DIURNAL RHYTHM OF TESTOSTERONE INDUCED BY HUMAN CHORIONIC-GONADOTROPIN (HCG) THERAPY IN ISOLATED HYPOGONADOTROPIC HYPOGONADISM - A COMPARISON BETWEEN SUBCUTANEOUS AND INTRAMUSCULAR HCG ADMINISTRATION

When human chorionic gonadotrophin (hCG) is used to stimulate testoste rone synthesis and release in males with hypogonadotrophic hypogonadis m, it is administered two or three times weekly by intramuscular injec tion. We have compared the pharmacokinetics of a twice weekly standard dose of hCG (5000 U) given for the first week by intramuscular inject ion and in the second week by self-administered subcutaneous injection . The patients studied had Kallmann's syndrome, isolated idiopathic hy pogonadotrophic hypogonadism or post-traumatic isolated hypogonadotrop hic hypogonadism. Salivary testosterone was collected twice daily at 0 8.00h and 20.00h, and serum testosterone was collected after 0, 24h, 7 2h, 120h and 168h each week. The cumulated serum and salivary testoste rone levels were comparable on both intramuscular and subcutaneous hCG . In normal males there is diurnal variation in testosterone, with pea k serum levels in the morning falling to a nadir in the evening. The e xact nature and controlling factors of this circadian rhythm have not been established. In four of the subjects, the twice weekly hCG inject ions, either subcutaneous or intramuscular, produced a regular testost erone diurnal rhythm. The other four patients had fluctuations in test osterone but with no strict diurnal pattern. This study provides evide nce that the luteinizing hormone-like action of hCG is necessary to pr ime the circadian rhythm but only a single bolus of hCG is sufficient to induce the rhythm in the absence of endogenous gonadotrophin produc tion. In conclusion, self-administered subcutaneous hCG is safe and pr oduces comparable levels of serum and salivary testosterone to that ad ministered by the intramuscular route. Moreover, it was very well acce pted by the patients and was preferred to conventional treatments. Hum an hCG in some patients with hypogonadotrophic hypogonadism produces n ormal physiological changes in daily testosterone levels.