雌孕激素周期联合应用对阴道出血及子宫内膜的影响

A randomized case-control study on the influence of percutaneous estradiol and progestin in cyclic combined regimen on endometrium and vaginal bleeding pattern in Chinese early postmenopausal women

目的 探讨经皮用雌二醇凝胶联合应用孕激素 3年对绝经后阴道出血与子宫内膜的影响。方法 开放随机前瞻性研究 3年。周期联合并用雌孕激素。雌激素为经皮用雌二醇 (E2 )凝胶。孕激素为口服微粉化天然孕酮 (MP)和醋甲羟孕酮 (MPA)。将 6 0名绝经 1～ 5年妇女随机分 4组 :(1)E2 1.5mg/d +MP 10 0mg /d ;(2 )E2 1.5mg/d +MPA 2mg /d ;(3)E2 0 .75mg/d +MP 10 0mg /d ;(4 )E20 .75mg/d +MPA 2mg /d。每日睡前使用 ,每月连用 2 5d ,停药 5d后进入下一疗程。分别在用药 0、12、2 4与 36个月时进行阴道B超测量子宫内膜厚度。用药后 12～ 36个月进行子宫内膜的细胞学检查 ,在用药期间记录阴道出血情况。结果 (1)病例完成情况 :5 9名 (98.3% )完成 1年研究 ;5 6名(93 3% )完成两年研究 ,5 1名 (85 % )完成 3年研究。 (2 )子宫内膜厚度 :各时间点各组子宫内膜厚度在用药前后的差异均无显著性 (P >0 .0 5 )。 (3)子宫内膜细胞学检查 :共有 5 3例妇女接受了子宫内膜细胞学检查 ,其中增殖型 16例 ,占 2 5 .8% ,分泌型 1例 ,占 1 6 % ;萎缩型 11例 ,17.7% ;混合型 2 3例 ,占 37.1% ;有增生倾向细胞 2例 ,占 3.2 %。 (4 )阴道出血情况 :阴道不规律出血率组 2最高 ;组 3最低。随用药时间延长 ,出血率明显降低。

Objective To observe the influence of percutaneous estradiol + micronized progesterone or medroxyprogesterone on endometrium and vaginal bleeding in Chinese post menopausal women. Methods A 3 year open randomized clinical study was designed. The estrogen and progestin were used continuous combined together in a cyclic regimen. The percutaneous estradiol was regarded as estrogen. The microprogesterone (MP) and medroxyprogesterone (MPA) were served as progestin. Sixty healthy women (naturally menopausal for l to 5 years) were recruited and divided into four groups. The regimen as follows: (1) percutaneous estradiol gel (gel) containing 1.5 mg of 17 β estradiol (E 2)/d plus micronized progesterone (MP) 100 mg /d in group 1 (G1, E 2 1 5+MP); (2) gel, 1.5 mg E 2/d plus medroxyprogesterone acetate (MPA), 2 mg/d in group 2 (G2, E 2 1.5+MPA); (3) gel, 0.75 mg E 2/d plus MP, 100 mg/d in group 3 (G3, E 2 0.75+MP); and (4) gel, 0.75 mg E 2/d plus MPA, 2 mg/d in group 4 (G4, E 2 0.75+MPA) . All were given for 25 d/month, and 5 days free. The transvaginal sonography was performed 0, 12, 24 and 36 months. The thickness of endometrium were measured. The endometrium biopsy by Pipella tube was conducted at 24th or 36th months. The vaginal bleeding was recorded. Results Fifty nine patients (98.3%) finished 1 year and 56 patients(93.3%) for 2 years, 51 (85%) for 3 years. There was no significant changes of endometrium. The thickness of endometrium before treatment in four groups were 0.25 cm,0.27 cm,0.22 cm,0.28 cm and after treatment 0.37 cm,0.30 cm,0.326 7cm and 0.3 cm respectively. No significant differences was found in four groups ( P >0.05). Fifty three patients had the Pipella biopsy. The pathological result showed: 16 cases (25.8%) proliferated, 1 case (1 6%) secretary; 11 cases (17.7%) atrophy; 23 cases (37.1%) mixed cell; tendency to hyperplsia in 2 cases (3 2%). During the treatment,the vaginal irregular bleeding rate was highest in G2 and lowest in G3. Conclusions Daily estrogel containing 0.75 mg and 1.5 mg E 2 combined with 100 mg progesterone and 2 mg medroxyprogesterone do not increase the thickness of endometrium significantly. The vaginal bleeding rate was lowwhen combined with 100 mg micronized progesterone. Addition of natural progesterone will low down the bleeding rate and improve the HRT compliance.