The Value of Pulsatile LH-RH Administration and HCG Therapy in the Investigation and Treatment of the Hypogonadal Male

Gordon, Derek (1988) The Value of Pulsatile LH-RH Administration and HCG Therapy in the Investigation and Treatment of the Hypogonadal Male. MD thesis, University of Glasgow.

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The present work investigates the value of pulsatile administration of LH-RH to hypogonadal males. In particular, the value of pulsatile LH-RH infusions in the differentiation of constitutional delay of puberty, short stature and hypogonadotrophic hypogonadism is assessed. Both the early endocrine effects and the effect of prolonged infusions on induction of fertility are studied. In addition, the effects of human chorionic gonadotrophin (HCG) on the pubertal development of boys presenting with delayed sexual development are evaluated. Prior relevant research and work published during the course of the present study are reviewed. Nocturnal surges in serum gonadotrophin and testosterone concentrations in pubertal boys are confirmed. Following six days of pulsatile LH-RH infusions at pulse doses ranging from 2.5 to 15mug/pulse subcutaneously at 90 min intervals, the naturally occuring diurnal hormone rhythms are pertubed. Exogenous administration of LH-RH stimulates gonadotrophin secretion above pre-infusion concentrations only at times of the day when endogenous secretion is at a minimum. At times of night-time hormone surges the effect of exogenous LH-RH administration is variable; the net effect on a group of pubertal boys was to leave nocturnal LH concentrations unaltered. Despite the alteration in gonadotrophin fluctuations thromughout the day and night caused by LH-RH administration serum testosterone concentration continued to show marked diurnal variation with post-infusion concentrations stimulated above pre-infusion levels thromughout the 24 hour periods. The dosage of LH-RH per pulse over the range 2.5 to 15mug/pulse did not appear to significantly alter the gonadotrophin response to LH-RH, given over 6 day periods. Mean gonadotrophin concentrations measured by sampling blood every 15 minutes, over 3 hour periods in the afternoon when endogenous secretion is low, showed a linear relationship between pre- and post-infusion concentrations. Patients with constitutional delay of puberty and boys with short stature showed similar increments in gonadotrophins following pulsatile LH-RH administration. However, males with hypogonadotrophic hypogonadism showed quantitatively greater increments when compared with the other two groups. The gonadotrophin responses to standard bolus injections (100mug I.V.) of LH-RH failed to differentiate between the boys with delayed puberty and short stature and the patients with hypogonadotrophic hypogonadism. Following pulsatile infusions of LH-RH to patients with short stature and delayed puberty, there were no significant differences in basal or peak LH concentrations, or increments in LH during LH-RH bolus tests. Patients with hypogonadotrophic hypogonadism, on the other hand, had significantly elevated basal and peak LH concentrations to the bolus tests. Increments in LH in the post-infusion bolus tests, however remained unchanged from the basal values. Peak FSH concentrations tended to fall in the post-infusion bolus LH-RH tests compared to pre-therapy tests in the short stature and delayed puberty groups. Basal and peak FSH concentrations rose in the hypogonadotrophic males in the post-infusion bolus tests. However, overlap between the groups prevented this test from adequately discriminating between the groups. Increments in serum testosterone following 6 days of pulsatile LH-RH administration were not different between the three patient groups; delayed puberty, short stature and hypogonadotrophic hypogonadism. The stimulated testosterone concentration showed a relationship to the basal testosterone and the patient's bone age. Little or no increment in testosterone occurred with pulsatile LH-RH infusions if the basal testosterone was undetectable or the patient's bone age was less than 12 years. The present work has confirmed that the prolactin response to TRH (200mug I.V.) was unable to differentiate between patients with pubertal delay or permanent hypogonadotrophic hypogonadism. Following pulsatile LH-RH infusions there were no significant differences in the basal, peak or incremental prolactin responses to TRH in either group of patients despite increases in both serum LH and testosterone in both groups. There is therefore no obvious relationship between exogenous LH-RH concentrations and the prolactin response to TRH. The present work confirms the ability of prolonged pulsatile infusion of LH-RH to induce the endocrine changes of puberty. (Abstract shortened by ProQuest.).

Item Type: Thesis (MD)
Qualification Level: Doctoral
Keywords: Medicine, Endocrinology
Date of Award: 1988
Depositing User: Enlighten Team
Unique ID: glathesis:1988-77645
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jan 2020 11:53
Last Modified: 14 Jan 2020 11:53

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