Stimulation of Sperm Production by Human Chorionic Gonadotropin after Prolonged Gonadotropin Suppression in Normal Men
Authors: MATSUMOTO ALVIN M. , BREMNER WILLIAM J. 
Published: December 2015

The precise hormonal milieu required for quantitatively normal spermatogenesis in man is unclear. The authors previously have shown that both supraphysiologic dosages of human chorionic gonadotropin (hCG) and physiologic dosages of human luteinizing hormone (hLH) can reinitiate sperm production in short‐term (four months) gonadotropin‐suppressed normal men who have prepubertal FSH levels. To determine whether normal FSH levels were necessary to stimulate sperm production after a prolonged period of gonadotropin and testicular suppression, the authors administered hCG to four normal men whose endogenous gonadotropin levels and sperm production were suppressed by prolonged exogenous testosterone (T) administration. After a 3‐month control period, all subjects received 200 mg of T enanthate intramuscularly (im) each week to suppress LH and FSH for a total of 9 months and until successive sperm concentrations (performed twice monthly) revealed azoospermia or severe oligozoospermia (mean sperm concentration < 3 × 106 spermatozoa/ml) for 6 months. Then, while continuing the same dosage of T enanthate, all four men simultaneously received 5000 IU of hCG im three times weekly for 6 months, replacing LH‐like activity and leaving FSH activity suppressed. The effect on sperm production of the selective FSH deficiency produced by hCG plus T administration after the period of prolonged gonadotropin suppression was determined.

Exogenous T administration resulted in severe suppression of sperm concentrations from 79 ± 7 × 106 spermatozoa/ml (mean ± SEM) during the control period to 0.8 ± 0.5 × 106/ml after 12 weeks of T treatment. With the addition of hCG to T, sperm concentrations increased significantly in all four subjects, reaching a mean of 24 ± 4 × 106 spermatozoa/ml after 12 weeks of hCG plus T administration. However, no subject achieved sperm concentrations consistently in his own control range during this period. Sperm morphology and motility were consistently normal in all men during hCG plus T administration.

Throughout the entire 9 months of prolonged exogenous T administration alone and 6 months of hCG plus T treatment, serum FSH was reduced to undetectable levels (< 25 ng/ml). Urinary FSH excretion was in the normal adult range during the control period (238 ± 29 mIU/h). FSH excretion was markedly suppressed to the ranges found in prepubertal children and adults with hypogonadotropic hypogonadism during the periods of prolonged T suppression (44 ± 15 mIU/h) and hCG plus T (38 ± 6 mIU/h) administration.

The authors conclude that sperm production can be reinitiated by hCG after prolonged gonadotropin and testicular suppression, despite markedly suppressed FSH levels. Normal levels of FSH are not an absolute requirement for reinitiation of sperm production in gonadotropin‐suppressed men. However, since neither supraphysiologic dosages of hCG nor physiologic dosages of hLH are able to return sperm counts to fully normal levels during selective FSH deficiency, it is hypothesized that normal levels of both FSH and LH are necessary for quantitatively normal spermatogenesis in man.