Wang Yuanyuan, Lai Tianjiao, Chu Danxia, Bai Jing, Yan Shuping, Qin Haixia, Guo Ruixia
Department of Gynecology, First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, China.
Department of Gynecology, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2024 Nov 20;44(11):2055-2062. doi: 10.12122/j.issn.1673-4254.2024.11.01.
To evaluate the efficacy of medroxyprogesterone acetate (MA) plus metformin as the primary fertility-sparing treatment for atypical endometrial hyperplasia (AEH) and early-stage grade 1 endometrial adenocarcinoma (G1 EAC) and the recurrence rate after treatment.
Sixty patients (aged 20-42 years) with AEH and/or grade 1 EAC limited to the endometrium were enrolled prospectively and randomized into two groups (=30) to receive oral MA treatment at the daily dose of 160 mg (control) or MA plus oral metformin (850 mg, twice a day) for at least 6 months. The treatment could extend to 12 months until a complete response (CR) was achieved, and follow-up hysteroscopy and curettage were performed every 3 months. For all the patients who achieved CR, endometrial expressions of IGFBP-rP1, p-Akt and p-AMPK were detected immunohistochemically.
A total of 58 patients completed the treatment. After 9 months of treatment, 23 (76.7%) patients in the combined treatment group and 20 (71.4%) in the control group achieved CR; two patients in the control group achieved CR after converting to the combined treatment. The recurrence rate did not differ significantly between the control group and combined treatment group (30.0% 22.7%, >0.05). Ten (35.7%) patients in the control group experienced significant weight gain of 5.7±6.1 kg, while none of the patients receiving the combined treatment exhibited significant body weight changes. Compared with the control group, the patients receiving the combined treatment showed enhanced endometrial expressions of IGFBP-rP1 and p-AMPK with lowered p-Akt expression.
Metformin combined with MA may provide an effective option for fertility-sparing treatment of AEH and grade 1 stage IA EAC, and the clinical benefits of metformin for controlling MA-induced weight gain and promoting endometrial expressions of IGFBP-rP1 and p-AMPK while inhibiting p-Akt expression warrants further study.
评估醋酸甲羟孕酮（MA）联合二甲双胍作为非典型子宫内膜增生（AEH）和早期1级子宫内膜腺癌（G1 EAC）主要保留生育功能治疗方法的疗效及治疗后的复发率。
前瞻性纳入60例年龄在20 - 42岁、AEH和/或局限于子宫内膜的1级EAC患者，随机分为两组（每组 = 30例），分别接受每日剂量160 mg的口服MA治疗（对照组）或MA联合口服二甲双胍（850 mg，每日2次）治疗至少6个月。治疗可延长至12个月直至达到完全缓解（CR），每3个月进行一次随访宫腔镜检查和刮宫术。对所有达到CR的患者，采用免疫组织化学法检测子宫内膜中IGFBP - rP1、p - Akt和p - AMPK的表达。
共有58例患者完成治疗。治疗9个月后，联合治疗组23例（76.7%）患者和对照组20例（71.4%）患者达到CR；对照组2例患者在转为联合治疗后达到CR。对照组和联合治疗组的复发率差异无统计学意义（30.0% 对22.7%，P > 0.05）。对照组10例（35.7%）患者体重显著增加5.7±6.1 kg，而接受联合治疗的患者均未出现显著体重变化。与对照组相比，接受联合治疗的患者子宫内膜中IGFBP - rP1和p - AMPK表达增强，p - Akt表达降低。
二甲双胍联合MA可能为AEH和1期IA级EAC的保留生育功能治疗提供有效选择，二甲双胍在控制MA引起的体重增加、促进子宫内膜中IGFBP - rP1和p - AMPK表达同时抑制p - Akt表达方面的临床益处值得进一步研究。
