Close Monitoring for Heart Risk Needed if Breast, Prostate Cancer Treatment Includes Hormones

The hormonal therapies used to treat many breast and prostate cancers raise the risk of a heart attack and stroke, and patients should be monitored regularly and receive treatment to reduce risk and detect problems as they occur, according to a new American Heart Association scientific statement, published today in the Association’s journal Circulation: Genomic and Precision Medicine.

“The statement provides data on the risks of each type of hormonal therapy so clinicians can use it as a guide to help manage cardiovascular risks during cancer treatment,” said Tochi M. Okwuosa, D.O., FAHA, chair of the scientific statement writing group, an associate professor of medicine and cardiology and director of Cardio-Oncology Services at Rush University Medical Center in Chicago.

Hormone-dependent cancers, such as prostate and breast cancer, are the most common cancers in the United States and worldwide not including skin cancers. As improvements in treatment – including increased use of hormonal therapies – allow people with these cancers to live longer, cardiovascular disease has emerged as a leading cause of illness and death in these patients.

Hormonal treatments for breast cancer include selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). SERMs block estrogen receptors in cancer cells so the hormone can’t spur tumor growth, while letting estrogen act normally in other tissues such as bone and liver tissue; examples of SERMs include tamoxifen and raloxifene. Aromatase inhibitors lower the amount of estrogen produced in post-menopausal women and include exemestane, anastrozole and letrozole. Endocrine treatments for prostate cancer, called androgen deprivation therapy, include some medications that decrease production of testosterone by their action on the brain and others that block testosterone receptors found in prostate cells and some prostate cancer cells.

The writing group reviewed existing evidence from observational studies and randomized controlled trials and found that:

  • Tamoxifen increases the risk of blood clots, while aromatase inhibitors increase the risk of heart attack and stroke more than tamoxifen. For breast cancer patients who require more than one type of hormonal therapy because of developed resistance to the initial medication, , there is an improvement in cancer outcomes. However, treatment with multiple hormones is associated with higher rates of cardiovascular conditions such as high blood pressure, abnormal heart rhythms and blood clots.
  • Androgen deprivation therapy (to reduce testosterone) for prostate cancer increases cholesterol and triglyceride levels, adds body fat while decreasing muscle and impairs the body’s ability to process glucose (which may result in type 2 diabetes). These metabolic changes are associated with a greater risk of heart attacks, strokes, heart failure and cardiovascular death.
  • The longer people receive hormonal therapy, the greater the increased risk of cardiovascular problems. Further research is required to better define the risks associated with duration of treatment.
  • The hormonal therapy-associated increase in CVD risk was highest in people who already had heart disease or those who had two or more cardiovascular risk factors – such as high blood pressure, obesity, high cholesterol, smoking or a family history of heart disease or stroke – when they began treatment.

“A team-based approach to patient care that includes the oncology team, cardiologist, primary care clinician, dietician, endocrinologist and other health care professionals as appropriate is needed to work with each patient to manage and reduce the increased risk of heart disease and strokes associated with hormonal therapy in breast and prostate cancer treatment,” Okwuosa said.

There are currently no definitive guidelines for monitoring and managing hormonal therapy-related heart risks. The statement calls for clinicians to be alert for worsening heart problems in those with prior heart disease or risk factors, and to recognize that even those without pre-existing heart problems are at higher risk because of their exposure to hormonal therapies.

“For patients who have two or more cardiovascular risk factors, it is likely that referral to a cardiologist would be appropriate prior to beginning hormone treatment. For patients already receiving hormonal therapies, a discussion with the oncology team can help to determine if a cardiology referral is recommended,” Okwuosa said.

The statement also calls for additional research in several areas, including:

  • Further evaluation of racial and ethnic disparities among breast and prostate cancer patients who have received hormone therapy. In the few studies that exist, racial and ethnic differences detected may be related to health inequities and other factors, and these are important areas to address.
  • Heart disease and stroke outcomes and risks should be added as primary endpoints in randomized trials of hormonal therapies.
  • Studies of specific hormonal medications are needed since each one may have different heart risks even if they work in the same way to treat breast or prostate cancer.

Source: American Heart Association

Gut Hormone Blocks Brain Cell Formation and is Linked to Parkinson’s Dementia

A gut hormone, ghrelin, is a key regulator of new nerve cells in the adult brain, a Swansea-led research team has discovered. It could help pave the way for new drugs to treat dementia in patients with Parkinson’s Disease.

