-to-consumer clinics often imply, and it is not the cardiovascular catastrophe the 2015 FDA label change suggested. The truthful synthesis from the randomized evidence — the Testosterone Trials (Snyder et al., NEJM 2016; PMID 26886521), the TRAVERSE trial (Lincoff et al., NEJM 2023; DOI 10.1056/NEJMoa2215025), the TRAVERSE bone substudy (Snyder et al., NEJM 2024), the TEAAM trial (Basaria et al., JAMA 2015; PMID 26284720), and the TOM trial (Basaria et al., NEJM 2010; PMID 20592293) — is that testosterone therapy after 65 produces modest improvements in sexual function and physical performance in men with confirmed hypogonadism, did not increase major cardiovascular events versus placebo over roughly three years in TRAVERSE, but did move three safety signals in the wrong direction: pulmonary embolism, atrial fibrillation, and clinical fractures. There is no convincing benefit signal for cognition, vitality, or general wellbeing in this age group. The Endocrine Society and AUA both treat age-related decline in testosterone alone as an insufficient reason to prescribe.

This article walks through each of the major trials that inform TRT decisions after 65, the safety signals that are age-specific or age-amplified, what guideline bodies actually recommend, and where the research still has gaps. It is educational context — not medical advice. For the broader cardiovascular safety picture, see our deep-dive on the TRAVERSE trial, and for the fracture signal specifically, the TRAVERSE bone substudy article covers it in detail.

Why TRT after 65 is a different question

The same testosterone preparation, prescribed at the same target serum level, has a different risk-benefit profile in a 70-year-old than in a 35-year-old. Three structural reasons drive this.

The baseline event rate is higher

Older men have more atherosclerosis, more atrial fibrillation, more prior venous thromboembolism, more prostate disease, and more polypharmacy. When a therapy nudges a relative risk slightly — say a hazard ratio of 1.4 for fractures, as the TRAVERSE bone substudy reported — the absolute increase in event rate is larger in a population with a higher baseline. The same hazard ratio translates to more absolute harm in a 70-year-old population than in a 40-year-old population.

The benefit signal is smaller

The Testosterone Trials, designed specifically for men 65 and older with confirmed low T, found real but modest benefits — clinically meaningful improvements in sexual function and a measurable but small improvement in walking distance. The Vitality Trial and the Cognitive Function Trial within the T-Trials did not show significant benefits at all. The popular framing of TRT as a fountain-of-youth treatment did not survive the randomized evidence in this age group.

Endogenous testosterone trajectories are uncertain

Cross-sectional data show that mean total testosterone drifts downward with age, but the magnitude and clinical meaning of that drift are contested. The Hormone Standardization Program reanalysis (Travison et al., JCEM2017; PMID 28324103) standardized assays across major cohorts and concluded that some of the observed age-related decline is confounded by health status — the men whose testosterone falls fastest tend to develop obesity, diabetes, and chronic disease. Healthy aging men, in some analyses, show only modest decline. This matters because it complicates the threshold question: at what level does "low for age" cross into pathological hypogonadism that warrants treatment?

The Testosterone Trials (T-Trials) — Snyder et al., NEJM 2016

Before TRAVERSE, the Testosterone Trials were the largest and most comprehensive randomized assessment of testosterone therapy in older men. The T-Trials enrolled 790 men aged 65 and older with two morning total testosterone measurements below 275 ng/dL and symptoms in at least one of three domains — sexual dysfunction, physical limitation, or reduced vitality. Participants were randomized to transdermal testosterone gel (titrated to mid-normal serum levels) or placebo for one year.

What makes the T-Trials important

The T-Trials were not a single trial. They were seven coordinated, NIH-funded trials sharing the same study population — Sexual Function, Physical Function, Vitality, Cognitive Function, Anemia, Bone, and Cardiovascular. Each trial was pre-specified, separately powered for its primary endpoint, and reported with explicit attention to multiple comparisons. The principal investigators were Peter Snyder (Penn), Shalender Bhasin (Brigham and Women's/Harvard), Susan Ellenberg, and a multi-site U.S. team. Primary publication: New England Journal of Medicine, February 18, 2016.

Why the T-Trial population matters

Eligibility required age 65+, two confirmed low testosterone measurements, and symptoms — meaning the T-Trial men are the closest randomized analog to the older-men population that clinics actually evaluate for TRT. The strict biochemical and symptomatic entry criteria mean the trial answers a sharp question: in older men who meet guideline criteria for hypogonadism, does testosterone therapy help across these specific domains?

