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Hormone therapies: can they prevent Alzheimer’s?

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A new study from the University of Health Sciences in Arizona found that women on hormone therapy were up to 58 percent less likely to develop neuro-degenerative diseases including Alzheimer’s disease. The risk reduction varied by type, route of administration, and duration of hormone therapy. The findings could lead to the development of a new precision medicine approach to prevent neurodegenerative diseases. But this new study goes against the trend of other research which showed that, on the contrary, hormones can have a negative effect on cognitive function. How are things then? We asked the professor Paolo Maria Rossini, Director of the Neuroscience and Neurorehabilitation Department of Irrcs San Raffaele, Rome.

Research on the protective role of estrogen

The study, published in Alzheimer’s & Dementia: Translational Research & Clinical Interventions, found that women undergoing menopausal hormone therapy for six years or more were 79 percent less likely to develop Alzheimer’s and 77 percent less. of likelihood of developing neurodegenerative diseases. “This is not the first study on the impact that hormone therapies can have on reducing neurodegenerative diseases,” he said. Roberta Diaz Brinton, director of the Arizona Center for Innovation in Brain Science and lead author of the research. “But the innovative aspect of this study is that it reveals the possibility of using precision hormone therapies in the prevention of neurodegenerative diseases, including Alzheimer’s.”

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Hormone Replacement Therapy

Hormone therapy is considered to be the most effective treatment for menopausal symptoms, which can include hot flashes, night sweats, insomnia, weight gain, and depression. During the study, the researchers looked at the care requests of nearly 400,000 menopausal women aged 45 or older. Specifically, they looked at the effects of individual hormone therapy drugs approved by the U.S. Food and Drug Administration, including estrogen and progestogen, and those of therapies for neurodegenerative diseases. In addition, they assessed the impacts on the risk of developing the disease of the type of hormone therapy, but also of the route of administration – oral versus transcutaneous – and duration.

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The results of the study

In this study, the researchers found that using the natural steroids estradiol or progesterone resulted in a greater reduction in risk than using synthetic hormones. Oral hormone therapies reduced the risk of neurodegenerative diseases, while hormone therapies administered through the skin reduced the risk of developing dementia. The overall risk was reduced most in patients aged 65 years or older. Furthermore, the protective effect of therapy lasting more than one year on Alzheimer’s, Parkinson’s disease and dementia was greater than with therapy given for less than a year. “The reduced risk of Alzheimer’s, Parkinson’s and dementia means these diseases share a common estrogen-regulated driver, and if there are common drivers, there may be common therapies,” said Brinton, who has been involved in neurodegenerative diseases for over 25 years. and the aging of the female brain. “The key is that hormone therapy is not a treatment, but it keeps the brain and the entire system running, leading to prevention. It is not reversing the disease; it’s preventing disease by keeping the brain healthy. “

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Lo studio Menopause

But not all studies agree on the protective role of hormones. For example, a 25-year research just published online in ‘Menopause’ has shown that longer exposure to endogenous estrogen is linked – in cognitively normal older women – to higher levels of CSF biomarkers of Alzheimer’s disease. So how are things? “It is an endless story that cyclically returns”, explains Paolo Maria Rossini, ?????. “Already in the 90s this epidemiological observation had emerged not only for the estrogen-progestin ‘replacement’ therapy taken to counteract the symptoms of menopause, but also for some anti-inflammatories, including some formulations of steroids”.

From theory to clinical practice

The problem is that despite these repeated reports, that is, those who had taken this type of treatment for a certain time then seemed to get sick less frequently, when we moved on to real clinical trials things went differently. “Even giving these drugs to asymptomatic subjects, but perhaps with some risk factor such as familiarity – explains Rossini – it was never shown superiority over placebo during the follow-up, that is, they fell ill with dementia with the same frequency and severity of those who did not take hormones ”.

Caution and more research

So how are the conclusions reached by this new study to be considered? “Until a clinical trial of treatment and prevention is carried out – explains the neurologist – it is difficult to make objective assessments. In this case, the use of the more ‘natural’ formulations (or at least defined as such by the researchers) would require a prospective placebo trial in a large population with an adequate follow-up of at least 5 years. Otherwise we will never know whether or not what they hypothesized on epidemiological data has a concrete relapse of treatment and prevention in the true sense of the term “. In short, based on the studies released so far it is still not clear whether in the future we could prevent neurodegeneration with hormones.

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Male hormones and Alzheimer’s

Is it possible to hypothesize a role of hormones also for men? “This is a whole other world not explored at all”, Rossini replies. “There are very ‘pilot’ studies with small numbers and short follow-ups from which no serious conclusions can be drawn.”


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