Women diagnosed with premenstrual symptoms have a slightly increased risk of developing cardiovascular disease later in life. This is shown by a new study from Karolinska Institutet published in Nature Cardiovascular Research.
Premenstrual symptoms include premenstrual syndrome (PMS) and the more severe form, premenstrual dysphoric disorder (PMDD). The symptoms, which appear a few days before menstruation and then subside, can be both psychological and physical.
The study included more than 99 000 women with premenstrual symptoms who were followed for up to 22 years. The researchers compared their health with women without these symptoms – both in the general population and by comparing them with their own sisters to take into account hereditary factors and upbringing.
The results show that women with premenstrual symptoms had about a ten per cent higher risk of developing cardiovascular disease. When the researchers also looked at different types of cardiovascular disease, they found that the link was particularly strong for heart rhythm disorders (arrhythmias), where the risk was 31 per cent higher, and for stroke caused by a blood clot, where the risk was 27 per cent higher. Even after the researchers took into account other factors such as smoking, BMI and mental health, the link between premenstrual symptoms and increased disease risk remained.
”The increased risk was particularly clear in women who were diagnosed before the age of 25 and in those who had also experienced postnatal depression, a condition that can also be caused by hormonal fluctuations,” says first author Yihui Yang, PhD student at the Institute of Environmental Medicine.
Research has not yet identified the cause of this link, but the researchers behind the study suggest three possible explanations. One is that women with premenstrual symptoms may have a disrupted regulation of the renin-angiotensin-aldosterone system (RAAS), which controls blood pressure and fluid balance in the body, among other things. The second is that these women have increased levels of inflammation in the body, which is a known risk factor for atherosclerosis and other heart problems. Finally, it may be because women with premenstrual symptoms may have metabolic abnormalities, which are linked to an increased risk of both stroke and heart attack.
”We hope that our findings will contribute to greater awareness that premenstrual disorders not only affect daily life but can also have consequences for long-term health,” says last author Donghao Lu, associate professor at the same department.
The age of menarche can offer valuable clues about a woman’s long-term risk for conditions like obesity, diabetes, heart disease and reproductive health issues, according to a study being presented Sunday at ENDO 2025, the Endocrine Society’s annual meeting in San Francisco.
The Brazilian study found that both early and late menarche – the age when women first get their period– are linked to different health risks. Women who had their first period before age 10 were more likely to develop obesity, hypertension, diabetes, heart problems and reproductive issues like pre-eclampsia later in life. Women who started their period after age 15 were less likely to be obese but had a higher risk of menstrual irregularities and certain heart conditions.
“We now have evidence from a large Brazilian population that confirms how both early and late puberty can have different long-term health impacts,” said study author Flávia Rezende Tinano of the University of Sao Paulo in Sao Paulo, Brazil. “While early menarche increases the risk for multiple metabolic and heart problems, late menarche may protect against obesity but increase certain heart and menstrual issues. Most women can remember when they had their first period, but they might not realise that it could signal future health risks. Understanding these links can help women and their doctors be more proactive about preventing conditions like diabetes, high blood pressure and heart disease.”
Tinano said the study is one of the largest of its kind in a developing country, providing valuable data on a topic that has mostly been studied in wealthier countries. “It highlights how early and late puberty can affect a woman’s long-term health, especially in underrepresented populations like those in Latin America,” she said.
The study was part of the Brazilian Longitudinal Study of Adult Health (ELSA-Brazil) and evaluated data from 7623 women ages 35 to 74. The age of their first period was categorised as early (less than 10 years old), typical (ages 10 to 15) or late (older than 15). They assessed the women’s health through interviews, physical measurements, lab tests and ultrasound imaging.
“Our findings suggest that knowing a woman’s age at her first period can help doctors identify those at higher risk for certain diseases,” Tinano said. “This information could guide more personalised screening and prevention efforts. It also emphasises the importance of early health education for young girls and women, especially in developing countries.”
Otago researchers have found the hormone prolactin plays an important role in regulating body temperature during pregnancy. Credit: University of Otago
Prolactin supports milk production and stimulates caregiving behaviour in mothers, now a University of Otago – Ōtākou Whakaihu Waka study has found that this key pregnancy hormone also regulates body temperature during pregnancy.
Senior author Dr Rosie Brown, of the Department of Physiology, says adjusting body temperature is a critical function of the central nervous system and is vital to keep both mum and baby healthy.
