testosterone
Testosterone replacement treats diagnosed hormone deficiency. It can improve sexual desire, but it also suppresses sperm production and requires blood-pressure and blood-count monitoring.
Androgen hormone
- Prescription formulations
- US Schedule III
What is testosterone used for?
Testosterone is an androgen hormone. Prescription products replace it when the body does not make enough because of a diagnosed medical condition.
Replacement trials studied men with diagnosed testosterone deficiency. The muscle and strength studies below used higher doses in healthy men.
Cypionate label · effects and interactions
Prescribing information
Depo-Testosterone (testosterone cypionate) US prescribing information, DailyMed.
The label reports an approximate eight-day half-life for intramuscular cypionate. It warns about blood-pressure increases, increased red-cell mass, edema, acne, breast changes, reduced sperm production and interactions with anticoagulants or diabetes treatment.
Product-specific labeling is not a head-to-head comparison of esters.
Read the original sourceGuideline · diagnosis and monitoring
Clinical practice guideline
Bhasin et al. Endocrine Society, 2018.
Diagnosis requires compatible symptoms and consistently low testosterone. Confirm with repeat morning fasting measurement and investigate the cause. Fertility plans and contraindications must be addressed before treatment.
Read the original sourceBhasin trial · muscle and strength
Randomized trial
The New England journal of medicine. PMID 8637535.
In a 43-man trial, above-normal testosterone exposure increased measured muscle size and strength. The testosterone-plus-training group gained 6.1 kg of fat-free mass; bench-press and squat increases were 22 kg and 38 kg.
- Participants / model
- Men with normal testosterone.
- Treatment
- 600 mg testosterone enanthate weekly or placebo, with or without standardized strength training.
- Follow-up
- 10 weeks.
This was a supraphysiologic research regimen, not replacement treatment. The trial was too short and small to establish long-term safety.
Read the original sourceDoes a low result mean I need treatment?
A diagnosis requires symptoms plus consistently low measurements. Repeat morning fasting testing matters, as does checking why the level is low. LH and FSH help distinguish a problem in the testes from a problem in the brain’s hormone signaling.
Age, fatigue or a single borderline result alone does not establish an indication.
Guideline · diagnosis and monitoring
Clinical practice guideline
Bhasin et al. Endocrine Society, 2018.
Diagnosis requires compatible symptoms and consistently low testosterone. Confirm with repeat morning fasting measurement and investigate the cause. Fertility plans and contraindications must be addressed before treatment.
Read the original sourceWill it improve libido, erections or energy?
In men with confirmed low testosterone, replacement can improve sexual desire and activity. Improvements in erections, energy and physical function are less consistent.
TRAVERSE · desire and erections
Randomized trial substudy
The Journal of clinical endocrinology and metabolism. PMID 37589949.
Among 1,161 participants with low libido, testosterone improved sexual activity and desire over two years. Erectile function did not improve significantly compared with placebo.
These were men with confirmed low testosterone and cardiovascular disease or risk, not people with normal levels.
Read the original sourceTestosterone Trials · symptoms
Randomized trials
The New England journal of medicine. PMID 26886521.
In 790 symptomatic men aged 65 or older with low testosterone, one year of gel improved sexual function and some mood measures. The primary vitality and physical-function trial outcomes were not significantly better than placebo.
A small walking-distance benefit appeared when participants from all three trials were pooled. This differs from success on the primary physical-function trial endpoint.
Read the original source| Question | What the trials found |
|---|---|
| Sexual desire and activity | Improved in the Testosterone Trials and the TRAVERSE sexual-function substudy. |
| Erectile function | Improved modestly in the older Testosterone Trials, but not significantly in the larger TRAVERSE sexual-function substudy. |
| Fatigue and walking | The Testosterone Trials missed their primary vitality and physical-function endpoints. |
| Mood | Small average improvements occurred; testosterone has not been established as a substitute for depression treatment. |
TRAVERSE · mood and energy
Randomized trial analysis
The Journal of clinical endocrinology and metabolism. PMID 38205962.
Small improvements in mood and energy occurred overall. Cognition and sleep did not improve. The subgroup with rigorously defined persistent depressive disorder was small and showed no significant benefit.
- Participants / model
- 5,204 participants; 2,643 with significant depressive symptoms, including 49 meeting the more stringent persistent-disorder definition.
How quickly should I expect a change?
The sexual-function studies assessed changes over months. TRAVERSE detected benefit by its six-month assessment and followed it through two years. That schedule cannot tell you the first day an individual should feel different.
TRAVERSE · desire and erections
Randomized trial substudy
The Journal of clinical endocrinology and metabolism. PMID 37589949.
Among 1,161 participants with low libido, testosterone improved sexual activity and desire over two years. Erectile function did not improve significantly compared with placebo.
These were men with confirmed low testosterone and cardiovascular disease or risk, not people with normal levels.
Read the original sourceWhat did the Russian trials show about metabolic health?
The randomized Moscow study enrolled 184 men with both low testosterone and metabolic syndrome. After 30 weeks, the testosterone group had greater reductions in weight, waist circumference and some inflammatory markers. Blood glucose and lipid measures did not improve.
Later reports followed participants during open-label treatment without preserving the original randomized placebo comparison. The study did not test testosterone as a replacement for diabetes or weight-management treatment.
Russia · randomized Moscow study
Randomized double-blind trial
Clinical endocrinology. PMID 20718771.
In 184 men with low testosterone and metabolic syndrome, 30 weeks of injectable testosterone undecanoate reduced weight, waist circumference and some inflammatory markers compared with placebo. Glucose and lipid measures did not improve.