What the seven T-Trials measured and found

Each of the seven coordinated trials reported a primary endpoint and a published interpretation. The pattern across the seven is the most useful summary an older man and his clinician can have when discussing realistic expectations.

The honest synthesis from the T-Trials

In older men with confirmed low testosterone and symptoms, one year of testosterone gel produced real benefits on sexual function, modest benefits on physical function, correction of unexplained anemia, and improvement in bone density. It did not improve vitality or cognition. It produced an imaging-level cardiovascular signal that TRAVERSE later softened with hard-endpoint data. Anyone framing TRT after 65 as a guaranteed energy, mood, and cognitive boost is not citing the randomized evidence.

TRAVERSE older-men subgroup data

TRAVERSE was the FDA-mandated cardiovascular safety trial published in NEJM in June 2023 (Lincoff et al.). It enrolled 5,246 men aged 45 to 80 with hypogonadism and pre-existing cardiovascular disease or high CV risk, and randomized them to transdermal testosterone gel or placebo for a mean follow-up of approximately 33 months. The primary MACE composite (cardiovascular death, nonfatal MI, nonfatal stroke) was non-inferior on testosterone — a hazard ratio of 0.96 with 95% confidence interval 0.78 to 1.17.

The older-age subgroup

TRAVERSE pre-specified subgroup analyses by age, including a subgroup of men 65 and older. The published primary paper and the FDA-reviewed sponsor briefing material show that the MACE result was consistent across age strata — no statistically significant interaction between age and treatment effect on the primary endpoint. In plain terms: the reassuring MACE finding held in older men as well as middle-aged men. Men aged 65 and older on testosterone did not have higher rates of heart attack, stroke, or cardiovascular death than men aged 65 and older on placebo, within the trial's power to detect.

What the older-men subgroup does not soften

The secondary safety signals — pulmonary embolism, atrial fibrillation, acute kidney injury, and (in the bone substudy) clinical fractures — also did not show age-specific interactions in the published reports, but these are the signals that matter clinically more in older men because of higher baseline risk. A doubling of relative PE risk on testosterone (0.9% vs 0.5% across all ages) becomes a larger absolute concern in a 75-year-old with prior DVT than in a 50-year-old without thromboembolic history.

The TRAVERSE bone substudy is the big older-men signal

The TRAVERSE bone substudy (Snyder et al., NEJM 2024) reported clinical fractures in 3.50% of testosterone-treated men versus 2.46% of placebo-treated men over a median 3.19 years — a hazard ratio of 1.43 (95% CI 1.04–1.97). The fracture signal was not concentrated in any single mechanism — falls, behavioral activation, and possible changes in bone quality at sites not captured by BMD were all hypothesized. Our companion article on the TRAVERSE bone substudy walks through the data in detail and contrasts it with the T-Trials bone substudy from 2017, which showed BMD improvement in this same age group. The decoupling between BMD (better on testosterone) and clinical fractures (worse on testosterone) is the central puzzle, and it matters most in the population most prone to fragility fractures — older men.

The TEAAM trial — Basaria et al., JAMA 2015

TEAAM (Testosterone's Effects on Atherosclerosis Progression in Aging Men) was a randomized, double-blind, placebo-controlled trial that enrolled 308 men aged 60 and older with low or low-normal testosterone (total T 100–400 ng/dL or free T below 50 pg/mL). Participants were randomized to transdermal testosterone gel (titrated to mid-normal range) or placebo for 3 years. The primary endpoint was the rate of change in common carotid artery intima-media thickness (CIMT) measured by ultrasound. Published in JAMA, August 11, 2015 (PMID 26284720).

What TEAAM found

TEAAM found no significant difference between testosterone and placebo on the rate of CIMT progression over 3 years. The trial also reported no significant difference in coronary artery calcium progression, sexual function, health-related quality of life, or mood between groups. TEAAM is one of the few trials specifically powered to detect a structural vascular effect of testosterone in older men, and it found none.

