周期联合经皮雌二醇与口服孕激素缓解更年期症状的比较研究

A comparison study of the effects and the side-effects of cyclic percutaneous estradiol combined oral progesterone on climacteric symptoms

目的比较两种经皮雌二醇剂量长期周期联合口服孕激素缓解更年期症状的疗效。方法 4年的随机开放平行组设计试验研究。雌激素为经皮17-β雌二醇(E_2)凝胶,口服孕激素为微粉化天然黄体酮(MP)与甲羟孕酮(MPA)。60名绝经早期妇女随机分为4组:G1:E_2 1.5 mg/d+MP100 mg/d;G2:E_2 1.5 mg/d+MPA2 mg/d;G3:E_2 0.715 mg/d+MP100 mg/d;G4:E_2 0.75 mg/d+MPA 2 mg/d。每周期连用25 d,停药5 d。按量表对主要观察指标包括更年期症状,以及乳房胀痛、阴道出血等方面不良反应进行评分。结果用药后,所有更年期症状均显著改善(P<0.01),用药3个月已降至较低水平,此后一直维持较低水平。其中血管舒缩、睡眠及情绪症状分下降较快而性症状分下降较慢(P<0.01)。更年期症状总分及各因子得分值及变化趋势均无显著组间差异(P=0.25～0.91)。但在用药1年内,1.5 mgE_2组和MP100 mg组的症状分改善率略高(P=0.26～0.96)。乳房胀痛分在用药期间随用药时间延长有所下降(P<0.01);1.5 mg E_2组显著高于0.75 mg E_2(P<0.01)。用药期间均无严重乳腺疾病发生。MP 100 mg/d组不规则阴道出血发生率显著低于MPA 2 mg/d组(P<0.01)。结论 0.75 mg及1.5 mg两种经皮雌二醇剂量长期周期连续联合不同孕激素均可有效改善更年期症状,且血管舒缩、睡眠及情绪症状较性症状改善更早。1.5 mg E_2缓解症状可能更迅速,但乳房胀痛及阴道不规则出血率的发生较低剂量组严重。联合MP 100 mg/d在避免阴道不规则出血和用药早期乳房胀痛方面优于MPA 2 mg/d。临床应用应个体化。

Objective： To compare the long-term effects and side-effects of treatment with cyclic percutaneous estradiol （1.5 mg/d or 0.75 rag/d） combined with two kinds of oral progesterone on climacteric symptoms. Methods： A 4-year open, randomized, parallel-group clinical trial was designed. The percutaneous 17/3-estradiol （E2） gel was used in a cyclic regimen combined with micronized progesterone （MP） or medroxyprogesterone acetate （MPA）. Sixty early postmenopausal women were randomly assigned into 4 groups： GI： E2 1.5 ＋MP100; G2： E2 1.5 ＋MPA 2; G3. E2 0.75 ＋MP 100; G4： E2 0.75 ＋MPA 2 （all doses in rag/d）. All were given for 25 d/month, and 5 days free. Main measurements included climacteric symptoms scale, breast pain and vaginal bleeding. Results： All the climacteric symptoms were alleviated by the treatment （P〈0.01）. The scores of the vasomotor and sleep factor and emotional factor decreased faster than the sex factor （P〈0.01）. There were no significant differences between groups in the change of the total score and the score of each factor.While the groups with 1.5 mg E2 and the groups with MP100 mg had percentage change in the first year （P=0. 26-0. 96）. As for breast pain, the score decreased with the treatment year （P〈0.01）. The groups of 1.5 mg E2 had more breast pain than 0.75rag E2 （P〈0. 01）. There was no serious disease of breast during the treatment. The occurrence of unscheduled vaginal bleeding in the groups with MP100mg was lower （P〈0. 01）. Conclusion： Both 0. 75 mg and 1.5 mg percutaneous estradiol combined with different progesterone could relieve climacteric symptoms, and the vasomotor, sleep and emotional symptoms were relieved faster. 1.5 mg E2 may reduce the symptoms more rapidly. There were less breast pain in the early treatment and unscheduled vaginal bleeding in the group with 0.75 mg E2 and when E2 combined with 100 mg MP. We should consider individualized HT in clinical practice.