- Participants / model
- Men aged 35–70 recruited in Moscow; 113 assigned testosterone and 71 placebo.
A disease-specific replacement study with metabolic and inflammatory endpoints, not a cardiovascular-outcomes or healthy-user weight-loss trial. The publication is in English; the trial took place in Russia.
Read the original sourceMoscow follow-up · open-label extension
Secondary analysis and open-label follow-up
Tishova Y et al. Diabetes, Obesity and Metabolism, 2024.
The report analyzes insulin-resistance measurements during the initial randomized phase and later open-label treatment, including participants switched from placebo.
Later within-group changes do not retain the original randomized placebo comparison. This is further reporting from the Moscow study, not an independent replication.
Read the original sourceWhat side effects and warning signs matter?
Testosterone can raise hematocrit and blood pressure. Acne, breast enlargement, fluid retention and reduced sperm production are also recognized risks.
Cypionate label · effects and interactions
Prescribing information
Depo-Testosterone (testosterone cypionate) US prescribing information, DailyMed.
The label reports an approximate eight-day half-life for intramuscular cypionate. It warns about blood-pressure increases, increased red-cell mass, edema, acne, breast changes, reduced sperm production and interactions with anticoagulants or diabetes treatment.
Product-specific labeling is not a head-to-head comparison of esters.
Read the original sourceA normal testosterone result does not replace safety monitoring. Blood pressure, blood counts, symptoms and formulation-specific checks still matter.
FDA · what changed in 2025
Regulatory safety communication
US FDA, February 28, 2025.
FDA requested removal of cardiovascular boxed-warning language after TRAVERSE, retained limitations for age-related hypogonadism and required blood-pressure warnings across testosterone products.
Read the original sourceGel label · transfer and monitoring
Prescribing information
Testosterone gel US prescribing information (AndroGel and generic testosterone gel), DailyMed SPL set ids f4e8d29b-8707-4d47-e053-2a95a90aecee and ee54c393-bcfe-4a52-b7b3-1da8750f35d9.
Testosterone can transfer from an application site to another person. Wash hands after application, cover the dried site and wash the site before anticipated skin contact. The label also requires hematocrit monitoring and describes anticoagulant, insulin and corticosteroid interactions.
Read the original sourceWho needs extra caution before starting?
The Endocrine Society advises against starting in people planning near-term fertility, with elevated hematocrit, untreated severe sleep apnea, uncontrolled heart failure, recent heart attack or stroke, thrombophilia, or relevant prostate or breast cancer concerns. Product contraindications and the individual diagnosis also apply.
Guideline · diagnosis and monitoring
Clinical practice guideline
Bhasin et al. Endocrine Society, 2018.
Diagnosis requires compatible symptoms and consistently low testosterone. Confirm with repeat morning fasting measurement and investigate the cause. Fertility plans and contraindications must be addressed before treatment.
Read the original sourceWhat did the largest heart-safety trial actually show?
In TRAVERSE, major cardiovascular events occurred in 7.0% with testosterone gel and 7.3% with placebo. The study met its noninferiority criterion, meaning it did not exceed the trial’s specified risk margin.
The cardiovascular finding applies to men with low testosterone and existing or high cardiovascular risk. The trial also recorded higher rates of atrial fibrillation, acute kidney injury, and pulmonary embolism with testosterone.
Atrial fibrillation, acute kidney injury and pulmonary embolism occurred more often with testosterone. Mean treatment lasted 21.7 months, with 33 months of follow-up.
TRAVERSE · cardiovascular outcomes
Randomized noninferiority trial
The New England journal of medicine. PMID 37326322.
Major cardiovascular events occurred in 7.0% with testosterone and 7.3% with placebo, HR 0.96 (95% CI 0.78 to 1.17), meeting the prespecified noninferiority criterion. Atrial fibrillation, acute kidney injury and pulmonary embolism occurred more often with testosterone.
- Participants / model
- 5,246 men aged 45 to 80 with symptoms, two fasting testosterone results below 300 ng/dL, and existing or high cardiovascular risk.
- Treatment
- 1.62% testosterone gel adjusted to 350 to 750 ng/dL, or placebo.
- Follow-up
- Mean treatment 21.7 months; follow-up 33 months.
- Funding
- AbbVie and others
This result does not establish safety of above-normal exposure or injection cycles.
Read the original sourceWhy did the FDA change the warnings?
In 2025, FDA requested removal of cardiovascular boxed-warning language after TRAVERSE. It also required warnings about increased blood pressure. Aveed’s separate injection-reaction boxed warning remains.
FDA · what changed in 2025
Regulatory safety communication
US FDA, February 28, 2025.
FDA requested removal of cardiovascular boxed-warning language after TRAVERSE, retained limitations for age-related hypogonadism and required blood-pressure warnings across testosterone products.
Read the original sourceAveed label · injection warning
Prescribing information
AVEED (testosterone undecanoate) US prescribing information, DailyMed.
Aveed is intramuscular testosterone undecanoate. Its boxed warning covers pulmonary oil microembolism and anaphylaxis. Each injection requires 30 minutes of observation in a healthcare setting under its restricted REMS program.
The initial injection, week-four injection and later ten-week intervals are specific to this product.
Read the original sourceCan testosterone reduce fertility, and what happens when I stop?
Yes. Testosterone from outside the body suppresses the signals that support natural testosterone and sperm production. Sperm production can fall substantially, sometimes to zero.
Xyosted label · weekly enanthate
Prescribing information
XYOSTED (testosterone enanthate) US prescribing information, DailyMed.
Xyosted is a weekly subcutaneous enanthate product. Its label reports steady state by six weeks and median peak time of 11.9 hours after dosing at week 12. It states no elimination half-life.