How TEAAM fits with TRAVERSE and the T-Trials

TEAAM, TRAVERSE, and the T-Trials together tell a relatively coherent story for older men: testosterone therapy does not appear to accelerate atherosclerosis progression at a structural level (TEAAM CIMT, TRAVERSE MACE non-inferiority), does produce small functional improvements (T-Trial sexual and physical function), and does not produce the broad anti-aging benefits often marketed. The Budoff cardiovascular imaging substudy of the T-Trials remains an outlier finding that TRAVERSE and TEAAM helped contextualize as not translating into hard cardiovascular events at the trial-population level.

The TOM trial and the frailty question

The TOM (Testosterone in Older Men with Mobility Limitations) trial (Basaria et al., NEJM 2010; PMID 20592293) enrolled 209 community-dwelling men aged 65 and older with limited mobility and total testosterone below 350 ng/dL. Participants were randomized to a high-dose testosterone gel (10 g/day, titrated upward) or placebo. The primary functional endpoints were leg-press and chest-press strength and physical performance.

Why TOM was stopped early

A trial-monitoring committee halted enrollment because of a higher rate of cardiovascular-related adverse events in the testosterone arm — 23 events in 106 men on testosterone vs 5 events in 103 men on placebo. The events were a heterogeneous mix (peripheral edema, hypertension, dysrhythmia, MI, syncope), and the small sample size and event count limit firm conclusions. The men in TOM were notably frail at baseline — more comorbidity, more medications, more functional limitation — than later trials like the T-Trials and TRAVERSE.

How TOM should be cited today

TOM is an important historical signal that contributed to FDA concern and shaped the design of TRAVERSE. With TRAVERSE's much larger sample (5,246 vs 209) and proper randomization across the full age and CV-risk range, the TOM signal has not been reproduced as a primary MACE excess. Most contemporary commentary treats TOM as a cautionary trial about high-dose testosterone in frail elderly men with cardiovascular comorbidity, rather than as definitive evidence of cardiovascular harm from physiologic-replacement TRT.

Does testosterone help frailty after 65?

Frailty is a clinical syndrome of decreased physiologic reserve — weakness, slow walking, low activity, exhaustion, and weight loss — that increases vulnerability to falls, hospitalization, and mortality. The question of whether testosterone improves frailty has been examined in multiple trials with consistent, modest findings.

What the trials show

• T-Trials Physical Function (Snyder et al., NEJM 2016): Across the broader T-Trials population, men on testosterone walked roughly 5–6 meters more on the 6-minute walk than placebo. The effect within the Physical Function Trial cohort specifically was smaller and did not meet the pre-specified ≥50 m threshold for response in a higher proportion of testosterone-treated men.
• Body composition meta-analyses: Multiple meta-analyses of testosterone trials in older men report consistent small gains in lean mass (typically 1–2 kg) and small reductions in fat mass on testosterone, alongside modest increases in grip strength. Effects on functional outcomes (gait speed, chair rise) are smaller and less consistent.
• Anabolic response is preserved but not amplified: Older muscle responds to testosterone, but the response is smaller per dose than in younger men, and dose-response data above mid-normal serum testosterone show diminishing returns.

Why testosterone is not a frailty treatment

Frailty is driven by sarcopenia, malnutrition, low physical activity, polypharmacy, depression, and cognitive decline — a multifactorial syndrome. Testosterone addresses one input. Randomized data support resistance training and protein adequacy as the largest movable factors in older-adult sarcopenia. The most defensible framing is that testosterone may be a useful adjunct in carefully selected hypogonadal older men alongside resistance training and protein, not a substitute for either.

Cardiovascular risk in older men

TRAVERSE is the most authoritative source on cardiovascular safety in older men on TRT, and the older-men subgroup did not show a different MACE pattern than the trial overall. The honest summary: in carefully selected older men with confirmed hypogonadism and pre-existing CV risk, transdermal testosterone titrated to mid-normal serum levels did not increase major cardiovascular events over roughly three years.

Where caution still applies

• Recent acute cardiovascular events: Men with MI, stroke, or unstable angina within the prior 3–6 months were excluded from TRAVERSE. Guideline bodies retain explicit caution about initiating TRT in this window.
• Decompensated heart failure: Excluded from TRAVERSE; Endocrine Society guidance continues to advise against TRT in this setting.
• Atrial fibrillation: TRAVERSE found a small absolute increase in new-onset AFib (3.5% vs 2.4%). Men with paroxysmal AFib should have explicit risk-benefit discussion.
• Venous thromboembolism history: The PE signal in TRAVERSE (0.9% vs 0.5%) is the most consistently flagged safety concern. Prior DVT/PE or known thrombophilia is a relative contraindication that gets stricter with age.

