Batulan Zarah, Maarouf Nadia, Shrivastava Vipul, O'Brien Edward
1Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Health Research Innovation Centre, GB42, 3280 Hospital Dr NW, Calgary, AB T2N 4Z6 Canada.
Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, Health Research Innovation Centre, Room GAA16, 3280 Hospital Drive NW, Calgary, AB T2N 4Z6 Canada.
Womens Midlife Health. 2018 Apr 27;4:7. doi: 10.1186/s40695-018-0037-y. eCollection 2018.
Some women with genetic risk of breast and/or ovarian cancer (e.g., BRCA1/2) opt to undergo prophylactic salpingo-oophorectomy (PSO, or surgical removal of the ovaries & fallopian tubes) in order to reduce their risk of cancer. As a consequence, these women experience "surgical menopause" - accompanied by more severe climacteric symptoms that occur in a much shorter time frame. While the risk of coronary artery disease (CAD) rises with menopause, little is known about how the sudden loss of ovarian function from PSO alters the whole-body physiology, and whether it predisposes women to premature CAD.
METHODS/DESIGN: To manage CAD risk there is a prerequisite for reliable biomarkers that can help guide risk assessment and therapeutic interventions. To address these needs, this prospective, observational cohort study will evaluate surrogate markers reflective of CAD health in women experiencing surgical menopause after PSO. Twenty women representing each of the following groups will be enrolled over 3 years (total participants = 240): (i) pre-menopausal PSO, (ii) post-menopausal PSO, (iii) pre-menopausal women undergoing other pelvic surgery, and (iv) pre-menopausal controls (no surgery). All participants will provide blood plasma samples pre- and 1, 3, 6, & 12 months post-operatively, with serial samples collectively assessed for measurements of the study's primary endpoints of interest. These include a hormone profile (estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), and progesterone) and both conventional (lipid profile) and novel biomarkers (Heat Shock Protein 27 (HSP27), HSP27-antibodies (HSP27 Ab), proprotein convertase subtilisin/kexin 9 (PCSK9), inflammatory cytokines) of CAD. Another aspect of this study is the measurement and analysis of retinal vessel diameters - an emerging physiological parameter reflective of CAD risk. Finally, a patient engagement exercise will result in the drafting of patient-generated questionnaires that address the well-being and health concerns of these women as they transition through premature menopause and work with our research team to identify and discuss their health priorities.
The protocol of our planned study investigating the effects of PSO on CAD is described herein. Characterization of novel CAD markers in women experiencing surgical menopause will yield new insights into the role of the functional ovary in modulating lipid parameters and other CAD risk factors such as HSP27 and HSP27 Ab.
一些有乳腺癌和/或卵巢癌遗传风险的女性（例如，携带BRCA1/2基因）选择接受预防性输卵管卵巢切除术（PSO，即手术切除卵巢和输卵管）以降低患癌风险。结果，这些女性经历了“手术绝经”，伴随着更严重的更年期症状，且这些症状在更短的时间内出现。虽然冠状动脉疾病（CAD）的风险会随着绝经而上升，但对于PSO导致的卵巢功能突然丧失如何改变全身生理机能，以及它是否会使女性易患过早发生的CAD，我们却知之甚少。
方法/设计：为了管理CAD风险，需要有可靠的生物标志物来帮助指导风险评估和治疗干预。为满足这些需求，这项前瞻性观察队列研究将评估PSO术后经历手术绝经的女性中反映CAD健康状况的替代标志物。在3年时间内将招募代表以下每组的20名女性（总参与者 = 240名）：（i）绝经前PSO组，（ii）绝经后PSO组，（iii）接受其他盆腔手术的绝经前女性，以及（iv）绝经前对照组（未手术）。所有参与者将在术前以及术后1、3、6和12个月提供血浆样本，对系列样本进行集体评估，以测量研究的主要关注终点。这些终点包括激素谱（雌二醇、促卵泡激素（FSH）、促黄体生成素（LH）和孕酮）以及CAD的传统（血脂谱）和新型生物标志物（热休克蛋白27（HSP27）、HSP27抗体（HSP27 Ab）、前蛋白转化酶枯草溶菌素/kexin 9（PCSK9）、炎性细胞因子）。本研究的另一个方面是测量和分析视网膜血管直径，这是一个反映CAD风险的新兴生理参数。最后，一项患者参与活动将促成患者生成问卷的起草，这些问卷涉及这些女性在经历过早绝经过程中的幸福感和健康问题，并与我们的研究团队合作，以确定和讨论她们的健康优先事项。
本文描述了我们计划开展的研究PSO对CAD影响的方案。对经历手术绝经的女性中的新型CAD标志物进行特征分析，将为功能性卵巢在调节脂质参数以及其他CAD风险因素（如HSP27和HSP27 Ab）中的作用带来新的见解。