The blood-pressure boxed warning was removed in March 2025, but blood-pressure monitoring remains in Warnings and Precautions.
Read the original sourceCypionate study · hormone and sperm suppression
Randomized study with PK/PD modeling
CPT: pharmacometrics & systems pharmacology. PMID 29436172.
In 31 healthy men receiving 14 weekly cypionate injections, modeling found greater and longer suppression of natural testosterone, LH and sperm production in the higher-dose groups.
- Treatment
- 100, 250 or 500 mg weekly in the study.
The abstract does not support a single recovery deadline for every patient. Suppression of sperm is not reliable contraception.
Read the original sourceDiscuss fertility before starting. Testosterone treatment should not be used as contraception, and a normal blood testosterone level does not prove that sperm production has recovered.
Guideline · diagnosis and monitoring
Clinical practice guideline
Bhasin et al. Endocrine Society, 2018.
Diagnosis requires compatible symptoms and consistently low testosterone. Confirm with repeat morning fasting measurement and investigate the cause. Fertility plans and contraindications must be addressed before treatment.
Read the original sourceCypionate study · hormone and sperm suppression
Randomized study with PK/PD modeling
CPT: pharmacometrics & systems pharmacology. PMID 29436172.
In 31 healthy men receiving 14 weekly cypionate injections, modeling found greater and longer suppression of natural testosterone, LH and sperm production in the higher-dose groups.
- Treatment
- 100, 250 or 500 mg weekly in the study.
The abstract does not support a single recovery deadline for every patient. Suppression of sperm is not reliable contraception.
Read the original sourceDoes stopping guarantee recovery?
The cypionate study found stronger and longer suppression with higher exposure. It does not provide a guaranteed recovery date. Persistent low libido, fatigue or fertility concerns after stopping need assessment, including semen testing when fertility is the question.
Stopping replacement also does not repair an underlying cause of hypogonadism. Do not assume a self-directed “post-cycle” combination will restore normal function.
Cypionate study · hormone and sperm suppression
Randomized study with PK/PD modeling
CPT: pharmacometrics & systems pharmacology. PMID 29436172.
In 31 healthy men receiving 14 weekly cypionate injections, modeling found greater and longer suppression of natural testosterone, LH and sperm production in the higher-dose groups.
- Treatment
- 100, 250 or 500 mg weekly in the study.
The abstract does not support a single recovery deadline for every patient. Suppression of sperm is not reliable contraception.
Read the original sourceGuideline · diagnosis and monitoring
Clinical practice guideline
Bhasin et al. Endocrine Society, 2018.
Diagnosis requires compatible symptoms and consistently low testosterone. Confirm with repeat morning fasting measurement and investigate the cause. Fertility plans and contraindications must be addressed before treatment.
Read the original sourceWhat did the large Chinese contraception trial find?
The study enrolled 1,045 fertile Chinese men. After a sperm-suppression phase, 855 entered the efficacy phase; nine pregnancies occurred over 1,554.1 person-years. Not everyone achieved or maintained sufficient suppression.
Sperm production returned to the normal fertile reference range in all but two participants. These results concern a monitored research regimen and selected participants. Ordinary testosterone treatment is not reliable contraception, and recovery cannot be assumed for an individual.
China · 1,045-man contraception trial
Multicenter phase III contraceptive trial
The Journal of clinical endocrinology and metabolism. PMID 19293262.
A multicenter Chinese phase III study recruited 1,045 healthy fertile men. Of 855 entering the contraceptive-efficacy phase after sperm suppression, nine pregnancies occurred during 1,554.1 person-years of exposure.
- Follow-up
- Six-month suppression phase and 24-month efficacy phase.
Suppression was inadequate in some men, and sperm rebound occurred in others. The study was not a placebo-controlled trial of routine testosterone replacement or an approved contraceptive instruction.
Read the original sourceWhat changes between gels, injections, tablets and pellets?
They deliver testosterone through different formulations. The route, oil or delivery system, dose and interval all affect exposure; the ester name alone does not determine the result.
| Product or form | What changes |
|---|---|
| Cypionate injection | Oil-based intramuscular product; its US label reports an approximate eight-day half-life. |
| Xyosted enanthate | Weekly subcutaneous autoinjector with product-specific trough testing and adjustment. |
| Aveed undecanoate | Long-interval intramuscular product with observation after each injection. |
| Nebido undecanoate | Different strength, volume and labeled interval from Aveed. |
| Oral undecanoate | Food-dependent oral formulation with different testing and dosing instructions from injections. |
| Gel | Daily skin delivery without an ester; transfer to another person is a particular concern. |
| Sustanon | A mixture of four esters. Its combined curve does not validate four separate half-life numbers. |
| TESTOPEL pellets | Subcutaneous implantation; implant-site infection or extrusion and less flexible adjustment are distinct concerns. |
Cypionate label · effects and interactions
Prescribing information
Depo-Testosterone (testosterone cypionate) US prescribing information, DailyMed.
The label reports an approximate eight-day half-life for intramuscular cypionate. It warns about blood-pressure increases, increased red-cell mass, edema, acne, breast changes, reduced sperm production and interactions with anticoagulants or diabetes treatment.
Product-specific labeling is not a head-to-head comparison of esters.
Read the original sourceXyosted label · weekly enanthate
Prescribing information
XYOSTED (testosterone enanthate) US prescribing information, DailyMed.
Xyosted is a weekly subcutaneous enanthate product. Its label reports steady state by six weeks and median peak time of 11.9 hours after dosing at week 12. It states no elimination half-life.
The blood-pressure boxed warning was removed in March 2025, but blood-pressure monitoring remains in Warnings and Precautions.
