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雄激素替代疗法对男性术后促性腺激素低下型性腺功能减退症患者骨代谢的影响:聚焦于雄激素受体 CAG 多态性的作用。

Effects of testosterone replacement therapy on bone metabolism in male post-surgical hypogonadotropic hypogonadism: focus on the role of androgen receptor CAG polymorphism.

机构信息

Division of Endocrinology, Department of Clinical and Molecular Sciences, Umberto I Hospital, Polytechnic University of Marche, Via Conca 71, 60126, Ancona, Italy.

出版信息

J Endocrinol Invest. 2014 Apr;37(4):393-400. doi: 10.1007/s40618-014-0052-2. Epub 2014 Jan 24.

Abstract

INTRODUCTION AND AIM

The relationship between androgen receptor (AR) CAG polymorphism and bone metabolism is highly controversial. We, therefore, aimed to evaluate the independent role of AR CAG repeat polymorphism on bone metabolism improvement induced by testosterone replacement therapy (TRT) in male post-surgical hypogonadotropic hypogonadism, a condition frequently associated with hypopituitarism and in which the effects of TRT have to be distinguished from those resulting from concomitant administration of pituitary function replacing hormones.

METHODS

12 men affected by post-surgical hypogonadotropic hypogonadism [mean duration of hypogonadism 8.3 ± 2.05 (SD) months] were retrospectively assessed before and after TRT (from 74 to 84 weeks after the beginning of therapy). The following measures were studied: parameters of bone metabolism [serum markers and bone mineral density (BMD)], pituitary dependent hormones and genetic analysis (AR CAG repeat number).

RESULTS

Total testosterone, estradiol, free T4 (FT4) and insulin-like growth factor-1 (IGF-1) increased between the two phases, while follicle stimulating hormone (FSH) decreased. While serum markers did not vary significantly between the two phases, BMD improved slightly but significantly in all the studied sites. The number of CAG triplets correlated negatively and significantly with all the variations (Δ-) of BMDs. Conversely, Δ-testosterone correlated positively and significantly with all studied Δ-BMDs, while Δ-FSH, Δ-estradiol, Δ-FT4, and Δ-IGF-1 did not correlate significantly with any of the Δ-BMDs. Multiple linear regression analysis, after correction for Δ-testosterone, showed that CAG repeat length was negatively and significantly associated with ∆-BMD of all measured sites.

CONCLUSIONS

Our data suggest that, in post-surgical male hypogonadotropic hypogonadism, shorter AR CAG tract is independently associated with greater TRT-induced improvement of BMD.

摘要

简介和目的

雄激素受体(AR)CAG 多态性与骨代谢之间的关系存在很大争议。因此,我们旨在评估 AR CAG 重复多态性对男性手术后促性腺激素低下性性腺功能减退症患者的骨代谢改善的独立作用,这种情况常与垂体功能减退症相关,其中 TRT 的作用必须与同时给予的垂体功能替代激素的作用区分开来。

方法

回顾性评估了 12 名手术后促性腺激素低下性性腺功能减退症患者(性腺功能低下的平均持续时间为 8.3±2.05 个月)在接受 TRT 前后(从开始治疗后 74 至 84 周)的情况。研究了以下指标:骨代谢参数[血清标志物和骨密度(BMD)]、垂体依赖性激素和基因分析(AR CAG 重复数)。

结果

总睾酮、雌二醇、游离 T4(FT4)和胰岛素样生长因子-1(IGF-1)在两个阶段之间增加,而卵泡刺激素(FSH)减少。虽然血清标志物在两个阶段之间没有显著变化,但所有研究部位的 BMD 都略有但显著改善。CAG 三核苷酸数与所有 BMD 变化(Δ-)呈负相关且显著相关。相反,Δ-睾酮与所有研究的Δ-BMD 呈正相关且显著相关,而 Δ-FSH、Δ-雌二醇、Δ-FT4 和 Δ-IGF-1 与任何 Δ-BMD 均无显著相关性。多元线性回归分析,在纠正 Δ-睾酮后,表明 CAG 重复长度与所有测量部位的Δ-BMD 呈负相关且显著相关。

结论

我们的数据表明,在手术后男性促性腺激素低下性性腺功能减退症中,较短的 AR CAG 重复序列与 TRT 诱导的 BMD 改善独立相关。

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