TRT Cuts Death Risk 22% in Kidney Disease Patients

For decades, nephrologists have avoided prescribing testosterone to men with chronic kidney disease. The concern was straightforward: CKD patients already carry elevated cardiovascular risk, and adding a hormone that raises hematocrit and blood pressure seemed reckless without evidence it was safe.

A 2026 study now provides that evidence. Published in the World Journal of Men's Health, the largest propensity-matched analysis of TRT safety in CKD to date found that testosterone therapy was not only safe but associated with a meaningful survival benefit.

Key Takeaways

• 3,090 men with CKD stages 3 through 5 and hypogonadism were propensity-matched: 1,545 receiving TRT vs 1,545 untreated
• TRT was associated with 22 percent lower all-cause mortality over a median 3.7-year follow-up (HR 0.78, 95% CI 0.63 to 0.98)
• No significant increase in stroke, heart attack, heart failure, prostate cancer, or dementia
• Survival benefit persisted across CKD subgroups including men on dialysis
• This is observational evidence, not a randomized trial -- correlation, not proven causation
• CKD patients need nephrology-supervised TRT, not standard telehealth protocols

Why This Study Matters

Testosterone deficiency is one of the most common and most overlooked complications of chronic kidney disease. Between 40 and 60 percent of men with moderate-to-severe CKD have clinically low testosterone levels, rising above 60 percent in dialysis patients. The mechanisms are well-understood: uremic toxins suppress the hypothalamic-pituitary-gonadal axis, chronic inflammation damages Leydig cells, and impaired renal clearance disrupts hormone metabolism.

The consequences are not trivial. Low testosterone in CKD patients is independently associated with frailty, sarcopenia, fatigue, depression, reduced quality of life, and -- in multiple observational studies -- higher mortality. Yet most nephrologists have historically declined to treat it, citing a lack of safety data in this high-risk population.

This study directly addresses that gap.

What the Researchers Did

The study, led by Lino Merlino from the Donal O'Donoghue Renal Research Centre at Northern Care Alliance (Manchester, UK), used the TriNetX Global Collaborative Network -- a federated database of anonymized electronic health records from over 150 healthcare organizations worldwide.

Study Design

Parameter	Detail
Design	Retrospective propensity-matched cohort
Database	TriNetX Global Collaborative Network
Population	Men 18 to 80 with CKD stages 3 to 5 and hypogonadism
TRT group	1,545 men who received testosterone within 6 months of hypogonadism diagnosis
Control group	1,545 propensity-matched men with CKD and hypogonadism, untreated
Matching variables	Demographics, comorbidities, laboratory values
Mean baseline eGFR	47.7 mL/min/1.73 m-squared (both groups)
Median follow-up	3.7 years
Publication	World Journal of Men's Health, 2026

The propensity-score matching is important. CKD patients who receive TRT are likely systematically different from those who do not -- they may be healthier, have more engaged clinicians, or have fewer comorbidities. Matching on demographics, baseline kidney function, and existing conditions attempts to balance those confounders, though residual confounding remains possible in any observational study.

What the Data Showed

Primary Outcome: Mortality

Men who received TRT had a 22 percent lower risk of death from any cause compared with matched controls over the study period.

All-cause mortality hazard ratio: 0.78 (95% CI 0.63 to 0.98)

That confidence interval just clears significance -- the upper bound of 0.98 means the true effect could be as small as a 2 percent mortality reduction. It is not a definitive answer, but it is a signal worth investigating in a randomized trial.

The mortality benefit persisted in subgroup analyses across CKD stage 3a, advanced CKD (stages 4 and 5), and dialysis patients.

Secondary Outcomes: Safety

The safety signals that historically kept nephrologists from prescribing testosterone were absent.

Outcome	Significant Difference?
Myocardial infarction	No
Stroke	No
Heart failure	No
Prostate cancer	No
Vascular dementia	No
Alzheimer disease	No

No secondary outcome showed a statistically significant increase in the TRT group. This does not mean the risk is zero -- it means this study, at this sample size and follow-up duration, did not detect a signal.

Context From Other CKD Research

This study aligns with a growing evidence base:

• A VA registry analysis of hypogonadal veterans found TRT was associated with delayed CKD progression, not acceleration
• A 2024 review in Asian Journal of Urology noted TRT safely improved quality of life, sexual function, and testosterone deficiency symptoms in men with moderate-to-severe CKD
• A 2025 study in Cardiovascular Diabetology found TRT was associated with reduced risk of acute kidney injury, kidney failure requiring dialysis, and cardiovascular events in men with diabetes and hypogonadism

What This Means for CKD Patients With Low Testosterone

If you have CKD and symptomatic testosterone deficiency, this study changes the conversation with your nephrologist. It does not mean you should start TRT without supervision. It means the safety concern that prevented the conversation from happening now has data on the other side.

