Complete FDA-Approved Testosterone Replacement Therapy Guide
The most comprehensive clinical resource for testosterone replacement therapy in the United States. Evidence-based protocols, all FDA-approved formulations, and expert clinical guidance.
Injectable Testosterone Formulations
FDA-approved injectable formulations offer the most reliable and cost-effective treatment options
Testosterone Cypionate Gold Standard FDA Approved
The most prescribed testosterone ester in the United States, offering optimal balance of efficacy, convenience, and cost-effectiveness.
📊 Clinical Data
- Half-life: 8 days
- Peak levels: 24-48 hours post-injection
- Duration: 10-14 days
- Bioavailability: 100% (intramuscular)
Dosing Protocols
| Protocol | Dosage | Frequency | Clinical Notes |
|---|---|---|---|
| Standard | 100-200mg | Weekly | Most stable levels, preferred protocol |
| Bi-weekly | 200-400mg | Every 14 days | FDA label, higher fluctuation |
| Microdosing | 20-50mg | Every 2-3 days | Minimizes peaks/troughs |
Available Forms
- Generic: 100mg/mL, 200mg/mL vials
- Depo-Testosterone®: Brand name by Pfizer
- Cost: $40-105/month (generic)
Testosterone Enanthate FDA Approved
Nearly identical to cypionate with slightly shorter half-life. Preferred in European protocols.
📊 Clinical Data
- Half-life: 4.5-7 days
- Peak levels: 36-48 hours
- Duration: 7-10 days
- Bioavailability: 100% (intramuscular)
Available Forms
- Generic: 200mg/mL vials
- Delatestryl®: Brand name by Endo Pharmaceuticals
- Xyosted®: Auto-injector (50mg, 75mg, 100mg weekly)
- Cost: $45-110/month (generic), $500+ (Xyosted)
Testosterone Undecanoate (Aveed®) FDA Approved REMS Program
Ultra-long-acting formulation requiring only 5 injections per year after loading phase.
⚠️ REMS Requirements
Due to risk of pulmonary oil microembolism (POME), must be administered in certified healthcare settings with 30-minute observation period.
Dosing Protocol
- Loading: 750mg at weeks 0, 4
- Maintenance: 750mg every 10 weeks
- Injection volume: 3mL deep IM
- Cost: $1,200-1,500 per injection
Xyosted® Auto-Injector FDA Approved Subcutaneous
First FDA-approved subcutaneous testosterone auto-injector for weekly self-administration.
Key Features
- Pre-filled single-use auto-injectors
- Subcutaneous administration (not IM)
- Available: 50mg, 75mg, 100mg
- No dose adjustments needed
- Cost: $500-700/month
Clinical Injection Guidelines
Recommended Sites
- Ventrogluteal (preferred)
- Vastus lateralis
- Deltoid (≤1mL only)
- Dorsogluteal (avoid if possible)
Needle Selection
- Gauge: 23-25G
- Length: 1-1.5" (IM)
- Length: 0.5" (SubQ)
- 3mL luer-lock syringe
Storage Requirements
- Room temp: 68-77°F
- Protect from light
- Do not refrigerate
- 28-day stability after puncture
Topical Testosterone Formulations
FDA-approved gels and solutions provide daily application convenience with steady hormone levels
⚠️ Transfer Risk Warning
All topical formulations carry risk of transfer to women, children, and pets. Strict precautions required including hand washing, covering application sites, and avoiding skin contact.
AndroGel® FDA Approved Market Leader
Most prescribed topical testosterone with two concentration options.
Formulations
| Concentration | Starting Dose | Application Sites | Bioavailability |
|---|---|---|---|
| 1% gel | 50mg (5g gel) | Shoulders, upper arms | 9-14% |
| 1.62% gel | 40.5mg (2 pumps) | Shoulders, upper arms only | 10-12% |
- Apply same time daily after showering
- Wash hands immediately after application
- Cost: $400-600/month (generic: $200-300)
Testim® FDA Approved
1% gel with pentadecalactone permeation enhancer for improved absorption.
Key Features
- 30% higher peak levels vs AndroGel 1%
- Starting dose: 50mg (5g tube)
- Distinctive odor from enhancer
- Slightly sticky texture
- Cost: $500-700/month
Fortesta® FDA Approved Thigh Application
2% gel allowing smaller application volume and unique thigh application site.
Unique Features
- Only gel approved for thigh application
- Starting dose: 40mg (4 pump actuations)
- Dose titration based on 2-hour levels
- Metered-dose pump bottle
- Cost: $600-800/month
Vogelxo® FDA Approved
1% gel available in tubes, packets, and pump.
