Research roundup: Advancing the understanding of female infertility, Hormone therapy in older women linked to tau accumulation, and more

Femtech World explores the latest research developments in the world of women’s health.

Breast cancer death rates have stopped going down

A new paper indicates that breast cancer mortality rates have stopped declining in women older than age 74, reconfirming that breast cancer mortality rates have stopped falling in women younger than age 40. This finding for older women is new.

Breast cancer is the second leading cause of cancer deaths in American women, with over 42,000 women dying of the disease in 2024. Before 1990, female breast cancer rates had been rising, and breast cancer mortality rates had been flat or increasing. Since 1990 there has been a steady decline in breast cancer mortality rates, which public health observers attribute both to the widespread use of mammograms and improvements in treatment.

The investigators conducting this study contend that mortality rates have stopped declining for women under 40 and over 74 due to significant increases in stage IV breast cancers at diagnosis in these two age groups. Stage IV (metastatic) breast cancer at diagnosis has an extremely poor prognosis: a 31 per cent five-year survival rate.

This study indicates that increasing rates of advanced stage breast cancer at diagnosis is an important reason breast cancer mortality rates are no longer declining at the rate they once did. The researchers believe that this may be due to healthcare protocols.

The researchers say that the fact that breast cancer mortality rates have stopped declining for women over age 74 is an alarming new trend.

Menopause symptoms associated with future memory and neuropsychiatric problems

Women who exhibit more menopausal symptoms are more likely to later have poorer cognitive function and mild behavioral impairments, both markers of dementia, a new study has shown.

Females are known to have a three-fold greater risk of developing Alzheimer’s disease and related dementias, and will be disproportionately affected by the increasing global dementia burden. A proposed factor that may confer special risk to females is the loss of estradiol at menopause.

In the new study, women who reported more perimenopausal symptoms had greater cognitive impairment, with higher ECog-II total scores as well as more mild behavioural impairment symptoms in mid- to late life, with higher MBI-C total scores.

Hormone therapy was not significantly associated with cognitive function but was linked to fewer behavioural symptoms.

The authors conclude that a higher menopausal symptom burden may indicate susceptibility to cognitive and behavioural changes later in life.

Findings may advance understanding of infertility in mothers

Oxytocin may have a newfound purpose in mammalian reproduction. In times of maternal stress, the hormone can delay an embryo’s development for days to weeks after conception, a new study in rodents shows. According to the authors, the findings about so-called “diapause” may offer new insights into pregnancy and fertility issues faced by humans.

Led by researchers at NYU Langone Health, the study explored diapause, in which an embryo temporarily stops growing early in its development before it attaches to the lining of its mother’s uterus, a key step leading to the formation of the placenta.

Known to occur in species ranging from armadillos to giant pandas to seals, diapause is thought to have evolved to help expectant mothers preserve scarce resources (e.g., breast milk) by delaying birth until they have enough to successfully take care of their offspring.

Although recent studies have uncovered evidence that a form of diapause may occur in humans, the underlying mechanisms behind it have until now remained unclear.

The findings in mice showed that one type of stress that may cause diapause is milk production and release (lactation), as it requires a mother to expend bodily nutrients to both nursing, already-born pups and to those growing in the womb.

The study revealed that the time between conception and birth (gestation), typically 20 days for these animals, was delayed by about a week in pregnant rodents that were already nursing a litter.

Further, the research team showed that this delay was brought about by a rise in the production of oxytocin, levels of which are known to go up as a mother lactates.

To confirm this role for the hormone, the researchers exposed mouse embryos in the lab to a single dose (either 1 microgram or 10 micrograms) of oxytocin, and found that even these small amounts delayed their implantation in the uterus by as much as three days.

Beyond just pausing pregnancy, the team found that surges of the chemical large enough to mimic the amounts and timing measured during nursing caused loss of pregnancy in the mice in nearly all cases.

The ‘silent’ X chromosome gives the ageing female brain a boost
Researchers may have discovered how the female brain remains resilient in ageing, potentially explaining how most women outlive men and retain their cognitive abilities longer.

