绝经后女性月经初潮年龄、绝经年龄及生殖期与认知功能的相关性

The relationship between age at menarche, age at menopause or reproductive lifespan and cognitive function in postmenopausal women

摘要

目的: 探讨绝经后女性月经初潮年龄、绝经年龄及生殖期与认知功能的关系。方法: 基于2018年中国健康与养老追踪调查数据,选取关键数据完整的绝经后女性1 829例,基于简易智力状态测验(MMSE)分为无认知障碍组(n=1 230)和认知障碍组(n=599),比较两组基本特征。采用Logistic回归分析生殖因素与认知功能的关系,并采用限制性立方样条曲线探讨二者是否存在非线性关系。结果: 认知障碍组与无认知障碍组婚姻状况、居住地、文化程度、吸烟状况、高血压、抑郁症状、睡眠时长、绝经年龄、生殖期及MMSE得分差异均有统计学意义(P均<0.05)。调整混杂因素后,Logistic回归分析结果显示,与绝经年龄51~55岁组相比,绝经年龄≤45岁组认知障碍比例更高(OR=1.59,95%CI:1.15~2.10,P=0.014);与生殖期36~40年组相比,生殖期≤30年组认知功能障碍比例更高(OR=1.68,95%CI:1.26~2.25,P=0.008);未发现初潮年龄与认知功能存在关联;平滑曲线拟合未发现生殖因素与认知功能存在非线性关系。结论: 绝经年龄较小(≤45岁)和生殖期较短(≤30年)的女性发生认知障碍的风险更高,初潮年龄与认知障碍未见显著关联。

Abstract

Objective: To investigate the relationship between age at menarche, age at menopause or reproductive lifespan and cognitive function in postmenopausal women. Methods: Based on data from the 2018 China Health and Retirement Longitudinal Study (CHARLS), a total of 1 829 postmenopausal women with complete key data were selected and divided into non-cognitive impairment group (n=1 230) and cognitive impairment group (n=599) according to the Mini-Mental State Examination (MMSE), and their basic characteristics were compared. Logistic regression analysis was used to examine the relationship between reproductive factors and cognitive function, and restricted cubic spline (RCS) curves were further plotted to examine potential nonlinear associations between the above factors and cognitive function. Results: There were statistically significant differences between the cognitive impairment group and the non-cognitive impairment group in marital status, place of residence, education level, smoking status, hypertension, depressive symptoms, sleep duration, age at menopause, reproductive span and MMSE scores (all P<0.05). After adjusting for confounding factors, Logistic regression analysis showed that compared to women with menopause age between 51-55 years, those with menopause age ≤45 years had a higher risk of cognitive impairment (OR=1.59, 95%CI: 1.15-2.10, P=0.014); compared to women with a reproductive span of 36-40 years, those with a reproductive span ≤30 years had a higher prevalence of cognitive impairment (OR=1.68, 95%CI: 1.26-2.25, P=0.008). No association was found between age at menarche and cognitive function. Smooth curve fitting did not reveal any nonlinear relationship between reproductive factors and cognitive function. Conclusion: Women with earlier menopause (≤45 years) and shorter reproductive lifespan (≤30 years) have a higher risk of cognitive impairment, while no significant association was observed between age at menarche and cognitive impairment.

关键词

女性 / 初潮年龄 / 绝经年龄 / 生殖期 / 认知功能

Key words

women / age at menarche / age at menopause / reproductive lifespan / cognitive function

参考文献

[1] GBD 2019 Dementia Forecasting Collaborators . Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019[J]. Lancet Public Health, 2022, 7(2): e105-e125.

[2] 付春迎, 于瑞洪, 王琪, 等 . 女性生育因素对主、客观认知功能的影响: 基于平阴队列的横断面研究[J]. 中国全科医学, 2025, 28(8): 980-988, 995.

[3] Gong J, Harris K, Lipnicki DM, et al. Sex differences in dementia risk and risk factors: individual-participant data analysis using 21 cohorts across six continents from the COSMIC consortium[J]. Alzheimers Dement, 2023, 19(8): 3365-3378.

