Effect of Choriogonadotropin Alpha (hCG) Injection on FSH Levels
hCG injection causes rapid and profound suppression of FSH levels through negative feedback on the pituitary gland, with FSH becoming undetectable or falling to prepubertal levels within days to weeks of administration. 1
Mechanism of FSH Suppression by hCG
hCG acts virtually identically to pituitary LH and stimulates testosterone production by testicular Leydig cells, which then exerts negative feedback on the hypothalamic-pituitary axis, suppressing both LH and FSH secretion. 2
The AUA guidelines note that hCG appears to have a small degree of FSH activity itself, but its primary effect on FSH levels is suppressive through the testosterone-mediated negative feedback mechanism. 2
Chronic hCG administration (5000 IU twice weekly) in normal men resulted in undetectable serum FSH levels (less than 25 ng/ml) and urinary FSH levels comparable to prepubertal children within the treatment period. 1
Time Course and Magnitude of FSH Suppression
FSH suppression occurs rapidly after hCG administration and remains suppressed throughout the duration of hCG treatment. 1
In controlled studies, FSH levels remained undetectable throughout 7 months of hCG administration alone, and continued to be suppressed when testosterone was added to the regimen. 1
The suppression is profound enough that it creates a state of selective FSH deficiency while maintaining elevated testosterone levels from the hCG-stimulated Leydig cell production. 1
Clinical Consequences of hCG-Induced FSH Suppression
The FSH suppression caused by hCG administration results in impaired spermatogenesis, with mean sperm concentration declining from 88 million/ml to 22 million/ml (a 75% reduction) during chronic hCG treatment. 1
This demonstrates that normal FSH levels are necessary for maintaining quantitatively normal spermatogenesis in men, as the selective FSH deficiency induced by hCG leads to oligospermia despite adequate testosterone levels. 1
One subject became azoospermic when testosterone was added to hCG, highlighting the critical role of FSH in sperm production that cannot be compensated for by testosterone alone. 1
Reversibility with FSH Replacement
When exogenous FSH (100 IU daily) or hMG (75 IU daily) was added to ongoing hCG administration, FSH levels increased to 213 ng/ml and sperm concentrations recovered significantly from 34 million/ml to 103 million/ml. 1
This recovery demonstrates that the FSH suppression is reversible and that restoration of FSH levels can rescue spermatogenesis even while hCG administration continues. 1
Pharmacokinetic Patterns After hCG Administration
After intramuscular hMG administration (which contains hCG), exogenous LH and hCG were barely detectable in serum, suggesting rapid clearance or tissue uptake. 3
After intravenous hMG injection, hCG concentrations increased to 7.6 IU/L at 30 minutes, followed by decline, demonstrating the transient nature of circulating hCG levels even as its biological effects on FSH suppression persist. 3
Critical Clinical Implications for Fertility Treatment
The AUA strongly recommends against using hCG or other hormonal therapy to induce testicular descent in cryptorchidism, citing low response rates (6-38% in controlled studies) and lack of long-term efficacy. 2
In fertility treatment contexts, providers must recognize that hCG administration will suppress FSH and potentially impair spermatogenesis, making it contraindicated as monotherapy in men seeking to optimize sperm production. 1
The evidence demonstrates that FSH is necessary for maintaining quantitatively normal spermatogenesis and cannot be replaced by hCG-stimulated testosterone production alone. 1
Special Considerations in Assisted Reproduction
Low-dose hCG (200 IU daily) can complete follicle maturation in female fertility treatment after FSH priming, with FSH levels declining rapidly after hMG discontinuation while estradiol and follicle growth continue under hCG stimulation. 4, 5
This demonstrates that while hCG suppresses endogenous FSH secretion, it can support late-stage follicular development through its LH-like activity, though this does not apply to male spermatogenesis where ongoing FSH is required. 4, 5