Department of Reproductive Medicine and Gynaecology, University Medical Centre Utrecht, Heidelberglaan 100, F05.126, PO Box 75500, 3584 CX Utrecht, The Netherlands.
Hum Reprod Update. 2012 Jul;18(4):405-19. doi: 10.1093/humupd/dms013. Epub 2012 Apr 23.
Increasing age and post-menopausal status are associated with decreasing androgen concentrations in females. Women with premature loss of ovarian function, such as primary ovarian insufficiency (POI) or iatrogenic menopause may be at increased risk for diminished testosterone levels at a relatively young age. Differentiation between a hypoandrogenic or normoandrogenic state in women with premature loss of ovarian function is problematic due to trueness and precision problems using various testosterone assays. The current meta-analysis was conducted to evaluate current literature reporting serum total testosterone concentrations under these conditions, including stratification for various testosterone assays.
A systematic review and meta-analysis of controlled observational studies were performed. The electronic databases of Pubmed, Embase and the Cochrane Library were systematically searched until October 2011 for comparative studies on total testosterone concentrations in women with spontaneous POI or iatrogenic menopause compared with controls. The literature search, data extraction and critical appraisal, using the Newcastle-Ottawa Scale, were performed by two independent investigators. The effect measure was the weighted mean difference (WMD) with 95% confidence interval (95% CI) in a random effects model.
A total of 206 articles for spontaneous POI and 1358 for iatrogenic menopause were reviewed, of which 9 and 17 papers, respectively, were selected for final analysis. Both groups demonstrated significantly lower total testosterone concentrations compared with controls [WMD (95% CI) -0.38 (-0.55 to -0.22) nmol/l, and -0.29 (-0.39 to -0.18) nmol/l, respectively], but with substantial between-study heterogeneity. Subgroup analysis for assay type was statistically significant for spontaneous POI only. Sensitivity analyses of high-quality studies did not change the results, and resulted in a substantial decrease in heterogeneity in spontaneous POI studies.
The current meta-analysis demonstrates that total testosterone concentrations are decreased in women with spontaneous POI or iatrogenic menopause. The potential implications of hypoandrogenism in these women remain to be elucidated.
随着年龄的增长和绝经后状态的出现，女性的雄激素浓度会逐渐降低。患有卵巢早衰（POI）或医源性绝经等疾病的女性，可能会在相对年轻的时候出现睾酮水平降低的风险增加。由于使用各种睾酮检测方法存在准确性和精密度问题，区分这些女性的低雄激素或正常雄激素状态存在困难。本研究旨在对目前关于这些情况下血清总睾酮浓度的文献进行评估，包括对各种睾酮检测方法进行分层。
对已发表的对照观察性研究进行了系统回顾和荟萃分析。系统检索了 Pubmed、Embase 和 Cochrane 图书馆的电子数据库，检索时间截至 2011 年 10 月，检索内容为关于自发性 POI 或医源性绝经女性与对照组相比的总睾酮浓度的比较研究。两名独立的研究人员进行了文献检索、数据提取和使用纽卡斯尔-渥太华量表进行的批判性评价。使用随机效应模型，测量指标为加权均数差值（WMD）及其 95%置信区间（95%CI）。
共回顾了 206 篇关于自发性 POI 的文章和 1358 篇关于医源性绝经的文章，其中分别有 9 篇和 17 篇文章被最终纳入分析。两组的总睾酮浓度均明显低于对照组[WMD（95%CI）分别为-0.38（-0.55 至-0.22）nmol/L 和-0.29（-0.39 至-0.18）nmol/L]，但存在很大的组间异质性。仅对检测方法进行亚组分析显示，检测方法类型具有统计学意义。对高质量研究的敏感性分析并未改变结果，但降低了自发性 POI 研究的异质性。
本荟萃分析表明，自发性 POI 或医源性绝经女性的总睾酮浓度降低。这些女性的低雄激素状态的潜在影响仍有待阐明。
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