Delivery Options
- Tubes: 50mg, 100mg doses
- Packets: 50mg, 100mg doses
- Pump: 12.5mg per actuation
- Application: shoulders/upper arms
- Cost: $400-600/month
Axiron® FDA Approved Underarm Application
2% topical solution with unique underarm application using applicator.
Application Protocol
- Starting dose: 60mg (30mg per axilla)
- Apply using provided applicator
- Compatible with deodorant use
- No-touch applicator reduces transfer risk
Clinical Advantages
- Reduced transfer risk vs other sites
- Quick drying (3-5 minutes)
- Alcohol-based solution
- Cost: $500-700/month
Transdermal Testosterone Patches
FDA-approved patch system providing continuous hormone delivery
Androderm® FDA Approved
The only FDA-approved testosterone patch system in the United States.
📊 Clinical Data
- Steady-state levels achieved in 7-10 days
- Mimics circadian rhythm when applied nightly
- Bioavailability: ~10% of applied dose
- No first-pass metabolism
Available Strengths & Dosing
| Strength | Testosterone Delivered | Application | Typical Use |
|---|---|---|---|
| 2mg/day patch | ~2mg over 24 hours | One patch nightly | Starting dose |
| 4mg/day patch | ~4mg over 24 hours | One patch nightly | Standard dose |
| 6mg/day (2 patches) | ~6mg over 24 hours | Two patches nightly | High dose |
Application Sites
- Back, abdomen, thighs, upper arms
- Avoid bony prominences and oily skin
- Rotate sites to prevent irritation
- Do not apply to scrotum
⚠️ Common Side Effects
Skin irritation occurs in up to 37% of patients. Pre-treatment with topical corticosteroids may help. Discontinuation due to skin reactions: ~10%.
Cost & Considerations
- Cost: $600-800/month
- Must be worn continuously
- May fall off during exercise/sweating
- MRI-safe but should be removed
Oral Testosterone Formulations
Modern FDA-approved oral options eliminate historical hepatotoxicity concerns
Jatenzo® FDA Approved 2019
Testosterone undecanoate soft gelatin capsules with lymphatic absorption.
Dosing Protocol
- Starting: 237mg twice daily
- Range: 158-396mg twice daily
- Must take with food (fat required)
- Titrate based on 6-hour post-dose levels
✓ Safety Profile
No liver enzyme elevation in 2-year studies. Safe alternative to methylated oral steroids.
Cost: $900-1,500/month
TLANDO® FDA Approved 2022
Fixed-dose testosterone undecanoate with simplified monitoring.
Key Features
- Fixed dose: 225mg twice daily
- No dose titration in 80% of patients
- Take with meals
- Check levels at 3-4 weeks only
Cost: $900-1,400/month
Methyltestosterone Not Recommended
17α-alkylated oral testosterone with significant hepatotoxicity.
⚠️ Black Box Warning
Associated with cholestatic jaundice, peliosis hepatis, liver tumors, and hepatocellular carcinoma. AUA guidelines recommend against use.
Still FDA-approved but contraindicated for TRT
Alternative Delivery Systems
FDA-approved specialized delivery methods for specific patient needs
Testopel® Pellets FDA Approved
Subcutaneous pellet implants providing 3-6 months of therapy.
Procedure Details
- 8-12 pellets (75mg each)
- Local anesthesia required
- 5mm incision in upper buttock
- 10-15 minute procedure
Considerations
- Infection rate: 0.3-6.8%
- Extrusion rate: up to 12%
- Cannot adjust dose between procedures
- Cost: $650-2,000 per procedure
Natesto® FDA Approved Nasal Gel
Intranasal testosterone gel with TID dosing.
Unique Features
- Dose: 11mg per nostril TID
- No transfer risk to others
- Maintains LH/FSH production
- May preserve fertility
Side Effects
- Nasal irritation: 10-20%
- Rhinorrhea, epistaxis possible
- Cost: $700-900/month
Striant® FDA Approved Buccal
Buccal adhesive testosterone system applied to gums.
