What is the recommended dosing for enclomiphene (clomiphene citrate) in men with hypogonadism?

Enclomiphene Dosing in Men with Hypogonadism

For men with hypogonadism, the recommended starting dose of enclomiphene citrate is 25 mg daily, which effectively increases testosterone levels while preserving fertility potential. 1, 2, 3

Mechanism and Rationale

Enclomiphene citrate is a selective estrogen receptor modulator (SERM) that works by:

• Blocking estrogen receptors in the hypothalamus and pituitary
• Increasing endogenous LH and FSH production
• Stimulating natural testosterone production
• Maintaining or improving spermatogenesis

Unlike exogenous testosterone therapy which suppresses the hypothalamic-pituitary-testicular axis, enclomiphene preserves or enhances fertility, making it particularly valuable for men who desire future fertility.

Dosing Protocol

1. Initial dosing: 25 mg daily orally 3

   • This dose has been shown to effectively raise testosterone levels into the normal range (>300 ng/dL)
   • Mean testosterone levels of approximately 525-604 ng/dL can be achieved after 6 weeks of treatment

2. Monitoring:

   • Check testosterone, LH, FSH, and estradiol at baseline
   • Recheck levels after 2-4 weeks of therapy
   • Further monitoring at 3 months and then every 6 months

3. Dose adjustments:

   • If testosterone remains low (<300 ng/dL), dose may be increased
   • If testosterone becomes excessively elevated or side effects occur, consider reducing to 12.5 mg daily

Clinical Evidence

Studies have demonstrated that enclomiphene at 25 mg daily:

• Increases total testosterone from baseline levels of ~165 ng/dL to ~525 ng/dL after 3-6 months 2
• Elevates LH and FSH, confirming restoration of the hypothalamic-pituitary-testicular axis
• Improves sperm counts in men with previously low counts 2
• Maintains these effects with continued treatment for up to 6 months

Long-term safety data with clomiphene citrate (the racemic mixture containing enclomiphene) shows:

• Effective testosterone elevation maintained for >3 years in 88% of patients
• Symptomatic improvement in 77% of men on long-term therapy
• Low incidence of side effects (8%) 4

Advantages Over Testosterone Therapy

Enclomiphene offers several advantages over exogenous testosterone for hypogonadal men:

• Preserves fertility by maintaining or increasing sperm production
• Avoids testicular atrophy associated with exogenous testosterone
• Does not require injections or topical applications
• Demonstrates more consistent testosterone levels throughout the day 3

Potential Side Effects

Monitor for:

• Mood changes (most common side effect)
• Visual disturbances (blurred vision)
• Breast tenderness
• Elevated estradiol levels

Important Considerations

1. Fertility preservation: For men with hypogonadism who desire fertility, enclomiphene is preferred over testosterone replacement therapy, which suppresses spermatogenesis 1

2. Patient selection: Enclomiphene is most effective in secondary (hypogonadotropic) hypogonadism with low/normal LH levels rather than primary testicular failure

3. Treatment duration: Long-term therapy appears safe and effective, with studies showing sustained benefits for >3 years 4

4. Monitoring: Regular assessment of testosterone, LH, FSH, and estradiol is recommended to ensure appropriate response and detect potential adverse effects

5. Efficacy limitations: May be less effective in men with pituitary disorders or previous pituitary surgery 5

By following this dosing protocol and monitoring recommendations, enclomiphene citrate can effectively restore testosterone levels while maintaining fertility potential in men with hypogonadism.