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针对低促性腺激素性性腺功能减退症女孩的青春期诱导个体化管理:来自大型多中心注册研究的最佳替代结局见解。

Towards an individualized management of pubertal induction in girls with hypogonadism: insight into the best replacement outcomes from a large multicentre registry.

机构信息

Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.

Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

出版信息

Eur J Endocrinol. 2023 Jun 7;188(6):467-476. doi: 10.1093/ejendo/lvad056.

Abstract

OBJECTIVE

An evidence-based pubertal induction scheme in hypogonadal girls is still to be established. Interestingly, literature data report a suboptimal uterine longitudinal diameter (ULD) in >50% of treated hypogonadal women, negatively influencing their pregnancy outcomes. This study aims to investigate auxological and uterine outcomes of pubertal induction in girls in the light of underlying diagnosis and therapeutic schemes used.

DESIGN

Retrospective analysis of longitudinal data from a multicentric registry.

METHODS

Auxological, biochemical, and radiological data were collected at baseline and during follow-up in 95 hypogonadal girls (chronological age > 10.9 years, Tanner stage ≤ 2) treated with transdermal 17β-oestradiol patches for at least 1 year. Induction was started at a median dose of 0.14 mcg/kg/day with a 6-monthly increase and was considered completed for 49/95 patients who started progesterone with a concomitant oestrogen adult dose.

RESULTS

At the end of induction, the achievement of the complete breast maturation was associated with a 17β-oestradiol dose at progesterone introduction. ULD showed a significant correlation with a 17β-oestradiol dosage. Final ULD was >65 mm in only 17/45 girls. At multiple regression analysis, pelvic irradiation represented the major determinant of reduced final ULD. After correction for uterine irradiation, ULD was associated with the 17β-oestradiol dose at progesterone introduction. Final ULD was not significantly different from the one assessed after progesterone introduction.

CONCLUSIONS

Our results provide evidence that progestins, hampering further changes in uterine volume and breast development, should be introduced only in the presence of a concomitant adequate 17β-oestradiol dose and an appropriate clinical response.

摘要

目的

目前仍需建立基于循证医学的促性腺激素低下女孩青春期诱导方案。有趣的是,文献数据报告称,接受治疗的促性腺激素低下女性中超过 50%存在子宫长径(ULD)不理想,这对她们的妊娠结局产生负面影响。本研究旨在根据潜在的诊断和治疗方案,研究青春期诱导对女孩的生长和子宫结局的影响。

设计

多中心注册的回顾性分析。

方法

对 95 名接受透皮 17β-雌二醇贴片治疗至少 1 年的促性腺激素低下女孩(年龄>10.9 岁,Tanner 分期≤2)的纵向数据进行回顾性分析。诱导起始剂量中位数为 0.14 mcg/kg/天,每 6 个月增加一次,49/95 名患者在开始孕激素的同时给予成人剂量雌激素,认为诱导完成。

结果

在诱导结束时,完全乳房成熟的实现与孕激素引入时的 17β-雌二醇剂量相关。ULD 与 17β-雌二醇剂量呈显著相关性。只有 17/45 名女孩的最终 ULD >65mm。在多元回归分析中,骨盆照射是最终 ULD 降低的主要决定因素。校正子宫照射后,ULD 与孕激素引入时的 17β-雌二醇剂量相关。最终 ULD 与引入孕激素后评估的 ULD 无显著差异。

结论

我们的结果表明,孕激素会阻碍子宫体积和乳房发育的进一步变化,只有在存在足够的 17β-雌二醇剂量和适当的临床反应时,才能引入孕激素。

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