Application
- 30mg tablet applied BID
- Adheres to gum above incisor
- 12-hour controlled release
- No first-pass metabolism
Considerations
- Gum irritation common
- Altered taste possible
- Must avoid dislodging
- Cost: $600-800/month
Comprehensive Formulation Comparison
Evidence-based selection criteria for optimal patient outcomes
| Formulation | Frequency | Peak Time | Steady State | Monthly Cost | Transfer Risk | Key Advantages |
|---|---|---|---|---|---|---|
| Cypionate IM | Weekly | 24-48h | 4-5 weeks | $40-105 | None | Gold standard, cost-effective |
| Enanthate IM | Weekly | 36-48h | 4-5 weeks | $45-110 | None | Similar to cypionate |
| Xyosted SC | Weekly | 36h | 6 weeks | $500-700 | None | Auto-injector convenience |
| Aveed IM | 10 weeks | 7 days | 3rd dose | $400-500 | None | Infrequent dosing |
| AndroGel | Daily | 2-4h | 3-5 days | $200-600 | High | No injections |
| Axiron | Daily | 2-8h | 14 days | $500-700 | Moderate | Underarm application |
| Androderm | Daily | 8-24h | 7-10 days | $600-800 | Low | Circadian mimicry |
| Jatenzo | Twice daily | 5h | 7 days | $900-1500 | None | Oral convenience |
| Testopel | 3-6 months | 1 month | Immediate | $200-500 | None | Long duration |
| Natesto | Three daily | 60 min | 3-5 days | $700-900 | None | Preserves fertility |
Evidence-Based Clinical Benefits
Comprehensive outcomes data from landmark clinical trials
Sexual Function Improvements
📊 Testosterone Trials (2016)
790 men aged ≥65 years with testosterone <275 ng/dL
- Sexual activity increased by 0.58 activities/week (p<0.001)
- Sexual desire improved in 64% vs 31% placebo
- Erectile function improved (IIEF +2.64 points)
- Effects seen within 3-6 weeks
- Greater benefit with baseline T <200 ng/dL
Metabolic Health Benefits
- HbA1c reduction: -0.7% in diabetic men
- Insulin sensitivity: +25% (HOMA-IR)
- Total cholesterol: -12 mg/dL
- LDL cholesterol: -14 mg/dL
- Inflammatory markers: CRP -0.54 mg/L
Body Composition Changes
- Lean mass: +1.9 kg average increase
- Fat mass: -1.2 kg average decrease
- Trunk fat: -0.9 kg reduction
- Muscle strength: +10-13% improvement
- Effects maximized with resistance training
Bone Density Improvements
⚠️ TRAVERSE Fracture Substudy
Despite BMD improvements, fracture rates were higher with TRT (3.5% vs 2.5%). Clinical significance unclear.
- Lumbar spine BMD: +3-8% at 12 months
- Femoral neck BMD: +1-3% at 12 months
- Bone formation markers increased
- Greater effect with lower baseline T
Cognitive Function
- Spatial memory: Modest improvements
- Verbal memory: No significant change
- Executive function: Mixed results
- Depression scores: -2.5 points (BDI)
- Quality of life: Improved in most studies
Cardiovascular Safety - TRAVERSE Study
✓ 2023 FDA Label Update
Cardiovascular warnings removed following TRAVERSE results showing no increased MACE risk.
- 5,246 men with CVD or high risk
- MACE rate: 7.0% TRT vs 7.3% placebo
- No difference in MI, stroke, or CV death
- Small BP increase: +2.4 mmHg systolic
- AFib slightly increased: 3.5% vs 2.4%
Clinical Monitoring Protocols
Evidence-based monitoring ensures safety and efficacy
Baseline Assessment
Required Labs
- Total testosterone (2 morning samples)
- Free testosterone (calculated or equilibrium dialysis)
- LH, FSH (distinguish primary vs secondary)
- Complete blood count
- Comprehensive metabolic panel
- Lipid panel
- PSA (men >40 or high risk)
Clinical Assessment
- Digital rectal exam (if indicated)
- Blood pressure measurement
- Calculate BMI
- Assess cardiovascular risk
- Screen for sleep apnea
- Fertility desires
- Medication review
3-6 Month Follow-up
Laboratory Monitoring
- Testosterone level (trough for injections)
- Hematocrit (target <54%)
- PSA if baseline obtained
- Symptom assessment
- Blood pressure check
Dose Adjustments
- Target T level: 400-600 ng/dL (trough)
- Adjust by 25-50mg increments
- Consider peak levels if symptoms persist
Annual Monitoring
- Testosterone and free testosterone
- CBC with hematocrit
- Comprehensive metabolic panel
- Lipid panel
- PSA (controversial if stable)
- DRE if indicated
- Bone density (if osteoporosis risk)
- Cardiovascular risk reassessment
Real Patient Transformations
"After struggling with fatigue and low libido for years, testosterone cypionate changed my life. I feel like I'm in my 30s again at 52. The weekly injections are easy, and the results have been incredible."
"As a veteran, I appreciate Arsenal's military-friendly approach. The Xyosted auto-injector works perfectly with my active lifestyle. No more mixing vials or worrying about technique."
"I travel constantly for work, so the oral Jatenzo has been perfect. No needles, no gels to worry about transferring. Just take with meals and go. Worth every penny."
📋 Medical Disclaimer
This information is for educational purposes only and does not constitute medical advice. All treatment decisions must be made by licensed medical providers based on individual patient assessment. FDA approval status current as of 2024. Individual results may vary. Testosterone replacement therapy requires a prescription from a licensed provider.