Dose-dependent increase in intratesticular testosterone by very low-dose human chorionic gonadotropin in normal men with experimental gonadotropin deficiency

Abstract

Context and objective: In men with infertility secondary to gonadotropin deficiency, treatment with relatively high dosages of human chorionic gonadotropin (hCG) stimulates intratesticular testosterone (IT-T) biosynthesis and spermatogenesis. Previously we found that lower dosages of hCG stimulated IT-T to normal. However, the minimal dose of hCG needed to stimulate IT-T and the dose-response relationship between very low doses of hCG and IT-T and serum testosterone in normal men is unknown.

Design, setting, patients, and intervention: We induced experimental gonadotropin deficiency in 37 normal men with the GnRH antagonist acyline and randomized them to receive one of four low doses of hCG: 0, 15, 60, or 125 IU sc every other day or 7.5 g daily testosterone gel for 10 d. Testicular fluid was obtained by percutaneous aspiration for steroid measurements at baseline and after 10 d of treatment and correlated with contemporaneous serum hormone measurements.

Results: Median (25th, 75th percentile) baseline IT-T was 2508 nmol/liter (1753, 3502 nmol/liter). IT-T concentrations increased in a dose-dependent manner with very low-dosage hCG administration from 77 nmol/liter (40, 122 nmol/liter) to 923 nmol/liter (894, 1017 nmol/liter) in the 0- and 125-IU groups, respectively (P<0.001). Moreover, serum hCG was significantly correlated with both IT-T and serum testosterone (P<0.01).

Conclusion: Doses of hCG far lower than those used clinically increase IT-T concentrations in a dose-dependent manner in normal men with experimental gonadotropin deficiency. Assessment of IT-T provides a valuable tool to investigate the hormonal regulation of spermatogenesis in man.

Figures

Figure 1

Study design.

Figure 2

A and B, Box plots of IT-T (A) and IT-DHT (B) in gonadotropin-suppressed subjects on d 10 by treatment group (n = 6 for the 0 IU hCG, n = 7 for the 15 IU hCG group, n = 5 for the 60 IU hCG group, and 125 IU hCG group and n = 8 for the testosterone group). Dotted lines represent the upper and lower limits of the baseline range.

Figure 3

A and B, Correlations between posttreatment serum and intratesticular testosterone (A) and DHT (B) for all subjects receiving hCG (n = 23). The dotted line represents the lower limit of the normal range for testosterone and serum DHT.

Figure 4

A and B, Correlations between posttreatment serum hCG and IT-T (A) and serum testosterone (B) for all subjects receiving hCG (n = 23). The dotted line represents the lower limit of the normal range for serum testosterone.