Can human chorionic gonadotropin (hCG) be used in patients with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels at the upper end of normal?

Using hCG When LH and FSH Are at the Upper End of Normal

Human chorionic gonadotropin (hCG) should not be used in patients with LH and FSH levels at the upper end of normal range, as this could disrupt the natural hormonal feedback system and lead to potential adverse effects without clinical benefit.

Physiological Considerations

hCG acts primarily as an LH analog in the body, with some minor FSH activity. According to the FDA label, "The action of HCG is virtually identical to that of pituitary LH, although HCG appears to have a small degree of FSH activity as well" 1. When LH and FSH are already at the upper end of normal, adding hCG would likely:

• Create supraphysiological levels of LH activity
• Potentially disrupt the hypothalamic-pituitary-gonadal axis
• Risk negative feedback suppression of natural gonadotropin production

Clinical Indications for hCG

hCG is primarily indicated in specific clinical scenarios:

1. Hypogonadotropic Hypogonadism: When LH and FSH levels are low, hCG can be used to stimulate testosterone production. As noted by the American Urological Association, "With gonadotropin treatment for HH, hCG injections are typically initiated with a response of serum testosterone monitored" 2.

2. Diagnostic Testing: hCG stimulation testing can be used to evaluate testicular function in specific scenarios, such as suspected anorchia 2, 3.

3. Fertility Treatment: In combination with FSH for men with hypogonadotropic hypogonadism to induce spermatogenesis 2, 3.

Risks of Inappropriate Use

Using hCG when LH and FSH are already at the upper end of normal carries several risks:

• Hormonal Imbalance: Potential for excessive estradiol conversion, which may cause gynecomastia or breast tenderness 3
• Disruption of Natural Feedback: May interfere with the body's natural hormonal regulation
• Unnecessary Side Effects: Including headache, irritability, restlessness, fatigue, and edema
• Financial Burden: Unnecessary medical costs without clinical benefit

Alternative Approaches

For patients with normal or high-normal LH and FSH levels who have concerns about:

1. Fertility issues: Consider direct evaluation of semen parameters and referral to reproductive specialists if abnormalities are found

2. Hypogonadal symptoms despite normal LH/FSH: Investigate other potential causes:

   • Androgen receptor sensitivity issues
   • Sex hormone binding globulin abnormalities
   • Other endocrine disorders
   • Non-hormonal causes of symptoms

Monitoring Recommendations

If hCG is used despite these concerns (which is not recommended), careful monitoring would be essential:

• Regular testosterone and estradiol measurements
• Periodic assessment of LH and FSH to detect potential suppression
• Monitoring for signs of gynecomastia and other side effects

Conclusion

The evidence clearly indicates that hCG therapy should be reserved for patients with documented low or low-normal LH and FSH levels. Using hCG when gonadotropins are already at the upper end of normal range is physiologically unsound and potentially harmful.