[4] Nebel RA, Aggarwal NT, Barnes LL, et al. Understanding the impact of sex and gender in Alzheimer′s disease: a call to action[J]. Alzheimers Dement, 2018, 14(9): 1171-1183.

[5] Jia L, Du Y, Chu L, et al. Prevalence, risk factors, and management of dementia and mild cognitive impairment in adults aged 60 years or older in China: a cross-sectional study[J]. Lancet Public Health, 2020, 5(12): e661-e671.

[6] Gong J, Harris K, Peters SAE, et al. Reproductive factors and the risk of incident dementia: a cohort study of UK Biobank participants[J]. PLoS Med, 2022, 19(4): e1003955.

[7] Prince MJ, Acosta D, Guerra M, et al. Reproductive period, endogenous estrogen exposure and dementia incidence among women in Latin America and China; A 10/66 population-based cohort study[J]. PLoS One, 2018, 13(2): e0192889.

[8] Bove R, Secor E, Chibnik LB, et al. Age at surgical menopause influences cognitive decline and Alzheimer pathology in older women[J]. Neurology, 2014, 82(3): 222-229.

[9] Song X, Wu J, Zhou Y, et al. Reproductive and hormonal factors and risk of cognitive impairment among Singapore Chinese women[J]. Am J Obstet Gynecol, 2020, 223(3): 410.e1-410.e23.

[10] Li FD, He F, Chen TR, et al. Reproductive history and risk of cognitive impairment in elderly women: a cross-sectional study in Eastern China[J]. J Alzheimers Dis, 2016, 49(1): 139-147.

[11] 游春娇, 徐艳杰, 余超, 等 . 女性高血压患者月经初潮年龄、绝经年龄及生殖期与认知功能的关系[J]. 中国医学科学院学报, 2023, 45(5): 760-767.

[12] Chou HT, Wu PY, Huang JC, et al. Late menarche, not reproductive period, is associated with poor cognitive function in postmenopausal women in Taiwan[J]. Int J Environ Res Public Health, 2021, 18(5): 2345.

[13] Zhao Y, Hu Y, Smith JP, et al. Cohort profile: the China Health and Retirement Longitudinal Study (CHARLS)[J]. Int J Epidemiol, 2014, 43(1): 61-68.

[14] 中华医学会妇产科学分会绝经学组 . 中国绝经管理与绝经激素治疗指南2023版[J]. 中华妇产科杂志, 2023, 58(1): 4-21.

[15] Guo M, Wu Y, Gross AL, et al. Age at menopause and cognitive function and decline among middle-aged and older women in the China Health and Retirement Longitudinal Study, 2011-2018[J]. Alzheimers Dement, 2025, 21(2): e14580.

[16] 韦慧燕, 刘乐, 杨光媚, 等 . 我国老年人认知功能障碍现状及其影响因素[J]. 医学与社会, 2022, 35(2): 55-59.

[17] Najar J, Östling S, Waern M, et al. Reproductive period and dementia: A 44-year longitudinal population study of Swedish women[J]. Alzheimers Dement, 2020, 16(8): 1153-1163.

[18] Gilsanz P, Lee C, Corrada MM, et al. Reproductive period and risk of dementia in a diverse cohort of health care members[J]. Neurology, 2019, 92(17): e2005-e2014.

[19] Han SL, Liu DC, Tan CC, et al. Male- and female-specific reproductive risk factors across the lifespan for dementia or cognitive decline: a systematic review and meta-analysis[J]. BMC Med, 2023, 21(1): 457.

[20] Xi H, Gan J, Liu S, et al. Reproductive factors and cognitive impairment in natural menopausal women: a cross-sectional study[J]. Front Endocrinol (Lausanne), 2022, 13: 893901.

[21] Conde DM, Verdade RC, Valadares ALR, et al. Menopause and cognitive impairment: a narrative review of current knowledge[J]. World J Psychiatry, 2021, 11(8): 412-428.

[22] Sochocka M, Karska J, Pszczołowska M, et al. Cognitive decline in early and premature menopause[J]. Int J Mol Sci, 2023, 24(7): 6566.

基金资助

江苏省卫生健康委医学科研立项项目(2021-254)

江苏大学医教协同创新基金一般项目(JDYY2023029)