# TRT Explained: How Testosterone Replacement Therapy Works

> Medically reviewed by Dr. Michael Chen, MD — Board-certified Endocrinologist
> Last updated: February 2026

## Hormones Involved

### Testosterone
The primary male sex hormone produced mainly in the testes. Responsible for muscle mass, bone density, fat distribution, red blood cell production, libido, and mood regulation.

### Luteinizing Hormone (LH)
Produced by the pituitary gland, LH signals the testes to produce testosterone. Exogenous TRT suppresses LH production through negative feedback.

### Follicle-Stimulating Hormone (FSH)
Also from the pituitary gland, FSH stimulates sperm production. TRT suppresses FSH, which is why it can affect fertility.

### Estradiol (E2)
A form of estrogen converted from testosterone via the aromatase enzyme. Monitoring E2 is important during TRT to prevent side effects from elevated estrogen.

### Sex Hormone-Binding Globulin (SHBG)
A protein that binds testosterone, making it unavailable for use. Only "free" (unbound) testosterone is biologically active.

## Mechanism of Action

TRT works by supplementing the body's testosterone supply from an external source. When administered, exogenous testosterone:

1. Enters the bloodstream and binds to androgen receptors throughout the body
2. Restores testosterone to normal physiological levels (typically 400-700 ng/dL)
3. Provides the hormonal signaling needed for normal male physiological functions
4. Suppresses the body's natural testosterone production through hypothalamic-pituitary-gonadal (HPG) axis feedback

## Delivery Methods

### Injectable Testosterone (Most Common)
- **Types:** Testosterone cypionate, testosterone enanthate
- **Frequency:** Typically weekly or biweekly injections
- **Administration:** Intramuscular (IM) or subcutaneous (SubQ) self-injection
- **Advantages:** Most cost-effective, stable levels with proper dosing, well-studied
- **Considerations:** Requires needle use, slight fluctuation between doses

### Topical Gels and Creams
- **Types:** AndroGel, Testim, compounded creams
- **Frequency:** Daily application to skin (shoulders, upper arms, or abdomen)
- **Advantages:** No needles, steady daily dosing
- **Considerations:** Risk of transfer to others through skin contact, daily commitment, may be less effective for some men

### Oral Testosterone
- **Types:** Testosterone undecanoate (Jatenzo), compounded oral formulations
- **Frequency:** Typically twice daily with food
- **Advantages:** No injections or topical application, convenient
- **Considerations:** Newer option with less long-term data, must be taken with fatty meals for absorption

### Testosterone Pellets
- **Types:** Testopel
- **Frequency:** Implanted subcutaneously every 3-6 months
- **Advantages:** Long-lasting, no daily or weekly routine
- **Considerations:** Requires minor in-office procedure, pellet extrusion possible

### Nasal Testosterone
- **Types:** Natesto
- **Frequency:** Three times daily
- **Advantages:** May preserve fertility better than other methods
- **Considerations:** Frequent dosing, nasal irritation possible

## Typical Treatment Protocols

A standard TRT protocol involves:

1. **Initial consultation** — symptom assessment and medical history review
2. **Baseline blood work** — total testosterone, free testosterone, SHBG, estradiol, CBC, PSA, lipid panel, metabolic panel
3. **Diagnosis** — confirmed low testosterone (below 300 ng/dL) with symptoms
4. **Starting dose** — commonly 100-200 mg/week of testosterone cypionate for injections
5. **Follow-up labs** — at 6-8 weeks to assess response
6. **Dose adjustment** — titrated based on symptom improvement and blood levels
7. **Ongoing monitoring** — blood work every 3-6 months (CBC, testosterone, estradiol, PSA)

## Lab Testing Essentials

### Key Biomarkers Monitored During TRT

| Biomarker | Purpose | Optimal Range |
|---|---|---|
| Total Testosterone | Primary hormone level | 400-700 ng/dL on treatment |
| Free Testosterone | Bioavailable hormone | Varies by age and lab |
| Estradiol (E2) | Estrogen balance | 20-40 pg/mL |
| Hematocrit/Hemoglobin | Red blood cell safety | Hematocrit below 54% |
| PSA | Prostate health screening | Age-appropriate baseline |
| Lipid Panel | Cardiovascular monitoring | Standard healthy ranges |
| Liver Function | Metabolic health | Standard healthy ranges |

### Testing Schedule
- **Before starting:** Comprehensive baseline panel
- **6-8 weeks after starting:** First follow-up to assess dose
- **Every 3-6 months:** Ongoing monitoring
- **Annually:** Comprehensive panel including PSA and lipids

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*This content is for informational purposes only and does not constitute medical advice. Always consult with a licensed healthcare provider before starting any hormone therapy.*