Delivery method matters

TRAVERSE used transdermal gel exclusively. Injection protocols produce higher peak serum testosterone and larger hematocrit increases than gel at equivalent weekly doses, per published comparative pharmacokinetic data. The TRAVERSE cardiovascular safety signal applies most directly to gel-equivalent protocols. For older men in particular — where hematocrit rises faster and viscosity-driven VTE matters more — gel or short-ester low-volume frequent injection protocols may carry a more favorable safety margin than high-peak weekly intramuscular protocols. Our TRT gel vs injections article covers the delivery comparison in more depth.

Prostate monitoring and PSA after 65

Prostate concerns are the most common safety question older men raise about TRT, and the data have shifted meaningfully since the early 2000s.

What TRAVERSE found on prostate cancer

TRAVERSE reported no significant increase in incident prostate cancer between the testosterone and placebo arms. Across the trial, prostate cancer was diagnosed in approximately 0.5% on testosterone vs 0.6% on placebo over the follow-up period. This is one of the most reassuring findings of the trial for older men specifically, because prostate cancer was the historical worry that most influenced clinician decisions.

What the AUA recommends

The American Urological Association (Mulhall et al., AUA Guideline 2018, amended 2024) continues to recommend PSA and digital rectal exam at baseline for men over 40 with risk factors, with PSA repeated at 3–12 months after initiating therapy and at least annually thereafter. The AUA does not treat the absence of a PSA signal as ground to abandon prostate monitoring. Our PSA on TRT article walks through the monitoring schedule, the 1.4 ng/mL velocity threshold, and when prescribers refer to urology.

BPH and lower urinary tract symptoms

TRAVERSE did not find a meaningful difference in lower urinary tract symptom (LUTS) scores between groups. Earlier concerns that TRT might worsen benign prostatic hyperplasia symptoms in older men have not been confirmed in randomized trials at physiologic replacement doses.

Hematocrit, viscosity, and VTE risk

Hematocrit rises predictably on testosterone therapy. The mechanism is well established — testosterone stimulates erythropoiesis via direct bone-marrow effects and increased erythropoietin sensitivity. In older men, the practical implications are amplified.

The 54% threshold

The Endocrine Society 2018 guideline (Bhasin et al., JCEM 2018; PMID 29562364) recommends therapy dose adjustment or temporary discontinuation if hematocrit exceeds 54%. This threshold is not derived from a randomized trial of hard outcomes — it is a pragmatic threshold informed by hyperviscosity physiology and the observation that thrombotic risk rises non-linearly above 54%. Older men reach this threshold faster and more often than younger men on equivalent doses.

How the TRAVERSE PE signal fits

TRAVERSE's small absolute but doubled relative pulmonary embolism rate (0.9% vs 0.5%) is the prospective hard-endpoint evidence the older trial literature lacked. The biological plausibility — testosterone raises hematocrit, hematocrit raises viscosity, viscosity raises VTE risk — links cleanly to the observed signal. For older men with any of the additional VTE risk factors (prior DVT/PE, immobility, recent surgery, known thrombophilia, active malignancy), the PE signal compounds.

Therapeutic phlebotomy and blood donation

Therapeutic phlebotomy is the standard intervention when hematocrit crosses thresholds. Some older men also donate at the Red Cross or community blood banks if they meet eligibility criteria. Our hematocrit on TRT article covers the management strategies in detail. Note that donation eligibility rules and age cutoffs vary by organization and country.

Falls, fractures, and bone — a contradictory picture

The bone story is the most cognitively dissonant part of the older-men evidence base. Two large randomized trials in the same age group point in opposite directions on bone outcomes.

T-Trials Bone substudy — BMD better on testosterone

The T-Trials Bone substudy (Snyder et al., JAMA Internal Medicine 2017; PMID 28241248) used quantitative CT (QCT) to measure volumetric bone mineral density and estimated bone strength at the spine and hip. After one year, testosterone-treated men showed statistically significant improvements in BMD and estimated strength versus placebo. The trial was not powered to detect clinical fractures and did not report fracture outcomes — bone density was the explicit endpoint.

