POSTMENOPAUSAL ESTROGEN & PROGESTIN INTERVENTION (PEPI) TRIAL

理论基础：绝经后雌激素/孕激素干预(PEPI)试验包括在七个中心对875名参与者进行为期三年的跟踪(123人是随机的，在霍普金斯中心进行跟踪)。这项试验是一项关于绝经后妇女激素治疗的随机、双盲、安慰剂对照临床试验。PEPI的主要目标是评估非对立雌激素和雌激素与周期或持续孕激素治疗相结合对四种不同生物/代谢系统的影响，这些生物/代谢系统已知会影响女性的心血管风险，据信会随着更年期或雌激素治疗而改变。这些系统是：脂肪代谢、血压、碳水化合物代谢和凝血/止血。PEPI的次要目标是评估不同替代方案对骨密度、子宫内膜和生活质量的影响，同时还监测对乳房的任何影响。这项研究是一项为期三年的观察性随访，旨在通过临时电话接触每年一次的临床访问来监测佩皮族妇女是否有任何延迟的经历。协议：每年在他们随机进入PEPI试验的周年纪念日，参与者将被要求参加诊所访问。在这次访问中，他们将接受全面的身体和盆腔检查，并进行巴氏试验，如果他们有子宫，还将接受子宫内膜活检(如果活检被拒绝或无法获得，将进行经阴道超声检查)。此时还将进行乳房X光检查。将测量身高、体重、腰围和臀围以及静息血压。将完成调查问卷，评估生活质量、体育活动、吸烟和饮酒情况。在最后一次访问时(在随机进入PEPI后72个月)，将对脊柱和髋部进行骨密度评估。这些评估的工具和方案将与PEPI研究中使用的相同，并根据后续行动的需要进行必要的修改。每次就诊后6个月将进行临时电话联系，以确定是否有任何临时用药变化和/或临床疾病。参与者此时还将被问及任何并发疾病、他们使用过的任何临时雌激素和孕激素、任何药物变化的原因，以及这些变化是否得到他们的医生的建议或批准。风险：PSFS是一项观察性研究，因此不存在与药物或设备干预相关的风险。作为后续工作的一部分，参与者将被要求完成关于性功能和情绪的问卷，他们可能会觉得尴尬或不舒服。参与者将被允许在私人区域完成这些问卷。参与者还将通过乳房X光检查和骨骼扫描接受辐射。这些手术的辐射暴露水平非常低，每年一次的乳房X光检查代表着对这个年龄段的女性推荐的临床治疗。那些有子宫的妇女也将在每年的访问中被要求接受子宫内膜活检。与此相关的风险包括出血、疼痛、抽筋、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.