Females carry two X chromosomes. One of them is ensconced in a corner in the cell called the Barr body, where it can’t express many genes, and scientists thought it didn’t do much of anything.

But the research team from UCSF discovered that as female mice reached the equivalent of about 65 human years, their ‘silent’ second X started expressing genes that bolster the brain’s connections, increasing cognition.

“In typical ageing, women have a brain that looks younger, with fewer cognitive deficits compared to men,” said Dena Dubal, MD, PhD, a professor of neurology and the David A. Coulter Endowed Chair in Aging and Neurodegenerative Disease at UCSF.

“These results show that the silent X in females actually reawakens late in life, probably helping to slow cognitive decline.”

Hormone therapy in older women linked to tau accumulation

A new study from Mass General Brigham researchers has found faster accumulation of tau, a key indicator of Alzheimer’s disease, in the brains of women over the age of 70 who took menopausal hormone therapy (HT) more than a decade before.

The results could help inform discussions between patients and clinicians about Alzheimer’s disease risk and HT treatment.

While the researchers did not see a significant difference in amyloid beta accumulation, they did find a significant difference in how fast regional tau accumulated in the brains of women over the age of 70, with women who had taken HT showing faster tau accumulation in specific regions of the brain. This difference was not seen in women younger than 70.

Studying the structure of energy transport enzymes could lead to new breast cancer treatments

Cancer cells hijack various cellular functions to find and exploit energy and other resources, including a group of enzymes called creatine kinases (CK) that help normal cells maintain a balance of energy.

These enzymes allow cells to transport energy produced at the mitochondria to where it is needed throughout the cell. Cancer cells rely on this machinery for shuttling energy to help meet their ravenous fuel demands. Studies of breast cancer cells have highlighted the importance of a type of CK called ubiquitous mitochondrial creatine kinase (uMtCK).

Scientists at Sanford Burnham Prebys and the Mayo Clinic published findings that provide a detailed structure of human uMtCK and show how its structure changes when bound to the energy storage molecules creatine or adenosine triphosphate (ATP).

To ascertain the structure of uMtCK, the scientists captured images using cryogenic electron microscopy (cryo-EM). This technology enables investigators to create 3D images of proteins and their ligands by rendering individual atoms. These blueprints may help scientists design new treatments that can stop cancer cells from seizing control of the cells’ energy supply chain to slow or stop tumor growth.

In addition to uncovering the 3D structures of uMtCK and how it interacts with other players involved in energy transport, the research team also tested the only available CK inhibitor called CKi to determine its potential to interrupt abnormal energy transport in breast cancer cells.

The scientists found that CKi successfully reduces breast cancer cell growth. The findings and tools used in this study helped validate that inhibition of the pathway can be effective for the treatment of breast cancer. However, CKi has been shown not to be selective for uMtCK, meaning it is likely to shut down other cellular processes that can lead to high toxicity.

New STI impacts 1 in 3 women: Landmark study reveals men are the missing link

A landmark study reveals that bacterial vaginosis (BV), a condition affecting nearly a third of women worldwide and causing infertility, premature births and newborn deaths, is in fact a sexually transmitted infection (STI), paving the way for a revolution in how it is treated.

Monash University and Alfred Health researchers at the Melbourne Sexual Health Centre say their findings hold the key to driving down stubborn and distressing recurrence rates of BV among women.

Authors Professor Catriona Bradshaw and Dr Lenka Vodstrcil say the standard practice of treating BV as an imbalance (disruption) to the vaginal microbiome means that more than 50 per cent of women get it back within three months after the standard week-long treatment of an oral antibiotic.

In their trial of 164 couples with BV in monogamous relationships, they found that treating BV as an STI, with both sexual partners treated simultaneously, achieves significantly higher cure rates than the current practice of only treating women.

In fact, they stopped the trial early when it became clear that BV recurrence was halved in the partner treatment group compared to treating women alone.