Category: Obstetrics & Gynaecology

Categories : Obstetrics & GynaecologyTags :

Why Women’s Health Drives Economic Resilience 

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By Merilynn Steenkamp, Managing Director, Southern Africa, Multi-Country Network, Roche Diagnostics

Across South Africa, women play a central role in sustaining economic activity. They lead classrooms, staff hospital wards, run small businesses, work in agriculture, build enterprises and manage households. In many communities, they are the primary earners and the primary caregivers.1

In March, as South Africa observes International Women’s Month, recognising women’s contribution also means ensuring that systems are structured to protect their health. Reliable access to early diagnostics remains one of the most practical levers available to support that protection.

When women experience illness, the impact extends well beyond a single diagnosis. Time away from work affects income, productivity and career progression. In informal employment, where many South African women operate without formal protections, illness can immediately reduce household earnings. The economic effects are felt first at the family level, then across communities.

Women make up the majority of South Africa’s health and social services workforce. They also carry a disproportionate share of unpaid care work in households². Globally, UN Women reports that women reinvest up to 90 percent of their income into their families and communities³. That reinvestment strengthens education, nutrition and long-term stability across generations.

Imagine a young nurse, working at a local clinic, earning a mid-level salary. As the sole breadwinner in her home, living month-to-month, she must use the funds available to pay school fees and associated costs for her children. As she also cares for her aged mother, five people rely on her steady income to survive. If she becomes seriously ill for an extended period of time, the effects are potentially catastrophic for her family, and compound pressure on the economy at large.

South Africa continues to carry a high burden of infectious diseases, including tuberculosis⁴ and HIV, while non-communicable diseases such as diabetes and cancer are rising. Cervical cancer remains the second most common cancer among South African women⁵. But when this cancer is detected early, the five-year relative survival rate exceeds 90 percent. That makes it imperative to raise awareness around early detection, as when cervical cancer is diagnosed at an advanced stage, survival drops significantly⁶.

Early and accurate diagnostics protect women’s ability to remain economically active, particularly for preventable illnesses. Early testing enables faster treatment, reduces complications and limits the need for more complex interventions later. In the case of infectious diseases, it also reduces transmission and protects colleagues, families and communities.

South Africa has a strong laboratory foundation to build on. The National Health Laboratory Service operates one of the largest diagnostic networks in the region, supporting large-scale testing every day⁷. Leveraging existing laboratory capacity allows screening and early detection programmes to expand in ways that are sustainable and aligned with national health priorities.

High-performance HPV testing, rapid HIV diagnostics, molecular tuberculosis testing and integrated blood panels are examples of tools that shorten the path from suspicion to confirmation. Reducing diagnostic delays supports workplace continuity and strengthens health system efficiency. In a country focused on improving workforce participation and economic resilience, this connection is direct.

Protecting women’s health strengthens household stability, supports workforce participation and reinforces economic resilience. Prioritising early diagnosis is a clear and measurable way to invest in South Africa’s long-term growth. 

It starts at home, with our mothers, sisters and daughters. Let’s keep reminding them, every now and then, to take a moment and consider their own well-being, for them, and for all of us.  

References

  1. Statistics South Africa. Quarterly Labour Force Survey (QLFS). Available at: https://www.statssa.gov.za/?page_id=16408
  2. Statistics South Africa. South Africa Time Use Survey. Available at: https://www.statssa.gov.za
  3. UN Women. Facts and figures: Economic empowerment. Available at: https://www.unwomen.org
  4. World Health Organization. Global Tuberculosis Report. Available at: https://www.who.int/teams/global-tuberculosis-programme/tb-reports
  5. Cancer Association of South Africa (CANSA). Cervical cancer. Available at: https://cansa.org.za/cervical-cancer/
  6. National Cancer Institute. Cervical Cancer Survival Rates. Available at: https://www.cancer.gov/types/cervical/survival
  7. National Health Laboratory Service (NHLS). About NHLS. Available at: https://www.nhls.ac.za/

Categories : Neurology Obstetrics & GynaecologyTags :

More Evidence Tying Epilepsy Drugs in Pregnancy to Developmental Risks

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Study adds weight to previously reported risks and calls for monitoring of new antiseizure drugs

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Findings published by The BMJ reinforce previous research linking use of the antiseizure drug valproate during pregnancy to neurodevelopmental disorders such as ADHD and autism in children, and indicate no substantial risk for several other antiseizure drugs including levetiracetam and lamotrigine.