Read the original sourceAveed label · injection warning
Prescribing information
AVEED (testosterone undecanoate) US prescribing information, DailyMed.
Aveed is intramuscular testosterone undecanoate. Its boxed warning covers pulmonary oil microembolism and anaphylaxis. Each injection requires 30 minutes of observation in a healthcare setting under its restricted REMS program.
The initial injection, week-four injection and later ten-week intervals are specific to this product.
Read the original sourceNebido · formulation and interval
Prescribing information
Nebido (testosterone undecanoate 1000 mg/4 mL) SmPC, electronic Medicines Compendium.
Nebido contains 1,000 mg testosterone undecanoate in 4 mL, with maintenance intervals of 10 to 14 weeks in its UK product information. The label distinguishes slow depot release from the clearance of free hormone.
250 mg of the ester corresponds to 157.9 mg testosterone. This chemical equivalence is not a dose-switching instruction.
Read the original sourceJatenzo label · oral undecanoate
Prescribing information
JATENZO (oral testosterone undecanoate) US prescribing information, DailyMed.
Jatenzo is an oral testosterone undecanoate formulation taken with food. Its absorption, dose adjustment and blood-test timing differ from injectable undecanoate.
Oral products and injection products are not interchangeable milligram for milligram.
Read the original sourceGel label · transfer and monitoring
Prescribing information
Testosterone gel US prescribing information (AndroGel and generic testosterone gel), DailyMed SPL set ids f4e8d29b-8707-4d47-e053-2a95a90aecee and ee54c393-bcfe-4a52-b7b3-1da8750f35d9.
Testosterone can transfer from an application site to another person. Wash hands after application, cover the dried site and wash the site before anticipated skin contact. The label also requires hematocrit monitoring and describes anticoagulant, insulin and corticosteroid interactions.
Read the original sourceSustanon · four esters
Prescribing information
Sustanon 250 (testosterone propionate, phenylpropionate, isocaproate and decanoate) SmPC, Aspen; electronic Medicines Compendium product 5373.
Sustanon contains propionate, phenylpropionate, isocaproate and decanoate in one injection. Its combined concentration profile cannot supply a measured half-life for each ester on its own.
Read the original sourceTESTOPEL · implant-specific risks
US prescribing information
DailyMed, label updated July 17, 2025.
Testosterone pellets are implanted under the skin. The label reports implant-site infection and pellet extrusion, often within the first month, and describes the preparation as less flexible for dose adjustment than other forms.
Postmarketing reports cannot provide a reliable event frequency.
Read the original sourceDoes a longer ester always give steadier levels?
No. A longer interval can also produce a larger difference between peak and trough. Comparing averages from different labels cannot prove that one product is clinically superior. The complete preparation and the tested schedule need to match.
Xyosted label · weekly enanthate
Prescribing information
XYOSTED (testosterone enanthate) US prescribing information, DailyMed.
Xyosted is a weekly subcutaneous enanthate product. Its label reports steady state by six weeks and median peak time of 11.9 hours after dosing at week 12. It states no elimination half-life.
The blood-pressure boxed warning was removed in March 2025, but blood-pressure monitoring remains in Warnings and Precautions.
Read the original sourceNebido · formulation and interval
Prescribing information
Nebido (testosterone undecanoate 1000 mg/4 mL) SmPC, electronic Medicines Compendium.
Nebido contains 1,000 mg testosterone undecanoate in 4 mL, with maintenance intervals of 10 to 14 weeks in its UK product information. The label distinguishes slow depot release from the clearance of free hormone.
250 mg of the ester corresponds to 157.9 mg testosterone. This chemical equivalence is not a dose-switching instruction.
Read the original sourceBehre study · oil changes the curve
Human pharmacokinetic study
European journal of endocrinology. PMID 10229906.
A small phase I study reported testosterone undecanoate half-lives of 33.9 days in castor oil and 20.9 days in tea seed oil. The preparations also differed in concentration, volume and injection sites.
- Participants / model
- 21 men with hypogonadism: 14 received the castor-oil preparation and seven the tea-seed-oil preparation.
These are formulation-specific estimates. The study does not isolate oil as the only causal difference.
Read the original sourceWhy do half-life charts disagree?
Some numbers describe release from an injection depot, others describe circulating hormone, and others come from a model. In one 21-man undecanoate study, different preparations produced estimates of 33.9 and 20.9 days. Those numbers cannot be assigned to every undecanoate product.
The Xyosted label states peak timing and steady state, but no elimination half-life. An absent number in that label is not proof that no human measurement exists anywhere.
Behre study · oil changes the curve
Human pharmacokinetic study
European journal of endocrinology. PMID 10229906.
A small phase I study reported testosterone undecanoate half-lives of 33.9 days in castor oil and 20.9 days in tea seed oil. The preparations also differed in concentration, volume and injection sites.
- Participants / model
- 21 men with hypogonadism: 14 received the castor-oil preparation and seven the tea-seed-oil preparation.
These are formulation-specific estimates. The study does not isolate oil as the only causal difference.
Read the original sourceXyosted label · weekly enanthate
Prescribing information
XYOSTED (testosterone enanthate) US prescribing information, DailyMed.
Xyosted is a weekly subcutaneous enanthate product. Its label reports steady state by six weeks and median peak time of 11.9 hours after dosing at week 12. It states no elimination half-life.
The blood-pressure boxed warning was removed in March 2025, but blood-pressure monitoring remains in Warnings and Precautions.
Read the original sourceCan I compare milligrams across esters?
