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The complex relationship between brain health and menopausal hormone therapy

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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.”

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Congress urged to invest over $20bn to close women’s health gap

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Congress is being urged to invest US$20bn over 10 years to close the women’s health gap.

The American College of Obstetricians and Gynecologists, the Society for Women’s Health Research and the Women First Research Coalition have unveiled the National Strategy to Close the Women’s Health Gap.

The framework calls for a coordinated national effort to improve women’s health research, care and outcomes.

It says women make up more than half of the US population, but their health needs across conditions and life stages have been understudied and underserved for decades.

Kathryn Schubert, president and chief executive of the Society for Women’s Health Research, said: “The women’s health gap has persisted for far too long.

“This strategy offers Congress a road map to improve health outcomes, drive innovation, and build a healthier future for women, families, and communities.”

The strategy notes that Congress required women to be included in National Institutes of Health-funded clinical research through the NIH Revitalization Act in 1993.

However, it says major gaps remain in women’s health research, clinical care and how evidence is put into practice.

The plan proposes US$7bn for research and innovation, including expanded federal investment in women’s health research across the NIH, VA, DoD and the Advanced Research Projects Agency for Health.

It would also establish a Women’s Health Research Interdisciplinary Fund at the NIH and create a national network of Women’s Health Centers of Excellence.

The centres would aim to accelerate the translation of research into clinical care and serve as training sites for researchers and clinicians.

A further US$1bn would be used for regulatory coordination and modernisation, including cross-agency collaboration and work to address sex differences in drug and treatment approvals.

Sex differences are biological differences between females and males that can affect disease risk, symptoms, treatment response and side-effects.

The funding would also support updated NIH tracking systems for women’s health research investment and publication standards on how sex as a biological variable is considered in research.

The strategy calls for US$4bn for data and evidence infrastructure, including a public-private partnership focused on women’s midlife health data.

It would also convene a public workshop to review existing women’s health research datasets and develop common data elements to fill gaps and make datasets more widely available.

Another US$7bn would go towards strengthening the clinical and research workforce.

This would include career pathways, loan repayment programmes, a women’s health clinical workforce loan repayment programme modelled on the National Health Service Corps and interdisciplinary training.

The workforce measures would include particular emphasis on rural and underserved areas.

The final US$1bn would support public awareness and education campaigns to improve health literacy, preventive care and participation in women’s health research.

Health literacy means a person’s ability to find, understand and use health information to make decisions about care.

The campaigns would use digital and traditional media developed in consultation with patient advocacy organisations and relevant medical societies.

Sandra E Brooks, chief executive of the American College of Obstetricians and Gynecologists, said: “Closing the women’s health gap requires not only funding research, but also investment in the people who conduct that research and those who translate research findings and discoveries into better patient care.

“Strengthening the women’s health research and clinical workforce is critical to accelerating the innovation needed to improve health outcomes for women.”

The strategy says women have higher annual out-of-pocket healthcare costs than men and live 25 per cent of their lives in poorer health.

Supporters say this strengthens the economic and public health case for long-term congressional investment.

The framework has been endorsed by organisations across women’s health, ageing, heart disease, autoimmune disease, cancer, reproductive medicine and neurological conditions, including the Women’s Alzheimer’s Movement at Cleveland Clinic, the National MS Society and UsAgainstAlzheimer’s.

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Stardust period tracker shares health data, study reveals

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Stardust shared sensitive period tracking data with third-party analytics firms, according to new privacy research from Mozilla.

The findings expose a privacy divide in femtech, where users often trust apps with highly sensitive reproductive health information.

The research was carried out by Mozilla’s Privacy Not Included team, which tested several period tracking apps.

It found that Stardust, a period tracker used by millions, shared users’ reproductive health data with analytics companies, a practice the research said contrasted with its privacy-first marketing.

Analytics companies collect and examine information about how people use digital products, often to help businesses understand user behaviour or improve marketing.

The findings raise questions about whether privacy promises made by health apps match what happens to users’ data.

According to research reported by TechCrunch, one other period tracking app tested by Mozilla received what researchers called a “squeaky clean” rating, suggesting similar services can operate without sharing sensitive health data in the same way.

Period tracking apps have come under greater scrutiny in the US since the 2022 overturning of Roe v Wade, which removed federal constitutional protection for abortion.

