目的:观察经皮雌二醇+微粒化孕酮或甲羟孕酮对绝经后妇女子宫内膜及阴道出血的影响。
方法:设计了一项为期3年的开放随机临床研究。雌激素和孕激素在循环方案中连续组合使用。经皮雌二醇被认为是雌激素。以微孕酮(MP)和甲羟孕酮(MPA)作为孕激素。招募了60名健康妇女(自然绝经1至5年),分为四组。方案如下:(1)经皮雌二醇凝胶(凝胶),含1.5mg的17β-雌二醇(E2)/d加微粉化孕酮(MP)100mg/d在第1组(G1,E21.5MP);(2)凝胶,1.5mgE2/d加醋酸甲羟孕酮(MPA),2mg/d(G2,E21.5+MPA);(3)凝胶,0.75mgE2/d加MP,第3组100mg/d(G3,E20.75+MP);和(4)凝胶,0.75mgE2/d加MPA,第4组2mg/d(G4,E20.75+MPA)。全部给予25d/月,5天免费经阴道超声检查0、12、24和36个月。测量子宫内膜厚度。在第24个月或第36个月进行Pipelle管子宫内膜活检。记录阴道出血情况。
结果:59名患者(98.3%)完成1年,56名患者(93.3%)完成2年,51(85%)为3年。子宫内膜无明显改变。四组治疗前子宫内膜厚度为0.25cm,0.27cm,0.22cm,0.28厘米,治疗后0.37厘米,0.30cm,0.3267厘米和0.3厘米。四组间无明显差别(P>0。05).53例患者接受了Pipelle活检。病理结果显示:16例(25.8%)增生,秘书1例(1.6%);萎缩11例(17.7%);混合细胞23例(37.1%);倾向增生2例(3.2%)。在治疗过程中,阴道不规则出血率G2最高,G3最低.
结论:每日含有0.75mg和1.5mgE2的雌激素与100mg孕酮和2mg甲羟孕酮联合使用不会显着增加子宫内膜厚度。与100mg微粉化孕酮联合使用时,阴道出血率低。添加天然黄体酮可以降低出血率,提高HRT依从性。
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 1 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 beta-estradiol (E2)/d plus micronized progesterone (MP) 100 mg/d in group 1 (G1, E2 1.5 + MP); (2) gel, 1.5 mg E2/d plus
medroxyprogesterone acetate (MPA), 2 mg/d in group 2 (G2, E2 1.5 + MPA); (3) gel, 0.75 mg E2/d plus MP, 100 mg/d in group 3 (G3, E2 0.75 + MP); and (4) gel, 0.75 mg E2/d plus MPA, 2 mg/d in group 4 (G4, E2 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 Pipelle 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 7 cm and 0.3 cm respectively. No significant differences was found in four groups (P > 0. 05). Fifty -three patients had the Pipelle 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 hyperplasia in 2 cases (3.2%). During the treatment, the vaginal irregular bleeding rate was highest in G2 and lowest in G3.
CONCLUSIONS: Daily estrogen containing 0.75 mg and 1.5 mg E2 combined with 100 mg progesterone and 2 mg
medroxyprogesterone do not increase the thickness of endometrium significantly. The vaginal bleeding rate was low when combined with 100 mg micronized progesterone. Addition of natural progesterone will low down the bleeding rate and improve the HRT compliance.