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The complex relationship between brain health and menopausal hormone therapy
A study suggests that menopausal hormone therapy (MHT) might have moderate effects on brain health, but this depends on past surgical history, the duration of treatment, and a woman’s age at last use.
The research investigates the associations between MHT and brain health in a large population of UK women.
Ovarian hormones such as oestrogens and progesterone fluctuate throughout a woman’s lifespan, and particularly during the years preceding menopause when ovarian function starts to decline.
MHT is often prescribed to minimise the symptoms of these fluctuations during the menopausal transition and is commonly thought to protect the brain and reduce the risk of Alzheimer’s disease, but the evidence to support this is conflicting.
The researchers used data from the UK Biobank, which contains de-identified genetic, lifestyle and health information and biological samples.
They analysed data from nearly 20,000 women who had MRI brain scans and were either current or past users of MHT or had never used MHT at all, most of whom reported to have passed menopause.
They studied brain MRI images to determine the ‘brain age gap’ – the difference between chronological and brain age – as well as other proxies of brain health.
Women who had taken MHT in the past had no significant difference in brain age to never-users.
But women who were current MHT users had on average higher grey and white-matter brain age gaps – indicating their brain age was older than their actual chronological age – than women who had never taken MHT. They also had smaller left and right hippocampus brain volumes.
Moreover, amongst past users, the age the women were when they last took MHT made a difference. Those who were older at the time of their last use after menopause had a higher brain age gap and lower hippocampal volumes. Similar results were found for women who took MHT for a longer duration.
Women on MHT who had surgery to remove their womb and/or both ovaries had a lower brain age gap than women on MHT without the same surgical history.
And unexpectedly, there was no difference in MHT-related variables such as dose or active ingredients, whether it was synthetic or bioidentical, or taken as a pill or a patch.
The researchers also assessed whether a known risk gene for Alzheimer’s disease, called APOE ɛ4, influenced the effect of MHT on proxies of brain health and found no link here either.
In considering the results, the authors commented that while some modest adverse brain health characteristics were associated with current MHT use and women being an older age at last use, the findings do not support a general neuroprotective effect of MHT nor severe adverse effects on the female brain.
Lead author Claudia Barth, a researcher in the Division for Mental Health and Substance Abuse at Diakonhjemmet Hospital, Oslo, Norway, said: “The results suggest subtle yet complex relationships between MHT use and brain health, highlighting the necessity for a personalised approach to MHT use. Importantly, our analyses provide a broad view of population-based associations and are not designed to guide individual-level decisions regarding the benefits versus risks of MHT use.”
The authors add that current MHT users were significantly younger than past and never-users and around a lower proportion were postmenopausal (67 per cent versus 80 per cent), suggesting that a larger proportion of these women may have been in perimenopause which is often associated with neurological symptoms such as cognitive decline and mood changes.
The need for MHT might therefore be an indicator of neurological changes during this transition, which then stabilise later in life, they suggest.
“Our results indicate that the effect of MHT on female brain health might vary depending on factors including timing, duration of use and past surgical history,” concludes senior author Ann Marie de Lange, senior research fellow in the Department of Clinical Neurosciences, Lausanne University Hospital, Switzerland.
“However, our study is cross-sectional and we cannot establish causality. Future studies mapping the long-term impacts of MHTs on brain health are of immense importance to understand individual risk profiles and benefits.
“Women worldwide face critical decisions regarding MHT use, yet the current lack of comprehensive research leaves them without the necessary evidence to make informed choices.”
An AI atlas has mapped how reproductive organs age through menopause, with the ovaries, vagina and uterus changing on different timelines.
To better understand how this process affects health, researchers at the Barcelona Supercomputing Center developed what they describe as the first large-scale atlas of female reproductive system ageing, using artificial intelligence.
The team combined 1,112 tissue images from 659 samples, covering 304 women aged 20 to 70, with gene expression data from thousands of genes.
This allowed them to reconstruct how seven key reproductive organs, including the uterus, ovary, vagina, cervix, breast and fallopian tubes, age over time.
The study used the supercomputing power of MareNostrum 5 together with advanced image-recognition methods to process the data.
Using deep learning techniques, the researchers detected visible tissue changes as well as the underlying molecular processes linked to ageing in each organ.
The result was a detailed, organ-by-organ map of the reproductive system’s ageing process.
The researchers found that not all organs age in the same way or at the same speed. The ovaries and vagina showed a more gradual ageing process that begins even before menopause officially starts.
By contrast, the uterus appeared to undergo more sudden changes around the time of menopause.
Even within a single organ, different tissues aged at different rates. In the uterus, for example, the mucosa, its inner lining, and the muscular layer did not change in sync. These tissues also appeared to be particularly sensitive to the hormonal and biological shifts associated with menopause.
Marta Melé, leader of the transcriptomics and functional genomics group at BSC and director of the study, said: “Our results show that it acts as a turning point that profoundly reorganises other organs and tissues of the reproductive system, and allows us to identify the genes and molecular processes that could be behind these changes.”
Building on the finding that organs age according to different patterns, co-first author Laura Ventura said the research “paves the way for personalised medicine where treatments are tailored to a woman’s specific molecular profile and the specific tissues showing the most age-related distress.”
The study also identified molecular signals linked to reproductive ageing that can be detected in blood samples from more than 21,441 women.
These biomarkers could allow doctors to monitor the condition of reproductive organs in a non-invasive way, potentially helping to anticipate risks such as pelvic floor complications without the need for biopsies.
