BACKGROUND Androgen excess is a key pathogenetic mechanism in polycystic ovary syndrome (PCOS), although hyperinsulinism also contributes to androgen secretion. Therapeutic approaches for adult patients not seeking fertility include combined oral contraceptives (COC), antiandrogens (AA) and/or insulin sensitizers, although these practices are supported by limited high-quality evidence. OBJECTIVE AND RATIONALE We aimed to assess the efficacy and safety of these common treatments for PCOS by conducting a meta-analysis of RCTs with the following review questions: Which is the more appropriate therapeutic approach for hyperandrogenic symptoms, hyperandrogenemia, and ovulatory dysfunction in adult women with PCOS not seeking fertility; What is the impact on classic cardiometabolic risk factors of the more common treatments used in those women; Does the combination of the antiandrogenic therapy plus metformin have any impact on efficacy or cardiometabolic profile? SEARCH METHODS We searched PubMed and EMBASE for articles published up to 16 September 2017. After deleting duplicates, the abstracts of 1522 articles were analysed. We subsequently excluded 1446 articles leaving 76 studies for full-text assessment of eligibility. Of them, 43 articles were excluded. Hence, 33 studies and 1521 women were included in the quantitative synthesis and in the meta-analyses. Meta-analyses calculated mean differences (MD), standardized mean differences (SMD), odds ratio (OR) and 95% CIs. Heterogeneity and inconsistency across studies was assessed by χ2 test and Higgins's I2 statistics. Quality and risk of bias of individual studies were assessed according to the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0. We then used the approach recommended by the Grading of Recommendations, Assessments, Development, and Evaluation (GRADE) group to indicate the global quality of evidence for a selection of primary outcomes. OUTCOMES Regarding efficacy, the MD in hirsutism score between COC and/or AA and metformin were not significant. The exclusion of one single study including most women with severe hirsutism yielded a significant effect in favour of COC and/or AA. When only those studies including an AA were compared with metformin, there were significant differences favouring antiandrogenic therapy. The combination of COC and/or AA with metformin was similar to COC and/or AA therapy alone in the whole group of patients. Post-intervention OR for the presence of regular menses favoured COC therapy. In terms of cardiometabolic impact, the MD in BMI were in favour of metformin. The negative effect of COC therapy on BMI was blunted by its combination with metformin. The MD in homoeostasis model assessment of insulin resistance (HOMA-IR) were also in favour of metformin therapy compared to COC and/or AA. The combination of COC and/or AA and metformin decreased MD in HOMA with respect to antiandrogenic therapy alone. There were no significant post-intervention SMD in circulating glucose levels between COC and/or AA and metformin. However, adding metformin to COC and/or AA yielded a beneficial effect on fasting glucose levels. Post-intervention OR for abnormal glucose tolerance showed no significant differences between COC and/or AA and metformin, although after excluding studies including an AA as a comparator (without COC) a significant effect in favour of metformin therapy was observed. There were no significant differences among therapies in lipid profile, blood pressure or prevalence of hypertension. The global quality of evidence was very low when addressing the impact of the treatments explored on prevalence of hypertension and lipid profiles, low in the case of hirsutism, BMI and blood pressure values, and high for endometrial protection and glucose tolerance. WIDER IMPLICATIONS These data provide further scientific evidence for the choice of treatment of women with PCOS. COC and AA are more effective than metformin for hyperandrogenic symptoms and endometrial protection. Their combination with metformin adds a positive effect on BMI and glucose tolerance. PROSPERO CRD REGISTRATION NUMBER CRD42016053457.

中文翻译：

---

联合口服避孕药和/或抗雄激素与胰岛素增敏剂治疗多囊卵巢综合征：系统评价和荟萃分析。

背景雄激素过多是多囊卵巢综合征 (PCOS) 的关键发病机制，尽管高胰岛素血症也有助于雄激素分泌。不寻求生育的成年患者的治疗方法包括联合口服避孕药 (COC)、抗雄激素 (AA) 和/或胰岛素增敏剂，尽管这些做法得到有限的高质量证据的支持。目的和理由 我们旨在通过对 RCT 进行荟萃分析，评估这些 PCOS 常见治疗的有效性和安全性，并提出以下综述问题： 哪种治疗方法更适合成年女性的高雄激素血症症状、高雄激素血症和排卵功能障碍PCOS不寻求生育; 在这些女性中使用的更常见的治疗方法对经典的心脏代谢危险因素有何影响？抗雄激素治疗加二甲双胍对疗效或心脏代谢谱有影响吗？搜索方法 我们在 PubMed 和 EMBASE 中搜索截至 2017 年 9 月 16 日发表的文章。删除重复内容后，分析了 1522 篇文章的摘要。我们随后排除了 1446 篇文章，留下 76 项研究进行资格全文评估。其中，43篇文章被排除在外。因此，33 项研究和 1521 名女性被纳入定量综合和荟萃分析。Meta 分析计算了平均差 (MD)、标准化平均差 (SMD)、优势比 (OR) 和 95% CI。通过 χ2 检验和 Higgins 的 I2 统计量评估研究的异质性和不一致性。根据 Cochrane 干预系统评价手册 5.1.0 评估个别研究的质量和偏倚风险。然后，我们使用了推荐、评估、发展和评估分级 (GRADE) 小组推荐的方法来指示选择主要结果的全球证据质量。结果 关于疗效，COC 和/或 AA 与二甲双胍之间多毛症评分的 MD 不显着。排除一项包括大多数患有严重多毛症的女性的单一研究对 COC 和/或 AA 产生了显着影响。当仅将包括 AA 的研究与二甲双胍进行比较时，抗雄激素治疗存在显着差异。在整个患者组中，COC 和/或 AA 与二甲双胍的组合与单独使用 COC 和/或 AA 治疗相似。干预后或存在规律的月经有利于 COC 治疗。在心脏代谢影响方面，BMI 中的 MD 支持二甲双胍。COC 治疗对 BMI 的负面影响因与二甲双胍联合使用而减弱。与 COC 和/或 AA 相比，胰岛素抵抗的稳态模型评估 (HOMA-IR) 中的 MD 也支持二甲双胍治疗。与单独的抗雄激素治疗相比，COC 和/或 AA 和二甲双胍的组合降低了 HOMA 的 MD。COC 和/或 AA 与二甲双胍之间的循环葡萄糖水平没有显着的干预后 SMD。然而，在 COC 和/或 AA 中添加二甲双胍对空腹血糖水平产生有益影响。异常葡萄糖耐量的干预后 OR 显示 COC 和/或 AA 与二甲双胍之间没有显着差异，尽管在排除包括 AA 作为比较（无 COC）的研究后，观察到有利于二甲双胍治疗的显着效果。不同疗法在血脂谱、血压或高血压患病率方面没有显着差异。在讨论所探索的治疗对高血压和血脂流行率的影响时，全球证据质量非常低，多毛症、BMI 和血压值低，而子宫内膜保护和葡萄糖耐量高。更广泛的意义 这些数据为 PCOS 女性的治疗选择提供了进一步的科学证据。对于高雄激素症状和子宫内膜保护，COC 和 AA 比二甲双胍更有效。它们与二甲双胍的组合增加了对 BMI 和葡萄糖耐量的积极影响。PROSPERO CRD 注册号 CRD42016053457。