不同剂量雌激素对重度宫腔黏连术后复发及月经的影响

Effects of different doses of estrogen on recurrence of severe intrauterine adhesion and menstrual outcomes after hysteroscopic adhesiolysis

目的探讨重度宫腔黏连（SIUA）患者宫腔镜下经宫颈宫腔黏连分离术（TCRA）后，应用不同剂量雌激素对黏连复发和月经的影响。方法选择2010年1月至2015年6月，于南京医科大学第一附属医院接受宫腔镜下TCRA的275例SIUA患者为研究对象。根据TCRA后雌激素治疗剂量，将其分为低剂量组（n=89）、中剂量组（n=82）、高剂量组（n=73）及对照组（χ2=31）。低、中、高剂量组TCRA后分别给予戊酸雌二醇3、6、9mg／d×21d联合醋酸甲羟孕酮10mg／dX5d治疗，对照组TCRA后未给予任何雌激素治疗。统计学分析4组患者年龄、孕次、产次、既往宫腔手术史、子宫内膜厚度、宫腔深度，治疗前、后美国生育协会（AFS）评分及月经情况，治疗后妊娠、不良反应情况及治疗疗效。结果①4组患者年龄、孕次、产次、既往宫腔手术史，以及TCRA前继发性闭经、月经量减少、继发不孕、复发性或稽留流产、周期性下腹痛、子宫内膜厚度及宫腔深度等一般临床资料比较，差异均无统计学意义（P〉0．05）。②不同剂量雌激素治疗前、后，4组AFS评分下降值比较，差异有统计学意义（F=43．750，P=0．000）；而低、中、高剂量组均较对照组显著增高，并且差异均有统计学意义（χ2=7．011、7．199、6．292，均为P=0．000）。低、中、高剂量组患者治疗前、后AFS评分下降值两两比较，治疗后4组患者月经恢复正常和月经量增多比例分别比较，以及治疗后低、中、高剂量组患者闭经或月经量过少比例两两比较，差异均无统计学意义（P〉0．05）。治疗后4组患者闭经或月经量过少比例比较，差异有统计学意义（χ2=39．490，P=0．000）。低、中、高剂量组患者闭经或月经量过少比例，均较对照组低，并且差异均有统计学意义（χ2=14．623、27．265、21．105，均为P=0．000）。③4组不良反应率比较，差异有统计学意义（χ2=37．182，P=0．000）。低、中、高剂量组不良反应率均较对照组高，高剂量组不良反应率高于低、中剂量组，并且差异均有统计学意义（P〈0．05）；低、中剂量组不良反应率比较，以及4组患者因不良反应导致停药率比较，差异均无统计学意义（P〉0．05）。④4组患者治疗总有效率比较，差异有统计学意义（χ2=39．490，P=0．000）。其中，低、中、高剂量组患者治疗总有效率，均较对照组高，差异均有统计学意义（P〈0．05）；低、中、高剂量组患者治疗总有效率分别两两比较，以及4组患者妊娠率比较，差异均无统计学意义（P〉0．05）。结论SIUA患者TCRA后，应用雌激素治疗，可有效减少SIUA复发，改善患者月经状况。不同剂量雌激素治疗SIUA患者，疗效无明显差异。

Objective To explore the effect of different doses of estrogen after transcervical resection of uterine adhesions （TCRA） on the recurrence and menstrual improvement of patients with severe intrauterine adhesion （SIUA）. Methods From January 2010 to June 2015, a total of 275 cases of patients with SIUA underwent TCRA by hysteroscopy in the First Affiliated Hospital of Nanjing Medical University were included as research subjects. According to the dose of estrogen after TCRA treatment, they were divided into 4 groups： low dose group （n=89）, moderate dose group （n=82）, high dose group （n=73） and control group （n=31）. Patients in low, moderate and high dose group received estradiol valerate 3, 6, 9 mg/d × 21 d, respectively and all combined with medroxyprogesterone acetate 10 mg/d ×5 d after TCRA. Patients in control group did not receive any estrogen after TCRA. The age, gravidity, parity, history of uterine surgery, endometrial thickness, uterine cavity depth, American Fertility Society （AFS） scores and menstruation before and after treatment, pregnancy, adverse reaction and treatment effects of four groups were analyzed by statistical methods. Results （DThere were no significant differences for the clinical data among the 4 groups such as ages, gravidities, parities, histories of uterine surgery, symptoms before TCRA by hysteroscopy including secondary amenorrhea, oligomenorrhea, secondary infertility, recurrent pregnancy loss, cyclic hypogastralgia, endometrial thickness and uterine cavity depth （P〉 0. 05）. （3）There was significant difference in the reduction of AFS scores before and after treatment among 4 groups （F=43. 750, P=0. 000）. The reduction of AFS scores before and after treatment in low, moderate, high dose group all were obviously higher than that in control group, and all the differences were statistically significant （t= 7. 011, 7. 199, 6.292; all P=0. 000）, but as to the multiple comparisons in low, moderate and high dose group, there were no significant differences （P〉0.05）. The improvement in menstruation as normal and increased menstruation after treatment showed no significant differences among the 4 groups （P〈0.05）, but there was statistical difference in the rate of oligomenorrhea and amenorrhea after treatment among the 4 groups （χ2 = 39. 490, P= 0. 000）. The rates of oligomenorrhea and amenorrhea after treatment in low, moderate and high dose group all were lower than that in the control group, and all the differences were statistically significant （χ2 = 14. 623, 27. 265, 21. 105 ; all P=0. 000）, but as to the multiple comparisons in low, moderate and high dose group, there were no significant differences （P〉0.05）. （3）There was significant difference in the rate of adverse reaction among 4 groups （χ2 = 37. 182, P= 0. 000）. And the rates of adverse reaction in low, moderate and high dose group all were higher than that in control group, the rate of adverse reaction in high dose group was higher than those in low and moderate group, and all the differences were statistically significant （P〈0. 05）. There was no statistical difference in the rate of adverse reaction between the tow and moderate group, and in the rate of drug withdrawal caused by adverse reaction among 4 groups （P〉0.05）. （4）There was significant difference in the total effective rate of treatment among 4 groups （χ2 = 39. 490, P= 0. 000）. And the total effective rates of treatment in low, moderate and high dose group all were higher than that in control group （P〈0.05）, but as to the multiple comparisons in low, moderate and high dose group, there were no significant differences （P〉0.05）. There was no significant difference in the pregnancy rate among 4 groups （P〉0.05）. Conelusions Conjugated estrogen treatment is effective to treat SIUA after TCRA, to reduce the reformation of SIUA and to improve menstruation of patients. Different doses of conjugated estrogen after the surgery do not affect the treatment effect of SIUA.