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Surges in oestrogen promote binge drinking in females, shows study

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The hormone oestrogen regulates binge drinking in females, causing them to “pregame” – consume large quantities of alcohol in the first 30 minutes after it’s offered, according to a new preclinical study.

The study establishes–for what is thought to be the first time–that circulating oestrogen increases binge alcohol consumption in females and contributes to known sex differences in this behaviour.

The findings could lead to novel approaches for treating alcohol use disorder.

“We know a lot less about what drives alcohol drinking behaviour in females because most studies of alcohol use have been done in males,” said senior author Dr. Kristen Pleil, an associate professor of pharmacology.

Yet females, too, overindulge and are more susceptible to the negative health effects of alcohol than males.

Recent studies indicate that, during the pandemic lockdown, women increased their heavy alcohol consumption more than men. That behaviour has important consequences for women’s health, said Dr. Pleil, “because many studies show this pattern of drinking enhances alcohol’s harmful effects.”

Indeed, women had many more alcohol-related hospital visits and complications than men during and since the pandemic.

In a 2021 study, Dr. Pleil and her team showed that a specific subpopulation of neurons in a brain region called the bed nucleus of the stria terminalis (BNST) were more excitable in female mice than in males. This enhanced activity correlated with their binge drinking behaviour.

But what makes this neural circuit more excitable in females?

“Oestrogen has such powerful effects on so many behaviours, particularly in females,” Dr. Pleil said. “So, it makes sense that it would also modulate drinking.”

To assess oestrogen’s potential involvement, the researchers, including first author Dr. Lia Zallar, who was a graduate student in the Pleil lab at the time of the research, began by monitoring the hormone levels throughout oestrous cycle of female mice.

Then, they served up the alcohol. They found that when a female has a high level of circulating oestrogen, she drinks much more than on days when her oestrogen is low.

That enhanced bingeing behaviour was reflected in heightened activity in those same neurons in the BNST.

“When a female takes her first sip from the bottle containing alcohol, those neurons go crazy,” Dr. Pleil said. “And if she’s in a high-oestrogen state, they go even crazier.”

That extra boost of neural activity means the mice hit the bottle even harder, particularly within the first 30 minutes after the alcohol was made available, a behaviour Dr. Pleil refers to as “front-loading.”

Cell-surface receptors allow oestrogen to act fast

Although the researchers suspected oestrogen would have an effect on drinking, they were surprised by its mechanism of action.

This steroid hormone typically regulates behaviours by binding to receptors that then travel to the nucleus, where they alter the activity of specific genes—a process that could take hours. However, Dr. Pleil and her team realised that something else must be happening when oestrogen infused directly into the BNST excited the neurons and triggered binge drinking within minutes.

So, the researchers tested oestrogen that had been doctored so it could not enter cells and bind to nuclear receptors—a feat of chemical engineering performed by Dr. Jacob Geri, assistant professor of pharmacology at Weill Cornell Medicine.

They determined that when oestrogen promotes bingeing, the hormone is binding to receptors on the neurons’ surface, where it directly modulates cell-cell communication.

“We believe this is the first time that anybody has shown that during a normal oestrous cycle, endogenous oestrogen made by the ovaries can use such a rapid mechanism to control behaviour,” Dr. Pleil said. That rapid action drives the front-loading of alcohol when oestrogen is high.

The team identified the oestrogen receptor that mediates this effect and determined that it is expressed in the excited BNST neurons and in neurons from other brain regions that excite them. The researchers are now investigating the signalling mechanisms for this effect, and they will also examine whether the same system regulates drinking in males.

“All of the infrastructure is there in males, too: the oestrogen receptors and the basic circuit organization,” Dr. Pleil said. The only difference will be the source of the oestrogen, which in males without an ovarian source relies on local conversion of testosterone to oestrogen in the brain.

Inhibiting the enzyme that synthesises oestrogens could offer a novel treatment for selectively reducing alcohol consumption when hormone levels surge. An FDA-approved version of such an inhibitor is currently used to treat women with oestrogen-sensitive cancers.

“Combining this drug with compounds that modulate the downstream effects of the chemicals produced by the BNST neurons could potentially provide a new, targeted approach for treating alcohol use disorder,” Dr. Pleil said.

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Motherhood

Expectations about sleep affect postpartum sleep quality, study finds

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Pregnant women’s expectations about postpartum sleep may predict sleep quality after birth, outweighing prior sleep and psychiatric history, a study suggests.

The findings suggest attitudes and beliefs about sleep during pregnancy could be a modifiable risk factor for postpartum sleep concerns.

