TRT Side Effects and Long-Term Risks

Testosterone replacement therapy is one of the most-prescribed and most-debated treatments in men’s health. With the publication of the TRAVERSE trial in 2023, the long-running cardiovascular controversy was substantially clarified, and in early 2025 the FDA revised testosterone labeling to reflect the newer evidence. Still, the broader question of TRT side effects — what is common, what is rare but serious, and what the long-term risks actually look like — continues to confuse men starting treatment. Most side effects are predictable, monitorable, and manageable. A few are serious enough to warrant specific vigilance. And one point matters above all others: testosterone is a prescription-only, controlled medication that must be diagnosed, dosed, and monitored by a licensed clinician. This article explains the risks; it deliberately does not provide any dosing instructions.

Common Side Effects

Acne and oily skin are among the most common cosmetic effects, particularly in younger men or those treated at the upper end of the dosing range. They typically appear within the first several weeks and improve with dose adjustment or topical therapy. Increased body hair growth and accelerated male-pattern baldness in genetically susceptible men also occur, because dihydrotestosterone (DHT) metabolites rise with TRT.

Fluid retention, mild ankle swelling, and modest weight gain (often as lean mass) are common in the first few months. Mood changes — most commonly improvement, but occasionally irritability or sleep disturbance — are reported. Site-specific issues depend on formulation: injection-site soreness with intramuscular testosterone, skin irritation or transfer concerns with gels (which can expose women and children to testosterone through skin contact), and minor extrusion or skin reactions with implanted pellets.

Hematologic: Erythrocytosis

The most common laboratory abnormality during TRT is erythrocytosis — an elevation of hematocrit above the normal range, sometimes well above it. Testosterone stimulates red-blood-cell production both directly and through the erythropoietin axis. The Endocrine Society Clinical Practice Guideline recommends taking action when hematocrit exceeds 54%: options a clinician may consider include reducing the dose, switching to a more stable delivery method, or therapeutic phlebotomy. MedlinePlus similarly lists a higher-than-normal red-blood-cell count among the effects that require medical attention.

The clinical significance of mild erythrocytosis remains debated, but extreme elevations are associated with increased blood viscosity and a theoretical thrombotic risk. Hematocrit checks are part of standard monitoring, and injection therapy tends to produce higher hematocrit elevations than gels in head-to-head studies. The exact timing and thresholds for intervention are decisions your prescriber makes based on your labs and history.

Cardiovascular Considerations and the 2025 FDA Labeling Change

The TRAVERSE trial — published in the New England Journal of Medicine in 2023 — randomized more than 5,200 middle-aged and older men with hypogonadism and high cardiovascular risk to TRT or placebo, with an average follow-up of about 22 months. The primary outcome (a composite of cardiovascular death, nonfatal heart attack, or nonfatal stroke) was non-inferior in the TRT arm. This represents the strongest evidence to date that, at appropriate doses in appropriately selected men, TRT does not increase major adverse cardiovascular events.

Key 2025 update: Informed by TRAVERSE and other data, the FDA required class-wide changes to testosterone product labeling in February 2025. The update removed the prior boxed warning about cardiovascular risk — the strong warning that had appeared on these products for years — and added a new warning about the risk of increased blood pressure (hypertension). In practical terms, this means clinicians now emphasize blood-pressure monitoring during treatment, and the older “black box” cardiovascular framing no longer reflects current labeling. Because drug labels are revised over time, confirm the current labeling and warnings for your specific product with your prescriber and pharmacist.

Importantly, TRAVERSE did identify increased rates of a few specific events in the TRT arm, including atrial fibrillation, pulmonary embolism, and acute kidney injury. Men with a history of atrial fibrillation, a recent venous blood clot, or significant heart disease should discuss timing and individual risk with their clinician before starting TRT. Blood pressure should be checked before and during therapy, consistent with the updated warning.

When to seek emergency care: Call 911 or go to the nearest emergency room if you experience chest pain, severe shortness of breath, sudden one-sided weakness or speech difficulty, or a swollen and painful leg while on TRT — these can signal a heart attack, pulmonary embolism, stroke, or deep-vein thrombosis.

Fertility Suppression

Exogenous testosterone suppresses the pituitary hormones LH and FSH, halting sperm production in the great majority of men within a few months of starting therapy. The result is very low or absent sperm counts. This is reversible in most cases after stopping TRT, but recovery can take many months to a couple of years and is not guaranteed. MedlinePlus explicitly notes that testosterone may decrease sperm count, especially at higher doses. Men who are trying to conceive, or who may want children in the future, should discuss fertility-preserving alternatives with their clinician — and reproductive-urology evaluation is appropriate before starting. Do not attempt to manage fertility with self-directed medications; these are prescriber decisions.

Prostate Considerations

The historical concern that TRT causes or accelerates prostate cancer has not been borne out in modern trials, though monitoring remains standard. Small PSA elevations are typical in the first year and generally stabilize thereafter. The Endocrine Society and the American Urological Association recommend a baseline PSA and, where appropriate, a digital rectal exam before initiation in men over a certain age, with PSA monitoring during treatment. MedlinePlus also lists a potential increase in prostate cancer risk among the warnings to discuss with your doctor. Men with active prostate cancer are generally not TRT candidates; men with previously treated prostate cancer can sometimes be treated after individualized assessment by a urologist.

