Changes in anterior pituitary response in patients with idiopathic hypothalamic hypogonadism caused by pulsatile GnRH therapy and testosterone replacement*

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OBJECTIVE: This study evaluated in male patients with idiopathic hypothalamic hypogonadism the effect of pulsatile GnRH therapy or testosterone replacement on the response of all anterior pituitary hormones to adequate dynamic stimuli. PATIENTS AND DESIGN: In nine patients with idiopathic hypothalamic hypogonadism--mean age 21 +/- 1 (mean +/- SE)--a combined pituitary stimulation (CPS) with 200 micrograms TRH, 100 micrograms GnRH, 100 micrograms CRH and 100 micrograms GRH and an insulin tolerance-test (ITT) with 0.1 U insulin/kg body weight were performed. Both tests were repeated during pulsatile GnRH therapy and thereafter on testosterone replacement. MEASUREMENTS: Hormone levels were measured by immunometric assays. For statistical analysis the area under the curve (AUC) was used as a measure for hormone response. RESULTS: Testosterone levels did not differ significantly during GnRH therapy (16.6 +/- 2.1 nmol/L) and testosterone replacement (18.5 +/- 1.7 nmol/L). No significant differences were observed before and during the two treatment modalities for TSH and ACTH. PRL increase was significantly higher during GnRH therapy (AUC: 73580 +/- 8940) compared to the rise before treatment (AUC: 36161 +/- 5853; p < 0.01) and on testosterone replacement (AUC: 49995 +/- 6158; p < 0.01). The GH response to CPS and ITT was higher under testosterone replacement (AUC: 1826 +/- 353 and 1423 +/- 125) compared with the pretreatment situation (AUC: 727 +/- 115; p < 0.05 and 541 +/- 110; p < 0.01) and also more pronounced than under GnRH therapy (AUC: 1148 +/- 180 and 798 +/- 129; p < 0.05). FSH and LH after CPS rose significantly more during GnRH therapy (AUC: 864 +/- 122 and 2215 +/- 219) than before (AUC: 418 +/- 61 and 1424 +/- 277; p < 0.01) and on testosterone treatment (342 +/- 83 and 1153 +/- 323; p < 0.05). CONCLUSION: These results show that GnRH exerts a stimulatory effect on PRL secretion and may modulate GH secretion independently from sex steroids.

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