BACKGROUND Current knowledge about the consequences of PCOS during the late reproductive years and after menopause is limited. OBJECTIVE AND RATIONALE We performed a systematic review and meta-analysis of data on the pathophysiology, clinical manifestations, diagnosis, prognosis, and treatment of women ≥45 years of age—peri- or postmenopausal—with PCOS. SEARCH METHODS Studies published up to 15 April 2023, identified by Entrez-PubMed, EMBASE, and Scopus online facilities, were considered. We included cross-sectional or prospective studies that reported data from peri- or postmenopausal patients with PCOS and control women with a mean age ≥45 years. Three independent researchers performed data extraction. Meta-analyses of quantitative data used random-effects models because of the heterogeneity derived from differences in study design and criteria used to define PCOS, among other confounding factors. Sensitivity analyses restricted the meta-analyses to population-based studies, to studies including only patients diagnosed using the most widely accepted definitions of PCOS, only menopausal women or only women not submitted to ovarian surgery, and studies in which patients and controls presented with similar indexes of weight excess. Quality of evidence was assessed using the GRADE system. OUTCOMES The initial search identified 1400 articles, and another six were included from the reference lists of included articles; 476 duplicates were deleted. We excluded 868 articles for different reasons, leaving 37 valid studies for the qualitative synthesis, of which 28 studies—published in 41 articles—were considered for the quantitative synthesis and meta-analyses. Another nine studies were included only in the qualitative analyses. Compared with controls, peri- and postmenopausal patients with PCOS presented increased circulating total testosterone (standardized mean difference, SMD 0.78 (0.35, 1.22)), free androgen index (SMD 1.29 (0.89, 1.68)), and androstenedione (SMD 0.58 (0.23, 0.94)), whereas their sex hormone-binding globulin was reduced (SMD −0.60 (−0.76, −0.44)). Women with PCOS showed increased BMI (SMD 0.57 (0.32, 0.75)), waist circumference (SMD 0.64 (0.42, 0.86)), and waist-to-hip ratio (SMD 0.38 (0.14, 0.61)) together with increased homeostasis model assessment of insulin resistance (SMD 0.56 (0.27, 0.84)), fasting insulin (SMD 0.61 (0.38, 0.83)), fasting glucose (SMD 0.48 (0.29, 0.68)), and odds ratios (OR, 95% CI) for diabetes (OR 3.01 (1.91, 4.73)) compared to controls. Women with PCOS versus controls showed decreased HDL concentrations (SMD −0.32 (−0.46, −0.19)) and increased triglycerides (SMD 0.31 (0.16, 0.46)), even though total cholesterol and LDL concentrations, as well as the OR for dyslipidaemia, were similar to those of controls. The OR for having hypertension was increased in women with PCOS compared with controls (OR 1.79 (1.36, 2.36)). Albeit myocardial infarction (OR 2.51 (1.08, 5.81)) and stroke (OR 1.75 (1.03, 2.99)) were more prevalent in women with PCOS than controls, the ORs for cardiovascular disease as a whole, coronary artery disease as a whole, breast cancer and age at menopause, were similar in patients and controls. When restricting meta-analysis to studies in which women with PCOS and controls had a similar mean BMI, the only difference that retained statistical significance was a decrease in HDL-cholesterol concentration in the former and, in the two studies in which postmenopausal women with PCOS and controls had similar BMI, patients presented with increased serum androgen concentrations, suggesting that hyperandrogenism persists after menopause, regardless of obesity. WIDER IMPLICATIONS Hyperandrogenism appeared to persist during the late-reproductive years and after menopause in women with PCOS. Most cardiometabolic comorbidities were driven by the frequent coexistence of weight excess and PCOS, highlighting the importance of targeting obesity in this population. However, the significant heterogeneity among included studies, and the overall low quality of the evidence gathered here, precludes reaching definite conclusions on the issue. Hence, guidelines derived from adequately powered prospective studies are definitely needed for appropriate management of these women.

