Tag: oestrogen

Hormone Therapy does not Increase Breast Cancer Recurrence Risk in Survivors

Research published in the Journal of the National Cancer Institute found that menopausal hormone therapy for breast cancer survivors is not associated with breast cancer reoccurrence, despite worries among some researchers and physicians.

Hot flashes and night sweats, as well as vaginal dryness and urinary tract infections, are common in breast cancer survivors, worsening quality of life and can lead patients to discontinue therapy. These symptoms may be alleviated by vaginal oestrogen therapy or menopausal hormone therapy (MHT). However, the safety of systemic and vaginal oestrogen use among breast cancer survivors, particularly those with oestrogen receptor-positive disease, has been unclear.

Many doctors caution breast cancer survivors against using MHT following the demonstration of an increased risk of breast cancer recurrence in two trials in the 1990s. Though later studies have not shown increased recurrence, they were seriously limited, with small sample sizes and short follow-up periods.

This study compared hormonal treatment with the risk of breast cancer recurrence and mortality in a large cohort of Danish postmenopausal women treated for early-stage oestrogen receptor-positive breast cancer.

Participants were diagnosed between 1997 and 2004 with early-stage breast cancer who received no treatment or five years of hormone therapy.

Among 8461 women, 1957 and 133 used vaginal oestrogen therapy or MHT, respectively, after diagnosis. No increase was seen in the risk of recurrence or mortality for those who received either vaginal oestrogen therapy or MHT.

“This large cohort study helps to inform the nuanced discussions between clinicians and breast cancer survivors about the safety of vaginal oestrogen therapy,” said Elizabeth Cathcart-Rake, writing in an accompanying editorial. “These results suggest that breast cancer survivors on tamoxifen with severe genitourinary symptoms can take vaginal estrogen therapy without experiencing an increase in their risk for breast cancer recurrence. However, caution is still advised when considering vaginal oestrogen for breast cancer survivors on aromatase inhibitors, or when considering menopausal hormonal therapy.”

Source: EurekAlert!

In Diabetes, Oestrogen Protects Against Cardiomyopathy

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Oestrogen may protect diabetes patients from cardiomyopathy, according to research published in Circulation: Heart Failure. The study showed that severe insulin resistance in the heart causes cardiomyopathy and death in male mice, but also showed that oestrogen protected female mice.

“Cardiovascular disease is the major cause of morbidity and mortality for diabetic patients,” explained Shaodong Guo, PhD, primary investigator for the study at Texas A&M.

“Previous studies have shown that while there’s a lower instance of both cardiovascular disease and Type 2 diabetes in premenopausal women than in their age-matched male counterparts, these incidences rise sharply after female menopause,” Prof Guo said.

This indicates that the ovaries and ovarian hormones, such as oestrogen, may protect from Type 2 diabetes and cardiovascular diseases, he said.

The study investigated the role of ovaries and oestrogen in cardiac function and energy metabolism with mice who had the the cardiac insulin receptor substrate, IRS, modified or suppressed to mimic cardiac insulin resistance.

“Our previous studies reported that impaired cardiac insulin signalling with loss of insulin receptor substrate IRS1 and IRS2 genes leads to death of male mice,” he said. “In this study, we wanted to know how the removal of the ovaries might affect cardiomyopathy in female mice and also what other impacts the loss of insulin receptors might have on energy metabolism and mitochondrial function.” 

Insulin resistance and signaling

About 90–95% of patients with Type 2 diabetes suffer from insulin resistance, a risk factor for heart failure. In healthy tissue, insulin binds to insulin receptors, activating a network of intracellular signalling pathways. Disruptions in these signalling pathways have been linked to mitochondrial dysfunction, cardiomyopathy, and impaired glucose and fatty acid metabolism, among other health issues.

In this study, mice lacking IRS developed dilated cardiomyopathy, and analysis showed lowered activity of genes important for mitochondrial function and energy metabolism.

“Type 2 diabetes patients and insulin-resistant patients exhibit mitochondrial dysfunction,” Prof Guo explained.

The study fills in some blanks in understanding the role of insulin and estrogen signaling in mitochondrial function.

Study findings

Guo said there were four important findings from the study:

  • All female mice that lacked insulin receptor substrates survived for more than a year.
  • Female mice without insulin receptor substrates were less likely to experience severe cardiac dysfunction and death if they had ovaries. If the mice also lacked ovaries but received oestrogen, it prolonged their lifespans. Doses of oestrogen also protected IRS-altered male mice from heart dysfunction. 

Guo said oestrogen also prevents cardiomyopathy induced by loss of cardiac insulin receptor substrates.

“And removal of the ovaries leads to the death of female cardiac IRS1 and IRS2 double genes knockout mice if there is no reintroduction of oestrogen,” he said.

Loss of IRS1 and IRS2 genes in heart tissue disrupts cardiac energy metabolism, gene activity involved in mitochondrial function, and whole-body energy metabolism. However, oestrogen partially reverses these effects.

Oestrogen is important for healthy cellular signalling pathways and promotes mitochondrial function.