The ester contributes to the stated mass. Nebido’s product information says 250 mg of undecanoate corresponds to 157.9 mg testosterone. Even after accounting for that chemistry, different absorption and schedules prevent a simple product substitution.
Nebido · formulation and interval
Prescribing information
Nebido (testosterone undecanoate 1000 mg/4 mL) SmPC, electronic Medicines Compendium.
Nebido contains 1,000 mg testosterone undecanoate in 4 mL, with maintenance intervals of 10 to 14 weeks in its UK product information. The label distinguishes slow depot release from the clearance of free hormone.
250 mg of the ester corresponds to 157.9 mg testosterone. This chemical equivalence is not a dose-switching instruction.
Read the original sourceWhich injection hurts less?
A 14-person crossover pilot reported less discomfort with subcutaneous than intramuscular administration. It compared routes, not individual esters. It cannot prove the common claim that propionate is inherently more painful.
Route crossover · injection discomfort
Open-label crossover pilot
American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists. PMID 29367424.
Fourteen transgender men compared their established intramuscular regimen with subcutaneous injections. Exposure was comparable on average and reported injection discomfort and anxiety were lower subcutaneously.
The sample was small with substantial variability. It does not establish that one ester hurts less than another.
Read the original sourceWhat if an implant causes a problem?
The implant site can become painful, inflamed or infected, and a pellet can come out. Report wound drainage, increasing redness, swelling or extrusion to the treating clinician. Changing exposure is less straightforward than stopping a daily gel, because the preparation is already implanted.
TESTOPEL · implant-specific risks
US prescribing information
DailyMed, label updated July 17, 2025.
Testosterone pellets are implanted under the skin. The label reports implant-site infection and pellet extrusion, often within the first month, and describes the preparation as less flexible for dose adjustment than other forms.
Postmarketing reports cannot provide a reliable event frequency.
Read the original sourceHow does it affect muscle, sexual function and hormone production?
Testosterone acts through androgen receptors in tissues. Its effects include sexual development and function, muscle and bone changes, and stimulation of red-cell production.
Injectable esters change delivery. Once the ester is removed, testosterone is the active hormone. Feedback to the brain and pituitary lowers the signals that normally stimulate the testes.
Cypionate label · effects and interactions
Prescribing information
Depo-Testosterone (testosterone cypionate) US prescribing information, DailyMed.
The label reports an approximate eight-day half-life for intramuscular cypionate. It warns about blood-pressure increases, increased red-cell mass, edema, acne, breast changes, reduced sperm production and interactions with anticoagulants or diabetes treatment.
Product-specific labeling is not a head-to-head comparison of esters.
Read the original sourceCypionate study · hormone and sperm suppression
Randomized study with PK/PD modeling
CPT: pharmacometrics & systems pharmacology. PMID 29436172.
In 31 healthy men receiving 14 weekly cypionate injections, modeling found greater and longer suppression of natural testosterone, LH and sperm production in the higher-dose groups.
- Treatment
- 100, 250 or 500 mg weekly in the study.
The abstract does not support a single recovery deadline for every patient. Suppression of sperm is not reliable contraception.
Read the original sourceExternal testosterone can therefore raise blood levels while suppressing endogenous testicular production and spermatogenesis.
Cypionate study · hormone and sperm suppression
Randomized study with PK/PD modeling
CPT: pharmacometrics & systems pharmacology. PMID 29436172.
In 31 healthy men receiving 14 weekly cypionate injections, modeling found greater and longer suppression of natural testosterone, LH and sperm production in the higher-dose groups.
- Treatment
- 100, 250 or 500 mg weekly in the study.
The abstract does not support a single recovery deadline for every patient. Suppression of sperm is not reliable contraception.
Read the original sourceDoes stronger bone density mean fewer fractures?
No. Testosterone improved bone-density measurements in one trial, but the larger TRAVERSE fracture study did not show fracture prevention.
In TRAVERSE, clinical fractures occurred in 3.50% of the testosterone group and 2.46% of the placebo group over a median 3.19 years. The hazard ratio was 1.43.
TRAVERSE · fractures
Randomized trial substudy
The New England journal of medicine. PMID 38231621.
Clinical fractures occurred in 91 of 2,601 men receiving testosterone (3.50%) and 64 of 2,603 receiving placebo (2.46%), HR 1.43 (95% CI 1.04 to 1.97).
- Follow-up
- Median follow-up 3.19 years.
Testosterone did not prevent fractures. The study does not establish the mechanism behind the difference.
Read the original sourceWhat happened to bone density?
In 211 older men, one year of gel improved spine trabecular bone density and estimated strength compared with placebo. These were imaging measurements. A later fracture trial recorded more clinical fractures with testosterone.
Testosterone Trials · bone density
Randomized trial
JAMA internal medicine. PMID 28241231.
In 211 older men with low testosterone, one year of treatment increased spine trabecular bone density by 6.8 percentage points more than placebo and estimated strength by 8.5 percentage points.
CT-derived density and estimated strength are not fracture outcomes.
Read the original sourceDoes it build muscle above normal testosterone levels?
Yes. A controlled trial demonstrated increases in muscle size and strength with above-normal testosterone exposure, including in men who did not train.
The testosterone-plus-training group gained 6.1 kg of fat-free mass over 10 weeks. Fat-free mass includes more than contractile muscle, although MRI measurements also showed muscle growth.
Bhasin trial · muscle and strength
Randomized trial
The New England journal of medicine. PMID 8637535.
In a 43-man trial, above-normal testosterone exposure increased measured muscle size and strength. The testosterone-plus-training group gained 6.1 kg of fat-free mass; bench-press and squat increases were 22 kg and 38 kg.
- Participants / model
- Men with normal testosterone.
