Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands.
Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Genes (Basel). 2022 May 27;13(6):966. doi: 10.3390/genes13060966.
Prior studies have reported inconsistent results or less well-explored associations between sex hormones and non-alcoholic fatty liver disease (NAFLD). Here, we aimed to investigate the associations of NAFLD with sex steroids and sex hormone-binding globulin (SHBG) in the population-based study and conduct a comprehensive systematic review and meta-analysis of all published observational studies.
Analyses included 755 men and 1109 women with available data on sex steroids, SHBG, and ultrasound-based NAFLD from the Rotterdam Study. Multivariable regression models were used to examine the associations. Additionally, we searched five databases from inception to 1 April 2022 and performed a systematic review and meta-analysis. Random-effects (DerSimonian-Laird) method was used for meta-analysis, odds ratios (ORs) were calculated for the effect estimate, subgroup and leave-one-out sensitivity analyses were conducted, and meta-regression was performed to explore the pooled statistics with high heterogeneity.
In the Rotterdam Study, lower levels of SHBG were associated with NAFLD in both sexes, while lower testosterone was associated with NAFLD only among women. Similarly, the meta-analysis of 16 studies indicated no sex-specific association between SHBG and NAFLD (men: OR = 0.37, 95%CI 0.21-0.53; women: OR = 0.40, 95%CI 0.21-0.60), yet there was a sex-specific association between testosterone and NAFLD (men: OR = 0.59, 95%CI 0.42-0.76; women: OR = 1.06, 95%CI 0.68-1.44). Moreover, men with NAFLD had lower estradiol levels than those without NAFLD.
Lower SHBG levels were associated with NAFLD in both sexes, but testosterone levels were associated in a sex-specific manner. In addition, our results showed estradiol with the potential as a protective factor for NAFLD in healthy men.
先前的研究报告称，性激素与非酒精性脂肪性肝病（NAFLD）之间的关系结果不一致或研究不够充分。在这里，我们旨在调查基于人群的研究中 NAFLD 与性激素和性激素结合球蛋白（SHBG）的关联，并对所有已发表的观察性研究进行全面的系统评价和荟萃分析。
分析包括来自鹿特丹研究的 755 名男性和 1109 名女性，这些人有可用的关于性激素、SHBG 和基于超声的 NAFLD 的数据。多变量回归模型用于检验相关性。此外，我们从建库开始到 2022 年 4 月 1 日搜索了五个数据库，并进行了系统评价和荟萃分析。使用随机效应（DerSimonian-Laird）方法进行荟萃分析，计算效应估计值的比值比（OR），进行亚组和逐个剔除敏感性分析，并进行荟萃回归以探索具有高度异质性的汇总统计数据。
在鹿特丹研究中，SHBG 水平较低与两性的 NAFLD 相关，而仅在女性中，睾丸激素水平较低与 NAFLD 相关。同样，16 项研究的荟萃分析表明，SHBG 与 NAFLD 之间没有性别特异性关联（男性：OR = 0.37，95%CI 0.21-0.53；女性：OR = 0.40，95%CI 0.21-0.60），但睾丸激素与 NAFLD 之间存在性别特异性关联（男性：OR = 0.59，95%CI 0.42-0.76；女性：OR = 1.06，95%CI 0.68-1.44）。此外，患有 NAFLD 的男性的雌二醇水平低于没有 NAFLD 的男性。
SHBG 水平较低与两性的 NAFLD 相关，但睾丸激素水平与 NAFLD 呈性别特异性相关。此外，我们的结果表明，雌二醇可能是健康男性 NAFLD 的保护因素。
