Tag: hormone replacement therapy

Oestrogen may Protect against Delirium in Older Women with UTIs

Photo by Karolina Grabowska

Delirium is common among women with urinary tract infections (UTIs) – especially those who have experienced menopause. In mouse models, researchers have been able to prevent symptoms of the condition by administering oestrogen. Their study was published in the peer-reviewed journal Scientific Reports.

“There has been a resurgence of interest in hormone replacement therapy, and this study, which builds on our previous work, shows that it may be a tool to mitigate delirium,” said Shouri Lahiri, MD, director of the Neurosciences Critical Care Unit and Neurocritical Care Research at Cedars-Sinai and senior author of the study. “I think it is a major step toward a clinical trial of oestrogen in human patients with UTIs.”

Lahiri said that delirium is a common problem in older women with UTIs.

“Even as a medical student, you know that if an older woman comes to the hospital and she’s confused, one of the first things you check is whether the patient has a UTI,” Lahiri said.

In previous studies, Lahiri’s team found a connection between delirium and an immune-regulating protein called interleukin 6 (IL-6). Events such as lung injury or UTI cause IL-6 to travel through the blood to the brain, causing symptoms such as disorientation and confusion. Oestrogen is a known suppressor of IL-6, so the investigators designed experiments to test its effects on UTI-induced delirium.

The researchers compared pre- and postmenopausal mice with UTIs and observed their behaviour in several types of specialised environments. They found that the mice in which menopause had been induced exhibited symptoms of delirium, such as anxiousness and confusion, while the others did not.

When they treated the mice with oestrogen, levels of IL-6 in the blood and delirium-like behaviour were greatly reduced. The behavioural differences were not related to UTI severity, as bacterial levels in the urine weren’t markedly different between the two groups, Lahiri said.

The investigators also looked at the direct effects of oestrogen on neurons, using what Lahiri called a “UTI in a dish.”

“We exposed individual neurons to an IL-6 inflammation cocktail to create UTI-like injury,” Lahiri said. “But when we added oestrogen to the cocktail, it mitigated the injury. So, we showed that there are at least two ways that oestrogen helps reduce symptoms of delirium. It reduces IL-6 levels in the blood and protects the neurons directly.”

Just how oestrogen acts to protect neurons is still unexplained. And before conducting a clinical trial, researchers need to identify which patients with UTIs are most likely to experience delirium and at what point oestrogen treatment might be most effective.

“Currently, it is common practice to treat UTI-induced delirium using antibiotics, even though there are no clinical trials that indicate this practice is effective and it is not supported by clinical practice guidelines,” said Nancy Sicotte, MD, chair of the Department of Neurology and the Women’s Guild Distinguished Chair in Neurology at Cedars-Sinai. “This work is an important step in determining whether modulating immune response via oestrogen replacement or other means is a more effective treatment.”

The team is also working to understand the different effects of delirium on females versus males, which was not a topic of this study. Effective treatment of delirium could be of long-term importance, Lahiri said, because it is a known risk factor for long-term cognitive impairments, such as Alzheimer’s disease and related dementia.

Source: Cedars-Sinai Medical Center

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!

No Dementia Risk with Hormone Replacement Therapy

Photo by Loren Joseph on Unsplash

A large UK study found that use of menopausal hormone therapy (MHT, also known as hormone replacement therapy, HRT) is not associated with increased dementia risk.

The study, published in the BMJ, found within the subgroup of women with a specific diagnosis for Alzheimer’s disease, a slight increasing risk association was found with use of oestrogen-progestogen treatments, but only seen for long-term usage (5 years or more).

This study “brings clarity to previously inconsistent findings and should reassure women in need of menopausal hormonal therapy,” said the researchers.

MHT relieves menopausal symptoms such as hot flushes, sleep disturbance, mood swings, memory losses and depression. Treatment includes oral tablets with oestrogen only, or oestrogen and progestogen combined, as well as patches, gels and creams.

Early signs of dementia are similar to some menopausal symptoms. Research has shown a beneficial link between oestrogen and age-related brain decline. However, in the largest trial of MHT, the Women’s Health Initiative Memory Study, an increased dementia risk was found among users of oestrogen-progestogen treatments. A recent study picked up a possible link to Alzheimer’s disease among users of both oestrogen-only and oestrogen-progestogen treatments, though the study has some issues.

To address this uncertainty, researchers set out to investigate the risks of developing dementia for women using commonly available menopausal hormone therapy treatments.

They used two UK primary care databases to analyse MHT prescriptions for the 118 501 women aged 55 and older diagnosed with dementia between 1998 and 2020 (cases), and 497 416 matched women without dementia (controls).

After adjusting for confounding factors, no overall associations were found between use of hormone therapy and risk of dementia, regardless of hormone type, application, dose, or duration of treatment. Only a slightly decreased risk of dementia was found in one subgroup: those under 80 years who had been taking oestrogen-only therapy for 10 years or more.
Analysis of cases with a specific diagnosis of Alzheimer’s disease showed a slight increase in risk associated with oestrogen-progestogen therapy. This rose gradually with each year of exposure, reaching an average 11% increased risk for use of between 5 and 9 years and an average 19% for use of 10 years or more, equivalent to, respectively, five and seven extra cases per 10 000 woman years.

As this is an observational study it cannot establish cause, and some limitations include incomplete recording of menopausal symptoms, particularly for women registered after their menopause. However, its large size counts in its favour.
According to the researchers, this study provides the most detailed estimates of risk for individual treatments, and their results are in line with existing concerns in guidelines about long term exposures to combined hormone therapy treatments.

“The findings will be helpful to policy makers, doctors, and patients when making choices about hormone therapy,” they concluded.

The findings do not change the recommendation that menopausal hormone therapy should not be used to prevent dementia, US researchers commented in a linked opinion article. However, it is helpful for providers to put dementia findings in context for patients, they added.

“The primary indication for hormone therapy continues to be the treatment of vasomotor symptoms, and the current study should provide reassurance for women and their providers when treatment is prescribed for that reason,” they concluded.

Source: News-Medical.Net