Some users and privacy advocates have warned that menstrual and reproductive health data could potentially be sought in legal cases.

The research also points to a broader regulatory problem for consumer health apps.

In the US, many health apps are not covered by HIPAA, the health privacy law that applies to medical providers and some healthcare organisations.

That means some consumer apps may be able to collect, share or monetise sensitive health data under rules that differ from traditional healthcare privacy protections.

The femtech market, estimated in the report at US$50bn, has grown quickly, but privacy regulation has not always kept pace with app development.

Stardust had not publicly responded to Mozilla’s findings at the time of the original report, and its privacy policy remained live on its website.

The issue is particularly sensitive for period tracking because the data can reveal patterns around fertility, pregnancy, contraception and reproductive health.

Mozilla’s wider Privacy Not Included initiative has examined consumer technology products for privacy and security concerns since launching in 2017, including connected devices, children’s toys and health apps.

The findings come as US lawmakers continue to debate stronger federal privacy rules for sensitive health information collected by consumer apps.

The American Data Privacy and Protection Act, which has been stalled in Congress since 2023, includes provisions addressing sensitive health information collected by consumer apps.

Experts have also warned that anonymised health data can sometimes be re-identified when combined with other information, such as location data.

Re-identification means linking supposedly anonymous data back to a specific person.

A 2019 study found that menstrual cycle data combined with location information could identify individual users with high accuracy.

State-level privacy laws in places such as California, Virginia and Colorado have also given consumers new rights around personal data, although enforcement can vary.

Privacy advocates say the research underlines the need for clearer data practices, stronger safeguards and greater transparency in femtech.

For users, the findings are a reminder that health apps do not automatically protect health information in the same way as healthcare providers.

The report suggests period tracker companies that put privacy first may be better placed to build trust in a market where long-term use depends on confidence.

Mozilla’s investigation suggests privacy promises in femtech do not always match practice, and that period trackers can function without sharing sensitive user data in the same way.

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Juno Bio secures US$3.8m for precision diagnostics

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Juno Bio has secured US$3.8m to expand its diagnostics platform for vaginal health and reproductive care.

The funding round was led by Ada Ventures, with participation from Artesian, Entrepreneur First and Illumina Accelerator.

The women’s health startup said the seed funding will support the launch of its first CLIA-certified sequencing laboratory in Oakland, California, and a new clinical vaginal microbiome and STI test for healthcare providers.

CLIA certification refers to US laboratory standards for testing human samples used in diagnosis, prevention or treatment decisions.

Dr Leighton Turner, co-founder and chief scientific officer of Juno Bio, said: “The vaginal microbiome is still one of the least understood systems in the body at a clinical scale.

“With our lab, we’re starting to build a measurement standard that clinicians can actually use.

“We believe the level of detail from this kind of testing can meaningfully improve how vaginal healthcare is provided.”

The company is developing precision diagnostics for vaginal health, where patients can experience recurring symptoms, inconsistent diagnoses and treatments based on trial and error.

Juno Bio said bringing testing in-house gives it greater control over the process, from sample handling to results, while allowing it to refine its technology and build what it says is one of the largest datasets focused on the vaginal microbiome.

The vaginal microbiome is the community of bacteria and fungi that naturally live in the vagina. Changes in this balance can be linked to infections, symptoms and wider reproductive health issues.

Juno Bio’s newly launched clinical test examines the wider vaginal microbiome and screens for four common sexually transmitted infections, or STIs.

Rather than looking for a single cause, the test is intended to give clinicians a broader picture of what may be contributing to symptoms.

Juno Bio says this matters because multiple infections can occur at the same time and microbiome changes may be linked to fertility, menopause or recurrent infections.

Dr Anna Powell of Johns Hopkins said: “Vaginal microbiome testing has the potential to significantly reshape how we understand and manage vaginal health, particularly for patients with recurrent or unexplained symptoms.

“While the field is still evolving, advances in sequencing and data interpretation are moving us closer to a future where more personalised, microbiome-informed care can complement existing diagnostic approaches.”

Check Warner, co-founding partner at Ada Ventures, added: “Juno Bio is setting a new standard for how vaginal health is understood and managed.

“What they’ve built at this stage, with this level of capital efficiency, is exceptional.

“We’re proud to support the team as they scale their clinical infrastructure and continue leading innovation in this critically underserved category.”

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