TRT Side Effects
What Happens & What You Control 2025
Quick Summary
TRT commonly causes acne (25-30%), mood changes (15-25%), fluid retention (10-17%), testicular shrinkage (65-70%), and elevated hematocrit (10-20%). Serious side effects like cardiovascular events occur in 1-5%. Most side effects are dose-dependent and manageable through dose adjustment, injection frequency changes, or symptom-specific treatments. Fertility suppression occurs in 65-90% but is reversible 6-18 months after stopping.
- Common side effects (acne, oily skin, mood swings, sleep issues) affect 20-30% and typically improve within 3-6 months as testosterone stabilizes
- Testicular shrinkage (65-70% of users) and fertility suppression (65-90%) are reversible—sperm production recovers 6-18 months after stopping TRT
- Cardiovascular risks (elevated hematocrit, blood clots) affect 5-15% and require regular monitoring every 3-6 months
- Most side effects manageable through dose adjustment, injection frequency changes, or switching testosterone formulations
You’re about to start TRT. Your doctor explained the benefits. But you’re scrolling through Reddit at 2 AM reading horror stories: “TRT ruined my life.” “Permanent side effects.” “My balls shrunk.” “Can’t have kids now.”
You’re terrified. Is this safe? What’s actually going to happen?
Here’s the direct answer: Most guys (70-80%) tolerate TRT well with mild side effects. The common stuff—acne (25-30%), mood swings (15-25%), testicular shrinkage (65-70%)—is manageable. The serious stuff—heart problems, blood clots—affects 1-5% and requires monitoring. Most side effects are controllable.
This guide tells you what actually happens, what’s common vs rare, what you can control, and when to worry.
The Direct Answer: What Side Effects Are Common
Very common (20-70% of guys):
- Testicular shrinkage (65-70%): Balls get smaller, usually painless, reversible
- Acne and oily skin (25-30%): Breakouts on face/chest/back, manageable
- Mood changes (15-25%): Irritability, mood swings with injection cycles
- Sleep disturbances (10-20%): Harder to fall asleep, middle-of-night waking
Moderately common (10-20%):
- Elevated hematocrit (10-20%): Thick blood, requires monitoring/donation
- Fluid retention (10-17%): Water weight gain, puffiness
- Gynecomastia risk (10-15%): Breast tissue growth from estrogen conversion
Uncommon but serious (1-10%):
- Cardiovascular events (1-5%): Blood clots, heart attacks (especially over 65)
- Severe polycythemia (2-5%): Dangerous blood thickness requiring phlebotomy
- Sleep apnea worsening (10-20%): Breathing problems during sleep
Most important: Most side effects are dose-dependent and manageable through adjustments.
The One Everyone Worries About: Testicular Shrinkage
Prevalence: 65-70% of TRT users
What actually happens: Your brain detects adequate testosterone from injections. It signals your testicles to stop producing their own. Testicles shrink 10-30% in size over 2-3 months.
What it feels like: Noticeable size reduction. Usually painless. You notice in the shower. Your partner might notice.
Is it permanent? No. Sperm production and testicular size typically recover 6-18 months after stopping TRT. 5-10% may have permanent partial atrophy after years without hCG.
How to prevent it: Add hCG (human chorionic gonadotropin) 250-500 IU, 2-3 times per week. hCG mimics LH and keeps testicles functioning. 85-90% of men maintain testicular size with hCG.
Cost: $50-150/month for hCG in addition to TRT.
Should you care? If you want to preserve fertility or maintain size for aesthetic reasons, add hCG. If neither matters, testicular atrophy is harmless.
The Annoying One: Acne and Oily Skin
Prevalence: 25-35% of TRT users
What happens: Testosterone increases sebum (oil) production in skin glands. Clogs pores. Causes acne breakouts, especially first 3-6 months.
Where it shows up: Face, chest, back. Similar to teenage acne.
Why it happens: Your body is adjusting to higher testosterone levels. Peaks coincide with injection timing (worse days 1-2 after injection).
