Palomba Stefano, Pasquali Renato, Orio Francesco, Nestler John E
Chair of Gynecology & Obstetrics, University Magna Graecia of Catanzaro, Catanzaro, Italy.
Clin Endocrinol (Oxf). 2009 Feb;70(2):311-21. doi: 10.1111/j.1365-2265.2008.03369.x. Epub 2008 Aug 7.
To date, no systematic review or meta-analysis has been published of direct head-to-head studies comparing clomiphene citrate (CC) vs. metformin, or the combination of both drugs as first-line therapy in anovulatory polycystic ovary syndrome (PCOS) patients seeking pregnancy. The aim of the current paper was to define, if possible, the best evidence-based recommendations regarding the use of CC and/or metformin as the initial treatment of PCOS women with anovulatory infertility.
Systematic review and meta-analysis of the head-to-head randomized controlled trials (RCTs) available in the literature.
A bibliographic search was performed using the following bibliographic databases: Medline, EMBASE, Biological Abstracts, Cochrane Controlled Trials Register and Cochrane Database of Systematic Reviews. Reference lists of included studies, other relevant review articles and textbooks were checked for additional citations of interest.
Four head-to-head RCTs were identified and qualified for inclusion in the analysis. No difference in fertility improvement was observed comparing CC with metformin (OR = 1.22, 95% CI 0.23-6.55, P = 0.815), whereas a significant (P < 0.0001) heterogeneity was observed. Homogeneous data showed no difference in fertility improvement between the combination treatment and CC monotherapy (OR = 0.99, 95% CI 0.70-1.40, P = 0.982), but a significant difference in comparison with metformin monotherapy (OR = 0.23, 95% CI 0.14-0.37, P < 0.0001).
In PCOS patients with anovulatory infertility and not previously treated, the administration of metformin plus CC is not better than monotherapy (metformin alone or CC alone), whereas to date no specific recommendation can be given regarding the use of CC or metformin as first-step drug.
迄今为止，尚未发表关于比较枸橼酸氯米芬（CC）与二甲双胍，或两种药物联合作为无排卵性多囊卵巢综合征（PCOS）不孕患者一线治疗的直接头对头研究的系统评价或荟萃分析。本文的目的是尽可能确定关于使用CC和/或二甲双胍作为PCOS无排卵性不孕女性初始治疗的最佳循证建议。
对文献中可用的头对头随机对照试验（RCT）进行系统评价和荟萃分析。
使用以下文献数据库进行文献检索：Medline、EMBASE、生物学文摘数据库、Cochrane对照试验注册库和Cochrane系统评价数据库。检查纳入研究的参考文献列表、其他相关综述文章和教科书，以获取其他感兴趣的引文。
确定了四项头对头RCT并符合纳入分析的条件。比较CC与二甲双胍时，未观察到生育改善方面的差异（OR = 1.22，95%CI 0.23 - 6.55，P = 0.815），但观察到显著的（P < 0.0001）异质性。同质数据显示联合治疗与CC单药治疗在生育改善方面无差异（OR = 0.99，95%CI 0.70 - 1.40，P = 0.982），但与二甲双胍单药治疗相比有显著差异（OR = 0.23，95%CI 0.14 - 0.37，P < 0.0001）。
在未经治疗的PCOS无排卵性不孕患者中，二甲双胍加CC的给药效果并不优于单药治疗（单独使用二甲双胍或单独使用CC），而迄今为止，关于使用CC或二甲双胍作为第一步药物尚无具体建议。
