Barrett-Connor E, Slone S, Greendale G, Kritz-Silverstein D, Espeland M, Johnson S R, Waclawiw M, Fineberg S E
Department of Family and Preventive Medicine, University of California, San Diego, La Jolla 92093-0607, USA.
Maturitas. 1997 Jul;27(3):261-74. doi: 10.1016/s0378-5122(97)00041-8.
To assess the efficacy of unopposed estrogen, and three estrogen/progestin regimens on selected heart disease risk factors among adherent women and to contrast those results with efficacy among all women in the PEPI study.
A 3-year, multicenter, randomized, double-blinded, placebo-controlled clinical trial.
A total of 847 healthy postmenopausal women aged 45 to 64 years of age with no known contraindication to hormone therapy, who attended their 36 month clinical visit.
Participants were randomized in equal numbers to one of the following treatments: (1) placebo; (2) conjugated equine estrogen (CEE) 0.625 mg daily; (3) CEE 0.625 daily plus medroxyprogesterone acetate (MPA) 10 mg, days 1-12; (4) CEE 0.625 daily plus MPA 2.5 mg daily; or (5) CEE 0.625 daily plus micronized progesterone (MP) 200 mg, days 1-12.
Analyses are based on adherent women, where adherence is defined as taking at least 80% of pills at each 6-month visit.
Adherence rates were high in all groups except women with a uterus assigned to unopposed CEE. The difference in HDL-C levels resulting from the CEE vs. CEE+MP was approximately three times larger than in the intent-to-treat analyses, reaching statistical significance (P < 0.05). In each active treatment, LDL-C decreased 10-15%. Triglycerides increased 15-20% in each opposed CEE arm and over 25% in the CEE only arm; this difference was not statistically significant. Fibrinogen increased by 7% among placebo adherers, but decreased or remained fairly stable among the active arm adherers. Systolic blood pressure increased 3-5% in all treatment arms. Women adherent to the CEE+MPA arms had twice the increase of 2 h glucose levels as women adherent to CEE only, or CEE+MP (8-9% vs. 3-4%). Two-hour insulin levels decreased 3-12% for all arms. The patterns of change for fibrinogen, SBP, 2 h glucose and insulin were similar to those from the intent-to-treat analyses.
In analyses limited to adherent women, all active treatments, compared to placebo, continued to have similar and favorable effects on LDL-cholesterol and fibrinogen and no significant effects on blood pressure or insulin levels. Given the overall high adherence rates in PEPI, the results are similar to the intent-to-treat analyses, as expected. Only the trend of HDL-C to have a larger increase in the CEE only arm (in the intent-to-treat analyses) gained statistical significance in analyses restricted to adherers.
评估单纯雌激素以及三种雌激素/孕激素方案对坚持服药女性特定心脏病风险因素的疗效，并将这些结果与PEPI研究中所有女性的疗效进行对比。
一项为期3年的多中心、随机、双盲、安慰剂对照临床试验。
共有847名年龄在45至64岁之间、无已知激素治疗禁忌症且参加了36个月临床随访的健康绝经后女性。
参与者被等数随机分为以下治疗组之一：（1）安慰剂；（2）每日服用0.625毫克结合马雌激素（CEE）；（3）每日服用0.625毫克CEE加第1至12天服用10毫克醋酸甲羟孕酮（MPA）；（4）每日服用0.625毫克CEE加每日服用2.5毫克MPA；或（5）每日服用0.625毫克CEE加第1至12天服用200毫克微粒化孕酮（MP）。
分析基于坚持服药的女性，坚持服药定义为在每次为期6个月的随访中至少服用80%的药丸。
除了被分配接受单纯CEE治疗的有子宫的女性外，所有组的服药依从率都很高。CEE与CEE+MP导致的高密度脂蛋白胆固醇（HDL-C）水平差异比意向性分析中的差异大约大三倍，达到统计学显著性（P<0.05）。在每种活性治疗中，低密度脂蛋白胆固醇（LDL-C）降低了10%-15%。在每种加用孕激素的CEE治疗组中甘油三酯升高了15%-20%，在单纯CEE治疗组中升高超过25%；这种差异无统计学显著性。安慰剂组坚持服药者的纤维蛋白原升高了7%，但在活性治疗组坚持服药者中降低或保持相当稳定。所有治疗组的收缩压升高了3%-5%。坚持服用CEE+MPA治疗组的女性2小时血糖水平升高幅度是仅坚持服用CEE或CEE+MP女性的两倍（8%-9%对3%-4%）。所有组的2小时胰岛素水平降低了3%-12%。纤维蛋白原、收缩压、2小时血糖和胰岛素的变化模式与意向性分析中的相似。
在仅限于坚持服药女性的分析中，与安慰剂相比，所有活性治疗对LDL胆固醇和纤维蛋白原仍有相似且有利的影响，对血压或胰岛素水平无显著影响。鉴于PEPI总体服药依从率较高，结果与意向性分析相似，正如预期的那样。仅在仅限于坚持服药者的分析中，单纯CEE治疗组HDL-C有更大升高的趋势（在意向性分析中）获得了统计学显著性。
