Violette Caroline J, Agarwal Ravi, Mandelbaum Rachel S, González José L, Hong Kurt M, Roman Lynda D, Klar Maximilan, Wright Jason D, Paulson Richard J, Obermair Andreas, Matsuo Koji
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA.
Expert Rev Anticancer Ther. 2023 Apr;23(4):385-395. doi: 10.1080/14737140.2023.2194636. Epub 2023 Mar 28.
Most patients diagnosed with endometrial hyperplasia or cancer are obese. Obesity, along with polycystic ovarian syndrome (PCOS) and type-2 diabetes mellitus (T2DM), may act synergistically to increase risk of malignant endometrial pathology. Incidence of malignant endometrial pathology is increasing, particularly in reproductive aged women. In patients who desire future fertility, the levonorgestrel intrauterine device (LNG-IUD) is often utilized. If the first-line progestin therapy fails, there is not an effective second-line adjunct option. Moreover, pregnancy rates following fertility-sparing treatment are lower-than-expected in these patients.
This clinical opinion provides a summary of recent studies exploring risk factors for the development of malignant endometrial pathology including obesity, PCOS, and T2DM. Studies assessing efficacy of fertility-sparing treatment of malignant endometrial pathology are reviewed, and a potential new adjunct treatment approach to LNG-IUD is explored.
There is an unmet-need for a personalized treatment approach in cases of first-line progestin treatment failure. Glucagon-like peptide 1 receptor agonists are a class of anti-diabetic agents, but may have a role in fertility-sparing treatment of obese patients with malignant endometrial pathology by reducing weight, decreasing inflammation, and decreasing insulin resistance; these changes may also improve chances of subsequent pregnancy. This hypothesis warrants further exploration.
大多数被诊断为子宫内膜增生或癌症的患者都肥胖。肥胖与多囊卵巢综合征（PCOS）和2型糖尿病（T2DM）可能协同作用，增加恶性子宫内膜病变的风险。恶性子宫内膜病变的发病率正在上升，尤其是在育龄妇女中。对于希望未来生育的患者，左炔诺孕酮宫内节育器（LNG-IUD）经常被使用。如果一线孕激素治疗失败，没有有效的二线辅助选择。此外，在这些患者中，保留生育功能治疗后的妊娠率低于预期。
本临床观点总结了近期探索恶性子宫内膜病变发生风险因素的研究，包括肥胖、PCOS和T2DM。回顾了评估恶性子宫内膜病变保留生育功能治疗疗效的研究，并探讨了一种针对LNG-IUD的潜在新辅助治疗方法。
在一线孕激素治疗失败的情况下，个性化治疗方法的需求尚未得到满足。胰高血糖素样肽-1受体激动剂是一类抗糖尿病药物，但可能通过减轻体重、减轻炎症和降低胰岛素抵抗，在肥胖的恶性子宫内膜病变患者的保留生育功能治疗中发挥作用；这些变化也可能提高后续妊娠的几率。这一假设值得进一步探索。