中文翻译：

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绝经过渡期间和绝经后的 PCOS：系统评价和荟萃分析

背景 目前关于 PCOS 在生育后期和绝经后的后果的知识有限。目的和基本原理我们对 45 岁以上（围绝经期或绝经后）PCOS 女性的病理生理学、临床表现、诊断、预后和治疗数据进行了系统回顾和荟萃分析。搜索方法 考虑了由 Entrez-PubMed、EMBASE 和 Scopus 在线设施识别的截至 2023 年 4 月 15 日发表的研究。我们纳入了横断面或前瞻性研究，报告了围绝经期或绝经后 PCOS 患者和平均年龄≥45 岁的对照女性的数据。三名独立研究人员进行了数据提取。定量数据的荟萃分析使用随机效应模型，因为研究设计和用于定义 PCOS 的标准的差异以及其他混杂因素导致了异质性。敏感性分析将荟萃分析限制于基于人群的研究、仅包括使用最广泛接受的 PCOS 定义诊断的患者、仅绝经期妇女或仅未接受卵巢手术的妇女的研究，以及患者和对照表现出相似症状的研究。体重超标指标。使用 GRADE 系统评估证据质量。结果 初步检索确定了 1400 篇文章，另外 6 篇文章包含在收录文章的参考文献列表中；删除了 476 个重复项。我们出于不同原因排除了 868 篇文章，留下 37 篇有效研究进行定性综合，其中 28 篇研究（发表在 41 篇文章中）被考虑进行定量综合和荟萃分析。另外九项研究仅纳入定性分析。与对照组相比，围绝经期和绝经后 PCOS 患者的循环总睾酮（标准化平均差，SMD 0.78（0.35，1.22））、游离雄激素指数（SMD 1.29（0.89，1.68））和雄烯二酮（SMD 0.58（0.23））增加, 0.94))，而性激素结合球蛋白减少 (SMD -0.60 (-0.76, -0.44))。患有 PCOS 的女性体重指数 (SMD 0.57 (0.32, 0.75))、腰围 (SMD 0.64 (0.42, 0.86)) 和腰臀比 (SMD 0.38 (0.14, 0.61)) 均有所增加，同时体内平衡模型评估也有所增加胰岛素抵抗 (SMD 0.56 (0.27, 0.84))、空腹胰岛素 (SMD 0.61 (0.38, 0.83))、空腹血糖 (SMD 0.48 (0.29, 0.68)) 和糖尿病比值比 (OR, 95% CI)与对照组相比，OR 3.01 (1.91, 4.73))。与对照组相比，患有 PCOS 的女性表现出 HDL 浓度降低 (SMD -0.32 (-0.46, -0.19)) 和甘油三酯升高 (SMD 0.31 (0.16, 0.46))，尽管总胆固醇和 LDL 浓度以及血脂异常的 OR与对照相似。与对照组相比，患有 PCOS 的女性患高血压的 OR 增加（OR 1.79 (1.36, 2.36)）。尽管心肌梗塞（OR 2.51（1.08，5.81））和中风（OR 1.75（1.03，2. 99)) 在患有 PCOS 的女性中比对照组更普遍，心血管疾病、冠状动脉疾病、乳腺癌和绝经年龄的 OR 在患者和对照组中相似。当将荟萃分析限制在 PCOS 女性和对照组平均 BMI 相似的研究中时，保留统计显着性的唯一差异是前者的 HDL 胆固醇浓度下降，而在绝经后 PCOS 女性的两项研究中，HDL 胆固醇浓度下降。与对照组的体重指数相似，患者的血清雄激素浓度升高，这表明，无论肥胖如何，绝经后高雄激素血症仍然存在。更广泛的影响 在患有多囊卵巢综合症的女性中，高雄激素血症似乎在生育后期和绝经后持续存在。大多数心脏代谢合并症是由体重超标和多囊卵巢综合征频繁共存引起的，这凸显了针对该人群肥胖的重要性。然而，纳入的研究之间存在显着的异质性，并且此处收集的证据总体质量较低，无法就该问题得出明确的结论。因此，为了对这些女性进行适当的管理，绝对需要从充分有力的前瞻性研究中得出的指导方针。