Management:
- Topical treatment: Salicylic acid cleanser, benzoyl peroxide, adapalene (Differin)
- Dose adjustment: Reduce TRT dose by 15-25% if acne is severe
- Injection frequency: Twice-weekly injections (smaller peaks) instead of once-weekly
- Prescription options: Tretinoin, oral antibiotics for severe cases
- Switch formulation: Gels provide steadier levels, less acne than injections
Timeline: Acne typically improves significantly after 6-12 months as hormone levels stabilize.
The Frustrating One: Mood Swings and Irritability
Prevalence: 15-25% of TRT users
What it looks like:
- Irritable or short-tempered (10-15%)
- Mood swings corresponding to injection cycles (20-30% with weekly injections)
- Anxiety, especially first 1-3 months (8-12%)
- The “roid rage” fear (mostly overblown—rare at therapeutic doses)
Why it happens: Fluctuating testosterone levels. Weekly injections cause peaks (days 1-2) and troughs (days 5-7). Mood swings correspond to these fluctuations.
How to fix it:
- More frequent injections: Inject twice weekly (every 3.5 days) instead of once weekly—stabilizes levels, dramatically reduces mood swings
- Check estradiol: Both high estrogen (>50 pg/mL) and low estrogen (<20 pg/mL) cause mood instability
- Adjust dose: Lower dose if testosterone levels are >800 ng/dL
- Switch to gel: Daily application provides steadiest levels, minimal mood fluctuation
The “roid rage” reality: Studies show significant aggression occurs mainly with supraphysiologic doses (500+ mg/week), not therapeutic TRT doses (100-200 mg/week). At therapeutic doses, mood typically improves (40-60% report better mood).
The Uncomfortable One: Fluid Retention and Swelling
Prevalence: 10-17% of TRT users
What happens: Testosterone causes sodium and water retention. Mild swelling (edema), especially ankles, feet, face. 2-8 pound water weight gain in first month.
What it looks like: Puffy ankles at end of day, tight rings, facial puffiness, slight blood pressure increase.
Management:
- Reduce sodium intake (<2,300 mg daily)
- Increase water intake (counterintuitive but helps)
- Moderate exercise (promotes fluid circulation)
- Monitor blood pressure weekly
- Check estradiol—high estrogen (>50 pg/mL) worsens water retention
- Reduce TRT dose by 10-20% if severe
Timeline: Usually improves after 2-4 months as body adapts.
The Dangerous One: Elevated Hematocrit (Thick Blood)
Prevalence: 10-20% of TRT users
Why it matters: Elevated hematocrit (red blood cell count) increases blood thickness. Thick blood increases risk of blood clots, stroke, heart attack.
Target range: Hematocrit <52-54%. Levels >54% require intervention.
What causes it: Testosterone stimulates red blood cell production. Levels creep up over months.
Symptoms: Usually none. Sometimes headaches, dizziness, flushing. Detected on blood work.
Management:
- Regular monitoring: Check hematocrit every 3-6 months
- Blood donation: Donate every 8-12 weeks to lower hematocrit (free at blood banks)
- Therapeutic phlebotomy: Doctor removes blood (like donation) if hematocrit >54%
- Dose reduction: Lower TRT dose by 20-30% if hematocrit consistently >52%
- Hydration: Drink more water (improves blood viscosity)
Red flag: Hematocrit >54% despite interventions—may need to stop TRT or significantly reduce dose.
The Fertility One: Sperm Production Suppression
Prevalence: 65-90% of TRT users
What happens: TRT shuts down your natural testosterone production via negative feedback loop. Suppresses FSH and LH. Sperm production declines significantly within 2-3 months. 40-50% reach azoospermia (zero sperm count).
Is it permanent? Usually no. Sperm production typically recovers to baseline within 6-18 months after stopping TRT. 67-90% of men recover normal sperm counts.
However: 5-10% of long-term users (2+ years) may have prolonged or incomplete recovery. Permanent impairment is rare but possible.
How to preserve fertility on TRT:
- hCG co-treatment: 250-500 IU, 2-3 times weekly. Maintains testicular function and sperm production in 80-90% of cases.
