Geraets Anouk, Ford Katherine, May Patrick, Kidd Emma, Leist Anja
Department of Social Sciences, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
Department of Psychology, Carleton University, Ottawa, Ontario, Canada.
BMJ Public Health. 2025 Jul 27;3(2):e002120. doi: 10.1136/bmjph-2024-002120. eCollection 2025.
Menopausal factors, including age at menopause, bilateral oophorectomy, hysterectomy and hormone replacement therapy (HRT), have been associated with dementia risk, which might be due to increased glucose levels after menopause. This study investigated the associations of these menopausal factors with glycaemia and dementia risk, and whether glycaemia mediates the association of menopausal factors with dementia risk.
We used longitudinal data from the population-based UK Biobank cohort (n=147 119 women; mean±SD age 55.2±8.0 years at baseline). Menopausal status, bilateral oophorectomy, hysterectomy, HRT and age at natural menopause, surgery and HRT were self-reported. Glycaemia was measured with fasting plasma glucose and haemoglobin A1c (HbA1c) levels. Dementia diagnoses were ascertained from hospital records. Cox proportional hazards regression analyses tested the associations between menopausal factors, glycaemia and dementia risk. Causal mediation models were used to test mediation.
After a mean follow-up of 12.5±1.6 years, 1385 participants had incident dementia. Though there was a direct effect of bilateral oophorectomy, hysterectomy, lifetime HRT and age at natural menopause and surgery on fasting plasma glucose and HbA1c levels, only age at natural menopause (HR=0.97 (95% CI 0.96 to 0.99) per year and HR=1.31 (95% CI 1.08 to 1.60) for early natural menopause) and lifetime HRT in women with natural menopause (HR=1.13 (95% CI 1.00 to 1.27)) were associated with dementia risk. Causal mediation analyses showed that up to 4.7% of the total effect of age at natural menopause on dementia risk was mediated by HbA1c levels, while both fasting plasma glucose and HbA1c affected the increased dementia risk for lifetime HRT in women with natural menopause.
We observed associations between bilateral oophorectomy, hysterectomy, lifetime HRT and age at natural menopause and surgery with glycaemia. An earlier age at natural menopause was associated with increased dementia risk, and HbA1c marginally mediated this association. Inconsistent associations between HRT and dementia risk require further research.
绝经因素，包括绝经年龄、双侧卵巢切除术、子宫切除术和激素替代疗法（HRT），都与痴呆风险相关，这可能是由于绝经后血糖水平升高所致。本研究调查了这些绝经因素与血糖及痴呆风险之间的关联，以及血糖是否介导了绝经因素与痴呆风险之间的关联。
我们使用了基于人群的英国生物银行队列的纵向数据（n = 147119名女性；基线时平均年龄±标准差为55.2±8.0岁）。绝经状态、双侧卵巢切除术、子宫切除术、HRT以及自然绝经、手术和HRT的年龄均为自我报告。通过空腹血糖和糖化血红蛋白（HbA1c）水平来测量血糖。痴呆诊断通过医院记录确定。Cox比例风险回归分析测试了绝经因素、血糖与痴呆风险之间的关联。使用因果中介模型来测试中介作用。
在平均随访12.5±1.6年后，1385名参与者发生了痴呆。虽然双侧卵巢切除术、子宫切除术、终身HRT以及自然绝经和手术的年龄对空腹血糖和HbA1c水平有直接影响，但只有自然绝经年龄（每年HR = 0.97（95%CI 0.96至0.99），早期自然绝经HR = 1.31（95%CI 1.08至1.60））以及自然绝经女性的终身HRT（HR = 1.13（95%CI 1.00至1.27））与痴呆风险相关。因果中介分析表明，自然绝经年龄对痴呆风险的总效应中，高达4.7%由HbA1c水平介导，而空腹血糖和HbA1c均影响自然绝经女性终身HRT导致的痴呆风险增加。
我们观察到双侧卵巢切除术、子宫切除术、终身HRT以及自然绝经和手术的年龄与血糖之间存在关联。自然绝经年龄较早与痴呆风险增加相关，且HbA1c在一定程度上介导了这种关联。HRT与痴呆风险之间不一致的关联需要进一步研究。
