Measurement of integrated concentration of GH by means of continuous withdrawal sampling is a method of evaluating physiological hormonal secretion. Integrated concentration of GH was evaluated in 5 subjects with idiopathic hypogonadal hypogonadism (range 19\p=n-\27 years) and in a 17-year-old male with idiopathic delay of puberty (5 males, 1 female) before and 30\p=n-\240 days after the start of pulsatile GnRH administration. Gonadotropins and testosterone or 17\g=b\-estradiol were restored, whereas 24-h integrated concentration of GH (before therapy 5.4 \ m=+-\ 1.3 IU/l; during GnRH 8.1 \ m=+-\ 2.0 IU/l; P< 0.05) was increased by GnRH therapy. However, no correlation was found between GH levels and sex steroid concentrations during GnRH pulsatile administration. These data further confirm that a physiological increase in gonadotropins and sex steroids can modulate GH synthesis and/or release.
The effect of short-term pulsatile LHRH administration was studied in 8 healthy subjects ranging from 60 to 81 yr to see if the decrease of pituitary gonadal function could be in part due to changes in the discharge of LHRH from the hypothalamus. Gonadotropin and testosterone (T) secretion was evaluated two weeks before and during LHRH (122-160 ng/kg bw every 120 min sc) infusion. In addition, a bolus dosage of LHRH (50 mu iv) was given both at the beginning and at the end of pulsatile LHRH administration in order to test gonadotrophs sensitivity. A significant increase in gonadotropin levels from day 0 to day 4 was found, and was followed by a subsequent decrease from day 7 to day 14. A slight significant increase in T levels was observed during LHRH administration (p less than 0.01). LH pulses were identified in 5 out of 8 subjects on day 0. On day 14, all the exogenous LHRH pulses were followed by significant LH bursts. There was not a significant decrease in the pituitary LH responsiveness to LHRH test from day 0 to day 14. Our study seems to indicate that pituitary - gonadal unit in normal elderly men can be modulated by pulsatile administration of LHRH. A pulse frequency of LHRH which is probably similar to the physiological one, could induce a slight increase in T levels via qualitative changes in LH activity. We can assume that clinical changes in gonadal activity might also be connected to some disturbances in endogenous LHRH pulsar.
A normal pituitary-gonadal function is reinduced by iv or sc pulsatile LHRH therapy, administered by a portable pump. In order to evaluate the differences between different sites of injection on the LHRH bioavailability, we compared the LHRH plasma concentration after a single LHRH injection in the lower abdominal wall and in the upper arm, in 5 patients with idiopathic hypogonadotropic hypogonadism, during LHRH treatment. Our data showed no significant differences in using both administration routes. In fact, LHRH absorption (secretory area and peak value) is quite similar. However, patients tolerated LHRH administration in the abdominal wall more so than in the upper arm. Both ways of administration are effective with regards to the pituitary responsiveness but we can not forget that patients compliance is of great importance in order to obtain the best results in a long-term therapy.
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