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Study analysis · eBioMedicine · 2026

Taking testosterone without low levels? You're nearly twice as likely to die.

Men who take testosterone without having low testosterone are almost twice as likely to die over 10 years compared to men who take it because they truly need it.

Reading level
Moderate certainty
Level 2b · Individual cohort studyAssociation, not causationNo causal claims

Overview

What the study found

The study in plain English — the bottom line, every takeaway we extracted, and what to do with them.

In simple terms

This study looked at men who got testosterone pills and noticed that those without a clear medical reason for it had more heart problems later. But it didn’t randomly assign who got it — so we can’t say the pills caused the problems. Maybe those men were sicker or took higher doses, and we just don’t know.

What’s the bottom line?

Some men get testosterone shots even when their bodies aren't low in testosterone. This study looked at what happened to them over 10 years compared to men who got it because they truly needed it.

How strong is this study?

This study is super big and used smart tricks to make the two groups as similar as possible, which makes it one of the best observational studies we have. But because it’s not a randomized experiment, we still can’t be 100% sure the testosterone itself was the problem — just that it was linked to more heart issues.

Reporting

40 / 100

  • COI disclosure+40/40
  • Data availabilitydata not shared
  • Code availabilitycode not shared
Methodology

56 / 100

  • Randomizationnot randomized
  • Blindingblinding unclear
  • Control group+15/15
  • Sample size (n=358957)+20/20
  • Follow-up+10/10
Publication

100 / 100

Statistical

77 / 100

  • P-values+15/15
  • Effect size+20/20
  • Confidence intervals+15/15
  • Pre-registrationnot pre-registered

Each component is scored out of 100 and then capped by the study design — a case series cannot reach the ceiling a randomised trial can, however well it is reported.

Where it sits

RCT reviews

Max 100

Randomized Trials

Max 90

Reviews of Cohort Studies

Max 85

Cohort Studies

Max 72

Reviews of Case-Control Studies

Max 63

Case-Control Studies

Max 58

Cross-Sectional & Case Series

Max 50

Expert Opinion

Max 5
StrongerWeaker
Cohort Studies
Level 2b
67

67 / 100

Probability of being correct

Groups of people are followed over time to see who develops an outcome. Strong for identifying risk factors and associations, but cannot prove causation as firmly as RCTs.

This design cannot establish causation — the findings describe an association, not a cause. This is an observational cohort study with no randomization. Although propensity-score matching and sensitivity analyses were used to reduce confounding, residual confounding by unmeasured factors (e.g., lifestyle, dosing patterns, clinical decision-making) cannot be ruled out. The study compares two groups of testosterone users, not users vs non-users, but still cannot isolate testosterone as the direct cause of outcomes.

No Conflicts

No conflicts of interest identified

No conflicts of interest were disclosed, and no funding sources were declared; the study used de-identified real-world data from a third-party platform with no indication of industry influence.

Independent Analysis Safeguards

  • Analyses performed within secure TriNetX analytics environment
  • Use of de-identified, aggregated data
  • Investigators had no role in treatment initiation or primary data capture
  • Methodological triangulation with propensity-score matching and sensitivity analyses

The study relies on de-identified EHR data from TriNetX, a third-party federated platform. No author affiliations, industry ties, or funding sources are disclosed. While the absence of a funding statement raises transparency concerns, there is no evidence of industry influence or author conflicts. The use of a federated data platform and strict de-identification protocols supports data integrity and independence.

Key takeaways

  1. 01

    Men without documented low testosterone had a 51% higher chance of heart problems, 90% higher chance of dying, 23% higher chance of stroke, 32% higher chance of heart failure, and 41% higher chance of cardiac arrest.

  2. 02

    These are big increases — for every 100 men treated without a clear medical reason, about 5 more will have a major heart event or die over 10 years compared to those treated with a confirmed diagnosis.

Surprising findings

  • Testosterone therapy without hypogonadism was linked to higher risk of heart failure and cardiac arrest — not just heart attacks.Most public debate focuses on heart attacks, but this study shows testosterone without medical need is tied to rhythm disturbances and pumping failure — suggesting different biological mechanisms at play.
  • The negative-control outcome (acute appendicitis) showed no increased risk.This means the cardiovascular risks aren't just due to poor health records or general illness — the link is specific to heart and brain events, not random outcomes.

Practical takeaways

If you're considering testosterone therapy, demand a confirmed diagnosis with two low testosterone blood tests and symptoms — don't accept a single lab value or vague 'low T' label.

This study can't prove testosterone causes harm — it shows association. Some men without documented hypogonadism may have had true deficiency not captured in records.

high confidence

Why this study matters

One in Three Men Get Testosterone Without a Medical Reason

Of the 358,957 men in the study, 35.4% (127,152) started testosterone therapy without any documented diagnosis of hypogonadism — meaning their testosterone levels weren't clinically low. This is off-label use at massive scale.

Most people think testosterone therapy is only for men with diagnosed low T — but this shows it's being prescribed to nearly 1 in 3 men without that medical basis, raising serious safety questions.

51% Higher Risk of Heart Attacks and Strokes

Men on testosterone without documented hypogonadism had a 51% higher risk of major cardiovascular events (MACE) — HR 1.51 — and a 90% higher risk of dying over 10 years (HR 1.90). That’s nearly double the death rate.

This isn't just about libido or muscle gain — it's about survival. For every 100 men treated without a diagnosis, about 5 more will die or have a heart event over 10 years.

Asian Men Face Triple the Risk

The cardiovascular risks were dramatically higher in Asian men: MACE risk jumped 139% (HR 2.39) and mortality soared 198% (HR 2.98) compared to men with hypogonadism.

This challenges the assumption that testosterone risks are uniform across races — suggesting genetic, metabolic, or prescribing differences may make some populations far more vulnerable.

Want the whole report?

Detailed mode opens the full scientific breakdown — every score component, the methodology, conflicts of interest, the evidence analysis behind each claim, and the raw study data.