However, the researchers say continued monitoring of the few signals – possible associations between a medicine and an unintended side effect – that emerged (eg, for zonisamide) will be important.

Antiseizure drugs are commonly and increasingly used by women of childbearing age for conditions like epilepsy, bipolar disorders, and migraine prevention. Women with epilepsy are advised to continue taking these during pregnancy, as uncontrolled seizures pose risks to both mother and child.

Yet, while valproate use during pregnancy has been linked to impaired neurodevelopment in children, information on other antiseizure drugs is limited.

To address this gap, researchers analysed claims data for pregnancies with diagnosed epilepsy from two large US public and commercial insurance databases, spanning the period from 2000 to 2021.

They compared 14,993 children exposed to at least one antiseizure medication during the second half of pregnancy with 8,887 unexposed children. Of these, 5,505 were followed for at least 5 years and 2,516 for at least 8 years after birth.

Potentially influential factors including mother’s age, ethnicity, mental health, substance use, other medication use and underlying conditions were also taken into account.

Valproate and zonisamide showed associations with several neurodevelopmental disorders, whereas levetiracetam and phenytoin were not associated with an increased risk of any of the studied outcomes.

Although no meaningful associations were found for topiramate and lamotrigine across most outcomes, there was a potential signal for intellectual disability (both drugs) and learning difficulty (topiramate only). However, the authors note that  these findings are based on small numbers and require confirmation in follow-up studies.

Several other drugs were also associated with a risk increase for intellectual disability. However, the authors note that these estimates are based on small numbers and therefore should be interpreted with caution.

Carbamazepine and oxcarbazepine also showed a modest risk increase for ADHD and behavioral disorders.

This is an observational study, so no definitive conclusions can be drawn about cause and effect, and the authors point to several limitations including relying on insurance claims data and the potential influence of other unmeasured factors such as underlying epilepsy type and severity.

However, the use of two large nationwide databases of insured pregnant women linked to their children enhanced the generalisability of their findings and enabled them to assess the risk of specific neurodevelopmental disorders associated with individual antiseizure medications. Results were also consistent after additional analyses, suggesting that they are robust.

As such, they conclude: “Our study reinforces the substantial risks of neurodevelopmental disorders associated with prenatal valproate exposure and suggests the need to further evaluate the safety of zonisamide during pregnancy.”

“Continued monitoring of newer antiseizure drugs and the few potential signals that emerged (ie, the moderate increased risk of ADHD and behavioural disorder after carbamazepine and oxcarbazepine exposure, and the association of several antiseizure drugs with intellectual disability) will be important,” they add.

Source: BMJ Group

Categories : Obstetrics & Gynaecology Surgeries & ProceduresTags :

“Two-for-one” C-section and Tummy Tuck Idea Alarms Surgeons

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The ‘mommy makeover’ is trending, and a growing number of patients are now asking whether cosmetic procedures such as a tummy tuck, liposuction, or breast augmentation can be performed at the same time as a Caesarean section. But surgeons warn that combining elective cosmetic surgery with a C-section can sharply escalate risk during an already vulnerable period for the body.

Professor Chrysis Sofianos, a triple-board certified plastic surgeon and Academic Head of the Division of Plastic and Restorative Surgery at the University of the Witwatersrand, says procedures such as a tummy tuck should only be considered once the body has adequately recovered after childbirth – typically around six months after delivery, depending on individual healing.

“Our practice is seeing a growing number of patients ask whether body-contouring surgery can be performed while they are already in theatre for a C-section. But this reflects a dangerous misunderstanding of surgical safety and postpartum physiology.

“While the idea may appear efficient or financially attractive, pairing medically necessary obstetric surgery with elective cosmetic procedures significantly increases operative risk at a time when the patient is physiologically vulnerable.”

Combining surgeries and compounding risks

C-sections account for around 75% of private sector hospital births in South Africa. Professor Sofianos notes that because there is often an overlap between women accessing private medical care and those who may later consider elective cosmetic procedures, more patients are likely to ask whether these operations can be combined.

