HCG / Human Chorionic Gonadotropin For Male Infertility

Introduction to HCG / Human Chorionic Gonadotropin for Male Infertility

Luteinizing hormone (LH) is the hormone from the pituitary gland which tells the Leydig cells in the testicles to make testosterone. Human chorionic gonadotropin (HCG) is a medication which has a similar structure and essentially the same hormonal action as LH. However, HCG has a much longer half-life (30 hours) than LH (30 minutes), with a peak onset of increased testosterone of about 72-96 hours after administration. [Madhusoodanan V. IBJU 2019] Since HCG works by increasing LH activity, if the LH is already elevated (over 20 IU/L) then HCG will likely not be effective at increasing testosterone levels.

Like SERMs and anastrazole, HCG works to increase endogenous production of testosterone. It is considerably more expensive than the two oral medications and must be given by injection (typically 3 times per week subcutaneously). The primary potential advantage of HCG over SERMs is that it does not require a functioning pituitary gland to work effectively. Therefore in men who have a non or poorly functioning pituitary along with low testosterone levels may benefit from the use of HCG. Permanent pituitary dysfunction can be congenital (e.g. Kallmans Syndrome) or result from local tissue destruction from a pituitary tumor or prior surgery/radiation to the area. Temporary decreases in pituitary function commonly occurs with the use of exogenous androgens which suppress pituitary release of FSH and LH. Even after stopping the androgens it can take some time before the pituitary will respond adequately to SERMs in terms of increasing LH (and therefore testosterone) levels.

However, it can sometimes be more effective when the pituitary gland is not responding to clomiphene, and is generally able to raise testosterone levels higher than can anastrazole (as long as baseline LH levels are not elevated above 20 IU/L). Like clomiphene, HCG can increase estradiol to abnormally high levels in some men through the conversion of testosterone to estradiol by the aromatase enzyme.

A common question is whether HCG is more effective than SERMs or anastrazole in treating male infertility. Remember that these medications do not directly improve sperm quality, but rather exert their effect by increasing testosterone production (and, in the case of SERMs and anastrazole, possibly FSH levels if these are low). Therefore, a man whose testosterone is pushed back up into the normal range by either SERMs, anastrazole, or HCG should have the same potential clinical benefit to sperm quality. HCG may be more effective in men who still have low testosterone levels on SERMs but whose LH is still not significantly increased (indicating an inadequate response by the pituitary gland to the SERM). Another difference is that, unlike clomiphene and anastrazole, HCG does not increase FSH production, although this should not matter clinically in men whose FSH is already elevated.