The Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Gynecol Oncol. 2020 May;157(2):348-356. doi: 10.1016/j.ygyno.2020.02.008. Epub 2020 Feb 19.
Our objectives were 1) to compare the efficacy of progestin therapy combined with metformin (Prog-Met) to Prog alone as primary fertility sparing treatment in women with atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) or early-stage endometrioid carcinoma (EC), and 2) to analyze the proportion of women achieving live birth following treatment.
A retrospective cohort study of all reproductive-aged women with AH/IN or EC treated with Prog ± Met from 1999-2018 was conducted. Complete response (CR) was assessed and Kaplan-Meier analysis used to calculate time to CR. Comparison of potential response predictors was performed with multivariable Cox regression models.
Ninety-two women met criteria; 59% (n = 54) were treated for AH/EIN and 41% (n = 38) for EC. Their median age, body mass index, and follow up time was 35 years, 37.7 kg/m, and 28.4 months, respectively. Fifty-eight women (63%) received Prog and 34 (37%) received Prog-Met. Overall, 79% (n = 73) of subjects responded to treatment with a CR of 69% (n = 63). There was no difference in CR (p = 0.90) or time to CR (p = 0.31) between the treatment cohorts. Overall, 22% experienced a disease recurrence. On multivariable analysis, EC histology was the only covariate associated with a decreased Prog response (HR 0.48; p = 0.007). Only 17% of the cohort achieved a live-birth pregnancy, the majority of which required assisted reproductive technologies (81%) and occurred in the Prog treatment group.
Our study does not support the use of Prog-Met therapy for treatment of AH/EIN or EC. Additionally, fewer than 20% of women achieved a live-birth pregnancy during the study period, with most requiring ART.
本研究的目的是 1）比较孕激素治疗联合二甲双胍（Prog-Met）与单纯孕激素治疗在治疗不典型增生/子宫内膜上皮内瘤变（AH/EIN）或早期子宫内膜样癌（EC）的女性中的疗效，2）分析治疗后活产的女性比例。
对 1999 年至 2018 年间所有接受孕激素±二甲双胍治疗的生育期妇女进行回顾性队列研究。评估完全缓解（CR），并使用 Kaplan-Meier 分析计算 CR 时间。采用多变量 Cox 回归模型比较潜在反应预测因子。
92 名女性符合标准；59%（n=54）为 AH/EIN 治疗，41%（n=38）为 EC 治疗。中位年龄、体重指数和随访时间分别为 35 岁、37.7kg/m 和 28.4 个月。58 名女性（63%）接受孕激素治疗，34 名（37%）接受孕激素-二甲双胍治疗。总体而言，79%（n=73）的患者对治疗有反应，CR 为 69%（n=63）。两组的 CR 无差异（p=0.90）或 CR 时间无差异（p=0.31）。总体而言，22%的患者疾病复发。多变量分析显示，EC 组织学是唯一与孕激素反应降低相关的协变量（HR 0.48；p=0.007）。该队列中仅有 17%的患者实现了活产妊娠，其中大多数需要辅助生殖技术（81%），且发生在孕激素治疗组。
本研究不支持孕激素-二甲双胍治疗用于治疗 AH/EIN 或 EC。此外，在研究期间，不到 20%的女性实现了活产妊娠，大多数需要辅助生殖技术。
