TRT Side Effects: Common, Serious and How They’re Managed

Testosterone replacement therapy can help men with low testosterone, but it is a prescription hormone with real risks. This guide explains TRT side effects in plain English: what is common, what is serious, what the largest heart-safety trial found, how each form differs, and how providers catch problems early.

The American Urological Association considers a man a candidate for testosterone therapy only when he has both low testosterone levels and symptoms or signs linked to low testosterone (AUA guideline).

The short answer

The most common TRT side effects are acne or oily skin, soreness where you inject, mild fluid retention, breast tenderness, smaller testicles and lower sperm production. The key serious risk is a rise in red blood cells (high hematocrit). FDA labels also list blood clots, higher blood pressure, worsening sleep apnea, prostate changes and mood changes. The TRAVERSE trial found no increase in major heart events versus placebo, but more atrial fibrillation, acute kidney injury and pulmonary embolism. Many problems show up on routine labs and can be managed by changing the dose, schedule or form.

Side effects at a glance

Side effect	What it looks like	How providers usually respond
Acne, oily skin	Breakouts on the back, chest or face	Acne treatment, dose review
Injection-site reactions	Pain, redness, bruising or a firm spot	Injection technique review
Fluid retention	Puffy ankles, hands or feet	Provider evaluation, dose review
Breast tenderness or growth	Sore or swollen tissue behind the nipple	Estradiol check, dose or form change
Smaller testicles, lower sperm count	Testicles feel smaller; fertility drops	Fertility planning before starting
High hematocrit	Often no symptoms; found on labs	Pause, lower dose, phlebotomy if indicated
Higher blood pressure	Higher home or clinic readings	Regular BP checks
Prostate changes	PSA rise, urinary symptoms	PSA tracking, urology referral if needed

Common side effects

Acne and oily skin

The Depo-Testosterone label lists acne, seborrhea (oily, flaky skin), male pattern baldness and extra body hair among the skin effects seen with androgens (DailyMed). A 2025 clinical review notes that topical retinoids or benzoyl peroxide can manage mild to moderate acne (Basheer et al., 2025).

Injection-site reactions

Testosterone injections can cause pain, redness, bruising, bleeding or hardness where the shot was given (MedlinePlus). Injection-site bruising is one of the most common reactions on the Xyosted autoinjector label (DailyMed). After the long-acting shot Aveed, patients stay in the healthcare setting for at least 30 minutes because it can cause serious breathing problems and allergic reactions (MedlinePlus).

Fluid retention

Some men notice swelling in the ankles or hands. FDA labeling warns that edema “may be a serious complication” in men who already have heart, kidney or liver disease (AndroGel label). New swelling should always be reported.

Breast tenderness and gynecomastia

Some testosterone is converted to estradiol, a form of estrogen. Labels note that gynecomastia (breast tissue growth) “may develop and persist” in men treated with androgens (AndroGel label). Options include lowering the dose, switching to a less aromatizing form, observation when estrogen is not elevated, and medication in selected cases (Basheer et al., 2025). Our guide to anastrozole and estrogen on TRT explains when estrogen management makes sense.

Testicular shrinkage and reduced fertility

The Endocrine Society states that testosterone therapy “suppresses spermatogenesis” (sperm production) and recommends against it in men planning fertility in the near term (Bhasin et al., 2018). The AndroGel label lists testicular atrophy and low sperm count among reported effects (DailyMed). In male contraception studies, about 70% of men had no sperm in their semen within six months. Most recovered sperm production after stopping, but only about half returned to their pre-treatment levels. Those studies were in men without low testosterone, so the numbers may not apply exactly to TRT patients (Flores and Mulhall, 2022). If children are in your future, read TRT and fertility before you start.

Serious testosterone side effects

High hematocrit (erythrocytosis)

This is one of the most important serious risks. Testosterone stimulates red blood cell production, and too many red cells thicken the blood. The Endocrine Society advises checking hematocrit at baseline, 3 to 6 months after starting and then yearly. If it goes above 54%, therapy is stopped until it falls to a safe level, the man is checked for low oxygen and sleep apnea, and treatment restarts at a reduced dose (Bhasin et al., 2018). The guideline also lists a hematocrit above 48% (above 50% for men living at high altitude) as a condition that raises risk. In trials summarized in one review, intramuscular cypionate or enanthate produced the largest hematocrit rise, about 4.0%, while patches and nasal gel caused much smaller increases (Basheer et al., 2025). On the Xyosted label, increased hematocrit was the most frequent adverse reaction (DailyMed).