“However, the more important question is whether they should. And the simple answer is no,” he says. “A C-section is already a major abdominal operation. Introducing additional surgical trauma before the body has recovered would introduce excessive strain and substantially raise the risk of complications.”

Pregnancy and the immediate postpartum period are associated with a hypercoagulable state, meaning the blood has an increased tendency to clot. Postpartum women therefore face a markedly elevated risk of venous thromboembolism, particularly in the first six weeks after delivery. Prolonging operative time and increasing tissue disruption may further elevate this risk by contributing to immobility, tissue stress, and inflammatory response.

A C-section on its own carries recognised complications, including haemorrhage, infection, anaesthetic complications, and clotting risk. Adding abdominoplasty (tummy tuck) can introduce additional risks such as bleeding, fluid accumulation, wound breakdown, delayed healing, and blood clots.

Liposuction also introduces risks, such as fluid imbalance, internal injury, infection, and, in rare but serious cases, fat embolism – a potentially life-threatening condition in which fat enters the bloodstream and compromises vital organs.

The false economy of combining procedures

Professor Sofianos also notes that combining procedures rarely provides the financial or practical advantages patients may assume.

“There is a common a misconception that theatre and anaesthetic fees can be consolidated if surgeries are combined into a single session. In reality, longer operative times, greater monitoring requirements, and the potential for complications may result in far higher medical costs. More importantly, financial reasoning should never supersede patient safety.”

He adds that the combined recovery period can also be far more demanding than patients anticipate.

“Recovery after a C-section already places significant physical, emotional, and psychological demands on a new mother. Adding major cosmetic surgery to that recovery period can complicate mobility, wound care, and pain management at a time when the patient must also care for a newborn.

“A more intensive recovery process may further require extended postoperative care, closer medical oversight, and additional support at home, all of which can add to the existing financial burden.”

Finally, he warns that operating during the immediate postpartum period might not produce the optimal long-term aesthetic result a patient may be looking for, and could expose them to unnecessary revision surgery later.

“Medically and ethically, I do not believe combined C-section and ‘mommy makeover’ surgeries should ever be considered. No responsible surgeon should minimise the compounded risks associated with performing such procedures. Ultimately, safe, staged care remains the gold standard for medical care, or allowing the body to recover fully before elective cosmetic surgery is undertaken.”

Categories : Obstetrics & GynaecologyTags :

Uneven Adherence to Magnesium Sulfate, Steroids in High-risk Pregnancies

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Prenatal magnesium sulfate and steroids can reduce the risks of cerebral palsy and respiratory complications in preterm infants. A review in the International Journal of Gynecology & Obstetrics found that despite being recommended internationally for pregnant women at risk of preterm delivery, these medications are used variably between and within countries.

When they analysed 2012–2024 information on 45 619 babies born at 24–32 weeks’ gestation at 1111 hospitals in an international network, along with information from the UK National Neonatal Research Database and a literature review, investigators found that on average, less than half of infants had been exposed to preterm magnesium sulfate in middle-income countries, and approximately three-quarters in high-income countries. Even within high-income countries, there were large discrepancies in care. Preterm steroids were used more frequently with less variation, although treatment gaps were still apparent.

“Our study has highlighted the international disparities in how two key treatments to protect pre-term babies are implemented. These gaps aren’t because of a lack of evidence,” said corresponding author Hannah B. Edwards, MA, MSc, of the University of Bristol, in the UK. “Lessons can be learned from successful implementation programs like PReCePT, which has transformed use of magnesium sulphate in pre-term births in England. The bigger-picture goal should now be to ensure that no matter where a baby is born, their mother has access to the evidence-based treatments that offer the best start in life.”

Source: Wiley

Categories : Obstetrics & GynaecologyTags :

Yawns in Healthy Foetuses Might Indicate Mild Distress

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Foetuses yawn in the womb, with more yawns associated with a lower weight at birth

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Even in the womb, where all oxygen is provided by the parental placenta, foetuses can – and do – yawn. More yawns during observation were associated with a lower weight at birth – potentially indicating mild foetal stress in the womb, according to a study published February 25, 2026 in the open-access journal PLOS One by Damiano Menin, of the Università degli Studi di Ferrara in Italy, and colleagues.

