Gawlik Aneta Monika, Hankus Magdalena, Szeliga Kamila, Antosz Aleksandra, Gawlik Tomasz, Soltysik Kamil, Drosdzol-Cop Agnieszka, Wilk Krzysztof, Kudela Grzegorz, Koszutski Tomasz, Malecka-Tendera Ewa
Department of Pediatrics and Pediatric Endocrinology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
Nuclear Medicine and Endocrine Oncology Department, Maria Skłodowska-Curie Memorial Institute and Cancer Center, Gliwice Branch, Gliwice, Poland.
Front Endocrinol (Lausanne). 2018 Feb 8;9:23. doi: 10.3389/fendo.2018.00023. eCollection 2018.
Estrogen replacement therapy (ERT) for Turner syndrome (TS) is a widely discussed topic; however, the optimal model of ERT for patients with delayed diagnosis and/or initiation of therapy is still unclear, mainly due to insufficient data. We present the results of a prospective observational single-center study in which the efficacy of late-onset puberty induction by one-regimen transdermal ERT in TS girls was evaluated.
The analysis encompassed 49 TS girls (63.3% with 45,X) with hypergonadotropic hypogonadism in whom unified transdermal ERT protocol was used for puberty induction (first two months 12.5 μg/24 h, thereafter 25.0 μg/24 h until breakthrough bleeding). Clinical visits for examination and therapy modification took place every 3-6 months. Transabdominal pelvic ultrasound examinations were performed at least twice: at the beginning and at the end of follow-up.
The mean (SD) age at ERT induction was 15.1 (1.3) years. The duration of follow-up was 2.4 (1.1) years. Half of all the patients had at least B2 after 0.57 years, B3 after 1.1 years, B4 after 1.97 years, and menarche after 1.82 years from ERT initiation. With earlier initiation of ERT (≤14 years), B2 ( = 0.059) was achieved faster and B4 ( = 0.018) significantly slower than with the later start of ERT. Thirty-four (94.4%) patients had at least stage B3 at menarche. The karyotype, initial weight, and body mass index had no impact on puberty tempo during ERT. The uterine volume increased significantly during ERT in all the study group ( < 0.0001), and in half of the patients, the increase was at least 12.4-fold. It did not correlate with the duration of treatment ( = 0.84) or the dose of estradiol per kilogram ( = 0.78), nor did it depend on karyotype ( = 0.71) or age at ERT initiation ( = 0.28). There were no differences in ΔhSDS during ERT ( = 0.63) between the two age groups (ERT ≤14 and >14 years).
The presented easy-to-use fixed-dose regimen for late-onset puberty induction allowed for a satisfactory rate of achieving subsequent puberty stages and did not influence the growth potential.
特纳综合征（TS）的雌激素替代疗法（ERT）是一个广泛讨论的话题；然而，对于诊断延迟和/或治疗开始延迟的患者，ERT的最佳模式仍不明确，主要是由于数据不足。我们展示了一项前瞻性观察性单中心研究的结果，该研究评估了单方案经皮ERT诱导TS女孩青春期发育延迟的疗效。
分析纳入了49例患有高促性腺激素性性腺功能减退的TS女孩（63.3%为45,X），采用统一的经皮ERT方案诱导青春期发育（前两个月12.5μg/24小时，此后25.0μg/24小时直至突破性出血）。每3 - 6个月进行一次临床检查和治疗调整。经腹盆腔超声检查至少进行两次：随访开始时和结束时。
ERT开始时的平均（标准差）年龄为15.1（1.3）岁。随访时间为2.4（1.1）年。所有患者中有一半在ERT开始后0.57年至少达到B2期，1.1年达到B3期，1.97年达到B4期，1.82年月经初潮。ERT开始较早（≤14岁）时，达到B2期（=0.059）更快，而达到B4期（=0.018）比ERT开始较晚时显著更慢。34例（94.4%）患者在月经初潮时至少达到B3期。核型、初始体重和体重指数对ERT期间的青春期发育速度没有影响。在所有研究组中，ERT期间子宫体积显著增加（<0.0001），半数患者子宫体积增加至少12.4倍。它与治疗持续时间（=0.84）、每千克雌二醇剂量（=0.78）均无相关性，也不取决于核型（=0.71）或ERT开始时的年龄（=0.28）。两个年龄组（ERT≤14岁和>14岁）在ERT期间的身高标准差变化（=0.63）没有差异。
所提出的用于诱导青春期发育延迟的易于使用的固定剂量方案，能使后续青春期阶段的达成率令人满意，且不影响生长潜力。
