Imagine menopause as a maze of hormonal changes, with women searching for relief. Menopausal hormone therapy (MHT) is like a guide through this labyrinth, alleviating symptoms but leaving behind unanswered questions. A recent study in South Korea delves into the association between MHT and dementia risk, using a national health insurance database as their treasure map. The study included over 1.3 million patients, revealing that different types of MHT have varied effects on dementia occurrence. Tibolone and oral estrogen alone raised the risk of Alzheimer’s disease dementia, while transdermal estrogen had no association with dementia risk. Interestingly, certain MHTs increased the risk of non-Alzheimer’s disease dementia, including Tibolone, combined estrogen plus progestin by manufacturer (CEPM), and oral estrogen alone. However, other MHTs like combined estrogen plus progestin by physician (CEPP) and topical estrogen showed no such risk. These findings give us a glimpse into the intricate relationship between hormonal therapies and dementia. To fully grasp their impact, further exploration is encouraged!

IntroductionMenopausal hormone therapy (MHT) is used to alleviate the symptoms associated with menopause, despite the lack of recommendations for MHT in preventing dementia. Recent nationwide studies have explored the association between MHT and dementia risk, but the findings remain limited. This study aims to investigate the association between MHT and the incidence of Alzheimer’s disease (AD) and non-AD dementia using national population data from Korea.MethodsWe conducted a retrospective study using data from the National Health Insurance Service in Korea between January 1, 2002, and December 31, 2019. Women over 40 years were eligible for this study and classified into the MHT or non-MHT groups. The MHT group consisted of women who used Tibolone (TIB), combined estrogen plus progestin by the manufacturer (CEPM), estrogen, combined estrogen plus progestin by a physician (CEPP), and transdermal estrogen during menopause. We compared the risk of dementia between the MHT and non-MHT groups.ResultsThe study included 1,399,256 patients, of whom 387,477 were in the MHT group, and 1,011,779 were in the non-MHT group. The median duration of MHT was 23 months (range: 10–55 months). After adjusting for available confounders, we found that different types of MHT had varying effects on the occurrence of dementia. TIB (HR 1.041, 95% confidence interval (CI) 1.01–1.072) and oral estrogen alone (HR 1.081, 95% CI 1.03–1.134) were associated with a higher risk of AD dementia. In contrast, there was no difference in the risk of AD dementia by CEPM (HR 0.975, 95% CI 0.93–1.019), CEPP (HR 1.131, 95% CI 0.997–1.283), and transdermal estrogen (HR 0.989, 95% CI 0.757–1.292) use. The use of TIB, CEPM, and oral estrogen alone increased the risk of non-AD dementia (HR 1.335, 95% CI 1.303–1.368; HR 1.25, 95% CI 1.21–1.292; and HR 1.128, 95% CI 1.079–1.179; respectively), but there was no risk of non-AD dementia in the other MHT groups (CEPP and topical estrogen).ConclusionOur findings indicate that MHT has varying effects on the incidence of AD and non-AD dementia. Specifically, TIB, CEPM, and oral estrogen alone increase the risk of non-AD dementia, while transdermal estrogen is not associated with dementia risk. It is essential to consider the type of MHT used when assessing the risk of dementia in women.

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