Prof Guo said the study shows that oestrogen enhances cardiac function, promotes energy metabolism, prevents cardiomyopathy and prolongs survival in both male and ovariectomy female mice lacking the insulin receptor substrates.  

“This study provides evidence for the gender difference for the incidence of cardiovascular disease and implies that oestrogen replacement therapy is feasible for the treatment of diabetic cardiomyopathy through enhancement of mitochondrial function and energy metabolism,” he said. “It also reveals some of the signalling pathways that may be potential therapeutic targets for the prevention or treatment of cardiovascular diseases in patients with Type 2 diabetes.” 

Guo also noted that diet could also play a role with oestrogens in foods.

“The study implies that food-derived oestrogens or phytoestrogens may play similar roles to oestrogen, as observed in mice,” he said. “This may help us reshape our knowledge of nutrient and food sciences related to plant hormones that can modulate chronic metabolic diseases such as Type 2 diabetes and associated cardiovascular complications.”

Source: Texas A&M University

Oestrogen from Hormone Replacement Therapy Reduces COVID Mortality

Older woman smiling
Photo by Ravi Patel on Unsplasj

A new study in Family Practice reported that receiving oestrogen in the form of hormone replacement therapy within six months of a recorded diagnosis of COVID was associated with a reduction in mortality from the disease.

While men and women are equally susceptible to the infection, men tend to have more severe disease, with higher rates of hospitalisation and mortality. A recent 38-country review of sex differences in COVID found men to have a 1.7 times higher mortality rate than women. Younger women or those with higher oestrogen levels are less likely to experience COVID complications.

Earlier studies have also shown that women have faster and greater immune responses to viral infections. Similar trends has been observed in previous pandemics, including the SARS-CoV (Severe Acute Respiratory Syndrome Corona Virus) and MERS-CoV (Middle East Respiratory Syndrome Corona Virus) outbreaks.

The reason for these sex differences is uncertain. Limited recent observational data suggest that oestrogen may reduce the severity of COVID disease. This study investigated the association between hormone replacement therapy or combined oral contraception use, and the likelihood of death in women with COVID. Researchers investigated combined oral contraception, which contains oestrogen, because some Recent observational data suggests that women taking oral contraceptives have a lower risk of acquiring COVID.

Investigators used a retrospective cohort with medical records from the Oxford-Royal College of General Practitioners Research and Surveillance Centre primary care database. They identified a group of 1 863 478 women over 18 from 465 general practices in England.  There were 5451 COVID cases within the cohort. Hormone replacement therapy was associated with a 22% reduction in all-cause mortality in COVID.

This suggests that oestrogen may well contribute a protective effect against COVID severity. This may explain why fewer women compared to men have been hospitalised, admitted to ICU, or died due to COVID during the pandemic.

“This study supports the theory that oestrogen may offer some protection against severe COVID,” said Christopher Wilcox, one of the paper’s authors. “We hope that this study can provide reassurance to patients and clinicians that there is no indication to stop hormone replacement therapy because of the pandemic.”

Source: EurekAlert!

Low Sex Hormone Levels Linked to Rotator Cuff Tears

Photo by Harlie Raethel on Unsplash

Patients with lower levels of sex hormones are more likely to need to undergo surgery for rotator cuff tears, suggests a study in The Journal of Bone & Joint Surgery

Sex hormone deficiencies “was associated with a significantly increased incidence of RCR within [two] independent databases,” according to the new research by Peter N. Chalmers, MD, and colleagues at University of Utah. These findings add to previous evidence that hormone levels may be a systemic factor contributing to the development of rotator cuff tears, a common condition that is a major cause of shoulder pain.

The study used health insurance data for nearly 230 000 adults under age 65 who underwent surgery to repair a torn rotator cuff from 2008 through 2017. Patients were matched for age, sex, and type of insurance to patients who did not undergo rotator cuff surgery.

Patients undergoing rotator cuff repair had an average age of 54 years, and 58% were men. Most patient characteristics were similar between those who underwent rotator cuff repair and those who did not, except tobacco use, which was more common in the surgical cohort.

Dr Chalmers and colleagues found that 27% of women and 7% of men undergoing rotator cuff surgery had diagnosed sex hormone deficiency, compared with 20% and 4% respectively in the control group. Controlling for other factors, rotator cuff repair likelihood was 48% higher in women with oestrogen deficiency and 89% higher in men with testosterone deficiency.

To confirm their findings, the researchers then accessed the Veterans Administration Genealogy database which has data on millions of individuals. Here, they found that rotator cuff repair was about 2.5 times more likely for women with oestrogen deficiency and three times more likely for men with testosterone deficiency.

This study builds on a prior study by the same research group, which demonstrated that women with mutations in an oestrogen receptor gene were more likely to develop rotator cuff disease, with higher rates of failed rotator cuff surgery.

Despite limitations such as not accounting for hormone replacement therapy, the observed association between sex hormone deficiency and rotator cuff repair strongly supports the theory that low oestrogen and testosterone levels may contribute to the development of rotator cuff tears. The researchers concluded that “Future prospective studies will be necessary to understand the relationship of sex hormones to the pathophysiology of rotator cuff disease.”

Source: EurekAlert!