Menopausal Hormone Therapy and Dementia

https://doi.org/10.1136/bmj-2022-072770.

Introduction:

Dementia rates in women are higher than men worldwide. This suggests that there are more risk factors within women for dementia. Oestrogen is a female sex hormone required for bone strength, to stimulate puberty, the menstrual cycle and pregnancy. It is known to have both protective and damaging properties on the nervous system. During menopause, oestrogen levels tend to drop, which can lead to symptoms such as hot flashes. To control oestrogen levels, many people undergo hormone replacement therapy, which consists of low doses of oestrogen. Some of these drugs also contain progestin, which is a synthetic replacement for progesterone (the female sex hormone responsible for stimulating the menstrual cycle). However, there could be an adverse effect of menopausal hormone therapy (HRT) on the risks of dementia.

Previous Research:

Early analyses linking HRT and dementia suggested that the hormones actually had a protective effect on the development of Alzheimer’s (a disease that is the most common cause of dementia). However, in 2003, a randomised trial was conducted by the Women’s Health Initiative called the ‘Memory Study’ which reported that menopausal hormone therapy was associated with an increased risk of dementia. Large scale studies have also found that menopausal therapy was positively associated with risks of dementia, but only if taken for a long period of time. The effect of short term use of menopausal hormone therapy was still undiscovered, but this study aimed at finding or negating the correlation.

Summary:

These women were tested to eradicate any family histories of dementia that could act as a confounding variable, breast cancer, gynaecological cancers and other diseases. Women who had undergone a hysterectomy (removal of the uterus) were excluded. In women who already had dementia, the study identified the first time they were diagnosed. Previous prescriptions dating back to two years before the women’s first diagnosis of dementia were obtained, specifically concerned with their history of menopausal hormone therapy. The scientists looked at women who used a combination of oestrogen and progestin in their drugs, as this combination was suggested to have the greatest effect on dementia risk. The researchers tried to use women who had similar backgrounds in their education, and similar levels of hypertension and thyroid disease, which could have acted as confounding variables for the study. The control variable for this experiment was females who did not have dementia, but were of similar ages as the women that were found to have dementia. The methodology involved estimating the duration of use of this progestin-oestrogen drug, which could have either been administered as one combined drug formulation, or as two separate medications taken simultaneously. A program was used to calculate the most probable daily dose of each medication, and obtained the recommended minimum and maximum dosages.

Conclusion:

The exposure to menopausal hormone therapy with oestrogen and progestin was positively associated with the rate of onset/progression of dementia and Alzheimer’s disease. The increased rate of onset/progression dementia also existed in women who had undergone this therapy at 55 years or younger. Individual treatments of either progestin or oestrogen were not associated with the development of dementia. The strengths of this study included the large population selected, an almost complete history of the treatment, a relevant population and the ability to distinguish between oestrogen and progestin treatments. The limitations were that the study could not isolate a specific type of dementia in this study, so the disease was studied as a whole. Additionally, a confounding variable was that oral menopausal therapy is a risk factor for a stroke - and strokes are a risk factor for dementia. In conclusion, there was a positive correlation found between menopausal hormone therapy and the development of dementia.

By Vedika

Sources:

Contributors, WebMD Editorial. “Menopause and Hormone Replacement Therapy.” WebMD, www.webmd.com/menopause/menopause-hormone-therapy

‌Pourhadi, Nelsan, et al. “Menopausal Hormone Therapy and Dementia: Nationwide, Nested Case-Control Study.” BMJ, vol. 381, June 2023, p. e072770, https://doi.org/10.1136/bmj-2022-072770.

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