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高泌乳素血症男性患者对多巴胺激动剂治疗的骨标志物和骨密度反应。

Bone marker and bone density responses to dopamine agonist therapy in hyperprolactinemic males.

作者信息

Di Somma C, Colao A, Di Sarno A, Klain M, Landi M L, Facciolli G, Pivonello R, Panza N, Salvatore M, Lombardi G

机构信息

Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Naples, Italy.

出版信息

J Clin Endocrinol Metab. 1998 Mar;83(3):807-13. doi: 10.1210/jcem.83.3.4674.

Abstract

The aim of this prospective study was to evaluate the bone mineral density (BMD) at lumbar spine and femoral neck levels and biochemical parameters of bone turnover in 20 consecutive hyperprolactinemic males before and after an 18-month treatment with different dopamine agonists. Six patients received bromocriptine at a dose of 2.5-10 mg/day; 7 patients received quinagolide at a dose of 0.075-0.3 mg/day; 7 patients received cabergoline at a dose of 0.5-1.5 mg/week. BMD, serum PRL, testosterone, dihydrotestosterone, and osteocalcin (OC), and urinary cross-linked N-telopeptides of type I collagen (Ntx) levels were measured before and every 6 months during treatment. At study entry, BMD values were lower in patients than controls at both lumbar spine (0.82 +/- 0.03 vs. 1.18 +/- 0.01 g/cm2; P < 0.001) and femoral neck (0.85 +/- 0.02 vs. 0.92 +/- 0.02 g/cm2; P < 0.05) levels. Osteopenia or osteoporosis was diagnosed in 16 patients at the lumbar spine and in 6 of them at the femoral neck level. A significant inverse correlation was found between lumbar spine and femoral neck BMD values and both PRL levels and disease duration (P < 0.01). In the 20 patients, serum OC levels were significantly lower (2.1 +/- 0.1 vs. 9.3 +/- 2.4 microg/L; P < 0.01), whereas Ntx levels were significantly higher (157.8 +/- 1.1 vs. 96.4 +/- 7.4 nmol bone collagen equivalent/mmol creatinine; P < 0.001) than control values. A significant inverse correlation was found between serum PRL and OC (P < 0.01), but not Ntx, levels. After 18 months of treatment, serum PRL levels were suppressed, and gonadal function was restored in all 20 patients, as shown by the normalization of serum T (from 2.2 +/- 0.2 to 5.0 +/- 0.2 microg/L) and dihydrotestosterone (0.3 +/- 0.02 vs. 0.5 +/- 0.01 nmol/L) levels, without any significant difference among groups. A progressive significant increase in serum OC levels together with a significant decrease in Ntx levels were observed after 6, 12, and 18 months of treatment in the 3 groups of patients. A slight, although significant, increase in BMD values was recorded in all patients after 18 months of bromocriptine, quinagolide, and cabergoline treatment, serum OC levels were normalized after treatment, whereas neither urinary Ntx levels nor BMD values were normalized by 18 months of treatment with dopaminergic agents. In conclusion, treatment with bromocriptine, quinagolide, and cabergoline for 18 months, although successfull in suppressing serum PRL levels and restoring gonadal function, was unable to restore lumbar spine and femoral neck BMD and normalize Ntx levels. However, BMD was slightly increased during treatment, suggesting that additional bone loss was prevented after treatment of hyperprolactinemia.

摘要

本前瞻性研究的目的是评估20例连续的高泌乳素血症男性患者在接受18个月不同多巴胺激动剂治疗前后腰椎和股骨颈部位的骨矿物质密度(BMD)以及骨转换的生化参数。6例患者接受剂量为2.5 - 10mg/天的溴隐亭治疗;7例患者接受剂量为0.075 - 0.3mg/天的喹高利特治疗;7例患者接受剂量为0.5 - 1.5mg/周的卡麦角林治疗。在治疗前及治疗期间每6个月测量BMD、血清泌乳素(PRL)、睾酮、二氢睾酮、骨钙素(OC)以及尿I型胶原交联N端肽(Ntx)水平。研究开始时,患者腰椎(0.82±0.03 vs. 1.18±0.01g/cm²;P < 0.001)和股骨颈(0.85±0.02 vs. 0.92±0.02g/cm²;P < 0.05)部位的BMD值均低于对照组。16例患者在腰椎被诊断为骨量减少或骨质疏松,其中6例在股骨颈部位也被诊断为骨量减少或骨质疏松。腰椎和股骨颈BMD值与PRL水平及病程之间均存在显著负相关(P < 0.01)。在这20例患者中,血清OC水平显著低于对照组(2.1±0.1 vs. 9.3±2.4μg/L;P < 0.01),而Ntx水平显著高于对照组(157.8±1.1 vs. 96.4±7.4nmol骨胶原当量/mmol肌酐;P < 0.001)。血清PRL与OC水平之间存在显著负相关(P < 0.01),但与Ntx水平无显著相关性。经过18个月的治疗,所有20例患者的血清PRL水平均被抑制,性腺功能得以恢复,血清睾酮(从2.2±0.2升至5.0±0.2μg/L)和二氢睾酮(0.3±0.02 vs. 0.5±0.01nmol/L)水平正常化,各治疗组之间无显著差异。在3组患者治疗6、12和18个月后,观察到血清OC水平逐渐显著升高,同时Ntx水平显著降低。在接受溴隐亭、喹高利特和卡麦角林治疗18个月后,所有患者的BMD值均有轻微但显著的升高,治疗后血清OC水平正常化,而使用多巴胺能药物治疗18个月后,尿Ntx水平和BMD值均未恢复正常。总之,溴隐亭、喹高利特和卡麦角林治疗18个月,虽然成功抑制了血清PRL水平并恢复了性腺功能,但未能恢复腰椎和股骨颈的BMD以及使Ntx水平正常化。然而,治疗期间BMD略有增加,表明高泌乳素血症治疗后可预防额外的骨质流失。

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