What is the best treatment plan for a 31-year-old male with hypogonadism, elevated oestradiol and prolactin levels?

Management of Iatrogenic Hypogonadism with Elevated Testosterone and Estradiol

The best treatment plan for this patient is to discontinue enclomiphene completely and allow hormone levels to normalize naturally, as the current testosterone levels of 41.8 nmol/L are significantly supraphysiological and pose health risks. 1, 2

Current Status Assessment

The patient presents with:

• Initial low-normal testosterone (12.4 nmol/L)
• Current supraphysiological testosterone (41.8 nmol/L) - well above target range
• Elevated estradiol (225 pmol/L) - rising despite supplements
• Elevated prolactin (364 mIU/L) - rising despite supplements
• Elevated LH (11.6 U/L) - indicating overstimulation

Treatment Recommendations

1. Immediate Discontinuation of Enclomiphene

   • Enclomiphene has caused excessive stimulation of the hypothalamic-pituitary-gonadal axis
   • Current testosterone level (41.8 nmol/L) far exceeds the recommended middle tertile range (450-600 ng/dL or approximately 15.6-20.8 nmol/L) 2
   • High testosterone levels increase risk of cardiovascular events, polycythemia, and other adverse effects 2

2. Discontinue All Current Supplements

   • Calcium D-Glucarate, zinc, DIM, and sulforaphane have not prevented rising estradiol and prolactin
   • Limited evidence supports efficacy of these supplements for hormone management 1
   • The American Urological Association notes that supplements have questionable clinical utility in treating male hormonal issues 1

3. Laboratory Monitoring

   • Repeat hormone panel (testosterone, estradiol, prolactin, FSH, LH) in 4 weeks
   • Add hematocrit/hemoglobin and liver function tests to assess for polycythemia and hepatotoxicity 2
   • Monitor for resolution of elevated prolactin, which is likely secondary to elevated estradiol

4. If Testosterone Remains Low After Normalization Period

   • Consider proper testosterone replacement therapy with target levels in mid-normal range (15.6-20.8 nmol/L) 2
   • Injectable testosterone cypionate/enanthate would be preferred due to better cost-effectiveness and similar clinical outcomes compared to transdermal options 2

Rationale for Discontinuing Current Approach

1. Dangers of Supraphysiological Testosterone

   • Increased risk of cardiovascular events, polycythemia, sleep apnea, and edema 2
   • The American Urological Association warns against excessive testosterone levels 1, 2

2. Rising Estradiol and Prolactin

   • Hyperprolactinemia can cause hypogonadotropic hypogonadism, creating a counterproductive hormonal environment 3, 4
   • Elevated estradiol can cause feminizing effects and further stimulate prolactin production

3. Ineffectiveness of Current Supplement Regimen

   • Despite adding multiple supplements and reducing enclomiphene dose, both estradiol and prolactin continued to rise
   • The American Urological Association notes that "the benefits of supplements are of questionable clinical utility" 1

Common Pitfalls to Avoid

1. Continuing SERMs Without Proper Monitoring

   • SERMs like enclomiphene can cause excessive stimulation of the HPG axis 1
   • The AUA guidelines state that "clinicians should inform the man with idiopathic infertility that the use of SERMs has limited benefits" 1

2. Ignoring Supraphysiological Hormone Levels

   • Failing to recognize that testosterone levels >30 nmol/L pose significant health risks 2
   • Not monitoring for adverse effects, particularly hematocrit elevation and blood pressure increases 2

3. Relying on Unproven Supplements

   • Using supplements without evidence-based support for hormone regulation 1
   • Expecting supplements to counteract powerful prescription medications like enclomiphene

By discontinuing all current medications and supplements and allowing the body to reset, the patient has the best chance of achieving appropriate hormone balance without the risks associated with supraphysiological testosterone levels.