- Planned breaks: Some guys cycle off TRT when planning to conceive (requires 6-18 months for recovery).
- Sperm banking: Freeze sperm before starting TRT if future fertility is important.
If you want kids soon: Discuss fertility preservation with your doctor before starting TRT. hCG is not guaranteed, and recovery takes 6-18 months.
The Cardiovascular Risk: Heart Problems and Blood Clots
Prevalence: 1-10% depending on age and risk factors
The concern: TRT may increase cardiovascular event risk (heart attack, stroke, blood clots) in certain populations:
- Men over 65: 10-15% increased risk
- Men with existing heart disease: 20-30% increased risk
- Younger, healthy men (<50): Neutral or possibly beneficial
The 2019 TRAVERSE trial: Large study (5,000+ men aged 45-80) found no significant increase in major cardiovascular events with TRT. However, men with recent cardiovascular events were excluded.
Risk factors that increase concern:
- Age >65
- History of heart attack, stroke, or blood clots
- Existing heart disease
- High blood pressure
- High cholesterol
- Smoking
- Obesity
- Elevated hematocrit >54%
Monitoring: Every 3-6 months check hematocrit, blood pressure, lipid panel. Early detection allows adjustment before serious events.
If you’re high-risk: TRT may not be appropriate. Discuss risks vs benefits with cardiologist.
The Prostate Question: Does TRT Cause Prostate Cancer?
Short answer: No. TRT does not cause prostate cancer.
The evidence: Multiple large studies, including a 2016 meta-analysis of over 3,000 men, found no increased prostate cancer risk with TRT. Prostate cancer rates are similar across testosterone levels.
However: TRT can accelerate growth of existing undiagnosed prostate cancer. This is why baseline PSA testing and digital rectal exam are required before starting TRT in men over 40-50.
Monitoring: PSA every 6-12 months. PSA increase >2 ng/mL in 1 year or >4 ng/mL total warrants further evaluation.
Benign prostatic hyperplasia (BPH): TRT commonly causes BPH symptoms in 5-15% of users—urinary frequency, weak stream, urgency. Managed with medications (finasteride, tamsulosin) if bothersome.
What You Can Control: Minimizing Side Effects
1. Dose Optimization
The problem: “More is better” mentality. Guys aim for testosterone levels >800 ng/dL thinking higher = more benefits.
The reality: Side effects are dose-dependent. Testosterone >800 ng/dL increases side effects (acne, mood swings, hematocrit elevation) without additional benefits.
Optimal range: 400-700 ng/dL. Achieves full symptom relief with minimal side effects in most guys.
Start low: Begin with 50-75 mg testosterone cypionate weekly. Titrate slowly based on labs and symptom response.
2. Injection Frequency
Weekly injections: Cause testosterone peaks (days 1-2) and troughs (days 5-7). Mood swings, acne, and energy fluctuations correspond to these cycles.
Twice-weekly injections: Inject every 3.5 days (e.g., Monday and Thursday). Maintains stable testosterone levels. Dramatically reduces mood swings, acne severity, and energy fluctuations.
Example: 100 mg/week total = 50 mg Monday, 50 mg Thursday (instead of 100 mg Monday only).
3. hCG Co-Treatment
Prevents: Testicular atrophy, fertility suppression, estrogen depletion
Protocol: 250-500 IU, 2-3 times weekly (e.g., 250 IU Monday/Wednesday/Friday)
Cost: $50-150/month in addition to TRT
Who needs it: Guys who want to maintain testicular size, preserve fertility, or prevent low estrogen symptoms
4. Estrogen Management
The balance: Testosterone converts to estrogen via aromatase enzyme. Too much estrogen causes gynecomastia, water retention. Too little causes joint pain, low libido, mood issues.
Target range: Estradiol 20-40 pg/mL (some guys feel best 25-35 pg/mL)
If estradiol is >50 pg/mL with symptoms:
- Low-dose aromatase inhibitor: 0.25 mg anastrozole twice weekly
- Reduce TRT dose (lowers estrogen proportionally)
- Lose weight (fat tissue produces aromatase)
Don’t crash estrogen: Some guys take too much AI, estradiol drops <10 pg/mL, feel terrible (joint pain, zero libido, ED). Estrogen is essential—don’t eliminate it.