The study, published in Cell Reports, has shown that prolactin acts within the brain’s hypothalamus to help regulate core body temperature throughout gestation.
“The body needs to function differently to cope during pregnancy – early on core body temperature rapidly elevates, likely because of rising progesterone levels, then increased metabolic heat occurs thanks to foetal growth, maternal tissue growth, and greater food intake,” Dr Brown says.
A mother must lose this extra metabolic heat both for herself and for her developing offspring.
“Despite all these thermal pressures, core body temperature actually reduces in late pregnancy, and we now know it is prolactin which helps keep a mum cool.
“This seems to be an important change to promote heat loss and to, ultimately, provide a safe environment for the foetus, as hyperthermia can impact brain development.”
Dr Brown says the finding provides better understanding of how the changing hormones of pregnancy and lactation act in the maternal brain to alter how the body functions and promote survival and wellbeing of a mother and her offspring.
“Obviously, that helps us understand what is happening at a cellular level during pregnancy, but understanding adaptable changes in body temperature in mammals may also be critical for animal reproduction in a world facing climate change.
“The prolactin pathway in the brain may be a mechanism that helps mammals adapt to future thermal challenges.”
A study of almost 1000 pregnant women in Zimbabwe found that a daily dose of a commonly used, safe and inexpensive antibiotic may have led to fewer babies being born early. Among women living with HIV, those who received the antibiotic had larger babies who were less likely to be preterm.
One in four live-born infants worldwide is preterm (born at 37 weeks’ gestation or before), is small for gestational age, or has a low birth weight. The mortality rate for these small and vulnerable newborns is high, with prematurity now the leading cause of death among children younger than 5 years of age. Maternal infections and inflammation during pregnancy are linked to adverse birth outcomes, particularly for babies born to mothers living with HIV, who have a greater risk of being born too small or too soon.
An international group of researchers, led by Professor Andrew Prendergast from Queen Mary University of London, and Bernard Chasekwa from the Zvitambo Institute for Maternal and Child Health Research in Zimbabwe, conducted the Cotrimoxazole for Mothers to Improve Birthweight in Infants (COMBI) randomised controlled trial, to examine whether prescribing pregnant women a daily dose of trimethoprim–sulfamethoxazole (a broad-spectrum antimicrobial agent with anti-inflammatory properties, widely used in sub-Saharan Africa) would result in heavier birth weights, decreased premature births, and better health outcomes for their babies.
993 pregnant women were recruited from three antenatal clinics in Shurugwi, a district in central Zimbabwe, and received either 960 mg of the drug or a placebo daily. The participants received regular antenatal care during their pregnancies and data regarding their birth outcomes were recorded.
The study, published in the New England Journal of Medicine, found that although birthweight did not differ significantly between the two groups, the trimethoprim–sulfamethoxazole group showed a 40% reduction in the proportion of preterm births, compared to the placebo group. Overall, 6.9% of mothers receiving the drug had babies born preterm, compared to 11.5% of mothers receiving the placebo, and no women receiving antibiotics had babies born prior to 28 weeks. For babies born to a small group of 131 women with HIV, the reduction in premature births was especially marked, with only 2% of births in the trimethoprim–sulfamethoxazole group preterm, as compared with 14% in the placebo group. Babies exposed to antibiotics during pregnancy also showed a 177 gram increase in their birth weight.
Bernard Chasekwa, first author, said: “Our trial, conducted within routine antenatal care and enrolling women predominantly from rural areas, showed that trimethoprim-sulfamethoxazole did not improve birthweight, which was our main outcome. However, there was an intriguing suggestion that it may have improved the length of pregnancy and reduced the proportion of preterm births. We now need to repeat this trial in different settings around the world to see whether antibiotics during pregnancy can help reduce the risk of prematurity.”
A real-world study based on information from an electronic health records–derived database reveals limited benefits of adding bevacizumab to first-line chemotherapy for patients with ovarian cancer, consistent with previous clinical trials. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.
Bevacizumab is a monoclonal antibody against vascular endothelial growth factor A that acts to inhibit malignant cell growth and blood vessel formation. It’s approved as a treatment for various types of cancer. In clinical trials of patients with ovarian cancer, adding bevacizumab to first-line chemotherapy did not prolong overall survival compared with chemotherapy alone, but this treatment strategy did improve overall survival in analyses limited to patients with high-risk prognostic factors—such as those with advanced disease and those who had residual cancer present after surgery. A final long-term analysis did not find an overall survival benefit associated with bevacizumab in the full patient cohort.
