Efficacy of treatments for polycystic ovarian syndrome management in adolescents: a systematic review and network meta-analysis

Limited evidence on treatment options for polycystic ovarian syndrome
(PCOS) has led to considerable variation in healthcare
practices. We aimed to compare the effects of metformin and/or
oral contraceptive pills (OCPs) in combination with pioglitazone,
spironolactone, flutamide, and lifestyle interventions among adolescents
aged 11-19 years with PCOS. Literature searches were performed in Medline,
Embase, and the Cochrane Central Register of Controlled Trials from
database inception through December 2018, with no language restriction.
Two reviewers screened titles and abstracts, assessed full text
eligibility, and extracted information from eligible trials. Evidence was
synthesized through network meta-analyses (NMA) using Bayesian
random-effects approach. We identified 37 RCTs, in which 2400 patients
were randomized. NMA showed no statistically important difference among
all interventions to improve menstrual regulation, or body mass index.
Moderate quality evidence showed hirsutism scores were reduced by multiple
interventions that included single and combination medications namely;
lifestyle intervention, metformin, OCP, spironolactone, pioglitazone,
metformin-OCP, metformin-spironolactone, metformin-flutamide, against
placebo. Moderate quality evidence showed OCP results in more dysglycaemia
compared to metformin (odds ratio 2.98; 95%credible interval 1.02, 8.96),
no intervention resulted in dysglycaemia reduction. In conclusion,
metformin and OCP as monotherapy or in combination with other
interventions compared to placebo can reduce hirsutism scores, but none of
these medications lead to effective menstrual cycle regulation or weight
reduction. However, the use of OCP leads to worse cardiometabolic risk
factors. Further research into new treatment options is urgently needed.

目前针对多囊卵巢综合征（Polycystic Ovarian Syndrome, PCOS）的治疗方案相关证据有限，导致临床医疗实践存在显著差异。本研究旨在对比二甲双胍、口服避孕药（Oral Contraceptive Pills, OCPs）联合吡格列酮、螺内酯、氟他胺以及生活方式干预，对11至19岁青少年多囊卵巢综合征患者的治疗效果。研究检索了Medline、Embase及Cochrane对照试验中心注册库自建库至2018年12月的文献，无语言限制。由两名研究者独立筛选文献标题与摘要、评估全文纳入资格，并从符合标准的试验中提取研究数据。采用贝叶斯随机效应模型的网络meta分析（Network Meta-Analyses, NMA）对证据进行整合。本研究共纳入37项随机对照试验（Randomized Controlled Trial, RCT），累计随机入组2400例患者。网络meta分析显示，所有干预措施在改善月经规律程度或体质量指数方面均无统计学意义上的显著差异。中等质量证据表明，多项干预措施（包括单一及联合用药方案，即生活方式干预、二甲双胍、口服避孕药、螺内酯、吡格列酮、二甲双胍-口服避孕药联合、二甲双胍-螺内酯联合、二甲双胍-氟他胺联合）相较于安慰剂，可降低多毛症评分。中等质量证据显示，口服避孕药相较于二甲双胍，更易引发糖代谢异常（优势比2.98；95%可信区间1.02, 8.96），且未发现任何干预措施可改善糖代谢异常。综上，二甲双胍与口服避孕药单药治疗或联合其他干预措施，相较于安慰剂，均可降低多毛症评分，但上述药物均未能有效调节月经周期或减轻体质量。然而，口服避孕药的使用会加重心脏代谢风险因素。亟需开展更多研究以探索新型治疗方案。