脉冲式GnRH治疗和睾酮替代治疗引起的特发性下丘脑性性腺功能减退患者垂体前叶反应的变化。

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

作者信息

Schopohl J, Mojto J, Losa M, Mehltretter G, Müller O A, von Werder K

机构信息

Medizinische Klinik, Klinikum Innenstadt, Ludwig Maximilian Universität München, Germany.

出版信息

Exp Clin Endocrinol Diabetes. 1995;103(3):184-90. doi: 10.1055/s-0029-1211348.

DOI:10.1055/s-0029-1211348

PMID:7584521

Abstract

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.

摘要

目的

本研究评估了在特发性下丘脑性性腺功能减退男性患者中，脉冲式GnRH治疗或睾酮替代治疗对所有垂体前叶激素对适当动态刺激反应的影响。

患者与设计

9例特发性下丘脑性性腺功能减退患者，平均年龄21±1岁（平均±标准误），进行了联合垂体刺激试验（CPS），给予200μg促甲状腺激素释放激素（TRH）、100μg促性腺激素释放激素（GnRH）、100μg促肾上腺皮质激素释放激素（CRH）和100μg生长激素释放激素（GRH），并进行了胰岛素耐量试验（ITT），给予0.1U胰岛素/kg体重。在脉冲式GnRH治疗期间及之后进行睾酮替代治疗时重复这两项试验。

测量

通过免疫测定法测量激素水平。统计分析采用曲线下面积（AUC）作为激素反应的指标。

结果

GnRH治疗期间（16.6±2.1nmol/L）和睾酮替代治疗期间（18.5±1.7nmol/L）睾酮水平无显著差异。在两种治疗方式之前和期间，促甲状腺激素（TSH）和促肾上腺皮质激素（ACTH）无显著差异。与治疗前（AUC：36161±5853；p<0.01）及睾酮替代治疗时（AUC：49995±6158；p<0.01）相比，GnRH治疗期间催乳素（PRL）升高显著更高（AUC：73580±8940）。与治疗前情况（AUC：727±115；p<0.05和541±110；p<0.01）相比，睾酮替代治疗时生长激素（GH）对CPS和ITT的反应更高（AUC：1826±353和1423±125），且比GnRH治疗时更明显（AUC：1148±180和798±129；p<0.05）。CPS后促卵泡生成素（FSH）和促黄体生成素（LH）在GnRH治疗期间（AUC：864±122和2215±219）比治疗前（AUC：418±61和1424±277；p<0.01）及睾酮治疗时（342±83和1153±323；p<0.05）升高更显著。