Geerlings M I, Ruitenberg A, Witteman J C, van Swieten J C, Hofman A, van Duijn C M, Breteler M M, Launer L J
Department of Epidemiology and Biostatistics, Erasmus University Medical Center, PO Box 1738, 3000 DR Rotterdam, the Netherlands.
JAMA. 2001 Mar 21;285(11):1475-81. doi: 10.1001/jama.285.11.1475.
Exogenous estrogen use may lower risk of dementia in postmenopausal women. A relationship between long-term exposure to endogenous estrogens and incident dementia has been hypothesized but not studied.
To determine whether a longer reproductive period, as an indicator of longer exposure to endogenous estrogens, is associated with lower risk of dementia and Alzheimer disease (AD) in women who have natural menopause.
The Rotterdam Study, a population-based prospective cohort study conducted in the Netherlands.
A total of 3601 women aged 55 years or older who did not have dementia at baseline (1990-1993) and had information on age at menarche, age at menopause, and type of menopause. Participants were reexamined in 1993-1994 and 1997-1999 and were continuously monitored for development of dementia.
Incidence of dementia, based on Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria, and AD, based on National Institute of Neurological Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria, compared by quartiles of reproductive period among women with natural menopause.
During 21 046 person-years of follow-up (median follow-up, 6.3 years), 199 women developed dementia, including 159 who developed AD. After adjusting for age, dementia was not clearly associated with length of reproductive period. However, after adjusting for multiple covariates, women with natural menopause and more reproductive years had an increased risk of dementia (adjusted rate ratio [RR] for women with >39 reproductive years [highest quartile] compared with <34 reproductive years [lowest quartile], 1.78; 95% confidence interval [CI], 1.12-2.84). The adjusted RR per year of increase was 1.04 (95% CI, 1.01-1.08). For risk of AD, the adjusted RRs were 1.51 (95% CI, 0.91-2.50) and 1.03 (95% CI, 1.00-1.07), respectively. Risk of dementia associated with a longer reproductive period was most pronounced in APOE epsilon4 carriers (adjusted RR for >39 reproductive years compared with <34 reproductive years, 4.20 [95% CI, 1.97-8.92] for dementia and 3.42 [95% CI, 1.51-7.75] for AD), whereas in noncarriers, no clear association with dementia or AD was observed.
Our findings do not support the hypothesis that a longer reproductive period reduces risk of dementia in women who have natural menopause.
外源性雌激素的使用可能会降低绝经后女性患痴呆症的风险。长期暴露于内源性雌激素与痴呆症发病之间的关系已被提出，但尚未得到研究。
确定较长的生育期（作为长期暴露于内源性雌激素的指标）是否与自然绝经女性患痴呆症和阿尔茨海默病（AD）的风险较低相关。
鹿特丹研究，一项在荷兰进行的基于人群的前瞻性队列研究。
共有3601名55岁及以上的女性，她们在基线时（1990 - 1993年）没有痴呆症，并且有初潮年龄、绝经年龄和绝经类型的信息。参与者在1993 - 1994年和1997 - 1999年接受了重新检查，并持续监测痴呆症的发展情况。
根据《精神疾病诊断与统计手册》第三版修订标准确定的痴呆症发病率，以及根据美国国立神经疾病和中风研究所/阿尔茨海默病及相关疾病协会标准确定的AD发病率，在自然绝经女性中按生育期四分位数进行比较。
在21046人年的随访期间（中位随访时间为6.3年），199名女性患了痴呆症，其中159名患了AD。在调整年龄后，痴呆症与生育期长度没有明显关联。然而，在调整多个协变量后，自然绝经且生育年限较多的女性患痴呆症的风险增加（生育年限>39年[最高四分位数]的女性与生育年限<34年[最低四分位数]的女性相比，调整后的率比[RR]为1.78；95%置信区间[CI]为1.12 - 2.84）。每年增加的调整后RR为1.04（95%CI为1.01 - 1.08）。对于AD风险，调整后的RR分别为1.51（95%CI为0.91 - 2.50）和1.03（95%CI为1.00 - 1.07）。生育期较长与痴呆症相关的风险在APOE ε4携带者中最为明显（生育年限>39年与生育年限<34年相比，痴呆症的调整后RR为4.20[95%CI为1.97 - 8.92]，AD为3.42[95%CI为1.51 - 7.75]），而在非携带者中，未观察到与痴呆症或AD有明显关联。
我们的研究结果不支持较长的生育期会降低自然绝经女性患痴呆症风险这一假设。