They also indicate that, among women expecting the poorest sleep, higher postpartum anxiety may further worsen sleep quality.

Sammy Dhaliwal, lead author is clinical health psychologist and research fellow in the department of obstetrics and gynaecology at the Perelman School of Medicine at the University of Pennsylvania.

Dhaliwal said: “Most pregnant women in our sample anticipated poor postpartum sleep before it occurred, and it was striking that those expectations predicted worse sleep outcomes even after accounting for factors such as prior sleep disorders, psychiatric history, and number of previous births.

“This suggests that attitudes and beliefs about sleep during pregnancy may represent a modifiable target for early intervention before postpartum sleep problems emerge.”

Sleep disturbance affects an estimated 60 to 80 per cent of postpartum women and is linked to a higher risk of depression and anxiety.

Researchers said it is often regarded as an expected part of life after childbirth rather than a health issue that may be addressed earlier.

The study enrolled 432 pregnant women at about 24 weeks of gestation, meaning around 24 weeks into pregnancy.

Participants completed measures of their expectations about postpartum sleep, current sleep quality using the Pittsburgh Sleep Quality Index, and mood using validated depression and anxiety scales.

Assessments were repeated at six, 12 and 24 weeks postpartum.

A subset of 49 women also wore wrist actigraphy devices at six to eight weeks postpartum.

Actigraphy uses a wearable device, similar to a watch, to estimate sleep and wake patterns based on movement.

The results showed that 70 per cent of pregnant women, or 301 of 432 participants, expected poor sleep in the postpartum period.

Researchers found that predicted sleep disruption during pregnancy was a significant predictor of postpartum sleep concerns.

Among first-time pregnant women without prior health concerns, those who expected greater sleep disturbance had significantly more disrupted sleep after birth, measured by both actigraphy and self-report.

Among women who expected the worst sleep quality, higher postpartum anxiety significantly worsened both measured sleep and self-reported sleep, independent of anxiety levels during pregnancy.

Dhaliwal said the findings point to two possible areas for intervention: addressing sleep-related beliefs during pregnancy and treating postpartum anxiety.

Dhaliwal said: “Postpartum sleep disruption is often treated only after problems develop, but our findings suggest there may be an opportunity to intervene earlier during pregnancy.

“Addressing sleep-related beliefs and postpartum anxiety during prenatal and postpartum care may help improve sleep and emotional well-being in new mothers.”

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Mental health

Pilates may improve heart and metabolic health in sedentary women, study finds

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A four-week Pilates programme may improve heart, metabolic and stress measures in previously sedentary women, a small study suggests.

Pilates is a mind-body form of exercise that has been linked to better fitness, balance, posture, muscular endurance, mental wellbeing and quality of life in different groups.

Built around breathing, concentration, control, precision, centring and flow, Pilates is already used in physiotherapy, rehabilitation and preventive health. The new study looked at whether a structured four-week programme could affect cardiovascular, metabolic, body and stress-related measures in sedentary adult women.

The longitudinal study included 30 sedentary women split into two age groups, 30 to 40 and 50 to 60.

All participants completed a standardised, supervised Pilates programme lasting four weeks, with three sessions a week lasting 50 to 60 minutes.

Researchers measured resting heart rate, systolic and diastolic blood pressure, body mass index, abdominal circumference, fasting blood glucose and serum cortisol at the start and end of the programme.

Systolic and diastolic blood pressure are the top and bottom readings in a blood pressure test. Cortisol is a hormone linked to the body’s stress response.

The four-week Pilates programme was linked to improvements in cardiovascular, metabolic, body and neuroendocrine measures, although not every change reached statistical significance within each age group.

In the younger group, significant reductions were seen in heart rate, blood pressure, body mass index and fasting blood glucose after the intervention.

The reduction in blood pressure after the programme was significantly greater in the older group than in the younger group.

Older participants also showed a greater reduction in glucose and cortisol levels after the intervention than younger participants.

Analysis also found significant links between cardiovascular, metabolic and neuroendocrine changes.

In the younger group, this was particularly seen between heart rate and blood pressure responses.

In the older group, it was particularly seen between changes in body mass index and fasting glucose.

The findings suggest Pilates could be a useful multidimensional exercise approach for cardiometabolic health and stress regulation in previously sedentary women.

The researchers said the larger reduction in blood pressure seen in the older group may reflect a higher cardiometabolic burden at the start, leaving more room for improvement after the programme.

