Menopause
Post-menopause memory decline linked to loss of oestrogen production in brain tissue – study
Oestrogen loss in brain tissue may help explain memory decline after menopause and women’s higher Alzheimer’s risk, a preclinical study suggests.
The findings suggest females may be especially sensitive to the loss of brain oestrogen in old age.
Scientists said the work could point to future treatments focused on restoring the brain’s supportive environment before memory loss develops.
Dr Hong Zhao, research professor of obstetrics and gynaecology in the division of reproductive science in medicine at Northwestern University Feinberg School of Medicine, said: “This study tells us that females, but not males, may be uniquely sensitive to loss of brain oestrogen at old age, potentially contributing to an increased risk of Alzheimer’s disease.”
Researchers at Northwestern University studied young and old male and female mice, with and without loss of brain oestrogen.
The study focused on the extracellular matrix, or ECM, a network of molecules in the space between brain cells. It helps support communication between cells and is important for memory, brain development and brain health. The ECM makes up nearly 20 per cent of the brain’s volume.
The ECM is especially abundant in the hippocampus, a part of the brain involved in learning and memory.
Scientists found that oestrogen loss, ageing and female sex were closely linked to changes in the ECM. The study is the first to examine oestrogen loss in the ECM.
The findings may help explain why women are at higher risk of Alzheimer’s disease, although the research was carried out in mice and further work is needed to understand whether the same mechanisms apply in humans.
Nearly two-thirds of people with Alzheimer’s disease in the US are women, but the reasons for this higher risk remain unclear.
Scientists have long suggested that falling oestrogen levels after menopause may reduce the brain’s natural protection against memory loss and neurodegeneration. Neurodegeneration means the gradual damage or loss of nerve cells in the brain.
Dr Serdar Bulun, chair of the department of obstetrics and gynaecology at Feinberg and a Northwestern Medicine physician, said: “We have provided some of the most compelling evidence that oestrogen is so important for memory function and other mood functions in the female brain.
“This should motivate clinicians to be more aware of the essential role of oestrogen for women’s brains, because once memory is gone, it’s gone.”
Before menopause, the ovaries are the main source of oestrogen in women. After menopause, oestrogen levels drop sharply, and only small amounts are produced in other parts of the body, including the brain, fat tissue, bone, muscle, blood vessels and breast tissue.
In mice, oestrogen is produced locally in the brain and gonadal fat in males, whereas in females it is produced mainly in the brain.
Research has shown that women with Alzheimer’s disease may have even lower oestrogen levels in the brain than women without the disease. The study further supports that.
The researchers used genetically engineered mouse models that lacked aromatase, an enzyme needed to produce oestrogen, either throughout the whole body or only in the brain.
They examined how the loss of oestrogen affected memory, behaviour and social function in male and female mice at young and old ages.
They also analysed changes in gene expression across the entire genome in the hippocampus in mice with brain-specific oestrogen loss at young and old ages in both sexes.
The authors said the findings suggest the ECM could become a target for future treatments.
Current Alzheimer’s treatments such as lecanemab and donanemab are designed to remove amyloid, an abnormal protein build-up in the brain that is one of the main signs of the disease.
However, researchers said it is still unclear how much these treatments help to slow memory loss or improve everyday functioning. Some studies suggest small benefits, while others show little meaningful improvement.
The study suggests a different approach could focus on restoring the brain’s supportive environment to help protect memory.
Zhao said: “Our findings will hopefully motivate future studies to better understand how this matrix is altered in postmenopausal women, and how it could potentially induce susceptibility to Alzheimer’s disease.”
Hormone replacement therapy, or HRT, has also been studied as a possible way to protect women from Alzheimer’s disease by restoring oestrogen levels.
However, clinical studies have produced mixed results, with some suggesting benefits for memory and cognitive function while others show little benefit or possible harm.
Zhao said differences may depend on the type of hormone treatment used, the age at which it begins and differences in study design.
She said: “More research is needed to understand how oestrogen affects the female brain and why oestrogen loss increases AD risk in women.
“Understanding these mechanisms could help researchers develop safer and more effective HRT strategies to prevent or slow the progression of AD in women.”
One in three US women older than 35 are no sure whether they are in perimenopause, new research has revealed.
The findings suggest uncertainty remains common, largely because of knowledge gaps, symptom confusion and difficulty getting confirmation or care.
Perimenopause is the transitional stage before a woman’s final period, when hormone levels fluctuate and symptoms can change over time.
It usually begins in the mid-40s, although timing varies widely, and can last for around four to eight years.