To investigate whether these findings also hold true in real-world clinical practice, researchers examined the electronic health records of 1,752 patients with stage III or IV ovarian cancer who initiated chemotherapy with or without bevacizumab in 2017–2023 and were followed for a median time of 1.5 years.
Among patients with high-risk prognostic factors, the median time to next treatment was significantly longer for those receiving chemotherapy plus bevacizumab compared with those receiving chemotherapy alone: 13.6 versus 11.7 months. (Time to next treatment is used to assess the duration of clinical benefit by measuring the time between initiating a treatment and starting the next line of therapy). In these patients, there was also a trend towards longer median overall survival for the combination therapy: 31.1 versus 27.4 months. Among patients without high-risk prognostic factors, outcomes did not differ with the addition of bevacizumab. Benefits therefore seemed limited to special subpopulations, mirroring the findings from clinical trials.
“Our results were similar to results from clinical trials,” said lead author Linda R. Duska, MD, MPH, of the University of Virginia School of Medicine. “Our findings suggest that clinicians should consider a patient’s risk factors before using bevacizumab with first-line chemotherapy in the treatment of advanced ovarian cancer.”
Deciding whether to start hormone therapy during the menopause transition, the life phase that’s the bookend to puberty and when a woman’s menstrual cycle stops, is a hotly debated topic. While hormone therapy is recommended to manage bothersome symptoms like hot flashes and night sweats, Matthew Nudy, assistant professor of medicine at the Penn State College of Medicine, said there’s confusion about the long-term effects of hormone therapy, especially on cardiovascular health.
However, long-term use of oestrogen-based hormone therapies may have beneficial effects on heart health, according to a new study led by Nudy. A multi-institutional team analysed data from hormone therapy clinical trials that were part of the Women’s Health Initiative (WHI), a long-term national study focused on menopausal women, and found that oestrogen-based hormone therapy improved biomarkers associated with cardiovascular health over time. In particular, the study suggests that hormone therapy may lower levels of lipoprotein(a), a genetic risk factor associated with a higher risk of heart attack and stroke.
“The pendulum has been swinging back and forth as to whether hormone therapy is safe for menopausal women, especially from a cardiovascular disease perspective,” Nudy said. “More recently, we’re recognising that hormone therapy is safe in younger menopausal women within 10 years of menopause onset, who are generally healthy and who have no known cardiovascular disease.”
The hormonal changes that accompany menopause come with an increased risk of cardiovascular disease. The decline in the oestrogen can lead to changes in cholesterol, blood pressure and plaque buildup in blood vessels, which increase the risk of heart attack and stroke.
The research team was interested in understanding the long-term effect of hormone therapy on cardiovascular biomarkers, which hasn’t been evaluated over an extended period of time. Prior research in the field primarily looked at short-term effects.
Here, the team analysed biomarkers associated with cardiovascular health over a six-year period from a subset of women who had participated in an oral hormone therapy clinical trial that was part of the WHI. Post-menopausal participants aged 50 to 79 were randomly assigned to one of two groups, an oestrogen-only group and an oestrogen plus progesterone group. They provided blood samples at baseline and at the one-, three- and six-years marks. In total, they analysed samples from 2696 women, approximately 10% of the total trial participants.
The research team found that hormone therapy had a beneficial effect on most biomarkers in both the oestrogen-only and the oestrogen-plus-progesterone groups over time. Levels of LDL cholesterol, the so-called “bad” cholesterol, were reduced by approximately 11% while total cholesterol and insulin resistance decreased in both groups. HDL cholesterol, the so-called “good” cholesterol, increased by 13% and 7% for the oestrogen-only and oestrogen-and-progesterone groups, respectively.
However, triglycerides and coagulation factors, proteins in the blood that help form blood clots, increased.
The decrease in lipoprotein(a) concentration was more pronounced among participants with American Indian or Alaska Native ancestry or Asian or Pacific Islander ancestry, by 41% and 38%, respectively. The reason why was unclear, Nudy said.
