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HRT should be given earlier as menopause ‘reshapes the brainʼ – Nature Scientific Reports

Hormone replacement therapy should be seen as a “protective” measure for peri-menopausal women to halt “rewiring” of the brain and should be prescribed earlier, before changes become irreversible, according to a study in published in Nature Scientific Reports.

Menopause “reshapes the brain”, with women experiencing a sharp decline in oestrogen at this time, often leading to symptoms including hot flushes, brain fog and mood changes. Academics at Weill Cornell Medical College, New York, and the University of Arizona found the transition also has a significant impact on the brain, including a reduction in grey matter and changes in blood flow.

Dr Roberta Diaz Brinton, co-author of the study, said taking HRT as soon as menopause symptoms start could have significant protective benefits.

She described menopause as being “like a renovation project on the brain, a restructuring, a rewiring … the idea that we can just suck it up is actually deleterious to womenʼs long term health”.

“Using oestrogen and hormone therapy at the time of menopausal symptoms [is key], not 10 [or] 15 years later. The brain has already changed and itʼs no longer going to respond to oestrogen therapy,” she said.

Some drug companies have argued that if NHS red tape is cut to allow substitute HRT medications to be offered countrywide, shortages could be eased within days.

In the study, the US researchers analysed brain scans of 161 women aged between 40 and 65, compared with 125 men of the same age.

Hot flushes are explained by the changes to the hypothalamus, which regulates the body temperature and is very sensitive to temperature changes, said Dr Lisa Mosconi, study co-author.

“Oestrogen also plays a big role in regulating energy levels in brain activity, so if oestrogen is not regulating or activating those regions correctly, the brain fog makes a lot of sense,” she said.

The results also found some of the changes to the brain resolved or partly stabilised post-menopause, with recovery associated with an increased cognitive performance.

Study details

Menopause impacts human brain structure, connectivity, energy metabolism, and amyloid-beta deposition

Lisa Mosconi, Valentina Berti, Jonathan Dyke, Eva Schelbaum, Steven Jett, Lacey Loughlin, Grace Jang, Aneela Rahman, Hollie Hristov, Silky Pahlajani, Randolph Andrews, Dawn Matthews, Orli Etingin, Christine Ganzer, Mony de Leon, Richard Isaacson & Roberta Diaz Brinton.

Published in Nature Scientific Reports on 9 June 2021


All women undergo the menopause transition (MT), a neuro-endocrinological process that impacts aging trajectories of multiple organ systems including brain. The MT occurs over time and is characterised by clinically defined stages with specific neurological symptoms. Yet, little is known of how this process impacts the human brain. This multi-modality neuroimaging study indicates substantial differences in brain structure, connectivity, and energy metabolism across MT stages (pre-menopause, peri-menopause, and post-menopause). These effects involved brain regions subserving higher-order cognitive processes and were specific to menopausal endocrine ageing rather than chronological ageing, as determined by comparison to age-matched males. Brain biomarkers largely stabilised post-menopause, and grey matter volume (GMV) recovered in key brain regions for cognitive ageing. Notably, GMV recovery and in vivo brain mitochondria ATP production correlated with preservation of cognitive performance post-menopause, suggesting adaptive compensatory processes. In parallel to the adaptive process, amyloid-β deposition was more pronounced in peri-menopausal and post-menopausal women carrying apolipoprotein E-4 (APOE-4) genotype, the major genetic risk factor for late-onset Alzheimer’s disease, relative to genotype-matched males. These data show that human menopause is a dynamic neurological transition that significantly impacts brain structure, connectivity, and metabolic profile during midlife endocrine agieng of the female brain.


Nature Scientific Reports article – Menopause impacts human brain structure, connectivity, energy metabolism, and amyloid-beta deposition (Open access)


See more from MedicalBrief archives:


Early menopause may raise dementia risk later – UK study of 150,000 women


HRT not linked to increased risk of dementia — Largest study yet


Education needed regarding efficacy of HRT for most women


The evidence base for HRT: What can we believe?


Rise in menopause cases before UK employment tribunals



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