- Treatment
- 600 mg testosterone enanthate weekly or placebo, with or without standardized strength training.
- Follow-up
- 10 weeks.
This was a supraphysiologic research regimen, not replacement treatment. The trial was too short and small to establish long-term safety.
Read the original sourceThat study does not establish a safe performance regimen. Observational studies of long-term anabolic-steroid users have found heart dysfunction and coronary disease, but they cannot isolate the contribution of testosterone from other drugs and exposures.
Long-term AAS use · heart imaging
Observational study
Circulation. PMID 28533317.
A cross-sectional study of 140 experienced male weightlifters associated long-term anabolic-steroid use with poorer left-ventricular function and more coronary atherosclerosis.
Participants used anabolic-steroid regimens, often involving multiple drugs. This is neither a testosterone-only experiment nor proof that every exposed person will develop the same injury.
Read the original sourceWhat needs monitoring, and which medicines can interact?
Monitoring needs to match the product. A trough before an injection and a measurement after a tablet or gel are not interchangeable tests.
Xyosted label · weekly enanthate
Prescribing information
XYOSTED (testosterone enanthate) US prescribing information, DailyMed.
Xyosted is a weekly subcutaneous enanthate product. Its label reports steady state by six weeks and median peak time of 11.9 hours after dosing at week 12. It states no elimination half-life.
The blood-pressure boxed warning was removed in March 2025, but blood-pressure monitoring remains in Warnings and Precautions.
Read the original sourceJatenzo label · oral undecanoate
Prescribing information
JATENZO (oral testosterone undecanoate) US prescribing information, DailyMed.
Jatenzo is an oral testosterone undecanoate formulation taken with food. Its absorption, dose adjustment and blood-test timing differ from injectable undecanoate.
Oral products and injection products are not interchangeable milligram for milligram.
Read the original source- Blood counts: check for increased hematocrit.
- Blood pressure: testosterone can increase it even when levels are in the intended range.
- Symptoms and prostate assessment: assess response and new urinary symptoms, with PSA testing when appropriate.
- Other medicines: anticoagulants may need closer INR monitoring; insulin requirements can change; corticosteroids can add fluid retention.
Gel label · transfer and monitoring
Prescribing information
Testosterone gel US prescribing information (AndroGel and generic testosterone gel), DailyMed SPL set ids f4e8d29b-8707-4d47-e053-2a95a90aecee and ee54c393-bcfe-4a52-b7b3-1da8750f35d9.
Testosterone can transfer from an application site to another person. Wash hands after application, cover the dried site and wash the site before anticipated skin contact. The label also requires hematocrit monitoring and describes anticoagulant, insulin and corticosteroid interactions.
Read the original sourceFDA · what changed in 2025
Regulatory safety communication
US FDA, February 28, 2025.
FDA requested removal of cardiovascular boxed-warning language after TRAVERSE, retained limitations for age-related hypogonadism and required blood-pressure warnings across testosterone products.
Read the original sourceGuideline · diagnosis and monitoring
Clinical practice guideline
Bhasin et al. Endocrine Society, 2018.
Diagnosis requires compatible symptoms and consistently low testosterone. Confirm with repeat morning fasting measurement and investigate the cause. Fertility plans and contraindications must be addressed before treatment.
Read the original sourceHow do I prevent gel transfer?
Wash your hands after application, let the site dry and cover it. Wash the application site before expected skin contact with another person. Follow the instructions for the exact gel, including where it can be applied.
Gel label · transfer and monitoring
Prescribing information
Testosterone gel US prescribing information (AndroGel and generic testosterone gel), DailyMed SPL set ids f4e8d29b-8707-4d47-e053-2a95a90aecee and ee54c393-bcfe-4a52-b7b3-1da8750f35d9.
Testosterone can transfer from an application site to another person. Wash hands after application, cover the dried site and wash the site before anticipated skin contact. The label also requires hematocrit monitoring and describes anticoagulant, insulin and corticosteroid interactions.
Read the original sourceDoes a vial label or test certificate prove the contents are safe?
No. A label can be wrong, and chemical analysis alone does not establish sterility or clinical safety.
A Swiss drug-checking pilot found that about half of 71 submitted anabolic-steroid samples did not match their declared contents. The selected samples do not establish a universal counterfeit rate or identify which untested vial is safe.
Swiss drug checking · product contents
Drug-checking observational study
Harm reduction journal. PMID 40484965.
A Swiss pilot tested 71 samples submitted by 52 clients. About half did not match their declared contents.
A selected sample of submitted products cannot establish the prevalence for every supplier or batch. Chemical identification does not prove sterility.
Read the original sourceWhat does prescription approval cover?
US testosterone products are approved for specified causes of testosterone deficiency. Their labels retain a limitation that safety and efficacy for age-related hypogonadism have not been established.
Testosterone is also a Schedule III controlled substance in the US. Approval of a particular product is not approval of an underground vial, a different formulation or performance use.
Cypionate label · effects and interactions
Prescribing information
Depo-Testosterone (testosterone cypionate) US prescribing information, DailyMed.
The label reports an approximate eight-day half-life for intramuscular cypionate. It warns about blood-pressure increases, increased red-cell mass, edema, acne, breast changes, reduced sperm production and interactions with anticoagulants or diabetes treatment.
Product-specific labeling is not a head-to-head comparison of esters.
Read the original sourceFDA · what changed in 2025
Regulatory safety communication
US FDA, February 28, 2025.
FDA requested removal of cardiovascular boxed-warning language after TRAVERSE, retained limitations for age-related hypogonadism and required blood-pressure warnings across testosterone products.