TRAVERSE Bone substudy — clinical fractures worse on testosterone

The TRAVERSE Bone substudy (Snyder et al., NEJM 2024) was a prospective, pre-specified sub-analysis of clinical fractures in the full TRAVERSE population over median 3.19 years follow-up. Clinical fractures occurred in 91 of 2,601 testosterone-treated men (3.50%) and 64 of 2,603 placebo-treated men (2.46%), hazard ratio 1.43 (95% CI 1.04–1.97). The fracture sites and types were heterogeneous, with no single dominant location.

How to reconcile better BMD with more fractures

Several hypotheses are on the table, none definitively confirmed:

1. Behavioral activation: Men feeling better and being more physically active on TRT may expose themselves to more fall opportunities — a higher rate of high-energy activities that generate fractures.
2. Bone quality vs density: BMD captures one aspect of bone strength. Microarchitecture, cortical porosity, and trabecular bundle integrity are not fully captured by DEXA or QCT, and these may move differently than density.
3. Fall risk modifications: Orthostatic hypotension, gait changes, or sleep disruption on testosterone could contribute.
4. Statistical play of chance: The 95% CI lower bound was 1.04 — borderline significant. Replication will matter.

The contradictory pattern is the single biggest evidence-base reason for caution in prescribing TRT to older men with high baseline fracture risk. Our TRAVERSE bone substudy article covers the mechanism debate and bone-monitoring implications in detail.

Cognition, mood, and depression evidence

Cognitive and mood claims dominate direct-to-consumer TRT marketing. The randomized evidence in older men is consistent and unflattering to those claims.

Cognition — T-Trials Cognitive Function Trial

The Cognitive Function Trial (Resnick et al., JAMA 2017; PMID 28245342) randomized older men with age-associated memory impairment and low testosterone to gel or placebo for one year. Primary endpoints were delayed paragraph recall and three additional cognitive composites — verbal memory, visual memory, and executive function. No significant treatment effect was observed on any primary endpoint. The trial does not support testosterone as a cognitive enhancer in older men.

Mood and depression

Smaller randomized trials of testosterone in older men with low-grade or subsyndromal depressive symptoms have shown mixed results. The Pope et al. meta-analyses and the more recent Walther et al. systematic review (JAMA Psychiatry 2019; PMID 30758536) suggest modest improvements in depressive symptom scales in some hypogonadal populations, with effect sizes smaller than first-line antidepressants. The T-Trials Vitality Trial — which measured FACIT-Fatigue and similar global wellbeing scales — did not find a benefit. Testosterone is not a first-line treatment for depression in older men.

Who in this age group might reasonably consider TRT

Synthesizing the guideline and trial evidence, a defensible profile of an older man who might reasonably be evaluated for TRT looks like this:

• Two morning total testosterone measurements below approximately 300 ng/dL (Endocrine Society and AUA threshold) on validated assays
• Symptoms consistent with androgen deficiency — most commonly low libido, erectile dysfunction not explained by other causes, or fatigue with no other identifiable driver
• No recent (within 3–6 months) acute cardiovascular event or unstable cardiovascular disease
• No prior unprovoked DVT or PE, no known thrombophilia, no active malignancy with thrombotic risk
• Baseline PSA appropriate for age and risk; no untreated prostate cancer
• Hematocrit below 50% before initiating therapy
• Willingness to engage with the monitoring schedule and to revise the decision if hematocrit, PSA, or symptom response is unfavorable

Profiles that warrant more caution

• Active or recent (within 3 months) acute cardiovascular event
• Decompensated heart failure
• Prior unprovoked VTE or known hereditary thrombophilia
• Untreated or recently treated prostate cancer (oncology consultation required)
• Baseline hematocrit above 50%
• Severe untreated obstructive sleep apnea
• High baseline fracture risk (prior fragility fracture, severe osteoporosis with multiple risk factors)

What guideline-based monitoring looks like

Older men on TRT carry a higher monitoring burden than younger men — partly because the safety signals are bigger, partly because baseline labs are more likely to be abnormal, and partly because dose response is less predictable.

