Sun A, Lin S, Wei Y
Department Obstetrical and Gynecological, Peking Union Medical College Hospital, Beijing 100730, China.
Zhonghua Yi Xue Za Zhi. 2001 Nov 10;81(21):1291-4.
To observe the influence of percutaneous estradiol + micronized progesterone or medroxyprogesterone on endometrium and vaginal bleeding in Chinese post-menopausal women.
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.
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.
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.
观察经皮雌二醇+微粒化孕酮或甲羟孕酮对中国绝经后女性子宫内膜及阴道出血的影响。
设计一项为期3年的开放随机临床研究。雌激素和孕激素采用连续联合的周期用药方案。将经皮雌二醇作为雌激素，微粒化孕酮（MP）和甲羟孕酮（MPA）作为孕激素。招募60名健康女性（自然绝经1至5年），分为四组。用药方案如下：（1）第1组（G1，E2 1.5+MP）：经皮雌二醇凝胶（凝胶），含17β-雌二醇（E2）1.5 mg/d加微粒化孕酮（MP）100 mg/d；（2）第2组（G2，E2 1.5+MPA）：凝胶，E2 1.5 mg/d加醋酸甲羟孕酮（MPA）2 mg/d；（3）第3组（G3，E2 0.75+MP）：凝胶，E2 0.75 mg/d加MP 100 mg/d；（4）第4组（G4，E2 0.75+MPA）：凝胶，E2 0.75 mg/d加MPA 2 mg/d。均每月给药25天，停药5天。在第0、12、24和36个月进行经阴道超声检查，测量子宫内膜厚度。在第24或36个月通过 Pipelle 管进行子宫内膜活检，并记录阴道出血情况。
59例患者（98.3%）完成1年治疗，56例患者（93.3%）完成2年治疗，51例（85%）完成3年治疗。子宫内膜无明显变化。四组治疗前子宫内膜厚度分别为0.25 cm、0.27 cm、0.22 cm、0.28 cm，治疗后分别为0.37 cm、0.30 cm、0.326 7 cm和0.3 cm。四组间差异无统计学意义（P>0.05）。53例患者进行了 Pipelle 活检。病理结果显示：增殖期16例（25.8%），分泌期1例（1.6%）；萎缩期11例（17.7%）；混合细胞期23例（37.1%）；有增生倾向2例（3.2%）。治疗期间，G2组阴道不规则出血率最高，G3组最低。
每日含0.75 mg和1.5 mg E2的雌激素分别联合100 mg孕酮和2 mg甲羟孕酮不会显著增加子宫内膜厚度。联合100 mg微粒化孕酮时阴道出血率较低。添加天然孕酮可降低出血率并提高激素替代疗法的依从性。