Yawning is a behaviour found across vertebrates – and no one quite knows why. In humans, foetuses yawn in the womb from about 11 weeks. Even though there is no air to breathe, they slowly open their mouths, make motions similar to inhalation and exhalation, and close their mouths again. To understand more about foetal yawns, the authors of this study used ultrasound to observe 32 healthy foetuses (56% female, 44% male) between 23 and 31 weeks. Each foetus was observed for 22.5 minutes.

The authors found that the foetuses yawned between zero and six times during the observation period, with an average of 3.63 yawns per hour. They also showed that foetuses that yawned more during their observations were more likely to have a low weight at birth, which is considered as an indicator of mild distress – though all foetuses in the study were born healthy.

The researchers did not perform any manipulations to see if they could affect foetal yawning and also did not record measures such as foetal heart rate or maternal temperature which might potentially be associated with the behaviour. Additionally, no high-risk pregnancies were observed. Based on their research, the authors suggest that frequent foetal yawning might be a sign of mild distress in the healthy foetus.

The authors add: “We found that yawning frequencies in the womb are negatively related to birth weight, potentially indicating a stress-related response in healthy fetuses. This suggests that even before birth, yawning may serve as an indicator of a foetus’s well-being.”

Provided by PLOS

Categories : Neurology Obstetrics & GynaecologyTags :

Second Pregnancy Uniquely Alters Women’s Brains

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A second pregnancy changes women’s brains in the same way as a first pregnancy, but in a different way than the first time. This is according to researchers from Amsterdam UMC, published in the scientific journal Nature Communications. The findings of Elseline Hoekzema and her colleagues show that a second pregnancy uniquely changes a woman’s brain, entailing both convergent and distinct neural transformations.

An earlier study by Elseline Hoekzema was the first to demonstrate that pregnancy changes the structure of the human brain. The research group also demonstrated that pregnancy changes the functioning of the brain. For the follow-up study, the results of which have now been published, 110 women were monitored: some were becoming mothers for the first time, others were having their second child, and a third group remained childless. Brain scans before and after pregnancy showed what changes occurred in the brain. “We have shown for the first time that the brain not only adapts during the first pregnancy, but also during the second,” says Hoekzema, head of the Pregnancy Brain Lab at Amsterdam UMC.

Different brain networks

The biggest changes during a first pregnancy occurred in the structure and activity of the so-called Default Mode Network. This part of the brain is important for many functions, including self-reflection and social processes. During a second pregnancy, this network changed again, but less dramatically. However, during a second pregnancy, there were more changes in brain networks related to paying attention and responding to stimuli. “It seems that during a second pregnancy, the brain changes more significantly in networks involved in responding to sensory stimuli and directing your attention,” explains researcher Milou Straathof, who analyzed the data. “These processes can be beneficial when caring for multiple children.”

Mental health of mothers

The researchers also found a connection between the changes in the brain and the bond between mother and child. This link was more prominent in the first pregnancy than during the second pregnancy. In addition, the researchers observed links between structural brain changes and peripartum depression, both during a first and a second pregnancy. This provides the first evidence that the changes that occur in a woman’s cerebral cortex during pregnancy are related to depression. In women who became mothers for the first time, this was particularly noticeable after giving birth. In women who had their second child, this was the case during pregnancy. “This knowledge can help us to better recognize and understand mental health issues in mothers. We must understand how the brain adapts to motherhood.”

The importance of research into the maternal brain

This study provides new insights into how the female brain adapts to motherhood and contributes to closing this important knowledge gap about female biology. Hoekzema: “The majority of women become pregnant one or more times in their lives, but only now are researchers beginning to unravel how this affects the female brain.” The results may also contribute to better care for mothers, for example, in the prevention and treatment of postpartum depression. The study also shows that the brain is flexible and can continually adapt to major changes in life.

Read the publication in Nature Communications: The effects of a second pregnancy on women’s brain structure and function

Source: University of Amsterdam Medical Centers

Categories : Cancer Obstetrics & GynaecologyTags :

Does a Past Abortion or Miscarriage Affect Breast Cancer Risk?

