绝经后内源性性激素与C反应蛋白之间的关联：通过区域肥胖调整能更清晰地了解吗？

Associations between postmenopausal endogenous sex hormones and C-reactive protein: a clearer picture with regional adiposity adjustment?

作者信息

Conroy Shannon M, Neilson Heather K, O'Reilly Rachel, Woolcott Christy G, Stanczyk Frank Z, Courneya Kerry S, Friedenreich Christine M

机构信息

1Cancer Prevention Institute of California, Fremont, CA 2Cancer Epidemiology and Prevention Research, Alberta Health Services-CancerControl, Calgary, Alberta, Canada 3Department of Obstetrics & Gynaecology and Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada 4Keck School of Medicine, University of Southern California, Los Angeles, CA 5Faculty of Physical Education and Recreation, University of Alberta, Edmonton, Alberta, Canada 6Departments of Oncology and Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

出版信息

Menopause. 2017 Sep;24(9):1040-1048. doi: 10.1097/GME.0000000000000883.

DOI:10.1097/GME.0000000000000883

PMID:28640164

Abstract

OBJECTIVE

To better understand the pathogenesis of inflammatory-related diseases after menopause, we studied the adiposity-independent association between endogenous sex hormones and C-reactive protein (CRP), a biomarker of inflammation.

METHODS

We conducted a secondary, cross-sectional analysis of baseline data from the Alberta Physical Activity and Breast Cancer Prevention Trial (2003-2007), including 319 healthy, postmenopausal women not using hormone therapy. Multivariable linear regression models related serum CRP levels to estrogens, androgens, and sex hormone-binding globulin (SHBG), all on the natural logarithmic scale. Models were adjusted for age, lipids, medication, and former menopausal hormone therapy use, and also for adiposity (body mass index [BMI], per cent body fat [via whole-body dual x-ray absorptiometry], or intra-abdominal fat area [via computed tomography]).

RESULTS

Without adiposity adjustment, estrone, total estradiol, and free estradiol were significantly positively associated with CRP, whereas SHBG was significantly inversely associated with CRP. Of all adiposity measures, adjustment for BMI caused the greatest attenuation of CRP-estrogen associations; only free estradiol (β = 0.24, 95% confidence interval [CI] 0.06, 0.43) and SHBG (β = -0.37, 95% CI -0.60, -0.13) associations remained significant. Inverse associations between CRP-total testosterone became stronger with BMI adjustment (β = -0.20, 95% CI -0.40, -0.01). Differential associations across categories of BMI, former hormone therapy use, and years since menopause were suggestive, but not statistically significant (Pheterogeneity > 0.05).

CONCLUSIONS

Prospective and systems epidemiological studies are needed to understand whether or not the cross-sectional associations we observed, independent of adiposity, between CRP-SHBG, CRP-total testosterone, and CRP-free estradiol, are causal.

摘要

目的

为了更好地理解绝经后炎症相关疾病的发病机制，我们研究了内源性性激素与炎症生物标志物C反应蛋白（CRP）之间与肥胖无关的关联。

方法

我们对阿尔伯塔省体育活动与乳腺癌预防试验（2003 - 2007年）的基线数据进行了二次横断面分析，该试验纳入了319名未使用激素疗法的健康绝经后女性。多变量线性回归模型将血清CRP水平与雌激素、雄激素和性激素结合球蛋白（SHBG）相关联，所有变量均采用自然对数尺度。模型针对年龄、血脂、药物治疗和既往绝经激素治疗使用情况进行了调整，同时也针对肥胖情况（体重指数[BMI]、体脂百分比[通过全身双能X线吸收法]或腹内脂肪面积[通过计算机断层扫描]）进行了调整。

结果

在未进行肥胖调整时，雌酮、总雌二醇和游离雌二醇与CRP显著正相关，而SHBG与CRP显著负相关。在所有肥胖指标中，对BMI进行调整导致CRP - 雌激素关联的衰减最大；只有游离雌二醇（β = 0.24，95%置信区间[CI] 0.06，0.43）和SHBG（β = -0.37，95% CI -0.60，-0.13）的关联仍然显著。随着BMI调整，CRP - 总睾酮之间的负相关变得更强（β = -0.20，95% CI -0.40，-0.01）。BMI类别、既往激素治疗使用情况和绝经后年限之间的差异关联具有提示性，但无统计学意义（异质性P > 0.05）。