Slone Epidemiology Center at Boston University, 72 East Concord Street, L-7, Boston, MA, 02118, USA.
Channing Division of Network Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
Horm Cancer. 2018 Apr;9(2):117-127. doi: 10.1007/s12672-017-0321-6. Epub 2018 Jan 12.
Prior research suggests that several endogenous hormones in premenopausal women are associated with breast cancer risk; however, few studies have evaluated associations of endogenous hormones with mammographic density (MD) in premenopausal women. We conducted a cross-sectional study of plasma hormone levels in relation to MD among 634 cancer-free premenopausal women in the Nurses' Health Study II. We measured percent MD from screening mammograms using a computer-assisted method. We assayed estradiol, estrone, and estrone sulfate in blood samples timed in early follicular and mid-luteal phases of the menstrual cycle as well as testosterone, androstenedione, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate, sex hormone-binding globulin (SHBG), and anti-Müllerian hormone in luteal or untimed samples. We used multivariable linear regression to quantify the association of %MD with quartiles of each hormone, adjusting for age, body mass index, and breast cancer risk factors. Women in the highest quartile of follicular estradiol levels had significantly greater %MD compared to those in the lowest quartile [difference, 6.7 percentage points; 95% confidence interval (CI) 2.2, 11.3; p-trend < 0.001]. Similar associations were observed for follicular free estradiol but not luteal-phase estradiol. Also, women in the top (vs. bottom) quartile of free testosterone had significantly lower %MD (difference, - 4.7; 95% CI - 8.7, - 0.8; p-trend = 0.04). Higher SHBG was significantly associated with higher percent MD (difference, 4.8; 95% CI 1.1, 8.6; p-trend = 0.002). Percent MD was not strongly associated with other measured hormones. Results were similar in analyses that excluded women with anovulatory cycles. Our findings suggest that follicular estradiol and SHBG may play an important role in premenopausal percent MD.
先前的研究表明，绝经前女性体内的几种内源性激素与乳腺癌风险有关；然而，很少有研究评估内源性激素与绝经前女性的乳腺密度（MD）之间的关系。我们对参加护士健康研究 II 的 634 名无癌症的绝经前女性进行了一项关于血浆激素水平与 MD 之间关系的横断面研究。我们使用计算机辅助方法从筛查性乳房 X 光片中测量 MD 的百分比。我们在月经周期的早期卵泡期和中期黄体期采集血液样本，检测雌二醇、雌酮和雌酮硫酸盐，在黄体期或不定期采集血液样本，检测睾酮、雄烯二酮、孕酮、脱氢表雄酮（DHEA）、DHEA 硫酸盐、性激素结合球蛋白（SHBG）和抗缪勒管激素。我们使用多变量线性回归来量化 %MD 与每种激素四分位的关联，同时调整年龄、体重指数和乳腺癌危险因素。与最低四分位相比，卵泡期雌二醇水平最高四分位的女性 MD 百分比明显更高[差异，6.7 个百分点；95%置信区间（CI）为 2.2，11.3；趋势检验 < 0.001]。在卵泡期游离雌二醇中观察到相似的关联，但黄体期雌二醇则不然。此外，与最低四分位相比，处于游离睾酮最高四分位的女性 MD 百分比明显较低[差异，-4.7；95%CI -8.7，-0.8；趋势检验 = 0.04]。较高的 SHBG 与较高的 %MD 显著相关[差异，4.8；95%CI 1.1，8.6；趋势检验 = 0.002]。与其他测量的激素相比，MD 百分比与其他测量的激素相关性不高。在排除不排卵周期女性的分析中，结果相似。我们的研究结果表明，卵泡期雌二醇和 SHBG 可能在绝经前 MD 百分比中发挥重要作用。