More surprising to the research team, they said, levels of lipoprotein(a), a type of cholesterol molecule, decreased 15% and 20% in the oestrogen-only and the oestrogen-plus-progesterone groups, respectively. Unlike other types of cholesterol, which can be influenced by lifestyle and health factors such as diet and smoking, concentrations of lipoprotein(a) are thought to be determined primarily by genetics, Nudy explained. Patients with a high lipoprotein(a) concentration have an increased risk of heart attack and stroke, especially at a younger age. There’s also an increased risk of aortic stenosis, where calcium builds up on a heart valve.
“As a cardiologist, this finding is the most interesting aspect of this research,” Nudy said. “Currently, there are no medications approved by the Food and Drug Administration (FDA) to lower lipoprotein(a). Here, we essentially found that oral hormone therapy significantly reduced lipoprotein(a) concentrations over the long-term.”
Nudy noted that the oestrogen therapy the women received in the clinical trial was conjugated equine oestrogens, a commonly prescribed form of oral oestrogen therapy. Before being absorbed by the body, oral hormone therapy is processed in the liver, through a process called first-pass metabolism. That process could increase inflammatory markers, which may explain the rise in triglycerides and coagulation factors.
“There are now other common formulations of oestrogen hormone therapy like transdermal oestrogen, which is administered through the skin,” Nudy said. “Newer studies have found that transdermal oestrogen doesn’t increase triglycerides, coagulation factors or inflammatory markers.”
For those considering menopause hormone therapy, Nudy recommended undergoing a cardiovascular disease risk assessment, even if the person hasn’t had a previous heart attack or stroke or hasn’t been diagnosed with cardiovascular disease. It will give health care providers more information when considering the best option to treat menopause symptoms.
“Currently, hormone therapy is not FDA-approved to reduce the risk of coronary artery disease or stroke,” Nudy said.
The study assessed the health records of 2776 women with a child diagnosed with congenital heart disease who were matched to 13 880 women whose children did not have this condition.
Investigators found that 4.4% of children with congenital heart disease and 2.8% of children with normal heart function had anaemia. After adjusting for potential influencing factors, the odds of giving birth to a child with congenital heart disease was 47% higher among anaemic mothers.
“We already know that the risk of congenital heart disease can be raised by a variety of factors, but these results develop our understanding of anaemia specifically and take it from lab studies to the clinic. Knowing that early maternal anaemia is so damaging could be a gamechanger worldwide,” said corresponding author Duncan B. Sparrow, PhD, of the University of Oxford. “Because iron deficiency is the root cause of many cases of anaemia, widespread iron supplementation for women—both when trying for a baby and when pregnant—could help prevent congenital heart disease in many newborns before it has developed.”
Women diagnosed with breast cancer who carry particular BRCA1 and BRCA2 genetic variants are offered surgery to remove the ovaries and fallopian tubes as this dramatically reduces their risk of ovarian cancer. Now, Cambridge researchers have shown that this procedure – known as bilateral salpingo-oophorectomy (BSO) – is associated with a substantial reduction in the risk of early death among these women, without any serious side-effects.
Women with certain variants of the genes BRCA1 and BRCA2 have a high risk of developing ovarian and breast cancer. These women are recommended to have their ovaries and fallopian tubes removed at a relatively early age – between the ages 35 and 40 years for BRCA1 carriers, and between the ages 40 and 45 for BRCA2 carriers.
Previously, BSO has been shown to lead to an 80% reduction in the risk of developing ovarian cancer among these women, but there is concern that there may be unintended consequences as a result of the body’s main source of oestrogen being removed, which brings on early menopause. This can be especially challenging for BRCA1 and BRCA2 carriers with a history of breast cancer, as they may not typically receive hormone replacement therapy to manage symptoms. The overall impact of BSO in BRCA1 and BRCA2 carriers with a prior history of breast cancer remains uncertain.
Ordinarily, researchers would assess the benefits and risks associated with BSO through randomised controlled trials, the ‘gold standard’ for testing how well treatments work. However, to do so in women who carry the BRCA1 and BRCA2 variants would be unethical as it would put them at substantially greater risk of developing ovarian cancer.
To work around this problem, a team at the University of Cambridge, in collaboration with the National Disease Registration Service (NDRS) in NHS England, turned to electronic health records and data from NHS genetic testing laboratories collected and curated by NDRS to examine the long-term outcomes of BSO among BRCA1 and BRCA2 PV carriers diagnosed with breast cancer. The results of their study, the first large-scale study of its kind, are published today in The Lancet Oncology.