5. Regular Monitoring
Labs every 3-6 months:
- Total testosterone (keep 400-700 ng/dL)
- Free testosterone
- Estradiol (keep 20-40 pg/mL)
- Hematocrit (keep <52%)
- PSA (men >40)
- Lipid panel
- Blood pressure
Early detection: Most serious side effects are preventable if caught early through monitoring.
Your Next Step (Managing Fear vs Reality)
If you’re considering TRT but scared of side effects: Start with conservative dosing (50-75 mg weekly), inject twice weekly (not once), add hCG for fertility/testicular preservation, monitor labs every 3 months initially. Most side effects are preventable or manageable with proper protocol.
If you’re on TRT and having side effects:
- Acne: Increase injection frequency to twice weekly, reduce dose by 15-25%, use topical treatments
- Mood swings: Inject twice weekly instead of once, check estradiol (aim 25-35 pg/mL)
- Water retention: Check estradiol, reduce sodium, increase water intake
- High hematocrit: Donate blood every 8-12 weeks, reduce dose, stay hydrated
Most important: Side effects don’t mean TRT doesn’t work for you. They mean your protocol needs adjustment. Work with your provider to optimize dosing, frequency, and adjunct medications. Most guys find a protocol that works without significant side effects.
This guide provides general information about TRT side effects based on clinical evidence. Individual experiences vary. Regular monitoring essential for safe long-term use. Consult with healthcare providers for personalized risk assessment and management. Last updated: February 2025.
Key Takeaways
- 1
Most TRT side effects are dose-dependent and improve when testosterone levels stabilize in therapeutic range (400-800 ng/dL)—higher doses cause more side effects.
- 2
Cardiovascular monitoring (hematocrit, lipids, blood pressure) every 3-6 months essential for early detection of serious side effects like elevated hematocrit (10-20% of users).
- 3
Testicular atrophy and fertility suppression occur in most TRT users but are reversible with hCG co-treatment or 6-18 months after stopping therapy.
- 4
Gynecomastia (breast tissue growth) affects 10-15% of users and results from testosterone converting to estrogen via aromatase—managed with AI or dose reduction.
- 5
Prostate effects from TRT are generally mild, but men over 50 require baseline PSA testing and regular prostate monitoring—TRT doesn't cause cancer but can accelerate existing disease.
- 6
Side effect profiles vary by delivery method—injections cause more mood fluctuations (20-30%), gels have higher skin reaction rates (15-40%).
Common Questions About TRT Side Effects
Common questions about testosterone answered by our research team.
Q What are the most common side effects of TRT?
Most common TRT side effects affect 20-30%: acne and oily skin (25-30%), mood changes and irritability (15-25%), sleep disturbances (10-20%), fluid retention and swelling (10-17%), testicular shrinkage (65-70%). Most are mild to moderate and improve within 3-6 months as testosterone levels stabilize. Acne typically responds to topical treatments or dose adjustment. Testicular atrophy can be prevented with hCG co-treatment. Mood changes often normalize once dosing is optimized to maintain stable testosterone levels throughout the week.
Q Can TRT cause serious heart problems?
TRT carries cardiovascular risks affecting 5-15% of users. Most significant concern is elevated hematocrit (red blood cell count) in 10-20%, increasing blood thickness and clot risk. Meta-analyses show TRT may increase cardiovascular event risk by 20-30% in men over 65 or with existing heart disease, while appearing neutral or possibly beneficial in younger, healthy men. The 2019 TRAVERSE trial found no significant increase in major cardiovascular events with TRT in men aged 45-80. Regular monitoring (every 3-6 months) of hematocrit, blood pressure, and lipids essential for early detection and management.
Q Will TRT make me infertile?
