低剂量与标准剂量结合雌激素联合天然孕酮或地屈孕酮治疗围绝经期综合征的疗效观察

目的:研究低剂量结合雌激素(CEE)与标准剂量CEE联合天然孕酮或地屈孕酮治疗围绝经期综合征的疗效比较。方法:本试验为单中心、前瞻性随机对照试验,2014年2月至2015年12月招募绝经早期有子宫、有绝经相关症状的妇女(共107例完成试验),随机分为3组:A组35例(低剂量CEE+天然孕酮)、B组37例(标准剂量CEE+天然孕酮)、C组35例(标准剂量CEE+地屈孕酮),采用连续序贯方案治疗12个周期,在第3、6、9、12周期结束后记录改良Kupperman评分,计算有效率,用药前与用药后抽血测定卵泡刺激素(FSH)、雌二醇(E2)。结果:在治疗3个周期后,改良Kupperman评分值均显著性下降(P均0.01),3组间的完全缓解率、显效率差异均无统计学意义,但B组有效率(89.2%)显著高于A组(60%,P=0.024)和C组(61.9%,P=0.035)。治疗结束后,3组的完全缓解率、显效率、有效率差异均无统计学意义(P0.05)。治疗结束后与治疗前比,3组的FSH值均有显著性降低(P0.001),E2值均显著性升高(P0.001)。治疗结束后,3组FSH值比较差异无统计学意义(P=0.26);E2值A组显著低于B组(P=0.002)及C组(P=0.004),B组与C组比较差异无统计学意义(P=0.832)。不良反应主要为阴道不规则流血和乳房胀痛,A、B、C组阴道不规则流血的发生率分别为20.91%、39.51%、19.99%,B组显著高于A与C组(PAB=0.034,PBC=0.015),A组与C组比较差异无统计学意义;乳房胀痛的发生率A、B、C组分别为30.22%、37.46%、68.06%,A、B两组差异无统计学意义,C组显著高于A、B组(PAC=0.008,PBC=0.002)。结论:低剂量雌激素补充已可满足大部分患者缓解围绝经期综合征的需求,加用天然孕酮比加用地屈孕酮对围绝经期症状的缓解作用更显著。

Effect of Low-dose or Standard-dose Conjugated Equine Estrogen Combined with Natural Progesterone or Dydrogesterone on Menopausal Syndrome

Objective:To explore the effect of low-dose conjugated combined estrogen (CEE) or standard-dose CEE combined with natural progesterone (P) or dydrogesterone (D) on menopausal syndrome.Methods:This was a single center,prospective,randomized controlled trial.Early menopausal women who complained of menopausal symptoms were recruited and randomized into 3 groups:group A (low-dose CEE + P),group B (standard dose CEE + P),group C(standard dose CEE + D).Using continuous sequential regimen,the duration of intervention was 12 cycles.Modified Kupperman index score was recorded after cycle 3,6,9,12.Effective rates were calculated and the changes of FSH,E2 were determined.The statistics analysis methods were t test,ANOVA and Chi-square test.Results:107 cases completed the trial.After 3 cycles of treatment,Kupperman index decreased significantly in all the 3 groups(P ＜0.01).The complete remission rate,marked remission rate were comparable among the 3 groups.The effective rate in group B was significantly higher than group A(89.2％ vs 60％,P=0.024) and group C(89.2％ vs 61.9％,P =0.035).After 12 cycles of treatment,the complete remission rate,marked remission rate and effective rate were comparable among 3 groups(P ＞0.05).The FSH levels were significantly decreased in all of the 3 groups after treatment and with no significance was observed.The E2 levels were significantly increased after treatment in all of the 3 groups.The level in group A was significantly lower than group B(P=0.002) and group C(P=0.004).There was no significant difference between group B and group C (P =0.832).The most common adverse reactions were irregular vaginal bleeding and breast tenderness.The incidence of irregular vaginal bleeding was 20.91％,39.51％ and 19.99％ in group A,group B and group C,group B was higher than group A and group B(PAB =0.034,PBC =0.015).The incidence of breast tenderness in the 3group was 30.22％,37.46％ and 68.06％,group C was higher than group A and B(PAC =0.008,PBC =0.002).Conclusions:Low-dose CEE can meet the need of most patients with menopausal syndrome.The effect is more obviously that adding natural progesterone ratio dydrogesterone.