POSTMENOPAUSAL ESTROGEN & PROGESTIN INTERVENTION (PEPI) TRIAL

理由：绝经后雌激素/黄体酮干预（PEPI）试验包括875名参与者，在7个中心随访3年（123名随机分配，在霍普金斯中心随访）。该试验是一项随机、双盲、安慰剂对照的绝经后妇女激素治疗临床试验。PEPI的主要目的是评估无拮抗雌激素和雌激素联合循环或持续黄体酮治疗对四种不同生物/代谢系统的影响，这些系统已知会影响女性心血管风险，并被认为会随着绝经或雌激素治疗而改变。这些系统是：脂质代谢、血压、碳水化合物代谢和凝血/止血。PEPI的次要目的是评估不同替代方案对骨矿物质密度、子宫内膜和生活质量的影响，同时也监测对乳房的影响。这项研究是一项为期三年的观察性随访，旨在通过每年的临床访问和临时电话联系来监测PEPI妇女的任何延迟体验。方案：每年在他们随机加入PEPI试验的周年纪念日，参与者将被要求参加一次诊所访问。在这次访问中，他们将接受完整的身体检查和盆腔检查，如果他们有子宫，则进行子宫内膜活检（如果活检被拒绝或无法获得，将进行经阴道超声评估）。乳房x光检查也将在这个时候进行。测量身高、体重、腰臀围和静息血压。将完成评估生活质量、身体活动、吸烟和饮酒情况的调查问卷。在最后一次访问时（随机分配到PEPI后72个月），将对脊柱和髋关节进行骨矿物质密度评估。这些评价的工具和方案将与PEPI研究中使用的相同，并根据需要进行修改，以配合后续工作。在每次门诊访问后6个月，将进行临时电话联系，以确定是否有任何临时药物变化和/或临床疾病。在这个时候，参与者还将被问及是否有任何并发疾病，是否使用过任何过渡性雌激素和黄体酮，药物变化的原因，以及这些变化是否得到了医生的建议或批准。风险：PSFS是一项观察性研究，因此没有与药物或器械干预相关的风险。作为随访的一部分，参与者将被要求完成关于性功能和情绪的问卷调查，他们可能会觉得尴尬或不舒服。参与者将被允许在一个私人区域完成这些问卷。参与者还将通过乳房x光检查和骨骼扫描暴露在辐射中。这些手术的辐射暴露水平极低，每年进行乳房x光检查是该年龄组妇女的推荐临床治疗方法。那些有子宫的妇女也会被要求在每年的检查中进行子宫内膜活检。与此过程相关的风险包括出血、疼痛、痉挛、感染和子宫穿孔。

Rationale: The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial included 875 participants followed at seven centers for three years (123 were randomized and followed at the Hopkins center). This trial was a randomized, double-blind, placebo-controlled clinical trial of hormone treatment in postmenopausal women. The primary objective of PEPI was to assess the effect of unopposed estrogen and estrogen combined with cyclic or continuous progestin therapies on four different biologic/metabolic systems that are known to influence cardiovascular risk in women and believed to change with menopause or estrogen therapy. These systems were: lipid metabolism, blood pressure, carbohydrate metabolism, and coagulation/hemostasis. Secondary objectives of PEPI were to evaluate the effects of different replacement regimens on bone mineral density, endometrium, and quality of life, while also monitoring any effect on the breast. This study is a three year observational follow-up designed to monitor PEPI women for any delayed experiences by means of annual clinical visits with interim telephone contacts. Protocol: Annually on the anniversary date of their randomization into the PEPI trial, participants will be asked to attend a clinic visit. At this visit, they will receive a complete physical and pelvic examination with a Papanicolaou test and if they have a uterus, an endometrial biopsy (if a biopsy is refused or impossible to obtain, a transvaginal ultrasound evaluation will be performed). A mammogram will also be performed at this time. Height, weight, waist and hip girth, and resting blood pressure will be measured. Questionnaires will be completed assessing quality of life, physical activity, smoking and alcohol use. At the final visit (72 months after randomization into PEPI) a bone mineral density evaluation will be performed of the spine and hip. The instruments and protocols for these evaluations wil be the same as used in the PEPI study, modified as necessary to be relevant to the follow-up. An interim telephone contact will be made at 6 months after each clinic visit to ascertain any interim medication change and/or clinical illness. Participants will also be asked at this time about any intercurrent illness, any interim estrogens and progestins they have used, the reasons for any medication changes, and whether these changes were recommended or approved by their physician. Risks: The PSFS is an observational study and so has no risks associated with drug or device interventions. As part of this follow-up, participants will be asked to complete questionnaires regarding sexual functioning and moods, which they may find embarrassing or discomforting. Participants will be allowed to complete these questionnaires in a private area. Participants will also be exposed to radiation through mammograms and a bone scan. The levels of radiation exposure for these procedures is extremely low and annual mammography represents recommended clinicl treatment for women in this age group. Those women who have a uterus will also be asked to undergo an endometrial biopsy at the annual visit. The risks associated with this procedure include bleeding, pain, cramping, infection and perforation of the uterus.