Background: Postmenopausal pregnenolone and/or progesterone levels in relation to endometrial and ovarian cancer risks have been infrequently evaluated. To address this, we utilized a sensitive and reliable assay to quantify prediagnostic levels of seven markers related to endogenous hormone metabolism. Methods: Hormones were quantified in baseline serum collected from postmenopausal women in a cohort study nested within the Breast and Bone Follow-up to the Fracture Intervention Trial (B∼FIT). Women using exogenous hormones at baseline (1992–1993) were excluded. Incident endometrial ( n = 65) and ovarian ( n = 67) cancers were diagnosed during 12 follow-up years and compared with a subcohort of 345 women (no hysterectomy) and 413 women (no oophorectomy), respectively. Cox models with robust variance were used to estimate cancer risk. Results: Circulating progesterone levels were not associated with endometrial [tertile (T)3 vs. T1 HR (95% confidence interval): 1.87 (0.85–4.11); P trend = 0.17] or ovarian cancer risk [1.16 (0.58–2.33); 0.73]. Increasing levels of the progesterone-to-estradiol ratio were inversely associated with endometrial cancer risk [T3 vs. T1: 0.29 (0.09–0.95); 0.03]. Increasing levels of 17-hydroxypregnenolone were inversely associated with endometrial cancer risk [0.40 (0.18–0.91); 0.03] and positively associated with ovarian cancer risk [3.11 (1.39–6.93); 0.01]. Conclusions: Using sensitive and reliable assays, this study provides novel data that endogenous progesterone levels are not strongly associated with incident endometrial or ovarian cancer risks. 17-hydroxypregnenolone was positively associated with ovarian cancer and inversely associated with endometrial cancer. Impact: While our results require replication in large studies, they provide further support of the hormonal etiology of endometrial and ovarian cancers.

中文翻译：

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内源性孕烯醇酮、孕酮和相关代谢物与绝经后妇女子宫内膜癌和卵巢癌风险的关联：B~FIT 队列

背景：很少评估与子宫内膜癌和卵巢癌风险相关的绝经后孕烯醇酮和/或孕酮水平。为了解决这个问题，我们使用了一种灵敏可靠的检测方法来量化与内源性激素代谢相关的七种标志物的诊断前水平。方法：在一项嵌套在骨折干预试验 (B∼FIT) 的乳房和骨骼随访中的队列研究中，对从绝经后妇女收集的基线血清中的激素进行量化。在基线（1992-1993 年）使用外源性激素的女性被排除在外。在 12 年的随访中诊断出偶发子宫内膜癌 (n = 65) 和卵巢癌 (n = 67)，并分别与 345 名女性（无子宫切除术）和 413 名女性（无卵巢切除术）的亚组进行了比较。具有稳健方差的 Cox 模型用于估计癌症风险。结果：循环孕酮水平与子宫内膜无关 [三分位数 (T)3 与 T1 HR (95% 置信区间): 1.87 (0.85–4.11); P 趋势 = 0.17] 或卵巢癌风险 [1.16 (0.58–2.33); 0.73]。孕酮与雌二醇比率水平升高与子宫内膜癌风险呈负相关 [T3 与 T1：0.29 (0.09–0.95)；0.03]。17-羟基孕烯醇酮水平升高与子宫内膜癌风险呈负相关[0.40 (0.18–0.91)；0.03] 并与卵巢癌风险呈正相关 [3.11 (1.39–6.93); 0.01]。结论：使用敏感和可靠的检测方法，本研究提供了新的数据，即内源性孕酮水平与子宫内膜癌或卵巢癌的风险没有密切相关。17-羟基孕烯醇酮与卵巢癌呈正相关，与子宫内膜癌呈负相关。影响：虽然我们的结果需要在大型研究中进行复制，但它们为子宫内膜癌和卵巢癌的激素病因提供了进一步的支持。