Division of Gynaecology, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary's Hospital, Manchester, United Kingdom.
Cancer Prev Res (Phila). 2021 Feb;14(2):263-274. doi: 10.1158/1940-6207.CAPR-20-0248. Epub 2020 Sep 30.
Obesity is the major etiologic 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 [body mass index (BMI) > 40 kg/m] 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 [estrogen receptor and progesterone receptor (PR)], mental wellbeing, and menstrual function. At 6 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 [interquartile range (IQR) 52-57] and 47 kg/m (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 morphologic 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. Novel strategies are urgently needed to prevent the rise in endometrial cancer diagnoses predicted by escalating obesity rates. Here, we show that women with class III obesity are willing to engage in risk reduction with a levonorgestrel intrauterine system, which could provide a strategy for an endometrial cancer prevention trial.
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）降低了子宫内膜癌及其前体非典型增生的风险。我们评估了 LNG-IUS 在高危女性中用于子宫内膜癌一级预防的可行性和接受度，以及其对子宫内膜组织生物标志物的影响。邀请患有 III 类肥胖（BMI>40kg/m）且子宫内膜组织学正常的女性参加 LNG-IUS 用于子宫内膜保护的临床试验。记录招募、LNG-IUS 成功插入和试验程序的依从性。我们测量了 LNG-IUS 对子宫内膜癌风险的循环生物标志物、子宫内膜增殖（Ki-67、pAKT、PTEN）、子宫内膜激素受体状态（雌激素受体和孕激素受体（PR））、心理健康和月经功能的影响。6 个月时，女性选择保留或取出 LNG-IUS。共有 103 名女性接受了评估，54 名女性收到了参与者信息表，35 名同意参加，25 名接受了 LNG-IUS。她们的中位年龄和 BMI 分别为 54 岁（IQR 52-57）和 47kg/m（IQR 44-51）。由于基线活检中有非典型增生/子宫内膜癌，有 3 名女性（3/35，9%）不符合条件。LNG-IUS 耐受性良好，对出血模式和心理健康有积极影响。LNG-IUS 与子宫内膜形态改变、Ki-67 减少和 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改变。除 1 名女性（96%）外，其余女性均保留了 LNG-IUS。LNG-IUS 似乎被一些 III 类肥胖女性接受，用于子宫内膜癌的一级预防，这可能为预防试验提供一种策略。迫切需要新的策略来预防肥胖率上升所预测的子宫内膜癌诊断的增加。在这里，我们表明，III 类肥胖的女性愿意接受左炔诺孕酮宫内节育系统来降低风险，这可能为子宫内膜癌预防试验提供一种策略。
