Peptide & Experimental
Testosterone & TRT
Androgenic sex hormone · Hormone replacement therapy for hypogonadism (testosterone deficiency) · Testosterone replacement therapy, TRT, testosterone substitution, testosterone gel, testosterone enanthate
Testosterone is the most important male sex hormone; testosterone replacement therapy (TRT) supplies it from outside when a deficiency has been diagnosed by a physician. The chain of effects in humans is well supported, and the largest safety trial reached its primary endpoint: no increased cardiovascular risk. This trial design cannot show protection of the heart.
What testosterone and TRT are
Testosterone acts via androgen receptors on muscle, bone, blood formation, fat metabolism, libido, drive and mood. Part of it is converted to estradiol, which is physiologically necessary, among other things for bone and libido. Levels decline slowly from about the mid-30s.
Hypogonadism - a pronounced testosterone deficiency - is only diagnosed when low measured values and matching symptoms coincide. Replacement therapy corrects this deficiency, as an injection, gel, patch or depot. The goal is correction, not exceeding the normal range.
Who the data apply to
The robust trials were conducted in men with a diagnosed deficiency, and in the large safety trial additionally with existing or high cardiovascular risk. For men with low-normal levels without a diagnosis, there is no approval trial.
This is the decisive point: user reports of more drive and libido also come from men with normal baseline levels. They show that the substance has an effect - not that the treatment was indicated.
What is well supported
- The primary endpoint of the largest safety trial was reached. TRAVERSE tested, double-blind and placebo-controlled, in 5,246 men aged 45 to 80 with testosterone below 300 ng/dl measured twice and elevated cardiovascular risk, whether the therapy increases cardiovascular risk. Cardiovascular death, heart attack or stroke occurred in 182 of 2,601 (7.0 percent) versus 190 of 2,603 (7.3 percent), HR 0.96 (95% CI 0.78-1.17), p below 0.001 for non-inferiority. There is no larger randomized safety test for this substance.
- The FDA then removed the warning on heart risk. On February 28, 2025, it changed the product information of all testosterone products class-wide: the boxed warning on cardiovascular risk was removed, explicitly based on TRAVERSE. At the same time, a new warning on blood pressure increases was added.
- The meta-analysis also finds no increased mortality. Braga 2025 pooled 23 randomized trials with 9,280 men aged 40 and older (mean age 64.6 years, at least twelve months of follow-up): all-cause mortality RR 0.85 (0.60-1.19; p=0.33), cardiovascular mortality RR 0.85 (0.65-1.12; p=0.25), heart attack RR 0.94 (0.69-1.28; p=0.70).
- With a diagnosed deficiency, the therapy is approved and the pathway is established in humans. Testosterone acts via androgen receptors on muscle, bone, blood formation, fat metabolism, libido and mood; replacement in hypogonadism has been approved for decades. In TRAVERSE, treatment lasted 21.7 months and follow-up 33.0 months.
What the studies show
TRAVERSE: not inferior, not protective
Lincoff 2023 randomized 5,246 men aged 45 to 80 with testosterone below 300 ng/dl measured twice and elevated cardiovascular risk, double-blind, to 1.62 percent gel or placebo; 21.7 months of treatment, 33.0 months of follow-up. The primary endpoint of cardiovascular death, nonfatal heart attack and nonfatal stroke occurred in 182/2601 (7.0 percent) versus 190/2603 (7.3 percent), HR 0.96 (95% CI 0.78-1.17), p below 0.001 for non-inferiority. What was tested was whether the risk does not increase.
Meta-analysis: arrhythmias increased
Braga 2025 pooled 23 randomized trials with 9,280 men aged 40 and older (testosterone up to 14 nmol/l, mean age 64.6 years, at least 12 months of follow-up). All-cause mortality RR 0.85 (0.60-1.19; p=0.33), cardiovascular mortality RR 0.85 (0.65-1.12; p=0.25), heart attack RR 0.94 (0.69-1.28; p=0.70) - all without a difference. Significantly increased were cardiac arrhythmias, with RR 1.53 (1.20-1.97; p below 0.01). This is a relative figure; the corresponding absolute difference is not reported in the sources.
Prostate: numbers too small for a statement
The TRAVERSE prostate analysis (Bhasin 2023, n=5,204, 21.8 months) counted high-grade prostate cancers in 5 of 2,596 men on testosterone (0.19 percent) and 3 of 2,602 on placebo (0.12 percent), HR 1.62 (0.39-6.77; p=0.51). The confidence interval covers both a marked risk reduction and a several-fold risk increase. From so few events, neither reassurance nor a warning can be derived.
Where the data stop
- That TRT protects the heart. TRAVERSE was designed for non-inferiority. Such a trial design can show that a risk is not increased - it cannot prove a protective effect.
- That men without diagnosed hypogonadism benefit. The study populations had a laboratory-confirmed deficiency. For low-normal levels without a diagnosis, there is no approval trial.
- That the prostate risk has been clarified. The event numbers are too small. Open is not the same as harmless.
