Menopause is often associated with increased weight gain and a higher risk of developing overweight and obesity. These changes can raise the likelihood of serious health problems, including cardiovascular disease and type 2 diabetes. In addition to weight gain, declining estrogen levels during menopause can trigger other changes in the body that may further increase cardiovascular risk. “This study provides important insights for developing more effective and personalized strategies for managing cardiometabolic risk in postmenopausal women,” says Regina Castaneda, M.D., postdoctoral research fellow at Mayo Clinic and first author of the study.

Exploring the Role of Hormone Therapy in Weight Loss

Hormone therapy remains the most effective first-line option for relieving common menopausal symptoms such as hot flashes and night sweats, which affect up to 75% of postmenopausal women. However, its potential role in enhancing weight-loss medications has not been well understood. Earlier studies have suggested that women using hormone therapy may lose more weight when treated with GLP-1-based drugs like semaglutide, but data on tirzepatide had been lacking.

To address this gap, researchers analyzed data from 120 adults with overweight or obesity who were treated with tirzepatide for at least 12 months. They compared outcomes between those who also used hormone therapy and those who did not, ensuring both groups had similar baseline characteristics.

Study Findings and Key Limitations

The analysis showed that women receiving both treatments lost significantly more weight. “In this observational study, women who used menopausal hormone therapy lost about 35% more weight than women taking tirzepatide alone. Because this was not a randomized trial, we cannot say hormone therapy caused additional weight loss,” says Maria Daniela Hurtado Andrade, M.D., Ph.D., endocrinologist at Mayo Clinic and senior author of the study.

“It is possible that women using hormone therapy were already engaged in healthier behaviors, or that menopause symptom relief improved sleep and quality of life, making it easier to stay engaged with dietary and physical activity changes.”

Potential Synergy Between Estrogen and GLP-1 Medications

Although more controlled studies are needed, researchers say the findings are clinically meaningful. Dr. Castaneda notes that the size of the observed difference justifies further investigation into how hormone therapy and GLP-1-based medications may work together. “The magnitude of this difference warrants future studies that could help clarify how GLP-1-based obesity medications and menopausal hormone therapy may interact. Interestingly, preclinical data suggest a potential synergy, with estrogen appearing to enhance the appetite-suppressing effects of GLP-1,” says Dr. Castaneda.

What Comes Next for Research

Future research will focus on confirming these results in randomized clinical trials and exploring whether the benefits go beyond weight loss. “Next, we plan to test these observations in a randomized clinical trial and determine if benefits extend beyond weight loss — specifically, whether hormone therapy also enhances the effects of these medications on cardiometabolic measures,” adds Dr. Hurtado Andrade. “If confirmed, this work could speed the development and adoption of new, evidence-based strategies to reduce this risk for millions of postmenopausal women navigating this life stage.”

This research was funded by the Mayo Clinic Center for Women’s Health Research.

Pancreatic cancer has a poor prognosis, with only about 10% of patients living longer than five years after diagnosis. However, doctors believe survival could improve significantly if the disease is caught earlier, when treatment is more effective. Despite this, there are currently no reliable screening tools available to detect pancreatic cancer in its early stages.

Testing Existing and New Blood Biomarkers

To address this gap, scientists from the University of Pennsylvania Perelman School of Medicine, Philadelphia, and Mayo Clinic, Rochester, Minnesota, analyzed blood samples from individuals with and without pancreatic cancer. They evaluated several biomarkers, including carbohydrate antigen 19-9 (CA19-9), commonly used to monitor treatment response, and thrombospondin 2 (THBS2), another previously studied marker.

Individually, these markers have limitations. CA19-9 levels can rise in non-cancerous conditions like pancreatitis or bile duct obstruction, and some people do not produce the marker at all due to genetic differences. As a result, neither marker alone is reliable enough for screening.

Newly Identified Proteins Improve Detection

By examining stored blood samples, the researchers identified two additional proteins that appear to be elevated in people with early-stage pancreatic cancer: aminopeptidase N (ANPEP) and polymeric immunoglobin receptor (PIGR). These newly identified biomarkers showed clear differences between cancer patients and healthy individuals.

When combined with CA19-9 and THBS2, the four-marker panel demonstrated strong performance. It correctly distinguished pancreatic cancer cases from non-cases 91.9% of the time across all stages, with a false positive rate of 5% in non-cases. For early-stage (stage I/II) cancer, the test detected 87.5% of cases.

“By adding ANPEP and PIGR to the existing markers, we’ve significantly improved our ability to detect this cancer when it’s most treatable,” said the study’s lead investigator, Kenneth Zaret, Ph.D., University of Pennsylvania’s Perelman School of Medicine.

Distinguishing Cancer From Other Conditions

An important advantage of the test is its ability to differentiate pancreatic cancer from other non-cancerous pancreatic conditions, including pancreatitis. This helps reduce the risk of misdiagnosis and unnecessary concern for patients.

Next Steps Toward Screening

“Our retrospective study findings warrant further testing in larger populations, particularly in people before they show symptoms,” Zaret said. “Such ‘prediagnostic’ studies would help determine if the test could be used as a screening tool for people at high risk of developing the disease based on family history, genetic screening results or personal history of pancreatic cysts or pancreatitis.”

