Obesity is the major aetiological driver for endometrial cancer. The levonorgestrel-intrauterine system (LNG-IUS) reduces the risk of endometrial cancer and its precursor, atypical hyperplasia. We assessed feasibility and uptake of the LNG-IUS for primary prevention of endometrial cancer in high-risk women and its impact on endometrial tissue biomarkers. Women with class-III obesity (BMI>40kg/m2) and histologically normal endometrium were invited to participate in a clinical trial of the LNG-IUS for endometrial protection. Recruitment, successful LNG-IUS insertion and adherence to trial procedures were recorded. We measured impact of the LNG-IUS on circulating biomarkers of endometrial cancer risk, endometrial proliferation (Ki-67, pAKT, PTEN), endometrial hormone receptor status (ER, PR), mental wellbeing and menstrual function. At six months, women chose to keep their LNG-IUS or have it removed. In total, 103 women were approached, 54 were offered a participant information sheet, 35 agreed to participate and 25 received a LNG-IUS. Their median age and BMI were 54 years (IQR 52,57) and 47kg/m2 (IQR 44,51) respectively. Three women (3/35, 9%) were ineligible due to atypical hyperplasia/endometrial cancer on their baseline biopsy. The LNG-IUS was well tolerated and had a positive overall effect on bleeding patterns and mental wellbeing. The LNG-IUS was associated with endometrial morphological change, reduced Ki-67 and PR expression but circulating biomarkers of endometrial cancer risk were unchanged. All but one woman (96%) kept her LNG-IUS. The LNG-IUS appears to be acceptable to some women with class-III obesity for primary prevention of endometrial cancer, which could provide a strategy for a prevention trial.

中文翻译：

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孕酮治疗肥胖女性子宫内膜癌保护 (PROTEC) 试验：可行性研究

肥胖是子宫内膜癌的主要病因。左炔诺孕酮宫内节育系统 (LNG-IUS) 可降低子宫内膜癌及其前体非典型增生的风险。我们评估了 LNG-IUS 在高危女性子宫内膜癌一级预防中的可行性和使用情况，及其对子宫内膜组织生物标志物的影响。III 级肥胖（BMI>40kg/m2）和组织学正常子宫内膜的女性被邀请参加 LNG-IUS 保护子宫内膜的临床试验。记录招募、成功插入 LNG-IUS 和遵守试验程序。我们测量了 LNG-IUS 对子宫内膜癌风险、子宫内膜增殖（Ki-67、pAKT、PTEN）、子宫内膜激素受体状态（ER、PR）、心理健康和月经功能的循环生物标志物的影响。六个月时，女性选择保留 LNG-IUS 或将其移除。总共接触了 103 名女性，向 54 名提供了参与者信息表，35 名同意参加，25 名获得了 LNG-IUS。他们的中位年龄和 BMI 分别为 54 岁 (IQR 52,57) 和 47kg/m2 (IQR 44,51)。三名女性 (3/35, 9%) 在基线活检时因非典型增生/子宫内膜癌不合格。LNG-IUS 耐受性良好，对出血模式和心理健康有积极的总体影响。LNG-IUS 与子宫内膜形态变化、Ki-67 和 PR 表达降低有关，但子宫内膜癌风险的循环生物标志物没有变化。除一名女性（96%）外，其他人都保留了她的 LNG-IUS。LNG-IUS 似乎可以被一些 III 级肥胖女性用于子宫内膜癌的一级预防，