HCG (Human Chorionic Gonadotropin)

In 29 normal men rendered gonadotropin-suppressed by weekly testosterone enanthate (200 mg), exogenous testosterone alone lowered intratesticular testosterone (ITT) by roughly 94%. Co-administration of hCG every other day increased ITT in a linear dose-dependent manner: post-treatment ITT was 25% below baseline at 125 IU, 7% below baseline at 250 IU, and 26% above baseline at 500 IU. This established that low-dose hCG can maintain ITT within the physiologic range needed for spermatogenesis despite full pituitary gonadotropin suppression.

Testosterone therapy shuts down the body's own signals to the testes, dropping the very high testosterone level inside the testes that sperm production depends on. This study showed that adding small doses of hCG, which mimics the natural LH signal, keeps that internal testicular testosterone at healthy levels. Higher hCG doses restored it fully, suggesting a way to protect fertility while on testosterone.

Thirty-seven healthy men were made experimentally gonadotropin-deficient (via a GnRH antagonist plus testosterone) and randomized to very low-dose hCG (0, 15, 60, or 125 IU) every other day for 10 days. Intratesticular testosterone rose dose-dependently from about 77 nmol/L in controls to about 923 nmol/L at 125 IU, and serum hCG concentrations correlated significantly with both intratesticular and serum testosterone. The data indicate that hCG doses far lower than those used clinically can meaningfully stimulate intratesticular androgen production.

Researchers temporarily switched off the natural hormones that drive the testes, then gave men tiny amounts of hCG. Even very small doses substantially raised testosterone inside the testes, and more hCG produced more testosterone. This suggests that fertility could potentially be supported with much lower hCG doses than are typically prescribed.

In a retrospective series of 26 hypogonadal men treated with testosterone replacement plus low-dose hCG (500 IU intramuscularly every other day), no patient became azoospermic over the follow-up period and semen parameters remained stable. Nine of the men contributed to a pregnancy with their partner during follow-up. The findings support concurrent low-dose hCG as a practical strategy to preserve spermatogenesis and fertility in men who require testosterone therapy.

Testosterone therapy commonly causes men to stop producing sperm. In this real-world group of men, adding low-dose hCG injections alongside testosterone kept sperm production going in every patient, and several went on to father children. It offers a clinically usable way to stay on testosterone without sacrificing fertility.