The study was supported by NIH grants U01CA210138, P50CA102701, S10 OD023586-01, P30 DK020579, UL1 TR002345, P30CA091842, and U01CA210138.

In a study published in Science Advances, researchers from the University of Adelaide found that losing the enzyme Caspase-2 causes liver cells to grow abnormally. This uncontrolled growth leads to inflammation, scarring, and a much higher likelihood of developing liver cancer.

These results challenge the growing interest in Caspase-2 inhibitors as a treatment to manage or prevent fatty liver disease. The findings suggest that targeting this pathway could have unintended consequences over time.

Caspase-2’s Role in Liver Cell Stability

According to lead researcher Dr. Loretta Dorstyn from the Centre for Cancer Biology, Caspase-2 is essential for keeping liver cells genetically stable. It also plays a separate role in regulating fat levels within the liver.

“Liver cells normally have extra copies of genetic material- known as polyploidy — and while this feature can help the liver cope with stress, our study shows that without the enzyme Caspase-2, abnormally high levels of polyploidy in the liver can be damaging,” Dr. Dorstyn said.

To investigate this further, scientists used genetically modified mice. In animals missing the enzyme, or carrying a nonfunctional version, liver cells became unusually large and showed significant genetic and cellular damage.

Long-Term Damage and Tumor Formation

“Over time, these mice developed chronic liver inflammation and characteristics of hepatitis-like liver disease including, scarring, oxidative damage and a type of cell death linked to inflammation. As the animals aged, they were much more likely to develop liver cancer.”

Older mice without functional Caspase-2 developed liver tumors far more often than normal mice. In some cases, cancer rates were up to four times higher, consistent with hepatocellular carcinoma.

Dr. Dorstyn noted that the findings overturn the assumption that inhibiting Caspase-2 is always beneficial.

“While inhibiting this enzyme can be protective in young animals or may help prevent fatty liver disease in the short term, our study shows that its long-term loss is clearly detrimental.

“Our study demonstrates that Caspase-2 is essential for removing damaged and abnormal liver cells as we age. Without it, these cells accumulate, and can become cancerous, while also creating an environment that predisposes the liver to cancer.”

Implications for Fatty Liver Treatments and Drug Development

Senior author Professor Sharad Kumar said the results carry important warnings for future therapies.

“There has been significant interest in targeting Caspase-2 to treat metabolic liver disease and reduce liver cancer risk,” Prof Kumar said.

“Our data shows that this approach could have serious unintended consequences later in life, increasing susceptibility to chronic liver inflammation, fibrosis and cancer.”

Liver disease continues to rise globally, driven by ageing populations, obesity, and metabolic conditions. In 2022 alone, liver cancer caused nearly 760,000 deaths worldwide, according to the World Cancer Research Fund, making it the sixth most common cancer.

The study, titled ‘Caspase- 2 deficiency drives pathogenic liver polyploidy and increases age- associated hepatocellular carcinoma in mice’, was published in Science Advances.

This area, called the lateral parafacial region, is located in the brainstem, the oldest part of the brain responsible for automatic functions like breathing, digestion, and heart rate.

“The lateral parafacial region is recruited into action causing us to exhale during a laugh, exercise or coughing,” says lead researcher Professor Julian Paton, director of Manaaki Manawa, Centre for Heart Research at Waipapa Taumata Rau, University of Auckland.

“These exhalations are what we call ‘forced’ and driven by our powerful abdominal muscles.

“In contrast, a normal exhalation does not need these muscles to contract, it happens because the lungs are elastic.”

How Breathing and Blood Pressure Are Connected

The team found that this brain region is also linked to nerves that constrict blood vessels, which increases blood pressure.

“We’ve unearthed a new region of the brain that is causing high blood pressure. Yes, the brain is to blame for hypertension!” says Paton.

“We discovered that, in conditions of high blood pressure, the lateral parafacial region is activated and, when our team inactivated this region, blood pressure fell to normal levels.”

These findings suggest that certain breathing patterns, particularly those involving strong abdominal muscle use, can contribute to elevated blood pressure. Identifying abdominal breathing in people with hypertension may help pinpoint the cause and guide more targeted treatment.

The study was recently published in the journal Circulation Research.

A Potential New Treatment Target

‘Can we target this brainstem region?’

The researchers then explored whether this part of the brain could be treated with medication.

“Targeting the brain with drugs is tricky because they act on the entire brain and not a selected region such as the parafacial nucleus,” says Paton.

A key breakthrough came when the team discovered that this region is activated by signals originating outside the brain. These signals come from the carotid bodies, small clusters of cells in the neck near the carotid artery that monitor oxygen levels in the blood.

Because the carotid bodies can be safely targeted with medication, they offer a promising alternative approach.

“Our goal is to target the carotid bodies, and we are importing a new drug that is being repurposed by us to quench carotid body activity and inactivate ‘remotely’ the lateral parafacial region safely, i.e., without needing to use a drug that penetrates the brain.”

This discovery could lead to new ways to treat high blood pressure, especially in people with sleep apnoea, where carotid body activity increases when breathing stops during sleep.