Lower urinary tract symptoms from benign prostatic hyperplasia (BPH) may worsen modestly on TRT, although this is inconsistent across trials. Men with significant baseline urinary symptoms warrant careful assessment before and during therapy.

Gynecomastia and Estrogen Effects

Some testosterone is converted (aromatized) to estradiol, and a subset of men on TRT develop breast tenderness or visible gynecomastia. This is more common at higher doses and in men with higher body fat, which carries more aromatase activity. Mild symptoms often improve with dose adjustment. Persistent gynecomastia is sometimes managed with selective estrogen receptor modulators or aromatase inhibitors, though these approaches are off-label and are decisions for a clinician. See our gynecomastia guide for the broader picture and estrogen dominance in men for related discussion.

Sleep Apnea

TRT can worsen obstructive sleep apnea in susceptible men, possibly through both airway and central mechanisms; MedlinePlus lists sleep apnea among the conditions to disclose before starting. Men with untreated severe sleep apnea should generally have it evaluated and treated before starting TRT, and new-onset snoring, gasping, or daytime sleepiness while on therapy warrants a sleep study.

Long-Term Risks Beyond Five Years

Long-term randomized data beyond five years remain limited. Observational cohorts and registry data suggest that, with appropriate monitoring, men maintained at physiologic testosterone levels do not show excess mortality compared with untreated men with hypogonadism. The biggest unknowns relate to very long-term (15- to 20-year) effects, which have not been formally studied in randomized trials. This uncertainty is one reason ongoing annual monitoring and individualized risk assessment remain the standard of care rather than a “set it and forget it” approach.

Monitoring Schedule

Guidelines recommend checking serum testosterone, hematocrit, and PSA at intervals your clinician sets — commonly at a few months, again later in the first year, and annually thereafter — with blood pressure now emphasized in light of the 2025 labeling change. A lipid panel is often included in baseline and follow-up labs. Symptom assessment and weight checks accompany lab monitoring. Bone-density testing may be reasonable in men with low baseline bone density. Men reporting new symptoms — chest pain, shortness of breath, leg swelling, or severe headache — should be evaluated promptly. The specific tests and timing are individualized; follow your prescriber’s plan rather than a generic schedule.

Who Should Not Use TRT

Absolute or relative contraindications include active untreated prostate cancer, active breast cancer (rare in men), erythrocytosis with a hematocrit over 54%, untreated severe sleep apnea, severe lower urinary tract symptoms, a recent heart attack or stroke, uncontrolled heart failure, untreated active venous thromboembolism, and current or planned attempts at conception. Poorly controlled high blood pressure also warrants caution given the updated blood-pressure warning. The AUA Guideline covers the full picture. For broader context on related conditions, see the medical conditions hub, the low testosterone guide, and the TRT options guide.

Frequently Asked Questions

Did the FDA remove the cardiovascular warning on testosterone?

In February 2025 the FDA required class-wide labeling changes that removed the previous boxed warning about cardiovascular risk — a change informed by the TRAVERSE trial — and added a new warning about the risk of increased blood pressure. This does not mean TRT is risk-free; it means the labeling now emphasizes blood-pressure monitoring rather than a broad cardiovascular black-box warning. Confirm the current labeling for your specific product with your prescriber, since labels are updated over time.

Does TRT cause hair loss?

It can. Testosterone is partially converted to dihydrotestosterone (DHT), the hormone that drives male-pattern baldness, so genetically susceptible men may notice accelerated thinning. Any medication used to counter this is a prescriber decision with its own side-effect profile; do not self-medicate.

Will TRT make my testicles smaller?

Often, yes. Suppression of LH and FSH reduces testicular size in most men within months. This change reflects fertility suppression and is partially reversible after stopping TRT. Men who want to preserve fertility or testicular size should discuss options with a clinician before starting rather than adjusting anything on their own.

How dangerous is a high hematocrit on TRT?

Mild elevation is common and is typically managed by dose adjustment or a formulation change. A hematocrit consistently over 54% is associated with increased blood viscosity and a theoretical clotting risk, and your clinician may recommend pausing treatment or therapeutic phlebotomy. Routine monitoring is designed to catch this before it becomes dangerous.

Why can’t I just buy testosterone online and dose it myself?

Testosterone is a prescription-only, DEA-scheduled medication for good reasons: it requires a proper diagnosis, careful dosing, and ongoing lab monitoring (hematocrit, PSA, testosterone levels, and now blood pressure). Products from unregulated sources carry risks of contamination, incorrect strength, and no medical oversight, and men who use them without monitoring face substantially higher rates of complications. Work with a licensed clinician.

The Bottom Line

TRT side effects are well characterized, monitorable, and mostly manageable with dose adjustment or a change in formulation. The cardiovascular concerns that dominated discussions a decade ago have been substantially clarified by the TRAVERSE trial, and in February 2025 the FDA removed the old boxed cardiovascular warning while adding a warning about increased blood pressure. The risk profile today is more nuanced — including attention to blood pressure, atrial fibrillation, pulmonary embolism, erythrocytosis, fertility, and prostate monitoring — rather than a single black-box concern. Men who start TRT with an appropriate diagnosis, regular monitoring, and an experienced clinician can expect meaningful symptomatic benefit at acceptable risk. Men who obtain testosterone through unregulated channels without monitoring face significantly higher risk. Verify the current labeling for your product with your prescriber, and never self-source or self-dose.