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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绝经过渡期和绝经后 PCOS：系统评价和荟萃分析


背景 目前关于 PCOS 在生育晚期和绝经后后果的了解有限。客观和基本原理 我们对 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评价和荟萃分析。检索方法 考虑了由 Entrez-PubMed、EMBASE 和 Scopus 在线设施确定的截至 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，这些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 的标准以及其他混杂因素的差异导致异质性。敏感性分析将meta分析限制在基于人群的研究，仅包括使用最广泛接受的PCOS定义诊断的患者，仅更年期妇女或仅未接受卵巢手术的妇女，以及患者和对照组具有相似的体重超标指标的研究。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 篇文章来自纳入文章的参考文献列表;删除了 476 个重复项。出于不同的原因，我们排除了 868 篇文章，留下 37 篇有效的研究用于定性综合，其中 28 项研究（发表在 41 篇文章中）被考虑用于定量综合和荟萃分析。另外 9 项研究仅纳入定性分析。 与对照组相比，患有 PCOS 的围绝经期和绝经后患者循环总睾酮 （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， 0.94）） 增加，而他们的性激素结合球蛋白降低 （SMD -0.60 （-0.76， -0.44））。患有 PCOS 的女性表现出 BMI 增加 （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）） 以及胰岛素抵抗 （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）） 和比值比 （OR， 95% CI） 的稳态模型评估增加糖尿病 （OR 3.01 （0.27， 0.84））、空腹血糖 （SMD 0.48 （0.29， 0.68）） 和比值比 （OR， 95% CI） （OR 3.01 （1.91， 4.73）） 与对照组相比。与对照组相比，患有 PCOS 的女性显示 HDL 浓度降低 （SMD -0.32 （-0.46， -0.19）） 和甘油三酯增加 （SMD 0.31 （0.16， 0.46）），即使总胆固醇和 LDL 浓度以及血脂异常的 OR 与对照组相似。与对照组相比，PCOS 女性患高血压的 OR 增加 （OR 1.79 （1.36， 2.36））。尽管心肌梗死 （OR 2.51 （1.08， 5.81）） 和中风 （OR 1.75 （1.03， 2.99）） 在 PCOS 女性中比对照组更普遍，但整体心血管疾病、整体冠状动脉疾病、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 女性和对照组女性平均 BMI 相似的研究时，唯一保持统计学意义的差异是前者 HDL-胆固醇浓度降低，而在两项研究中，患有 PCOS 的绝经后女性和对照组具有相似的 BMI，患者表现为血清雄激素浓度升高， 表明无论肥胖与否，绝经后雄激素过多症仍然存在。更广泛的影响 多雄激素血症似乎在 PCOS 女性的育龄晚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 PCOS 频繁共存驱动的，这凸显了针对该人群肥胖的重要性。然而，纳入研究之间的显著异质性，以及这里收集的证据总体质量低，无法就该问题得出明确的结论。因此，绝对需要从有足够把握度的前瞻性研究中得出的指南来适当管理这些女性。