Read the original sourceStudies and sources
Guideline · diagnosis and monitoring
Clinical practice guideline
Bhasin et al. Endocrine Society, 2018.
Diagnosis requires compatible symptoms and consistently low testosterone. Confirm with repeat morning fasting measurement and investigate the cause. Fertility plans and contraindications must be addressed before treatment.
Read the original sourceTRAVERSE · cardiovascular outcomes
Randomized noninferiority trial
The New England journal of medicine. PMID 37326322.
Major cardiovascular events occurred in 7.0% with testosterone and 7.3% with placebo, HR 0.96 (95% CI 0.78 to 1.17), meeting the prespecified noninferiority criterion. Atrial fibrillation, acute kidney injury and pulmonary embolism occurred more often with testosterone.
- Participants / model
- 5,246 men aged 45 to 80 with symptoms, two fasting testosterone results below 300 ng/dL, and existing or high cardiovascular risk.
- Treatment
- 1.62% testosterone gel adjusted to 350 to 750 ng/dL, or placebo.
- Follow-up
- Mean treatment 21.7 months; follow-up 33 months.
- Funding
- AbbVie and others
This result does not establish safety of above-normal exposure or injection cycles.
Read the original sourceTRAVERSE · desire and erections
Randomized trial substudy
The Journal of clinical endocrinology and metabolism. PMID 37589949.
Among 1,161 participants with low libido, testosterone improved sexual activity and desire over two years. Erectile function did not improve significantly compared with placebo.
These were men with confirmed low testosterone and cardiovascular disease or risk, not people with normal levels.
Read the original sourceTestosterone Trials · symptoms
Randomized trials
The New England journal of medicine. PMID 26886521.
In 790 symptomatic men aged 65 or older with low testosterone, one year of gel improved sexual function and some mood measures. The primary vitality and physical-function trial outcomes were not significantly better than placebo.
A small walking-distance benefit appeared when participants from all three trials were pooled. This differs from success on the primary physical-function trial endpoint.
Read the original sourceTRAVERSE · mood and energy
Randomized trial analysis
The Journal of clinical endocrinology and metabolism. PMID 38205962.
Small improvements in mood and energy occurred overall. Cognition and sleep did not improve. The subgroup with rigorously defined persistent depressive disorder was small and showed no significant benefit.
- Participants / model
- 5,204 participants; 2,643 with significant depressive symptoms, including 49 meeting the more stringent persistent-disorder definition.
Testosterone Trials · bone density
Randomized trial
JAMA internal medicine. PMID 28241231.
In 211 older men with low testosterone, one year of treatment increased spine trabecular bone density by 6.8 percentage points more than placebo and estimated strength by 8.5 percentage points.
CT-derived density and estimated strength are not fracture outcomes.
Read the original sourceTRAVERSE · fractures
Randomized trial substudy
The New England journal of medicine. PMID 38231621.
Clinical fractures occurred in 91 of 2,601 men receiving testosterone (3.50%) and 64 of 2,603 receiving placebo (2.46%), HR 1.43 (95% CI 1.04 to 1.97).
- Follow-up
- Median follow-up 3.19 years.
Testosterone did not prevent fractures. The study does not establish the mechanism behind the difference.
Read the original sourceBhasin trial · muscle and strength
Randomized trial
The New England journal of medicine. PMID 8637535.
In a 43-man trial, above-normal testosterone exposure increased measured muscle size and strength. The testosterone-plus-training group gained 6.1 kg of fat-free mass; bench-press and squat increases were 22 kg and 38 kg.
- Participants / model
- Men with normal testosterone.
- Treatment
- 600 mg testosterone enanthate weekly or placebo, with or without standardized strength training.
- Follow-up
- 10 weeks.
This was a supraphysiologic research regimen, not replacement treatment. The trial was too short and small to establish long-term safety.
Read the original sourceCypionate study · hormone and sperm suppression
Randomized study with PK/PD modeling
CPT: pharmacometrics & systems pharmacology. PMID 29436172.
In 31 healthy men receiving 14 weekly cypionate injections, modeling found greater and longer suppression of natural testosterone, LH and sperm production in the higher-dose groups.
- Treatment
- 100, 250 or 500 mg weekly in the study.
The abstract does not support a single recovery deadline for every patient. Suppression of sperm is not reliable contraception.
Read the original sourceCypionate label · effects and interactions
Prescribing information
Depo-Testosterone (testosterone cypionate) US prescribing information, DailyMed.
The label reports an approximate eight-day half-life for intramuscular cypionate. It warns about blood-pressure increases, increased red-cell mass, edema, acne, breast changes, reduced sperm production and interactions with anticoagulants or diabetes treatment.
Product-specific labeling is not a head-to-head comparison of esters.
Read the original sourceAveed label · injection warning
Prescribing information
AVEED (testosterone undecanoate) US prescribing information, DailyMed.
Aveed is intramuscular testosterone undecanoate. Its boxed warning covers pulmonary oil microembolism and anaphylaxis. Each injection requires 30 minutes of observation in a healthcare setting under its restricted REMS program.
The initial injection, week-four injection and later ten-week intervals are specific to this product.
Read the original sourceXyosted label · weekly enanthate
Prescribing information
XYOSTED (testosterone enanthate) US prescribing information, DailyMed.
Xyosted is a weekly subcutaneous enanthate product. Its label reports steady state by six weeks and median peak time of 11.9 hours after dosing at week 12. It states no elimination half-life.
The blood-pressure boxed warning was removed in March 2025, but blood-pressure monitoring remains in Warnings and Precautions.