Pre-TRT baseline panel

• Two morning fasting total testosterone measurements (1–4 weeks apart)
• SHBG and calculated or measured free testosterone
• LH and FSH (to distinguish primary vs secondary hypogonadism)
• Estradiol (sensitive assay if available)
• PSA and digital rectal exam in men over 40
• Complete blood count (hematocrit, hemoglobin)
• Comprehensive metabolic panel and lipid panel
• HbA1c
• Sleep history; consider polysomnography or home sleep test if sleep apnea is suspected

Initial follow-up

• At 6–8 weeks: total testosterone (trough timing matched to delivery method), hematocrit, blood pressure
• At 3–6 months: total T, hematocrit, PSA, sensitive estradiol, symptom reassessment
• If hematocrit >54%: dose reduction, frequency change, or therapeutic phlebotomy
• If PSA velocity exceeds 1.4 ng/mL/year or absolute PSA exceeds age-appropriate thresholds: urology referral

Ongoing annual monitoring

• Total testosterone, hematocrit, PSA, blood pressure, lipids, HbA1c annually
• Fracture risk reassessment in men with prior fractures or osteoporosis risk factors
• Symptom-driven retitration; documented periodic re-evaluation of whether continuing therapy is the right call

Our TRT blood work schedule article walks through the full panel structure in deeper detail, and the PSA on TRT piece covers the prostate monitoring rhythm specifically.

What the research does not answer

The randomized trial base is the strongest it has ever been for older men, but several practical questions remain open.

Long-term safety beyond ~3 years

TRAVERSE mean follow-up was approximately 33 months. T-Trials follow-up was 12 months. TEAAM follow-up was 36 months. None of these trials characterize TRT safety at 10, 15, or 20 years of continuous use — durations that are common in real-world prescribing. The cumulative effect of small annual risk increases on fractures, AFib, and PE over decades is not directly characterized.

High-dose and injection-based protocols in older men

TRAVERSE used transdermal gel. The T-Trials used gel. TEAAM used gel. None of the large randomized trials in older men tested high-dose intramuscular protocols, supraphysiologic targeting, or weekly injection regimens. The safety inference for older men using injection-based TRT is extrapolated, not directly observed.

Men without baseline cardiovascular risk

TRAVERSE required pre-existing CV disease or high CV risk for enrollment. Older men with clean cardiovascular profiles are underrepresented in the strongest safety dataset. The presumption is that clean-profile men have at least as favorable a safety margin, but this is presumed rather than tested.

Hard cognitive and dementia endpoints

The Cognitive Function Trial was 12 months and used cognitive composite endpoints, not incident dementia diagnosis. Whether TRT affects long-term dementia risk in older hypogonadal men is unanswered by current randomized data.

Plain-English summary for men and families

If you are 65 or older and considering TRT — or you are a family member of someone in that position — here is the honest synthesis of the randomized evidence.

1. For confirmed hypogonadism with clear symptoms, TRT can be appropriate. The T-Trials show real benefits on sexual function and modest benefits on physical performance and anemia in older men who meet criteria.
2. Cardiovascular safety in carefully selected men is reassuring, not perfect. TRAVERSE found no MACE excess. Pulmonary embolism, atrial fibrillation, and acute kidney injury all moved in the wrong direction by small absolute amounts. Personal CV history matters.
3. The fracture finding is the biggest cautionary signal specific to older men. Better bone density on TRT (T-Trials) did not translate to fewer fractures (TRAVERSE). Men with high fracture risk should weigh this carefully.
4. Cognition and vitality are not improved by TRT in this age group. The randomized evidence does not support TRT for memory, executive function, or general energy and wellbeing in older men.
5. Prostate cancer risk did not increase in TRAVERSE. This is the most reassuring single safety finding for older men, but PSA monitoring remains the standard regardless.
6. Monitoring is intensive and lifelong. If you start TRT after 65, expect a baseline panel, 6-week and 3-month follow-up labs, and at least annual labs thereafter. Hematocrit, PSA, blood pressure, and fall risk all warrant ongoing attention.
7. Older men respond to testosterone, but the response is smaller per dose than in younger men. Combine with resistance training and adequate protein. Do not expect TRT to do the work of behavior change.

A brief scenario

Consider a 72-year-old man with two morning total testosterone levels of 230 ng/dL, persistent low libido, fatigue not explained by sleep or thyroid, controlled hypertension, prior coronary stent placed 8 years ago, no VTE history, PSA 1.8 ng/mL, and hematocrit 44%. Pre-TRAVERSE, many clinicians would have declined to prescribe. Post-TRAVERSE, the conversation is richer. His MACE risk on testosterone is not meaningfully different from placebo per randomized data in a similar population. His prostate baseline is favorable. His hematocrit floor allows room to titrate. The bone substudy fracture signal warrants discussion — he has no prior fragility fracture, but his prescriber may add a fall-risk assessment and a baseline DEXA. A 3-month trial of carefully titrated transdermal gel with the full monitoring schedule, and an explicit pre-discussed off-ramp if the labs or symptoms do not justify continuation, is a defensible plan.