Blood-borne factors such as hormones regulate the process of brain cell formation – known as neurogenesis – and cognition in adult mammals.

The research team focused on the gut hormone acyl-ghrelin (AG), which is known to promote brain cell formation. A structure change to the hormone results in two distinct forms: AG and unacylated-ghrelin (UAG).

The team, led by Dr Jeff Davies of Swansea University Medical School, studied both AG and UAG to examine their respective influences over brain cell formation.

This research is relevant to Parkinson’s as a large proportion of those with the disease experience dementia, which is linked to a loss of new nerve cells in the brain. This loss leads to a reduction in nerve cell connectivity, which plays a vital role in regulating memory function.

The team’s key overall findings were:

  • the UAG form of ghrelin reduces nerve cell formation and impairs memory
  • Individuals diagnosed with Parkinson’s disease dementia have a reduced AG:UAG ratio in their blood

Dr Jeff Davies of Swansea University Medical School, lead researcher, said:

“Our work highlights the crucial role of ghrelin as a regulator of new nerve cells in the adult brain, and the damaging effect of the UAG form specifically.

This hormone represents an important target for new drug research, which could lead ultimately to better treatment for people with Parkinson’s.

Our findings show that the AG:UAG ratio could also serve as a biomarker, allowing earlier identification of dementia in people with Parkinson’s disease.”

The team included collaborators from Newcastle University (UK) and Monash University (Australia). They examined the role of AG and UAG in the brain, and also compared blood collected from Parkinson’s disease patients diagnosed with dementia with cognitively intact PD patients and a control group.

They found:

  • Higher levels of UAG, using both pharmacological and genetic methods, reduced hippocampal neurogenesis and brain plasticity.
  • AG helped reverse spatial memory impairments
  • UAG blocks the process of brain cell formation prompted by AG
  • The Parkinson’s patients with dementia were the only one of the three patient groups examined to show a reduced AG:UAG ratio in their blood.

The research was published in Cell Reports Medicine.

Source: Swansea University

‘Love Hormone’ Could Hold Key to Treating COVID

The so-called love hormone, oxytocin, may be worth investigating as a treatment for COVID-19, a new study suggests.

One of the most serious complications of infection with the new coronavirus is a “cytokine storm,” in which the body attacks its own tissues.

There are currently no U.S. Food and Drug Administration-approved treatments for COVID-19, which means that “repurposing existing drugs that can act on the adaptive immune response and prevent the cytokine storm in early phases of the disease is a priority,” according to the researchers.

Previous research suggests that oxytocin — a hormone that’s produced in the brain and is involved in reproduction and childbirth — reduces inflammation.

In this new study, researcher Ali Imami, a graduate research assistant at the University of Toledo in Ohio, and colleagues used a U.S. National Institutes of Health database to analyze characteristics of genes treated with drugs closely related to oxytocin.

The investigators found that one drug in particular, carbetocin, has similar characteristics (called a signature) to genes with reduced expression of the inflammatory markers that trigger cytokine storm in COVID-19 patients.

Carbetocin’s signature suggests that the drug may trigger activation of immune cells called T-cells that play an important role in immune response. In addition, carbetocin’s signature is also similar to that of lopinavir, an antiretroviral medication under study as a treatment for COVID-19.

All of these factors indicate that oxytocin may have potential as a targeted treatment for cytokine storms in COVID-19 patients, the researchers said in a news release from the American Physiological Society.

“Understanding the mechanisms by which oxytocin or the oxytocin system can be a new immune target is crucial,” the authors concluded in their report, which was published online recently in the journal Physiological Genomics.

However, they added that “safety and efficacy of intravenous oxytocin in hospitalized patients with COVID-19 remains to be assessed.”

Source: HealthDay

Plant-Based Diets May Support Healthy Testosterone Levels

Men who follow plant-based diets have testosterone levels that are basically the same as the levels in men who eat meat, a study shows. This finding dispels a widespread notion that men need large amounts of animal protein to support healthy levels of this hormone.

“We found that a plant-based diet was associated with normal testosterone levels, levels that are the same as occur in men who eat a traditional diet that includes more meat,” says Ranjith Ramasamy, MD, an associate professor and director of reproductive urology at the University of Miami Health System. He coauthored the study, which appeared in the World Journal of Urology, with Manish Kuchakulla, a medical student, also at the University of Miami Miller School of Medicine.

“The old idea that men needed to consume a traditional diet with plenty of meat to have a healthy testosterone level was based on pure conjecture, not based on evidence,” Ramasamy says.

