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Oestrogens play a hidden role in cancers, inhibiting a key immune cell

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Oestrogens are known to drive tumour growth in breast cancer cells that carry its receptors, but a new study by Duke Cancer Institute researchers unexpectedly finds that oestrogens play a role in fuelling the growth of breast cancers without the receptors, as well as numerous other cancers.

The researchers describe how oestrogens not only decrease the ability of the immune system to attack tumours, but also reduce the effectiveness of immunotherapies that are used to treat many cancers, notably triple-negative breast cancers. Triple-negative breast cancers are an aggressive form of disease that are negative for oestrogen, progesterone, and the HER2 receptor proteins

Informed by retrospective analysis of patient data and experiments in mice, the researchers found that anti-oestrogen drugs reversed the effects of oestrogens, restoring potency to immunotherapies.

“The treatment for triple-negative breast cancer has been greatly improved with the advent of immunotherapy,” said senior author Donald McDonnell, Ph.D., professor in the departments of Medicine, Pharmacology and Cancer Biology, and Cell Biology at Duke University School of Medicine.

“Developing ways to increase the anti-cancer activity of immunotherapies is a primary goal of our research,” McDonnell said.

“Here we have found a simple way bolster the effectiveness of immunotherapy for this type of breast cancer and the benefit was even seen in other cancers, including melanoma and colon cancers.”

McDonnell and colleagues, including lead author Sandeep Artham, a postdoctoral associate in the McDonnell lab, focused on a type of white blood cell called eosinophils, which are typically activated during allergic reactions and inflammatory diseases.

Eosinophils have recently been identified as important in tumours, and a phenomenon called tumour associated tissue eosinophilia, or TATE, is associated with better outcomes among patients with multiple types of cancer, including colon, oesophageal, gastric, oral, melanoma and liver cancers.

In their studies, the Duke team described how oestrogens decrease the number of eosinophils and TATE in mice. The hormone contributes to increased tumour growth in oestrogen receptor-negative breast cancer tumours and in melanoma tumours, which do not rely on oestrogen receptors for tumour growth.

Conversely, anti-oestrogen therapies inhibited oestrogen receptor signalling and enhanced the efficacy of immunotherapies, slowing tumour growth.

“These findings highlight the importance of oestrogen-receptor signalling as a regulator of eosinophil biology and TATE and highlight the potential near-term clinical application of anti-oestrogen drugs to increase the benefits of immunotherapies in multiple tumour types,” McDonnell said.

He said clinical trials are being planned using an investigational anti-oestrogen drug called lasofoxifene among patients with triple-negative breast cancers.

The research has been published in the journal Science Advances.

Hormonal health

Study links small bowel microbiome differences to women’s health

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Small bowel microbiome differences between women and men may help explain why some conditions are more common in women, a study suggests.

The small bowel microbiome is the community of microorganisms living in this part of the digestive tract, where they play vital roles in immune function, metabolism and hormonal regulation.

Researchers found differences between women and men in the composition and organisation of these microbial communities. One bacterial community containing Granulicatella was found only in women.

The study was conducted by investigators at Cedars-Sinai Health Sciences University.

Ruchi Mathur, director of clinical research and clinical operations for the Medically Associated Science and Technology (MAST) Program at Cedars-Sinai and corresponding author of the study, said: “One intriguing finding was a bacterial community containing Granulicatella, which we found only in women.

“Bacteria in this community appear at increased levels in women with polyendocrine metabolic ovarian syndrome, formerly known as polycystic ovary syndrome.”

The researchers also identified differences between women and men in how microbes in the small bowel produce fructans, complex carbohydrates known to trigger digestive symptoms in irritable bowel syndrome (IBS).

IBS is far more common in women than men.

Mathur, who is also a professor of medicine, said: “Our findings show that biological sex is a critical variable in the small bowel microbiome.

“We must consider it as we move toward more personalised approaches to understanding and treating disease.”

