Testicular Responsiveness Following Chronic Administration of hCG (1500 IU Every Six Days) in Untreated Hypogonadotropic Hypogonadism

Summary The observation that the testosterone (T) response to a single intramuscular injection of hCG is prolonged suggests that currently used regimens (2-3 injections per week) to stimulate endogenous androgen secretion in hypogonadotropic hypogonadism (HH) patients have to be reassessed. Moreover, during the last few years, Leydig cell steroidogenic desensitization has been found after massive doses of hCG. The aim of the present investigation, carried out in 6 HH patients who showed no signs of puberty, was to study the effect of 1500 IU hCG administered every six days over a period of one year to induce the onset of pubertal development. To evaluate the kinetics of the response of T, 17α-hydroxy-progesterone (17α-OHP) and 17β-oestradiol (E2), blood samples were taken basally and 1, 2,4 and 6 days after drug injection. This dynamic study was performed after the first injection and after the 4th and 12th month of treatment. During this one year time period, a progressive increase in testicular size was observed. Comparing plasma T levels (mean ± SE) before the first injection (11.2 ± 4.7 ng/dl) with the corresponding values at the 4th (38.7 ± 10.5 ng/dl) and 12th months (99.5 ± 19.9 ng/dl) of therapy, a progressive and significant increase was observed. T reached a maximum elevation 58 hours after hCG injection at the 4th month (198.3 ± 42 ng/dl; P < 0.01) and at the 12th month (415.6 ± 62.6 ng/dl; P < 0.05), whereas it remained unchanged following the first hCG injection. No significant increase in plasma 17α-OHP or E2 was found at any of the time points, suggesting that testicular desensitization did not occur. These results show that hCG administered every six days at 1500 IU is able to induce some gonadal development in young untreated HH patients.