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Photo by National Cancer Institute

The potential effect of induced abortion and miscarriage on the risk of breast cancer has remained debated and has been a persistent source of misinformation. Many previous studies have been small and based on self-reported data. Now, a study published in Acta Obstetricia et Gynecologica Scandinavica found that prior abortion or miscarriage was not linked with an increased risk of developing pre- or postmenopausal breast cancer.

In the nationwide Finnish registry-based study, investigators analysed data on 31 687 women with breast cancer diagnosed in 1972–2021 and 158 433 women without breast cancer.

The risk of breast cancer was found to be similar among women with a history of induced abortion and women with no history of abortion, both before and after 50 years of age. Risks were also similar among women with and without a past miscarriage.

In addition, breast cancer risks did not vary significantly by the number of abortions or miscarriages, nor by the time of first abortion or miscarriage.

“Miscarriage or induced abortion as potential risk factors for breast cancer has continued to raise concerns and has led to the spread of misinformation. In this study using high-quality Finnish registry data, we can reliably eliminate these concerns,” said corresponding author Oskari Heikinheimo, MD, PhD, of the University of Helsinki and Helsinki University Hospital. “Induced abortion or miscarriage are not risk factors for breast cancer, even if there are several of them. This information is important and reassuring for millions of women around the world.”

Source: Wiley

Categories : Obstetrics & GynaecologyTags :

Research Links High Doses of Antioxidants to Offspring Birth Defects

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Antioxidants have been marketed as miracle supplements, touted for preventing chronic diseases and cancers; treating COPD and dementia; and slowing aging. While antioxidant therapies are widely used to treat male infertility, a new study from the Texas A&M College of Veterinary Medicine and Biomedical Sciences (VMBS) found that regularly consuming high doses of antioxidants negatively influences sperm DNA and may lead to offspring born with differences in craniofacial development.

In a study, published in the journal Frontiers in Cell and Developmental Biology, a team of researchers led by Dr Michael Golding examined the effects of N-acetyl-L-cysteine (NAC) and selenium (Se) – two widely used antioxidants – in mouse models.

They found that offspring of male mice exposed to antioxidants for six weeks exhibited skull and facial shape differences, even while the father’s health didn’t change.

These findings suggest that men should exercise caution when consuming high doses of antioxidants, especially if they’re planning to have children in the near future.   

When good goes too far

Antioxidants like NAC — which is a key ingredient in many nutritional supplements, including multivitamins — are often used to treat oxidative stress, which can be caused by excessive alcohol consumption.

Because Golding’s lab has been studying the effects of parental alcohol consumption on offspring – and has successfully correlated this consumption to a whole host of issues in children born to males who consumed excessive amounts of alcohol, including craniofacial abnormalities – his team was interested in the impacts of adding NAC or Se to a male mouse’s diet.

“We know alcohol causes oxidative stress and we were looking to push back on it by adding a supplement known to lower oxidative stress,” said Golding, a professor in the VMBS’ Department of Veterinary Physiology and Pharmacology. “When we realised that offspring born to males that had only been given NAC were displaying skull and facial differences, it was a surprise because this molecule is universally thought to be good.

“When we sat down to think it through, we realised that it makes sense – you take a multivitamin to ensure that you’re in balance, but if the thing that you’re taking to ensure you’re in balance is unbalanced (the dose of antioxidants is too high), then you’re not doing a good thing.”

It is well established that high doses of antioxidants can have negative impacts; research has proven that antioxidants can diminish the effects of exercise in endurance athletes, for example, and, in the case of professional athletes, can lead to negative outcomes in performance metrics.

“Sperm health is another performance metric; it’s just not one that we think about in everyday life,” Golding said. “If you’re taking a high dose antioxidant, you could be diminishing your reproductive fitness and part of the journey toward the bad outcome is going to be the effects on the offspring.”

What the face reveals about the brain

Among their unanticipated findings was that female offspring, in particular, exhibited significantly closer-set eyes and smaller skulls, which are also symptoms of foetal alcohol syndrome.

“There’s a very commonly accepted truism in paediatric medicine that the face mirrors the brain, because the brain and the face form at the same time,” Golding said. “When your face migrates (during gestation), it’s using cues from your brain to know where to go, and if the two things are not aligned, there’s either a delay or some kind of abnormality in brain development.