Who This Study Applies To

• Men with CKD stages 3 through 5 (eGFR below 60)
• Confirmed hypogonadism on morning bloodwork
• Symptoms consistent with testosterone deficiency: fatigue, sarcopenia, depression, low libido

Who This Study Does Not Apply To

• Men with normal kidney function (standard TRT safety data applies instead)
• Men with CKD but normal testosterone levels
• Men with active cancer or unstable cardiovascular disease

Monitoring Requirements for TRT in CKD

CKD patients on TRT need tighter monitoring than men with normal kidney function. The standard TRT bloodwork schedule is a starting point, but nephrologists should add kidney-specific parameters.

Baseline and Ongoing Labs

Test	Frequency	Why It Matters in CKD
Total and free testosterone	Baseline, 6 weeks, then every 6 months	Confirm deficiency and dose adequacy
Hematocrit	Baseline, 6 weeks, 3 months, then every 6 months	CKD patients often have erythropoietin therapy; TRT compounds hematocrit rise
Cystatin C-based eGFR	Baseline, 3 months, then every 6 months	Creatinine-based eGFR is unreliable on TRT due to muscle-mass changes
Blood pressure	Every visit	TRT can raise blood pressure; CKD patients are already hypertension-prone
PSA	Baseline, 6 months, then annually	Standard prostate monitoring
Potassium	Baseline, 6 weeks, then with regular CKD panels	Relevant in advanced CKD; some testosterone formulations affect fluid balance

Formulation Considerations

The study captured multiple testosterone formulations but did not compare them head-to-head. For CKD patients, clinicians should consider:

• Transdermal gel or cream offers more stable levels with less hematocrit spike than intramuscular injections
• Testosterone cypionate or enanthate injections at lower doses with more frequent dosing (twice weekly rather than weekly) can smooth pharmacokinetic peaks
• Avoid long-acting formulations like pellets or testosterone undecanoate in advanced CKD where dose adjustment flexibility is important

Limitations to Keep in Mind

This is an observational study. It cannot prove that TRT caused the mortality reduction. Possible explanations for the survival benefit include:

1. Residual confounding -- men who received TRT may have been healthier or had more proactive medical care despite matching
2. Healthy user bias -- men well enough to seek TRT treatment may be fundamentally different from those who do not
3. Incomplete adherence data -- the study could not verify that patients actually took their testosterone consistently
4. Limited power for rare outcomes -- 1,545 patients per group may not be enough to detect modest increases in rare events like prostate cancer

The 22 percent mortality reduction is a hypothesis-generating finding. It needs confirmation from a prospective randomized trial -- which will be difficult to fund and conduct in this population.

How to Use This Information

If You Have CKD and Suspect Low Testosterone

1. Ask your nephrologist to check total testosterone, free testosterone, and LH on an early-morning blood draw
2. If levels are low and symptoms are present, bring this study to the conversation
3. Request referral to an endocrinologist or urologist experienced in TRT
4. Discuss monitoring frequency, formulation choice, and coordination between your kidney team and prescriber
5. Do not start TRT through a telehealth clinic without informing your nephrologist

If You Are on TRT and Develop Kidney Problems

If you are currently on TRT and your kidney function appears to be declining, do not assume TRT is the cause. Creatinine rises on TRT due to muscle-mass gains, which makes eGFR look artificially low. Ask for a cystatin C-based eGFR to get an accurate picture before making any treatment changes.

Comparing Clinics for CKD Patients

Most online TRT clinics are designed for men with normal kidney function and will screen out significant CKD. If you have CKD stages 3 through 5, you need a prescriber who understands renal pharmacology and can coordinate with your nephrologist. Look for academic medical centers or endocrinology practices with experience managing hormones in CKD.

The Bottom Line

For 37 million Americans with chronic kidney disease, testosterone deficiency has been a treatable condition that went untreated because safety data did not exist. This study begins to fill that gap.

A 22 percent mortality reduction in a propensity-matched cohort of 3,090 men with CKD is not proof of benefit -- it is evidence that the safety concern blocking treatment may have been overcautious. No signal of increased cardiovascular events, prostate cancer, or cognitive decline was detected over nearly four years of follow-up.

The next step is a prospective randomized trial. Until that happens, this study gives nephrologists, endocrinologists, and patients a reason to have the conversation they have been avoiding.

References

1. Merlino L, Rainone F, Tollitt J, et al. Safety of Testosterone Therapy in Chronic Kidney Disease: A Propensity Score-Matched Cohort Study. World Journal of Men's Health. 2026;44:e24.
2. Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR. Low serum testosterone and mortality in male veterans. Archives of Internal Medicine. 2006;166(15):1660-1665.
3. Khurana KK, et al. Testosterone Replacement Therapy is Associated with Delayed Progression of Chronic Kidney Disease. Annals of Nephrology and Pathology. 2019.
4. Yeo JK, et al. Effects of Testosterone Treatment on Quality of Life in Patients With Chronic Kidney Disease. American Journal of Men's Health. 2020;14(3).
5. Grossmann M. Hypogonadism and male obesity: Focus on unresolved questions. Clinical Endocrinology. 2018.