Read the original sourceGel label · transfer and monitoring
Prescribing information
Testosterone gel US prescribing information (AndroGel and generic testosterone gel), DailyMed SPL set ids f4e8d29b-8707-4d47-e053-2a95a90aecee and ee54c393-bcfe-4a52-b7b3-1da8750f35d9.
Testosterone can transfer from an application site to another person. Wash hands after application, cover the dried site and wash the site before anticipated skin contact. The label also requires hematocrit monitoring and describes anticoagulant, insulin and corticosteroid interactions.
Read the original sourceJatenzo label · oral undecanoate
Prescribing information
JATENZO (oral testosterone undecanoate) US prescribing information, DailyMed.
Jatenzo is an oral testosterone undecanoate formulation taken with food. Its absorption, dose adjustment and blood-test timing differ from injectable undecanoate.
Oral products and injection products are not interchangeable milligram for milligram.
Read the original sourceNebido · formulation and interval
Prescribing information
Nebido (testosterone undecanoate 1000 mg/4 mL) SmPC, electronic Medicines Compendium.
Nebido contains 1,000 mg testosterone undecanoate in 4 mL, with maintenance intervals of 10 to 14 weeks in its UK product information. The label distinguishes slow depot release from the clearance of free hormone.
250 mg of the ester corresponds to 157.9 mg testosterone. This chemical equivalence is not a dose-switching instruction.
Read the original sourceSustanon · four esters
Prescribing information
Sustanon 250 (testosterone propionate, phenylpropionate, isocaproate and decanoate) SmPC, Aspen; electronic Medicines Compendium product 5373.
Sustanon contains propionate, phenylpropionate, isocaproate and decanoate in one injection. Its combined concentration profile cannot supply a measured half-life for each ester on its own.
Read the original sourceBehre study · oil changes the curve
Human pharmacokinetic study
European journal of endocrinology. PMID 10229906.
A small phase I study reported testosterone undecanoate half-lives of 33.9 days in castor oil and 20.9 days in tea seed oil. The preparations also differed in concentration, volume and injection sites.
- Participants / model
- 21 men with hypogonadism: 14 received the castor-oil preparation and seven the tea-seed-oil preparation.
These are formulation-specific estimates. The study does not isolate oil as the only causal difference.
Read the original sourceFDA · what changed in 2025
Regulatory safety communication
US FDA, February 28, 2025.
FDA requested removal of cardiovascular boxed-warning language after TRAVERSE, retained limitations for age-related hypogonadism and required blood-pressure warnings across testosterone products.
Read the original sourceRoute crossover · injection discomfort
Open-label crossover pilot
American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists. PMID 29367424.
Fourteen transgender men compared their established intramuscular regimen with subcutaneous injections. Exposure was comparable on average and reported injection discomfort and anxiety were lower subcutaneously.
The sample was small with substantial variability. It does not establish that one ester hurts less than another.
Read the original sourceLong-term AAS use · heart imaging
Observational study
Circulation. PMID 28533317.
A cross-sectional study of 140 experienced male weightlifters associated long-term anabolic-steroid use with poorer left-ventricular function and more coronary atherosclerosis.
Participants used anabolic-steroid regimens, often involving multiple drugs. This is neither a testosterone-only experiment nor proof that every exposed person will develop the same injury.
Read the original sourceSwiss drug checking · product contents
Drug-checking observational study
Harm reduction journal. PMID 40484965.
A Swiss pilot tested 71 samples submitted by 52 clients. About half did not match their declared contents.
A selected sample of submitted products cannot establish the prevalence for every supplier or batch. Chemical identification does not prove sterility.
Read the original sourceChina · 1,045-man contraception trial
Multicenter phase III contraceptive trial
The Journal of clinical endocrinology and metabolism. PMID 19293262.
A multicenter Chinese phase III study recruited 1,045 healthy fertile men. Of 855 entering the contraceptive-efficacy phase after sperm suppression, nine pregnancies occurred during 1,554.1 person-years of exposure.
- Follow-up
- Six-month suppression phase and 24-month efficacy phase.
Suppression was inadequate in some men, and sperm rebound occurred in others. The study was not a placebo-controlled trial of routine testosterone replacement or an approved contraceptive instruction.
Read the original sourceRussia · randomized Moscow study
Randomized double-blind trial
Clinical endocrinology. PMID 20718771.
In 184 men with low testosterone and metabolic syndrome, 30 weeks of injectable testosterone undecanoate reduced weight, waist circumference and some inflammatory markers compared with placebo. Glucose and lipid measures did not improve.
- Participants / model
- Men aged 35–70 recruited in Moscow; 113 assigned testosterone and 71 placebo.
A disease-specific replacement study with metabolic and inflammatory endpoints, not a cardiovascular-outcomes or healthy-user weight-loss trial. The publication is in English; the trial took place in Russia.
Read the original sourceMoscow follow-up · open-label extension
Secondary analysis and open-label follow-up
Tishova Y et al. Diabetes, Obesity and Metabolism, 2024.
The report analyzes insulin-resistance measurements during the initial randomized phase and later open-label treatment, including participants switched from placebo.
Later within-group changes do not retain the original randomized placebo comparison. This is further reporting from the Moscow study, not an independent replication.
Read the original sourceTESTOPEL · implant-specific risks
US prescribing information
DailyMed, label updated July 17, 2025.
Testosterone pellets are implanted under the skin. The label reports implant-site infection and pellet extrusion, often within the first month, and describes the preparation as less flexible for dose adjustment than other forms.
Postmarketing reports cannot provide a reliable event frequency.
Read the original sourceWhy is testosterone in S tier?
S reflects clinically meaningful effects in controlled replacement trials. High-dose performance use and different esters or formulations have separate exposure and safety evidence.