Study links menopausal hormone therapy to increased risk of dementia and Alzheimer's

By Dr. Sanchari Sinha Dutta, Ph.D.Jul 3 2023

A study of Danish women aged 50 – 60 reveals that continuous and cyclic menopausal hormone therapy can increase the risk of dementia and Alzheimer’s disease.

The study is published in the British Medical Journal (BMJ).

Study: Menopausal hormone therapy and dementia: nationwide, nested case-control study. Image Credit: Image Point Fr / Shutterstock

Background

Dementia refers to a group of symptoms affecting memory, thinking, and social abilities. It affects women more than men globally. Alzheimer’s disease is the most common form of dementia.

Estrogen is a steroid hormone responsible for the development and functioning of the female reproductive system. This hormone has both neuroprotective and neuro-damaging properties. Synthetic estrogen is commonly used as hormone replacement therapy for managing menopause-related symptoms.

Studies investigating the effect of menopausal hormone therapy on dementia risk have produced contradicting results. While some studies have shown a positive association between estrogen hormone therapy and the risk of dementia, some have reported no such association.

In this nationwide study, scientists have explored the association between continuous and cycling estrogen-progestin therapy and the risk of dementia in Danish women aged 50 – 60.

Study design

The study included 5,589 incident cases of all-cause dementia and 55,890 age-matched, dementia-free controls. The participants were identified between January 2000 and December 2018 from a nationwide population of all Danish women. The study participants had no history of dementia or contraindications for the use of menopausal hormone therapy at baseline.

The data on first-time dementia diagnosis or first-time prescription of dementia-specific medications were collected from National Registries to identify cases with all-cause dementia.

The analysis of menopausal hormone therapy included type of therapy (continuous or cyclic), duration of therapy, and age at usage.

Important observations

Among participants with all-cause dementia, about 79% had late-onset dementia, and 26% had Alzheimer’s disease. The median age of participants at diagnosis was 70 years. Compared to dementia-free participants, participants with all-cause dementia were more likely to have low educational background and family income. Dementia patients were more likely to live alone and have hypertension, diabetes, and thyroid disease.

Before the first diagnosis of dementia, about 32% of cases and 29% of controls had received combined estrogen-progestin hormone therapy. About 66% of them had treatment cessation more than 8 years before dementia diagnosis. About 8.7% of them were still undergoing treatment at the time of diagnosis.

The median age of treatment initiation was 53 years for both incident cases and controls. The median duration of treatment was 3.8 years and 3.6 years for cases and controls, respectively.

Among cases with estrogen-progestin therapy, about 25% and 39% had received continuous and cyclic progestin therapy, respectively, and 30% had received both continuous and cyclic estrogen-progestin therapy before the first dementia diagnosis. Similar proportions were noticed for dementia-free control participants.

Association between hormone therapy and risk of dementia

A higher risk of developing all-cause dementia was observed among participants who had received menopausal estrogen-progestin therapy compared to those who had never received hormone therapy. A similar association was observed for participants with late-onset dementia or Alzheimer’s disease.

The participants with longer treatment duration had a higher risk of all-cause dementia compared to those with shorter treatment duration. However, both continuous and cyclic treatment regimens had a similar impact on dementia risk.

The association between hormone therapy and dementia risk persisted for participants who only received menopausal estrogen-progestin therapy at the age of 55 years or younger. No association was observed between progestin-only therapy or vaginal estrogen-only therapy and the risk of all-cause dementia, late-onset dementia, and Alzheimer’s disease. 

Study significance

The study establishes a positive association between menopausal estrogen-progestin hormone therapy and the risk of all-cause dementia, late-onset dementia, and Alzheimer’s disease. This association persists for short-term users who receive the therapy only at the age of 55 years or younger.

As mentioned by the scientists, women receiving hormone therapy may have a predisposition to both menopause-related symptoms and dementia. With an observational study design, such residual bias cannot be excluded. Thus, further studies are required to establish a causal link between menopausal hormone therapy and the risk of dementia.