Diurnal rhythm of testosterone induced by human chorionic gonadotrophin (hCG) therapy in isolated hypogonadotrophic hypogonadism: a comparison between subcutaneous and intramuscular hCG administration.

When human chorionic gonadotrophin (hCG) is used to stimulate testosterone synthesis and release in males with hypogonadotrophic hypogonadism, it is administered two or three times weekly by intramuscular injection. We have compared the pharmacokinetics of a twice weekly standard dose of hCG (5000 U) given for the first week by intramuscular injection and in the second week by self-administered subcutaneous injection. The patients studied had Kallmann's syndrome, isolated idiopathic hypogonadotrophic hypogonadism or post-traumatic isolated hypogonadotrophic hypogonadism. Salivary testosterone was collected twice daily at 08.00 h and 20.00 h, and serum testosterone was collected after 0, 24 h, 72 h, 120 h and 168 h each week. The cumulated serum and salivary testosterone levels were comparable on both intramuscular and subcutaneous hCG. In normal males there is diurnal variation in testosterone, with peak serum levels in the morning falling to a nadir in the evening. The exact nature and controlling factors of this circadian rhythm have not been established. In four of the subjects, the twice weekly hCG injections, either subcutaneous or intramuscular, produced a regular testosterone diurnal rhythm. The other four patients had fluctuations in testosterone but with no strict diurnal pattern. This study provides evidence that the luteinizing hormone-like action of hCG is necessary to prime the circadian rhythm but only a single bolus of hCG is sufficient to induce the rhythm in the absence of endogenous gonadotrophin production. In conclusion, self-administered subcutaneous hCG is safe and produces comparable levels of serum and salivary testosterone to that administered by the intramuscular route. Moreover, it was very well accepted by the patients and was preferred to conventional treatments. Human hCG in some patients with hypogonadotrophic hypogonadism produces normal physiological changes in daily testosterone levels.