Menopause age and type and dementia risk: a pooled analysis of 233 802 women

Objectives: It is not clear whether the association between younger age at menopause and increased risk of dementia is modified by type of menopause. We examined the association of age at menopause or hysterectomy with dementia risk in three groups of women: those with natural menopause, premenopausal bilateral oophorectomy (surgical menopause) or premenopausal hysterectomy (without bilateral oophorectomy).

Study design: Individual-level data from 233 802 women in five prospective cohort studies (from four countries) were harmonized and pooled. Cox proportional hazards models were used to assess the associations of age at natural menopause, surgical menopause or premenopausal hysterectomy, with age at dementia, death (where available) or end of follow-up, whichever came first.

Results: The study followed women to the median age of 72 years (quartiles 67, 76 years). The median follow-up time was 13 years, with 3262 dementia cases during this period. Compared with women with menopause at 50-52 years, women with menopause <40 years had a higher risk of dementia (adjusted hazard ratio (aHR): 1.47, 95% confidence interval (CI): 1.39, 1.56). This level of risk was comparable to that of current smoking and stroke, which are well-established risk factors for dementia. Increased risk of dementia associated with surgical menopause or premenopausal hysterectomy (compared to natural menopause) was not apparent after adjustment for age at menopause (aHR 0.99, 95% CI: 0.93, 1.04 and aHR 0.97, 95% CI: 0.95, 1.00, respectively).

Conclusion: Women who experience menopause before the age of 40 years have a higher risk of dementia irrespective of type of menopause.