The greater reduction in fasting glucose and cortisol in older participants may similarly suggest that people with higher baseline metabolic and neuroendocrine dysfunction could benefit more from structured exercise such as Pilates.

Although Pilates is known to improve body composition through energy use, neuromuscular activation and support for healthier habits, the researchers said the fall in body mass index over four weeks is unlikely to be explained by Pilates alone.

They noted that participants were also told to avoid alcohol, sugar-containing products and sugar-sweetened drinks during the intervention, which may have contributed to the change.

In the younger group, the link between heart rate and blood pressure suggested coordinated cardiovascular responses after Pilates.

The researchers also found that cortisol appeared to be linked to blood pressure and body mass index, suggesting stress-related changes may be tied to cardiovascular and body regulation after the intervention.

In the older group, the link between body mass index and fasting glucose highlighted the relationship between body fat and metabolic regulation.

A positive link between blood pressure and body mass index in this group also suggested that improvements in vascular regulation may be associated with reductions in body mass.

Overall, the findings suggest Pilates-related physiological changes may involve interconnected cardiovascular, body, metabolic and neuroendocrine mechanisms, with different response patterns by age.

The study has important limits. It did not include a non-exercise control group, so it cannot prove Pilates directly caused the changes.

The sample size was also small, which limits how far the findings can be applied more widely.

The authors also noted that cortisol was measured using a single fasting morning sample, which limits conclusions about broader hypothalamic-pituitary-adrenal axis regulation, the system involved in the body’s stress response.

They said larger studies with longer follow-up will be needed to confirm whether Pilates causes these physiological changes over time.

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Diagnosis

Being female not a universal stroke risk factor for patients with AF, study finds

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Female sex may not raise stroke risk across all atrial fibrillation (AF) patients, with higher risk mainly seen in women aged 75 and older, a study suggests.

Researchers said stroke prevention for women with the condition should be more personalised, especially for patients under 75.

Dr Amitabh C Pandey, director of cardiovascular translational research at Tulane University School of Medicine, said: “For years, female sex has been included as a risk factor along with other factors such as high blood pressure and diabetes, meaning women were more likely to be prescribed anticoagulants.

“Our study shows younger women may not have as much added stroke risk as previously thought, while older women, particularly those over 75, appear to have a higher risk that deserves close attention.”

The new Tulane University study challenges a long-standing assumption in heart care that being female automatically increases stroke risk for patients with atrial fibrillation.

Atrial fibrillation, often called AF, is a common heart rhythm disorder that causes the heart to beat irregularly.

It is associated with a higher risk of stroke and is often treated with anticoagulants, also known as blood thinners.

The study found that stroke risk did not increase equally across all female patients with AF.

Instead, researchers said being female may act more as a risk modifier, with increased stroke risk seen primarily among women aged 75 and older or those with a greater burden of other health conditions.

Clinicians often use a scoring system to decide whether people with AF should be prescribed blood thinners.

The system gives points for factors including age, heart failure, diabetes, previous stroke, vascular disease and high blood pressure.

Women also receive one point for sex alone.

Researchers said this can mean women with AF become eligible for blood thinners earlier or more often than men with otherwise similar risk profiles.

While blood thinners can help prevent clot-related strokes, they can also increase the risk of bruising, prolonged bleeding, gastrointestinal bleeding and other serious complications.

The researchers analysed approximately 950,000 patients with AF using TriNetX, a large anonymised electronic health record database.

They compared stroke outcomes between male and female patients across three age groups: younger than 65, 65 to 74, and 75 and older.

Male and female patients were matched based on age, other health problems and whether they had been prescribed anticoagulation medicine.

Among patients younger than 75, the study found no significant difference in one-year stroke risk between men and women.

However, among patients aged 75 and older, women had a modest but statistically significant increase in stroke risk compared with men.

In patients aged 75 and older with no additional risk factors beyond age, women had about one additional stroke per 629 patients compared with their male counterparts.

The findings support growing interest in a newer AF risk score, known as CHA2DS2-VA, which removes sex as a standalone risk factor.

However, researchers said more studies are needed and medical guidance remains inconsistent.

Han Feng, assistant professor at Tulane University School of Medicine, said: “This general approach came from women being underrepresented in AFib trials and studies comprising only about one-third of study populations.

“Our study shows not all women with AFib have the same risk profile, and these decisions should be individualised.

Pandey said: “These findings highlight the need for modern tools and approaches that can personalise risk profiles to individuals.

“The goal is not to undertreat patients who need stroke prevention, but to better identify who is most likely to benefit from anticoagulation and who may be exposed to unnecessary risk.”

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