Status, approval and legal
Testosterone preparations are prescription-only medicines and approved for diagnosed testosterone deficiency; diagnosis and monitoring, including blood tests, belong in the hands of a physician. On February 28, 2025, the FDA changed the product information class-wide: the warning on cardiovascular risk was removed based on TRAVERSE, and at the same time a new warning on blood pressure increases was added for all testosterone products.
In 2025, the BfArM pointed to the sharply rising number of prescriptions, some of them outside the approval.
Safety
In TRAVERSE, atrial fibrillation, acute kidney injury and pulmonary embolism occurred more often on testosterone; for atrial fibrillation, 91 versus 63 cases are reported. The meta-analysis confirms the signal with increased cardiac arrhythmias. Testosterone temporarily suppresses the body’s own sperm production and can raise red blood cells.
BK-Score Well supported, heavily overhyped
| Human evidence | 9 | |
|---|---|---|
| Mechanism | 9 | |
| Safety data | 9 | |
| Hype gap | 4 | |
| Track record of use | 10 |
Replacement in diagnosed hypogonadism has been approved for decades, and the chain of effects in humans is established beyond doubt – the question is who gets treated. The TRAVERSE trial (Lincoff et al., NEJM 2023) randomized 5,246 men, treated for a mean of 21.7 months and followed for 33 months: cardiovascularly non-inferior, but more atrial fibrillation (91 versus 63 cases) and more acute kidney failure. In 2025, the BfArM pointed to the sharply rising number of prescriptions, some of them outside the approval. For men with low-normal levels without a diagnosis, there is no approval trial.
The score rates the state of knowledge, not the substance. “Safety data 9” means well studied – not harmless. “Track record of use 9” means used long and widely – that is not proof of efficacy.
Subjective assessment by Biohacking Kompakt based on published scoring rules – not a scientific rating and not a medical recommendation. Rules and all ratings (German)
Frequently asked questions about Testosterone & TRT
Does testosterone really work?
With a deficiency diagnosed by a physician, the effect on libido, muscle mass, body fat and bone density is well supported. The informative trials were conducted exclusively in men with diagnosed hypogonadism. For men with low-normal levels without a diagnosis, there is no approval trial, which is why these findings cannot be transferred to them.
Does testosterone therapy protect the heart?
No, the TRAVERSE trial does not show that. It was designed as a non-inferiority trial and tested whether the therapy does not increase risk. Major cardiovascular events occurred in 7.0 percent on testosterone and 7.3 percent on placebo, hazard ratio 0.96. A protective effect cannot be derived from this.
What are the side effects of testosterone?
In TRAVERSE, atrial fibrillation, acute kidney injury and pulmonary embolism occurred more often on testosterone than on placebo. A meta-analysis of 23 randomized trials found cardiac arrhythmias significantly increased, relative risk 1.53. In addition, sperm production is temporarily suppressed and red blood cells may rise.
Is testosterone approved in Germany?
Testosterone preparations are prescription-only medicines and approved for diagnosed testosterone deficiency. Use without a diagnosed deficiency is not covered by this approval. In 2025, the BfArM pointed to the sharply rising number of prescriptions, some of them outside the approval. Diagnosis and monitoring belong in the hands of a physician.
Does testosterone increase the risk of prostate cancer?
The question is open. In the TRAVERSE prostate analysis, high-grade prostate cancers occurred in 5 of 2,596 men on testosterone and 3 of 2,602 on placebo. The confidence interval ranges from 0.39 to 6.77. The event numbers are too small for a robust statement in either direction.
Why did the FDA remove the heart warning?
On February 28, 2025, the FDA changed the product information of all testosterone products class-wide. Based on the TRAVERSE results, the previous warning on cardiovascular risk was dropped. At the same time, a new warning on blood pressure increases was added. So one warning was removed while another was newly included.
The podcast episode (in German)
Episode 22
Testosterone & TRT: testosterone replacement therapy fact-checked
The podcast by Paul Höser (Episode 22). AI-generated German episode with realistic voices (ElevenLabs), supplemented with expert research and deliberately framed positively but responsibly: TRT for a genuine deficiency confirmed by a physician is well supported and often very effective; the TRAVERSE trial has eased the heart concerns, while the question of prostate risk remains open. Clearly named: blood tests (hematocrit), suppressed fertility and the strict distinction from high-dose/gray-market use. Information only, not medical advice, no dosing recommendation – testosterone is prescription-only; please have a deficiency checked by a physician and therapy supervised by a physician.
Related
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Sources
- Lincoff 2023, N Engl J Med - TRAVERSE, cardiovascular safety (PMID 37326322)
- Braga 2025, Am J Cardiovasc Drugs - meta-analysis of 23 RCTs (PMID 40694252)
- Bhasin 2023, JAMA Netw Open - TRAVERSE, prostate endpoints (PMID 38150256)
- FDA February 28, 2025 - class-wide labeling change for testosterone products
Open in the database – with search, filters and comparison (German app)
Information only, not medical advice and no usage or dosing recommendation. Prescription-only and unapproved substances belong in medical hands. Last updated: 2026-10-04.