Blood clots

FDA labels describe postmarketing reports of deep vein thrombosis (DVT) and pulmonary embolism (PE) in men using testosterone (Depo-Testosterone label). In the TRAVERSE trial, venous clots were numerically more common with testosterone gel than placebo, 1.7% versus 1.2% (AndroGel label). The Endocrine Society recommends against starting testosterone in men with thrombophilia, an inherited tendency to form clots (Endocrine Society).

Higher blood pressure

In February 2025, after required ambulatory blood pressure studies confirmed an increase, the FDA announced class-wide label changes that add a warning about increased blood pressure to testosterone products (FDA). Labels state testosterone “can increase blood pressure,” and some products are not recommended with uncontrolled hypertension (AndroGel label).

Worsening sleep apnea

Testosterone “may potentiate sleep apnea in some patients, especially those with risk factors such as obesity” (AndroGel label). The Endocrine Society recommends against starting therapy in men with untreated severe obstructive sleep apnea (Endocrine Society). Tell your provider about any difficulty breathing during sleep (MedlinePlus).

Prostate effects

Men with an enlarged prostate (BPH) should be monitored for worsening urinary symptoms, and known or suspected prostate cancer is a contraindication (Xyosted label). PSA usually rises modestly, about 0.3 ng/mL on average in pooled data (Basheer et al., 2025). The Endocrine Society advises urology referral if PSA rises more than 1.4 ng/mL above baseline in the first 12 months, is confirmed above 4.0 ng/mL, or the prostate exam is abnormal (Endocrine Society). For the full research picture, see does testosterone cause prostate cancer?

Mood changes

Labels list anxiety, depression, hostility and emotional swings among reported effects (AndroGel label), and the Xyosted label includes a warning about depression and suicidal thoughts (DailyMed).

Cholesterol changes

Changes in blood lipids “may require dose adjustment or discontinuation” of testosterone therapy (AndroGel label).

Does TRT raise heart attack or stroke risk? What TRAVERSE found

For years, the biggest worry about testosterone therapy was the heart. The TRAVERSE trial, published in the New England Journal of Medicine in 2023, tested that directly (Lincoff et al., 2023). It enrolled 5,246 men aged 45 to 80 with symptoms of low testosterone and existing heart disease or a high risk of it (Cleveland Clinic).

• Major heart events (heart attack, stroke or cardiovascular death) occurred in 7.0% of the testosterone group and 7.3% of the placebo group. Testosterone was noninferior to placebo.
• Atrial fibrillation, acute kidney injury and pulmonary embolism were more common in the testosterone group.

In February 2025 the FDA announced class-wide label changes that add the TRAVERSE results to all testosterone products and remove Boxed Warning language about increased cardiovascular risk, while keeping the limitation of use for age-related low testosterone (FDA). In short: reassuring on heart attacks and strokes, but not risk-free. See our article on testosterone and heart health.

Side effects by form: injections, gels and pellets

The form you use changes which risks matter most. Our comparison of testosterone injections vs cream vs pellets covers convenience and cost; here is the safety view.

Form	Side effects to know
Injections (cypionate, enanthate)	Site pain or bruising; larger hematocrit rise than patches or nasal gel
Gels and creams	Skin irritation; passing testosterone to women and children by contact
Pellets	Infection, bleeding, bruising or pellet extrusion at the implant site

Gels carry a boxed warning. The FDA label warns that virilization has been reported in children secondarily exposed to testosterone gel. Children and women should avoid contact with unwashed or unclothed application sites. The label tells users to wash their hands with soap and water right after applying and to cover the area with clothing once the gel has dried. Skin irritation where the gel is applied is also among the most common side effects (AndroGel label).

Pellets can cause implant-site problems. The Testopel label reports infection (cellulitis and abscess) and pellet extrusion at or near the implant site, with most cases in the first month after insertion (DailyMed).

