Universidad de Alcalá, Madrid, Spain.
Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Madrid, Spain.
Hum Reprod Update. 2023 Nov 2;29(6):741-772. doi: 10.1093/humupd/dmad015.
Current knowledge about the consequences of PCOS during the late reproductive years and after menopause is limited.
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.
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.
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.
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.
目前关于多囊卵巢综合征（PCOS）在女性晚生育期和绝经后时期的后果的知识有限。
我们对≥45 岁围绝经期或绝经后患有 PCOS 的妇女的病理生理学、临床表现、诊断、预后和治疗进行了系统评价和荟萃分析。
截至 2023 年 4 月 15 日，通过 Entrez-PubMed、EMBASE 和 Scopus 在线设施，对已发表的研究进行了检索。我们纳入了报告围绝经期或绝经后患有 PCOS 的患者和平均年龄≥45 岁的对照女性的数据的横断面或前瞻性研究。三名独立研究人员进行了数据提取。由于研究设计和用于定义 PCOS 的标准存在差异等混杂因素，因此使用随机效应模型对定量数据进行了荟萃分析。敏感性分析将荟萃分析限制在基于人群的研究、仅包括使用最广泛接受的 PCOS 定义诊断的患者的研究、仅包括绝经后妇女或仅包括未接受卵巢手术的妇女的研究，以及患者和对照的体重过度指数相似的研究。使用 GRADE 系统评估证据质量。
最初的搜索确定了 1400 篇文章，另外从纳入文章的参考文献中又纳入了 6 篇；删除了 476 篇重复的文章。由于不同的原因，我们排除了 868 篇文章，留下 37 篇有效研究进行定性综合分析，其中 28 篇研究（发表在 41 篇文章中）被纳入定量综合分析和荟萃分析。另外 9 项研究仅在定性分析中被纳入。与对照组相比，患有 PCOS 的围绝经期或绝经后妇女的循环总睾酮（标准化均数差，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））升高，而其性激素结合球蛋白减少（SMD-0.60（-0.76，-0.44））。患有 PCOS 的妇女的 BMI（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））以及稳态模型评估的胰岛素抵抗（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））和糖尿病的比值比（OR，95%CI）（OR 3.01（1.91，4.73））都高于对照组。与对照组相比，患有 PCOS 的妇女的高密度脂蛋白（HDL）浓度降低（SMD-0.32（-0.46，-0.19）），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 与对照组相似。与对照组相比，患有 PCOS 的妇女的高血压 OR 升高（OR 1.79（1.36，2.36））。尽管患有 PCOS 的妇女心肌梗死（OR 2.51（1.08，5.81））和中风（OR 1.75（1.03，2.99））的发生率高于对照组，但患者和对照组的心血管疾病、冠状动脉疾病、乳腺癌和绝经年龄的 OR 相似。当将荟萃分析限制在 PCOS 患者和对照组的女性具有相似平均 BMI 的研究中时，唯一保留统计学意义的差异是前者的 HDL-胆固醇浓度降低，而在两项 PCOS 绝经后妇女和对照组具有相似 BMI 的研究中，患者的血清雄激素浓度升高，表明绝经后仍存在高雄激素血症，无论肥胖与否。
在患有 PCOS 的女性中，高雄激素血症似乎在晚生育期和绝经后持续存在。大多数心血管代谢合并症是由体重过度和 PCOS 的共同存在驱动的，突出了针对该人群肥胖的重要性。然而，纳入研究之间存在显著的异质性，以及这里收集的证据总体质量较低，使得我们无法就这个问题得出明确的结论。因此，对于这些女性的适当管理，肯定需要从充分的、有针对性的前瞻性研究中获得指南。