“So, if you see abnormalities in the midline of the face, you’re probably going to see midline abnormalities in the brain,” he said. “People with these abnormalities typically have problems with impulse control, neurological conditions like epilepsy, and other developmental issues.”

Whether the offspring in this project will exhibit central nervous system dysfunction will require further study.

The dose makes the difference

While the lab continues to research this “unexplored frontier,” Golding says in the case of antioxidants, too much of a good thing can, in fact, be too much, especially in the absence of a medical reason to take an antioxidant supplement.

Because many men regularly take high doses of these supplements – including products that contain antioxidant-rich ingredients – it’s important to pay attention to how much of these compounds are listed on the label. This includes NAC, which is one of the key ingredients in many multivitamins and is often found in high doses in these pills.

“The larger message here is that there’s a balance,” Golding said. “Think of yourself as a plant — if you stick your plant out in the sun too long, it’s going to get dehydrated. If you overwater your plant, it gets root rot. But if you have the right balance of sunshine and water, that’s when growth occurs. Health is in that domain.

“If your vitamins are providing 1,000% of the recommended daily amount, you should be cautious,” he said. “If you stick to the 100% range, then you should be OK.”

Categories : Gastrointestinal Obstetrics & GynaecologyTags :

Do Hormones Explain Why Women Experience More Gut Pain?

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UCSF researchers discover that oestrogen can turn on pain signals associated with conditions like irritable bowel syndrome.

A zoomed in image of the lining of the colon. Cells that produce the hormone  PYY (peptide YY) are in green. Cells that produce the neurotransmitter serotonin are in magenta. PYY triggers the release of serotonin, which activates pain-sensing nerve fibers. Image by Archana Venkataraman/UCSF

Women are dramatically more likely than men to suffer from irritable bowel syndrome (IBS), a chronic condition causing abdominal pain, bloating, and digestive discomfort. Now, scientists at UC San Francisco have discovered why.

Oestrogen, the researchers report in Science, activates previously unknown pathways in the colon that can trigger pain and make the female gut more sensitive to certain foods and their breakdown products. When male mice were given oestrogen to mimic the levels found in females, their gut pain sensitivity increased to match that of females.

The findings not only explain the female predominance in gut pain disorders but also point to potential new ways to treat the conditions.

“Instead of just saying young women suffer from IBS, we wanted rigorous science explaining why,” said Holly Ingraham, PhD, professor UCSF and co-senior author of the study. “We’ve answered that question, and in the process identified new potential drug targets.”

The research also suggests why low-FODMAP diets – which eliminate certain fermentable foods, such as onions, garlic, honey, wheat, and beans – help some IBS patients, and why women’s gut symptoms often fluctuate with their menstrual cycles.

“We knew the gut has a sophisticated pain-sensing system, but this study reveals how hormones can dial that sensitivity up by tapping into this system through an interesting and potent cellular connection,” said co-senior author David Julius, PhD. Julius won the 2021 Nobel Prize for Physiology or Medicine for his work on pain sensation.

Search for oestrogen

Previous research had hinted that oestrogen was to blame for higher rates of IBS in females, but not why. To understand how oestrogen might be involved, Ingraham’s and Julius’s teams first needed to see exactly where the hormone was working in the gut.

“At the time I started this project, we didn’t know where and how oestrogen signalling is set up in the female intestine,” said Archana Venkataraman, PhD, a postdoc in Ingraham’s lab and co-first author of the research. “So, our initial step was to visualise the oestrogen receptor along the length of the female gut.”

The team expected to see oestrogen receptors in enterochromaffin (EC) cells, which were already known to send pain signals from the gut to the spinal cord. Instead, they got a surprise: oestrogen receptors were clustered in the lower part of the colon and in a different cell type known as L-cells.

The scientists pieced together a complex chain reaction that occurs when oestrogen binds to the L-cells. First, oestrogen causes L-cells to release a hormone called PYY (peptide YY). PYY then acts on neighbouring EC cells, triggering them to release the neurotransmitter serotonin, which activates pain-sensing nerve fibres. In female mice, removing the ovaries or blocking oestrogen, serotonin, or PYY dramatically reduced the high gut pain observed in females.