TRT suppresses natural testosterone production and sperm production in 65-90% of users, often causing temporary infertility. Sperm counts decline significantly within 2-3 months of starting TRT, reaching azoospermia (zero sperm) in 40-50% of users. However, this is usually reversible—sperm production typically recovers to baseline within 6-18 months after stopping TRT, with 67-90% recovering normal sperm counts. For men wanting to preserve fertility while on TRT, hCG co-treatment (250-500 IU, 2-3 times weekly) maintains testicular function and sperm production in 80-90% of cases. Men planning to have children should discuss fertility preservation options before starting TRT.
Q Does testosterone therapy cause prostate cancer?
Current evidence shows TRT does not cause prostate cancer in men with normal baseline PSA levels. Multiple large studies, including a 2016 meta-analysis of over 3,000 men, found no increased prostate cancer risk with TRT. The 'androgen hypothesis' (testosterone fuels prostate cancer) has been largely disproven—prostate cancer rates are similar across testosterone levels. However, TRT can accelerate growth of existing undiagnosed prostate cancer, which is why baseline PSA testing and digital rectal exam are required before starting TRT in men over 40-50. Men on TRT should have PSA monitored every 6-12 months. TRT does commonly cause benign prostatic hyperplasia (BPH) symptoms in 5-15% of users, causing urinary frequency and weak stream.
Q How do you prevent or reduce TRT side effects?
Most TRT side effects can be prevented or minimized: 1) Start with conservative dosing (50-75 mg testosterone cypionate weekly) and titrate slowly based on lab results, 2) Use more frequent injections (twice weekly instead of once weekly) to maintain stable testosterone levels and reduce mood swings, 3) Add hCG (250-500 IU, 2-3 times weekly) to prevent testicular atrophy and maintain fertility, 4) Monitor and manage estrogen—consider low-dose aromatase inhibitor (0.25 mg anastrozole twice weekly) if estradiol rises above 40-50 pg/mL causing gynecomastia or water retention, 5) Donate blood or do therapeutic phlebotomy if hematocrit exceeds 52-54% to reduce cardiovascular risk, 6) Switch formulations if side effects persist—some men tolerate gels better than injections or vice versa. Regular lab monitoring every 3-6 months allows early detection and adjustment.
Q What are the long-term risks of staying on TRT?
Long-term TRT (5+ years) carries several risks requiring ongoing monitoring: Cardiovascular effects—sustained elevation of hematocrit and potential atherosclerosis progression, especially in men over 65 (10-15% increased risk). Fertility—prolonged suppression may lead to permanent impairment in 5-10% of long-term users, particularly after 2+ years without hCG. Prostate enlargement—BPH symptoms gradually worsen in 15-25% of long-term users, potentially requiring medication or surgery. Testicular atrophy—permanent in some cases after years without hCG support. Sleep apnea—TRT worsens or causes sleep apnea in 10-20% of users through increased neck circumference and muscle mass. Dependency—natural testosterone production may not fully recover after years of TRT, making discontinuation difficult. Benefits typically outweigh risks when properly monitored with labs every 3-6 months and symptom management.
Q Can TRT cause mood swings and aggression?
TRT can cause mood changes in 15-25% of users with varied effects. Common mood-related side effects: irritability and short temper (10-15%), especially when testosterone levels fluctuate, anxiety (8-12%), particularly in first 1-3 months, mood swings corresponding to injection cycles (20-30% with weekly injections), and improved mood and reduced depression (40-60%, often the intended benefit). The 'roid rage' stereotype is largely exaggerated—studies show significant aggression occurs mainly with supraphysiologic doses (500+ mg/week), not therapeutic TRT doses (100-200 mg/week). Mood stability improves significantly with more frequent injections (every 3.5 days) or daily gel application maintaining steady testosterone levels. If mood swings persist, checking estradiol is important—both high (>50 pg/mL) and low (<20 pg/mL) estrogen can cause mood instability.
Have more questions? Our research is continuously updated. If you don't see your question answered here, check our complete guides or contact our team.
Layla Reyes
BCPA, MPH - Patient Advocate & Telehealth Specialist
Medical review by Dr. Amara Okonkwo, PharmD, BCPS - Clinical Pharmacotherapy Specialist
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