How providers monitor and reduce risk

Monitoring is what keeps TRT side effects manageable. A responsible online TRT program should include:

• Baseline labs: testosterone, hematocrit, PSA when age-appropriate and more. See our list of TRT blood work tests.
• Follow-up labs at 3 to 6 months, then yearly, matching the Endocrine Society schedule for hematocrit (Bhasin et al., 2018).
• A sensible testosterone target. The Endocrine Society recommends keeping levels in the mid-normal range for healthy young men during treatment (Bhasin et al., 2018). Read more about the optimal testosterone level on TRT.
• Estradiol checks when there are breast symptoms or other signs of high estrogen.
• Blood pressure checks at visits and at home.
• Dose and interval adjustments. Splitting a weekly dose into smaller, more frequent doses may keep levels steadier and help limit hematocrit rise (Basheer et al., 2025).
• Therapeutic phlebotomy when indicated, a blood draw that lowers red cell mass. The Endocrine Society calls it effective for treatment-related erythrocytosis (Bhasin et al., 2018).

Your prescriber individualizes dose, form and schedule from your labs, symptoms and history. Never change your dose on your own.

When to call your provider and when to get emergency care

Most TRT side effects are not emergencies, but some need prompt attention. Call your provider right away if you notice (MedlinePlus):

• Leg pain, swelling, warmth or redness, which can signal a blood clot
• Swelling of the hands, feet, ankles or lower legs
• Difficulty breathing, especially during sleep
• Painful or enlarged breasts
• Trouble urinating, weak urine flow or blood in the urine
• Erections that happen too often or last too long
• Yellow skin or eyes, dark urine or upper-right belly pain
• Depression, anxiety or other mood changes

MedlinePlus also lists chest pain, shortness of breath, pain in the arms, back, neck or jaw, slow or difficult speech, dizziness or faintness, and weakness or numbness of an arm or leg as symptoms that need an immediate call (MedlinePlus). If you think you may be having a heart attack, call 911 or your local emergency number right away (MedlinePlus).

Frequently asked questions

What are the most common TRT side effects?

Acne or oily skin, injection-site soreness, mild fluid retention, breast tenderness, testicular shrinkage and lower sperm production. A rise in hematocrit is also common and is found on blood work.

How soon do side effects of testosterone start?

Injection-site soreness can show up after the first shot. Other effects, such as hematocrit changes, develop over time, which is why the Endocrine Society recommends rechecking hematocrit 3 to 6 months after starting.

Does TRT cause heart attacks?

In the TRAVERSE trial of men with low testosterone and existing heart disease or high heart risk, major heart events were similar with testosterone (7.0%) and placebo (7.3%). Atrial fibrillation, acute kidney injury and pulmonary embolism were more common with testosterone.

Is high hematocrit on TRT dangerous?

Too many red blood cells can thicken the blood. The Endocrine Society advises stopping therapy if hematocrit goes above 54%, checking for low oxygen and sleep apnea, and restarting at a lower dose once it falls. Therapeutic phlebotomy is another option when indicated.

Will TRT make me infertile?

Testosterone therapy suppresses sperm production and can cause infertility while you are on it. In studies, most men recovered sperm production after stopping, though only about half returned to their previous level. Plan ahead if you want children.

Do gels and injections have different TRT side effects?

Yes. Gels can transfer to others through skin contact, and they carry a boxed warning about children who were exposed this way. Injections can cause site soreness and, in studies, raised hematocrit more than patches or nasal gel.

Does TRT cause prostate cancer?

Testosterone is not used in men with known or suspected prostate cancer. PSA is tracked during treatment, with urology referral if it rises past set thresholds.

Can TRT raise blood pressure?

Yes. In 2025 the FDA announced class-wide label changes that include a warning about increased blood pressure. Regular blood pressure checks are part of safe treatment.

Can TRT cause hair loss?

Male pattern baldness is listed among the skin and hair effects on testosterone labels.

Do TRT side effects go away?

Many TRT side effects improve with a dose, schedule or form change made by your prescriber. Reduced sperm production usually improves after stopping, though recovery can take months and is not always complete.

Talk to a licensed provider

Side effects are easiest to manage when someone is watching your labs from day one. MultiGen Wellness licensed providers review your history and blood work, explain the risks that apply to you, and adjust treatment as needed. It is $247 to start (includes your first provider visit), then $97 per visit; medications are priced separately. Contact us or call 1-800-259-0015.