TRT (Testosterone Replacement Therapy)
- What it is: The direct administration of exogenous testosterone (usually via injection, gel, or patch) to restore testosterone levels.
- Goal: Raise circulating testosterone levels directly.
- Typical Use: For men with primary hypogonadism or consistently low T levels with symptoms.
Enclomiphene
- What it is: A selective estrogen receptor modulator (SERM), specifically the trans-isomer of clomiphene.
- Goal: Stimulate the body’s own production of testosterone by increasing LH and FSH from the pituitary.
- Typical Use: For men with secondary hypogonadism (where the issue lies in the hypothalamus or pituitary) and who wish to preserve fertility.
Mechanism of Action
| Feature | TRT | Enclomiphene |
| How it works | Provides synthetic testosterone | Blocks estrogen receptors in the hypothalamus, increasing GnRH → LH/FSH → testicular testosterone production |
| Endogenous production | Suppressed | Stimulated |
| Impact on fertility | Often suppresses sperm production | Usually maintains or improves sperm count |
Pros and Cons
TRT Pros
- Rapid symptom relief.
- Predictable testosterone levels.
- Effective in primary hypogonadism.
TRT Cons
- Suppresses natural testosterone and sperm production.
- Requires lifelong commitment in many cases.
- Potential need for ancillary medications (e.g., hCG, anastrozole).
Enclomiphene Pros
- Stimulates natural testosterone.
- Maintains fertility and testicular size.
- Oral administration (convenient).
Enclomiphene Cons
- May take longer to see full effects.
- Not as effective if testicular function is severely impaired.
- Off-label in many countries (not FDA-approved as standalone in the U.S., although used via compounding pharmacies).
Ideal Candidates
| TRT | Enclomiphene |
| Men with primary hypogonadism | Men with secondary hypogonadism |
| Those who do not desire fertility | Men trying to conceive |
| Failed other therapies | Mild-to-moderate symptoms and intact HPT axis |
Side Effects
TRT
- Erythrocytosis (high red blood cell count)
- Gynecomastia
- Acne
- Testicular atrophy
- Infertility
Enclomiphene
- Mood swings or irritability
- Headaches
- Potential visual disturbances (rare)
- Less risk of erythrocytosis or testicular shrinkage
Monitoring & Labs
- TRT: Monitor hematocrit, estradiol, PSA, LH/FSH (to confirm suppression), lipids.
- Enclomiphene: Monitor LH/FSH (to confirm stimulation), testosterone, estradiol.
Summary
| Trait | TRT | Enclomiphene |
| Direct testosterone increase | ✅ | ❌ |
| Preserves fertility | ❌ | ✅ |
| Requires injections/gels | ✅ | ❌ (oral) |
| Long-term suppression of HPTA | ✅ | ❌ |
| Fast symptom improvement | ✅ | ⚠️ (slower onset) |
Bottom Line
- Choose TRT for fast symptom resolution, especially if fertility isn’t a concern or in cases of primary testicular failure.
Choose Enclomiphene when trying to preserve fertility, when you want to stimulate natural production, or when avoiding injections.