Where this fits in the broader TRT picture

For deeper context, the TRAVERSE trial deep-dive walks through the full cardiovascular safety analysis, and the TRAVERSE bone substudy article covers the fracture data and mechanism debate. For men weighing alternatives, our enclomiphene vs TRT and clomid vs TRT articles cover the non-testosterone routes, though selective estrogen receptor modulators (SERMs) are less commonly used in this age group. For lab-level monitoring detail, see the TRT blood work schedule. For prostate-specific monitoring, see PSA on TRT. For hematocrit management, see hematocrit on TRT. For the broader pillar overview, the testosterone therapy pillar guide is the natural next read.

Sources referenced in this article

• Snyder PJ, Bhasin S, Cunningham GR, et al. "Effects of Testosterone Treatment in Older Men." New England Journal of Medicine. 2016;374(7):611-624. PMID 26886521.
• Snyder PJ, Kopperdahl DL, Stephens-Shields AJ, et al. "Effect of Testosterone Treatment on Volumetric Bone Density and Strength in Older Men With Low Testosterone: A Controlled Clinical Trial." JAMA Internal Medicine. 2017;177(4):471-479. PMID 28241248.
• Roy CN, Snyder PJ, Stephens-Shields AJ, et al. "Association of Testosterone Levels With Anemia in Older Men: A Controlled Clinical Trial." JAMA Internal Medicine. 2017;177(4):480-490. PMID 28241124.
• Budoff MJ, Ellenberg SS, Lewis CE, et al. "Testosterone Treatment and Coronary Artery Plaque Volume in Older Men With Low Testosterone." JAMA. 2017;317(7):708-716. PMID 28253386.
• Resnick SM, Matsumoto AM, Stephens-Shields AJ, et al. "Testosterone Treatment and Cognitive Function in Older Men With Low Testosterone and Age-Associated Memory Impairment." JAMA. 2017;317(7):717-727. PMID 28245342.
• Lincoff AM, Bhasin S, Flevaris P, et al. "Cardiovascular Safety of Testosterone-Replacement Therapy" (TRAVERSE trial). New England Journal of Medicine. 2023;389(2):107-117. DOI 10.1056/NEJMoa2215025.
• Snyder PJ, Bhasin S, Cunningham GR, et al. "Testosterone Treatment and Fractures in Men With Hypogonadism" (TRAVERSE bone substudy). New England Journal of Medicine. 2024. DOI 10.1056/NEJMoa2308836.
• Basaria S, Harman SM, Travison TG, et al. "Effects of Testosterone Administration for 3 Years on Subclinical Atherosclerosis Progression in Older Men With Low or Low-Normal Testosterone Levels: A Randomized Clinical Trial" (TEAAM). JAMA. 2015;314(6):570-581. PMID 26284720.
• Basaria S, Coviello AD, Travison TG, et al. "Adverse Events Associated With Testosterone Administration" (TOM trial). New England Journal of Medicine. 2010;363(2):109-122. PMID 20592293.
• Bhasin S, Brito JP, Cunningham GR, et al. "Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline." Journal of Clinical Endocrinology & Metabolism. 2018;103(5):1715-1744. PMID 29562364.
• Mulhall JP, Trost LW, Brannigan RE, et al. "Evaluation and Management of Testosterone Deficiency: AUA Guideline." Originally 2018, amended 2024.
• Travison TG, Vesper HW, Orwoll E, et al. "Harmonized Reference Ranges for Circulating Testosterone Levels in Men of Four Cohort Studies in the United States and Europe." Journal of Clinical Endocrinology & Metabolism. 2017;102(4):1161-1173. PMID 28324103.
• Walther A, Breidenstein J, Miller R. "Association of Testosterone Treatment With Alleviation of Depressive Symptoms in Men: A Systematic Review and Meta-analysis." JAMA Psychiatry. 2019;76(1):31-40. PMID 30758536.

This article was written by the TRT FAQ Editorial Team and reviewed against the primary trial publications and current Endocrine Society and AUA guidance. It is educational content, not medical advice. Last content review: May 2026.