For decades, scientists believed PYY primarily suppressed appetite – drug companies even tried developing it as a weight-loss medication. But those clinical trials failed due to a troubling side effect that was never fully explained; participants experienced severe gut distress. The new findings mesh with this observation and suggest a completely new role for PYY.

“PYY had never been directly described as a pain signal in the past,” said co-first author Eric Figueroa, PhD, a postdoc in Julius’ lab. “Establishing this new role for PYY in gut pain reframes our thinking about this hormone and its local effects in the colon.”

This video shows what happens to the enterochromaffin (EC) cells in the colon when they are treated with PYY. Upon PYY treatment, calcium activity increases in the EC cell, causing it to fluoresce more brightly as it releases serotonin that is detected by nearby pain-sensing nerve fibres. Video by Eric Figueroa/UCSF

A link between IBS and diet

Increased PYY wasn’t the only way that L-cells responded to oestrogen. Levels of another molecule, called Olfr78, also went up in response to the hormone. Olfr78 detects short-chain fatty acids – metabolites produced when gut bacteria digest certain foods. With more Olfr78 receptors, L-cells become hypersensitive to these fatty acids and are more easily triggered to become active, releasing more PYY.

“It means that oestrogen is really leading to this double hit,” said Venkataraman. “First it’s increasing the baseline sensitivity of the gut by increasing PYY, and then it’s also making L-cells more sensitive to these metabolites that are floating around in the colon.”

The observation may explain why low-FODMAP diets help some IBS patients. FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) are carbohydrates that gut bacteria ferment into those same fatty acids sensed by Olfr78. By eating fewer FODMAPs, patients may be preventing the activation of Olfr78, and, in turn, keeping L-cells from churning out more of the pain signalling PYY.

While men have this same cellular pathway, their lower oestrogen levels keep it relatively quiet. However, the pathway could engage in men taking androgen-blocking medications, which block the effects of testosterone and can elevate oestrogen in some cases, potentially leading to digestive side-effects.

The new work suggests potential ways to treat IBS in women and men alike.

“Even for patients who see success with a low-FODMAP diet, it’s nearly impossible to stick to long term,” Ingraham said. “But the pathways we’ve identified here might be leveraged as new drug targets.”

The researchers are now studying how such drugs might work, as well as asking questions about what other hormones, such as progesterone, might play a role in gut sensitivity and how pregnancy, lactation, and normal menstrual cycles affect intestinal function.

By Sarah C.P. Williams

Source: University of California – San Francisco

Categories : Cancer Obstetrics & GynaecologyTags :

Hot Flush Treatment has Anti-breast Cancer Activity, Study Finds

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A drug mimicking the hormone progesterone has anti-cancer activity when used together with conventional anti-oestrogen treatment for women with breast cancer, a new Cambridge-led trial has found.

In the two-week window that we looked at, adding a progestin made the anti-oestrogen treatment more effective at slowing tumour growth. What was particularly pleasing to see was that even the lower dose had the desired effectRebecca Burrell

A low dose of megestrol acetate (a synthetic version of progesterone) has already been proven as a treatment to help patients manage hot flushes associated with anti-oestrogen breast cancer therapies, and so could help them continue taking their treatment. The PIONEER trial has now shown that the addition of low dose megestrol to such treatment may also have a direct anti-cancer effect.

Around three-quarters of all breast cancers are ER-positive. This means the tumours are abundant in a molecule known as an oestrogen receptor, ‘feeding’ on the oestrogen circulating in the body. These women are usually offered anti-oestrogens, medication that reduces level of oestrogen and hence deprives the cancer of oestrogen and inhibits its growth. However, reducing oestrogen levels can bring on menopause-like symptoms, including hot flushes, joint and muscle pain, and potential bone loss.

In the PIONEER trial, post-menopausal women with ER-positive cancers were treated with an anti-oestrogen with or without the progesterone mimic, megestrol. After two weeks of treatment, those that received the combination saw a greater decrease in tumour growth rates compared to those treated with an anti-oestrogen only.

Although further work is required in larger patient cohorts and over a longer period of time to confirm the findings, researchers at the University of Cambridge say the trial suggests that megestrol could help improve the lives of thousands of women for whom anti-oestrogen medication causes uncomfortable side-effects and can lead to some women stopping taking the medication.