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Fertility

Weight loss surgery improves menstrual health and PMOS symptoms, study finds

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Weight loss surgery was linked to more regular periods and fewer polyendocrine metabolic ovarian syndrome (PMOS) symptoms in women aged 18 to 45 living with obesity in a recent study.

The researchers recommend that women undergoing the procedure have access to preconception care and reproductive counselling to support their reproductive health.

Researchers at the University of Surrey analysed data over 24 months from 84 women who underwent bariatric surgery and 18 women living with obesity who did not have surgery.

Of those who underwent surgery, 49 had gastric bypass procedures and 35 had gastric sleeve surgery.

Women who underwent metabolic bariatric surgery lost more than 30kg on average at 12 and 24 months after the procedure.

Among women with polycystic ovaries, the condition persisted in only 10 per cent after 24 months.

Women also reported a resolution of clinical hirsutism, or excess body hair, by 12 months.

Women who had previously experienced irregular periods reported more regular menstrual cycles after surgery.

Professor Martin Whyte, co-author of the study and professor of metabolic medicine at the University of Surrey, said: “A large proportion of those undergoing bariatric surgery are women of reproductive age, who may be planning a pregnancy in the coming years.

“So much remains unknown about the impact of this type of surgery on women who are planning to have children.

“This raises the question of when the ideal time after surgery is to conceive.”

Women have a higher prevalence of obesity than men, with 57 per cent of women in the UK classified as overweight and 27 per cent living with obesity, which can affect fertility and the health of an unborn baby.

The researchers said 17 women had healthy pregnancies following surgery.

Although this was not specifically examined in the study, no difference in birth weight was observed between babies conceived within or after the first year.

Dr Kathryn Hart, co-author of the study and associate professor in nutrition and dietetics at the University of Surrey, said: “What we have found is that bariatric surgery positively affects the reproductive health of women living with obesity and can improve the likelihood of them having a healthy pregnancy after surgery.

“Dysregulated hormone levels, irregular periods and conditions such as polycystic ovaries are affected by obesity.

“By reducing this, what we have seen is that it can lead to improvements without the need for medication.

“We would suggest that clinicians consider medical intervention for obesity to treat irregularities in the menstrual cycle and issues with fertility.”

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Wellness

Women more likely than men to get health advice from influencers, study finds

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Young women are more likely than young men to get health and wellness information from social media influencers, a US survey has found.

Among adults aged 18 to 29, 57 per cent of women said they received health and wellness information from influencers, compared with 47 per cent of men.

The Pew Research Center study surveyed 5,023 US adults and examined how young people consume health and wellness content online.

Local university students said influencer content frequently appeared in their social media feeds.

Kabija Koroma, a local university student, said: “It’s more exercise stuff, more like protein and like meals and like how to get ready and like the outfits of the day of videos on TikTok or lately. My favourite ones.”

About 51 per cent of women under 30 said they often consumed influencer content focused on beauty and personal appearance, compared with 18 per cent of men.

The study also found that 21 per cent of women often saw content about therapies outside mainstream medicine, compared with 10 per cent of men.

At least one-third of both young women and young men often encountered influencer content about mental health and weight loss. Around half or more of both groups regularly saw fitness-related content.

Another local university student, Ania Davis, said: “I see a lot like how to meal prep and how to get your morning started. Affirmations stuff. But I do also ask the adults around me because sometimes the internet is not right.”

Researchers also looked at why young adults sought health and wellness information from influencers.

About 51 per cent of young women said they watched the content because they wanted to change their health or lifestyle.

Women were also more likely than men to say they enjoyed hearing from people who shared their background or beliefs, at 23 per cent compared with 14 per cent.

Nineteen per cent of young women said they used influencer content to learn about topics they did not want to ask their doctors about, compared with 10 per cent of young men.

Despite regularly using social media, some students said they did not rely solely on influencer content when making decisions about their health and wellness.

Koroma said: “I’m always on TikTok 24/7 and Instagram, but I also like to ask people older than me because I don’t know everything.”

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