Menopausal Hormone Therapy Linked to Dementia Risk

The terapia hormonal sustitutiva (THS) or hormone replacement therapy that is used to alleviate the menopause symptomssuch as bothersome hot flashes and night sweats, is administered as pills, patches placed on the skin, gels, creams, or injections, which contain estrogen or a combination of estrogen and progestin.

Long-term use of menopausal hormone therapy has been linked to adverse effects such as increased risk of developing dementia in large observational studies, and now large research from Denmark that has been published in the scientific journal The BMJ suggests that the Use of menopausal hormone therapy is associated with a higher rate of dementia and Alzheimer’s.

This is the largest observational study on this topic to date and has shown an increased risk in long-term users of HRT, but also in short-term users around the age of menopause (55 years or younger). ), as currently recommended.

Women who had received estrogen-progestin therapy had a 24% increased rate of developing all-cause dementia and Alzheimer’s

For this reason, its authors call for new research to be carried out “to explore whether the association observed in this study between the use of hormone therapy in menopause and the increased risk of dementia illustrates a causal effect”, and they emphasize that it is justified. further study “to determine whether these findings represent a true effect of menopausal hormone therapy on dementia risk, or whether they reflect an underlying predisposition in women who need these treatments.”

In an editorial published in the same journal, US researchers note that while this study has several strengths, the observed associations should not be used to infer a causal relationship between hormone therapy and dementia risk, noting that “risk factors Confusion could be producing a false signal of an increased risk of dementia in younger women using hormone therapy for a short or long term,” so “these findings cannot inform shared decision-making about the use of hormone therapy.” for menopausal symptoms.

Higher dementia rates with long-term use of HRT

Scientists in Denmark evaluated the association between the use of combined estrogen-progestin therapy (synthetic progestin) and the development of dementia according to the type of hormone treatment, duration of use, and age of use. Taking data from the national registry, they identified 5,589 cases of dementia and 55,890 without dementia (controls) age-matched between 2000 and 2018 of all Danish women aged 50-60 in 2000 with no history of dementia and no known reason preventing them from using the hormone therapy for menopause.

Other factors that could influence the results, such as educational and economic level or suffering from hypertension, diabetes or thyroid problems, were also taken into account. The median age at diagnosis was 70 years. Before a diagnosis, 1,782 (32%) cases and 16,154 (29%) controls had received estrogen-progestin therapy since a mean age of 53 years. The median duration of use was 3.8 years for dementia cases and 3.6 years for controls.

The results reveal that, compared with people who had never used the treatment, women who had received estrogen-progestin therapy had a 24% increased rate of developing all-cause dementia and Alzheimer’s disease, including those who received treatment at age 55 or younger. Rates were highest with longer use, from 21% for one year or less to 74% over 12 years of use.

The increased rate of dementia was similar between continuous (estrogen and progestin taken daily) and cyclical (estrogen plus progestin taken 10 to 14 days per month) treatment regimens. The use of progesterone alone and vaginal estrogen were not associated with the development of dementia.

An observational study that cannot determine the cause

Being a observational study, the authors have not been able to establish the cause, nor have they been able to separate vascular dementia from other types of dementia, nor to distinguish the effects of pills from other forms of hormone therapy delivery, such as patches. Importantly, they also have not been able to rule out the possibility that women using hormone therapy may have a greater predisposition to both vasomotor symptoms of menopause and dementia.

However, its findings should be taken into account because it is a large study based on high-quality treatment data and with a long follow-up time. In addition, its authors have been able to investigate the formulations of cyclical and continuous hormones separately, as well as the age of initiation of menopausal hormone therapy and the duration of treatment, which allowed them to analyze an important aspect such as the risk of dementia. in short-term users of menopausal hormone therapy around the age of menopause onset, as recommended in treatment guidelines.

Sarah-Naomi Jamesprincipal investigator of the MRC Unit for Lifelong Health and Aging at University College London (United Kingdom) has highlighted some limitations of the study in statements to SMC Spain: “the study has fundamental limitations in its ability to interpret and understand the true causal pathways underlying the observed association, as both exposure (why HRT would be prescribed in the first place, and why certain types and duration of medication use would be prescribed) and outcome (diagnosis of dementia) have many things at stake. that influence them, so this association may be artificial.

“For example, changes in sleep or mood are very common symptoms of menopause and reasons to request HRT; At the same time, we are beginning to understand that sleep and mood may play an important role in the expression and progression of dementia.” And he adds that: The best way to find out if HRT medication causes dementia is through clinical trials. and, to date, there is insufficient evidence to support a direct relationship with medication, so this new study should not change practice [clínica]”.

“What is clear from this study is that more research is warranted to understand the exacerbated risk of Alzheimer’s in women, including the role and patterns of HRT in dementia-causing diseases, but also to understand the broader context. comprehensive, covering the symptoms of menopause, as well as the course of life and sociocultural influences that affect women in this transition period of their lives”, concludes the expert.

For his part, Cindy Farquhar, postgraduate professor of Obstetrics and Gynecology at the University of Auckland (New Zealand) and editor-coordinator of Cochrane Gynaecology and Fertility, believes (also in statements to SMC Spain): “In general, the risk of dementia throughout life for 65-year-old women is 1 in 5. Women with symptoms, particularly hot flashes and sleep disturbances, should consider the findings of this study and weigh the benefits (improvement of symptoms) against possible harms, including increased risk of developing dementia and Alzheimer’s. Women can choose to continue using hormone therapy, but it may be advisable to limit its use to one year at the lowest dose that improves symptoms. There is a motto that probably applies in this case: ‘the best medicine is less medicine’. In the future, research could focus on the use of estrogen-only and progesterone, as this was not associated with an increased risk of dementia. [en el estudio danés]”.


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