Recent years have seen a dramatic uptick in public interest in various forms of plant-based diets, as measured in many ways, including trends for the terms “vegan,” “vegetarian,” and “plant-based” in Google searches. “The number of US consumers who say that they adhere to a plant-based diet increased by 500% between 2014 and 2017, and sales of plant-based foods rose 20% in 2018 compared to the year prior,” the authors wrote.

Meanwhile, previous studies on the effects of different types of diets on testosterone levels have been inconsistent. Some research has shown plant-based diets to be associated with lower levels of testosterone, while others have shown that plant-based diets don’t affect testosterone levels.

The researchers used National Health and Nutrition Examination Survey data about 191 men between the ages of 18 and 75, which had been gathered in 2003–2004, because that data set was the only available one that included both testosterone levels, as measured in blood samples, and details of each person’s diet.

Unlike most previous studies that treat all plant-based diets as equal, the researchers distinguished between healthier and less healthy plant-based diets. “You can eat a lot of soda, chips, and juice, which are plant foods but aren’t healthy foods,” Kuchakalla says.

To see whether men with more healthful and less healthful plant-based diets had different testosterone levels, the researchers divided the men who ate mostly plant-based foods into two groups—those who scored high on an index for healthful plant-based food consumption and those who merely scored high on an index for plant-based food consumption.

The researchers considered testosterone levels below 300 ng/dL to indicate a deficiency, in keeping with the American Urological Association. Their analyses showed that the kind of diet a man followed didn’t affect testosterone levels.

“Whether a man ate a traditional diet with lots of animal foods, a healthy plant-based diet, or a less healthy plant-based diet simply did not matter. We found no differences,” Kuchakulla says.

The researchers emphasized that, in addition to supporting healthy testosterone levels, plant-based diets confer many health advantages to individuals, populations, and the planet.

Plant-based diets have proven to reduce the risks of many conditions, including hypertension, heart disease, heart attacks, strokes, and many cancers.

“Plant-based diets also reduce a person’s carbon footprint, so they can help us address global warming,” Kuchakulla says. “Studies have shown that a shift to a more sustainable eating pattern with a reduction in animal-based foods can result in more than a 70% reduction in greenhouse gas emissions,” the research team wrote.

Source: University of Miami Health System, Miller School of Medicine


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World-first Study on Blood Hormone could Reduce Cardiovascular Deaths

Kim Thomas wrote . . . . . . . . .

A simple blood test could identify seemingly-healthy people with a high hidden risk of heart disease thanks to a world-first discovery by University of Otago, Christchurch researchers.

Researchers from the University’s Christchurch Heart Institute studied the blood samples and cardiology scans of 665 healthy young and middle-aged people with no previous heart conditions. They found people with high levels of a hormone in the blood, called C-type Natriuretic Peptide (CNP), were significantly more likely to have stiffening of the arteries, reduced pumping action of the heart, higher fat levels in the blood and liver, and reduced kidney function—all signs of increased risk of heart disease.

The discovery could one day enable doctors to identify those people whose lives could be saved from a future heart attack by interventions such as drugs or lifestyle changes.

The study is the first to describe a link between the blood hormone CNP and inflammation across a range of tissues including arteries and the heart. The results were recently published in the prestigious Peptides journal.

Lead researcher Dr. Tim Prickett says CNP seems to protect arteries from hardening and blocking. This means it is working hard and present in higher levels in those with potentially poor, and undetected, cardiovascular health.

“We examined two quite different groups of healthy people—one group age 28 years, the other age 50 years—both without history of heart or kidney disease. High levels of CNP in both age groups were found in people who had stiffer arteries, reduced pumping action of the heart, higher fat levels in the blood and liver, and reduced kidney function.”

Dr. Prickett says inflamed and blocked arteries can cause numerous physical problems including scarring and stiffness and damage to organs such as the heart, liver and kidneys. “We found that CNP in the blood stream reflects an increased production of CNP in these tissues, as part of a protective response to inflammation.”

He says the finding that CNP acts to protect the body is key to helping save lives through early detection of serious conditions such as atherosclerosis, which can lead to heart attack or stroke.

This is one of a number of discoveries by the Christchurch Heart Institute over the past 25 years. The research group has discovered and developed blood tests for heart disease diagnosis and treatment, some of which are used in hospitals and emergency departments in New Zealand and around the globe.

Source: Medical Xpress


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