Symptoms can include hot flushes, psychological symptoms and urogenital symptoms, which affect the urinary and genital areas.
Dr Stephanie Faubion, medical director for The Menopause Society and one of the study authors, said: “This large study showed that one in three US women aged older than 35 years are not sure whether they are in perimenopause.
“Further, the study highlights that symptom confusion, misconceptions, and barriers to care are leaving many women without the clarity and support they need during the menopause transition.
“Recognising perimenopause uncertainty as a common experience can help shift the conversation from searching for a diagnosis to providing women with the information, validation, and support they need to navigate this natural life transition with confidence.”
More than 7,600 US women aged 35 and older took part in the study, which looked at how common uncertainty around perimenopause is and what may be driving it.
Overall, 34 per cent of participants said they were unsure of their reproductive stage.
Uncertainty varied by age and symptom burden, reaching 42 per cent among women aged 40 to 44 and 37 per cent among those with severe symptoms.
Symptom confusion was the most common factor, cited in 56 per cent of responses.
This included difficulty making sense of bodily changes and telling perimenopause apart from other possible causes, such as premenstrual syndrome, thyroid disease or mental health conditions.
Knowledge gaps and information-seeking made up 28 per cent of responses, reflecting limited awareness, age-based assumptions and attempts to find reliable information.
Barriers to confirmation and care made up 16 per cent, including dismissive healthcare encounters and reluctance to acknowledge perimenopause.
Younger women aged 35 to 39 were more likely to cite knowledge gaps, while healthcare barriers were most common among women aged 40 to 44.
The researchers said clinicians should take a more flexible approach to recognising the emotional, cognitive and physical symptoms that can occur during perimenopause.
They said healthcare professionals should not rely too heavily on irregular periods as the main sign, because some women have symptoms before major cycle changes.
A new menopause drug has been approved for NHS use in Scotland, offering a non-hormonal option for women who cannot take HRT.
The Scottish Medicines Consortium has recommended that women can now be prescribed fezolinetant, also known as Veoza, for symptoms such as hot flushes and night sweats.
Some women cannot take HRT, leaving them with limited treatment options for symptoms that can be severe and long-lasting.
Dr Timir Patel, medical director of Astellas UK, said the company was “pleased that this important additional treatment option will be available to women in Scotland, helping to support more personalised care for those experiencing hot flushes and night sweats”.
Fezolinetant works by selectively blocking a neurotransmitter in the brain involved in triggering hot flushes.
Clinical trials have shown the drug can reduce both the frequency and severity of hot flushes and night sweats.
About 400,000 women in Scotland are said to be of menopausal age, with manufacturer Astellas Pharma Ltd saying up to 48,000 could benefit from the treatment.
Dr Rob Peel, chair of the Scottish Medicines Consortium, said: “We know that menopausal hot flushes and night sweats can substantially affect quality of life.
“For those who cannot take HRT, effective treatment options are limited. Fezolinetant provides a non-hormonal treatment option, and we know our decision will be welcomed.”
Dr Kay McAllister, consultant gynaecologist and clinical lead for menopause services at NHS Glasgow and Greater Clyde, said: “Today’s decision marks a positive development for the wellbeing of Scottish women.
“In clinical practice, I see how hot flushes and night sweats impact sleep and overall quality of life in my patients.
“The availability of this targeted treatment offers a welcome choice and further options for patients.”
Avni Wellness has secured Rs 4 crore, around US$470,000, in seed funding to expand its products and digital commerce capabilities.
The Mumbai-based women’s health start-up plans to strengthen its online retail operations and increase its presence across digital marketplaces.
It will also expand its cycle nutrition product range and grow its women-led network of micro-entrepreneurs.
Founded in 2021 by Sujata Pawar and Apurv Agarwal, Avni Wellness offers science-backed, toxin-free products spanning adolescence, reproductive years and menopause.
Its portfolio includes a patented antimicrobial reusable sanitary pad and a liposomal iron supplement designed to address iron deficiency among women in India.
Liposomal supplements encase nutrients in tiny fat-like particles intended to support absorption.
The company also offers products for polycystic ovary syndrome, or PCOS, calcium supplementation, urinary and vaginal health and seed-based hormonal nutrition. PCOS is a condition that can affect hormone levels, periods and fertility.
Proteus Partners led the funding round, with participation from angel investors Puru Gupta, Sreejith Moolayil, A. Velumani and Somya Nigam.
Avni Wellness said it aims to address gaps in women’s healthcare in India by focusing on hormonal health, nutrition and long-term wellbeing while incorporating livelihood generation and sustainability into its model.
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