PIONEER was led by Dr Richard Baird from the Department of Oncology at the University of Cambridge and Honorary Consultant Medical Oncologist at Cambridge University Hospitals NHS Foundation Trust (CUH). He said: “On the whole, anti-oestrogens are very good treatments compared to some chemotherapies. They’re gentler and are well tolerated, so patients often take them for many years. But some patients experience side effects that affect their quality of life. If you’re taking something long term, even seemingly relatively minor side effects can have a big impact.”

Some ER-positive breast cancer patients also have high levels of another molecule, known as progesterone receptor (PR). This group of patients also respond better to the anti-oestrogen hormone therapy.

To explain why, Professor Jason Carroll and colleagues at the Cancer Research UK Cambridge Institute used cell cultures and mouse models to show that the hormone progesterone stops ER-positive cancer cells from dividing by indirectly blocking ER. This results in slower growth of the tumour. When mice treated with anti-oestrogen hormone therapy were also given progesterone, the tumours grew even more slowly.

Professor Carroll, who co-leads the Precision Breast Cancer Institute and is a Fellow of Clare College, Cambridge, said: “These were very promising lab-based results, but we needed to show that this was also the case in patients. There’s been concern that taking hormone replacement therapy – which primarily consists of oestrogen and synthetic versions of progesterone (called progestins) – might encourage tumour growth. Although we no longer think this is the case, there’s still been residual concern around the use of progesterone and progestins in breast cancer.”

To see whether targeting the progesterone receptor in combination with an anti-oestrogen could slow tumour growth in patients, Dr Baird and Professor Carroll designed the PIONEER trial, which tested adding megestrol, a progestin, to the standard anti-oestrogen treatment letrozole.

A total of 198 patients were recruited at ten UK hospitals, including Addenbrooke’s Hospital in Cambridge, and randomised into one of three groups: one group received only letrozole; one group received letrozole alongside 40mg of megestrol daily; and the third group received letrozole plus a much higher daily dose of megestrol, 160mg. In this ‘window of opportunity’ trial, treatment was given for two weeks prior to surgery to remove the tumour. The percentage of actively growing tumour cells was assessed at the start of the trial and then again before surgery.

In findings published today in Nature Cancer, the team showed that adding megestrol boosted the ability of letrozole to block tumour growth, with comparable effects at both the 40mg and 160mg doses.

Joint first author Dr Rebecca Burrell from the Cancer Research UK Cambridge Institute and CUH said: “In the two-week window that we looked at, adding a progestin made the anti-oestrogen treatment more effective at slowing tumour growth. What was particularly pleasing to see was that even the lower dose had the desired effect.

“Although the higher dose of progesterone is licenced as an anti-cancer treatment, over the long term it can have side effects including weight gain and high blood pressure. But just a quarter of the dose was as effective, and this would come with fewer side effects. We know from previous trials that a low dose of progesterone is effective at treating hot flushes for patients on anti-oestrogen therapy. This could reduce the likelihood of patients stopping their medication, and so help improve breast cancer outcomes. Megestrol – the drug we used – is off-patent, making it a cost-effective option.”

Because women in the trial were only given megestrol for a short period of time, follow-up studies will be needed to confirm whether the drug would have the same beneficial effects with reduced side-effects over a longer period of time.

The research was funded by Anticancer Fund, with additional support from Cancer Research UK, Addenbrooke’s Charitable Trust and the National Institute for Health and Care Research Cambridge Biomedical Research Centre.

Personalised and precise cancer treatments underpin the focus of care at the future Cambridge Cancer Research Hospital. The specialist facility planned for the Cambridge Biomedical Campus will bring together world-leading researchers from the University of Cambridge and its Cancer Research UK Cambridge Centre and clinical excellence from Addenbrooke’s Hospital under one roof in a brand-new NHS hospital.

Reference

Burrell, RA & Kumar, S, et al. Evaluating progesterone receptor agonist megestrol plus letrozole for women with early-stage estrogen-receptor-positive breast cancer: the window-of-opportunity, randomized, phase 2b, PIONEER trial. Nature Cancer; 5 Jan 2026: DOI: 10.1038/s43018-025-01087-X

Republished from University of Cambridge under a Creative Commons licence.

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