O'Connor Kathleen A, Ferrell Rebecca J, Brindle Eleanor, Shofer Jane, Holman Darryl J, Miller Rebecca C, Schechter Deborah E, Singer Burton, Weinstein Maxine
Department of Anthropology, Center for Studies in Demography and Ecology, University of Washington, Box 353100, Seattle, WA 98195, USA.
Cancer Epidemiol Biomarkers Prev. 2009 Mar;18(3):828-36. doi: 10.1158/1055-9965.EPI-08-0996. Epub 2009 Feb 24.
Detailed characterization of estrogen dynamics during the transition to menopause is an important step toward understanding its potential implications for reproductive cancers developing in the transition years. We conducted a 5-year prospective study of endogenous levels of total and unopposed estrogen. Participants (n=108; ages 25-58 years) collected daily urine specimens for 6 months in each of 5 consecutive years. Specimens were assayed for estrone-3-glucuronide (E1G) and pregnanediol-3-glucuronide. Linear mixed-effects models were used to estimate exposure to total and unopposed estrogen by age and reproductive stage. Reproductive stage was estimated using menstrual cycle length variance. E1G mean area under the curve and mean E1G 5th and 95th percentiles represented total estrogen exposure. An algorithm identifying days of above-baseline E1G that coincided with the days of baseline pregnanediol-3-glucuronide was used to identify days of unopposed estrogen. Mean E1G area under the curve increased with age in the pretransition and early transition and decreased in the late transition. Ninety-fifth percentile E1G levels did not decline until after menopause, whereas 5th percentile levels declined from the early transition to the postmenopause. The number of days of unopposed estrogen was significantly higher during the transition compared with the pretransition. Given the length of time women spend in the transition, they are exposed to more total and unopposed estrogen than has been previously appreciated. Coupled with epidemiologic evidence on lifetime exposure to estrogen, these results suggest that variation in the amount of time spent in the transition may be an important risk factor for reproductive cancers.
详细描述围绝经期过渡期间雌激素动态变化，是理解其对该过渡阶段发生的生殖系统癌症潜在影响的重要一步。我们针对总雌激素和无对抗雌激素的内源性水平开展了一项为期5年的前瞻性研究。参与者（n = 108；年龄25 - 58岁）在连续5年中每年收集6个月的每日尿液样本。对样本进行雌酮 - 3 - 葡萄糖醛酸苷（E1G）和孕二醇 - 3 - 葡萄糖醛酸苷检测。采用线性混合效应模型，根据年龄和生殖阶段估算总雌激素和无对抗雌激素的暴露情况。利用月经周期长度变异估算生殖阶段。E1G曲线下平均面积以及E1G第5和第95百分位数代表总雌激素暴露量。一种算法用于识别与基线孕二醇 - 3 - 葡萄糖醛酸苷天数相符的高于基线E1G的天数，以此确定无对抗雌激素的天数。在围绝经期过渡前和早期，E1G曲线下平均面积随年龄增加，在围绝经期过渡后期则下降。直到绝经后，E1G第95百分位数水平才下降，而第5百分位数水平从围绝经期过渡早期到绝经后有所下降。与围绝经期过渡前相比，围绝经期过渡期间无对抗雌激素的天数显著更多。鉴于女性在围绝经期过渡阶段所经历的时间长度，她们暴露于更多的总雌激素和无对抗雌激素，这一情况比之前所认识到的更为严重。结合关于雌激素终生暴露的流行病学证据，这些结果表明，围绝经期过渡阶段所经历时间的变化可能是生殖系统癌症的一个重要风险因素。