According to the researchers, this could lead to simpler and more accessible clinical tools for tracking women’s health over time.
Ovarian cancer cases are rising among younger adults in England, with bowel cancer showing a similar pattern, a new study suggests.
Researchers said excess weight is a key contributor, but is unlikely on its own to explain the pattern.
The authors wrote: “These patterns suggest that while similar risk factors across ages are likely, some cancers may have age-specific exposures, susceptibilities, or differences in screening and detection practices.”
They added: “Although overweight and obesity are linked to 10 of the 11 cancers evaluated and account for a substantial proportion of cancer cases, both BMI-attributable and BMI-non-attributable incidence rates have increased, though the latter more slowly, suggesting other contributors.”
The study analysed cancer incidence, meaning new diagnoses, in England between 2001 and 2019 across more than 20 cancer types, comparing adults aged 20 to 49 with those aged 50 and over.
Among younger women, cases of 16 out of 22 cancers increased significantly over the period, while among younger men, 11 out of 21 cancers increased significantly.
In particular, there was a significant rise in 11 cancers with known behavioural risk factors among adults under 50. These were thyroid, multiple myeloma, liver, kidney, gallbladder, bowel, pancreatic, endometrial, mouth, breast and ovarian cancers.
Rates of all 11 also rose significantly among adults aged 50 and over, with the notable exceptions of bowel and ovarian cancer.
Five cancers, endometrial, kidney, pancreatic, multiple myeloma and thyroid cancer, increased significantly faster in younger than in older women, while multiple myeloma increased faster in younger than in older men.
The researchers looked at established risk factors including smoking, alcohol intake, diet, physical inactivity and body mass index, a measure used to assess whether someone is underweight, a healthy weight, overweight or obese.
With the exception of mouth cancer, all 11 cancers were associated with obesity. Six, liver, bowel, mouth, pancreatic, kidney and ovarian, were also linked to smoking.
Four, liver, bowel, mouth and breast, were associated with alcohol intake. Three, bowel, breast and endometrial, were linked to physical inactivity, and one, bowel, was associated with dietary factors.
But apart from excess weight, trends in those risk factors over the past one to two decades were stable or improving among younger adults.
That suggests other factors may also play a part, including reproductive history, early-life or prenatal exposures, and changes in diagnosis and detection.
The study noted that red meat consumption fell among younger adults, while fibre intake remained stable or slightly improved in both sexes between 2009 and 2019, although more than 90 per cent of younger adults were still not eating enough fibre in 2018.
Established behavioural risk factors accounted for a substantial share of cancer cases.
Excess weight was the risk factor associated with most cancers in 2019, ranging from 5 per cent for ovarian cancer to 37 per cent for endometrial cancer.
The researchers said the findings were based on observational data, meaning the study could identify patterns but could not prove cause and effect.
They also noted there were no consistent long-term national data for several risk factors, that the analysis was limited to England rather than the UK, and that cancer remains far more common overall in older adults despite the rise in cases among younger people.
Early miscarriage care after a first loss could prevent about 10,000 pregnancy losses a year in the UK, according to a new study.
The study by Tommy’s National Centre for Miscarriage Research and Birmingham women’s hospital involving 406 women found a 4 per cent reduction in the risk of future miscarriage for women on the graded model of care compared with usual care.
Women in England, Wales and Northern Ireland currently become eligible for specialised NHS care for early baby loss only after they have had at least three miscarriages.
Tommy’s has called for women to become eligible after one miscarriage, saying this could reduce the risk of future miscarriages and improve health outcomes for mothers.
Researchers said that would translate to 10,075 fewer miscarriages a year across the UK.
Kath Abrahams, chief executive of Tommy’s, said women were being “left without early access to services that could help prevent future losses and reduce the debilitating feelings of isolation and hopelessness that we know affect so many who experience pregnancy loss”.
She said: “Our pilot study indicates that providing support after a first miscarriage, with escalating care after further losses, is not only effective but achievable without significant additional workload for NHS teams who are already working extremely hard to deliver good care.
“Put simply, it is the right thing to do. We will do all we can to drive that change across the UK so that more women and families are supported after every miscarriage.”
The graded model of miscarriage care proposed by Tommy’s is already available in Scotland, and the charity is calling for it to be introduced across the whole of the UK.
The graded model includes nurse-led support after one miscarriage, with advice on reducing risk factors such as low vitamin D, folic acid intake, alcohol consumption and caffeine use.
Women who received the specialised care were 47 per cent more likely to have a risk factor identified and receive relevant advice to help prevent future miscarriages than women receiving usual care, the study found.
Among women who had experienced two miscarriages and received the specialised care, one in five were found to have thyroid dysfunction or anaemia, both conditions that can affect pregnancy outcomes.
About one in four pregnancies ends in miscarriage, most often within the first 12 weeks of pregnancy.
The report comes ahead of the long-awaited final findings of the government’s investigation into maternity care in England. Interim findings uncovered a range of failures, including claims that NHS hospitals that caused harm to women and babies during childbirth often resorted to a “cover-up” of their mistakes, falsified medical records and denied bereaved parents answers.
Women’s health minister Gillian Merron said: “Pregnancy and baby loss can have a devastating impact on women and families, who too often feel they have been left without the care and support they need.
“I welcome the findings of this important report, and this will be carefully considered as part of our ongoing work to make sure women get the high-quality, compassionate NHS care they deserve.”
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