The team identified a total of 3400 women carrying one of the BRCA1 and BRCA2 cancer-causing variants (around 1700 women for each variant). Around 850 of the BRCA1 carriers and 1,000 of the BRCA2 carriers had undergone BSO surgery.
Women who underwent BSO were around half as likely to die from cancer or any other cause over the follow-up period (a median follow-up time of 5.5 years). This reduction was more pronounced in BRCA2 carriers compared to BRCA1 carriers (a 56% reduction compared to 38% respectively). These women were also at around a 40% lower risk of developing a second cancer.
Although the team say it is impossible to say with 100% certainty that BSO causes this reduction in risk, they argue that the evidence points strongly towards this conclusion.
Importantly, the researchers found no link between BSO and increased risk of other long-term outcomes such as heart disease and stroke, or with depression. This is in contrast to previous studies that found evidence in the general population of an association between BSO and increased risk of these conditions.
First author Hend Hassan, a PhD student at the Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, and Wolfson College, Cambridge, said: “We know that removing the ovaries and fallopian tubes dramatically reduces the risk of ovarian cancer, but there’s been a question mark over the potential unintended consequences that might arise from the sudden onset of menopause that this causes.
“Reassuringly, our research has shown that for women with a personal history of breast cancer, this procedure brings clear benefits in terms of survival and a lower risk of other cancers without the adverse side effects such as heart conditions or depression.”
Most women undergoing BSO were white. Black and Asian women were around half as likely to have BSO compared to white women. Women who lived in less deprived areas were more likely to have BSO compared to those in the most-deprived category.
Hassan added: “Given the clear benefits that this procedure provides for at-risk women, it’s concerning that some groups of women are less likely to undergo it. We need to understand why this is and encourage uptake among these women.”
Professor Antonis Antoniou, from the Department of Public Health and Primary Care, the study’s senior author, said: “Our findings will be crucial for counselling women with cancer linked to one of the BRCA1 and BRCA2 variants, allowing them to make informed decisions about whether or not to opt for this operation.”
Professor Antoniou, who is also Director of the Cancer Data-Driven Detection programme, added: “The study also highlights the power of exceptional NHS datasets in driving impactful, clinically relevant research.”
The research was funded by Cancer Research UK, with additional support from the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre.
The University of Cambridge is fundraising for a new hospital that will transform how we diagnose and treat cancer. Cambridge Cancer Research Hospital, a partnership with Cambridge University Hospitals NHS Foundation Trust, will treat patients across the East of England, but the research that takes place there promises to change the lives of cancer patients across the UK and beyond. Find out more here.
Research team finds moderate risk for preterm birth, low birth weight
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An updated systematic review finds that consuming cannabis while pregnant appears to increase the odds of preterm birth, low birth weight and infant death. This study by researchers at Oregon Health & Science University appears in JAMA Pediatrics.
Study lead author Jamie Lo, MD, MCR, is a physician-scientist who provides prenatal care for high-risk pregnancies at OHSU.
“Patients are coming to me in their prenatal visits saying, ‘I quit smoking and drinking, but is it safe to still use cannabis?’” said Lo, associate professor of obstetrics and gynaecology (maternal-foetal medicine) in the OHSU School of Medicine. “Until direct harms have been proven, they perceive it to be safe to use.”
In fact, cannabis remains one of the most common substances used in pregnancy that’s still illegal under federal law, and, unlike declines in prenatal use of alcohol or nicotine, cannabis use is continuing to increase. Lo said many of her patients are reluctant to give up cannabis during pregnancy because it helps to reduce common prenatal symptoms such as nausea, insomnia and pain.
Researchers updated the systematic review and meta-analysis, drawing on a total of 51 observational studies involving 21.1 million people to examine the potential adverse effects of cannabis use in pregnancy. The researchers found eight new studies since their previous update, raising the certainty of evidence from “very-low-to-low” to “moderate” for increased odds of low birth weight, preterm birth and babies being small for their gestational age.
The updated review also indicated increased odds of newborn mortality, though still with low certainty.
Researchers noted that the new systematic review includes a larger proportion of human observational studies examining people who only use cannabis, but don’t also use nicotine. And even though the evidence is low to moderate for adverse outcomes, Lo noted that the findings are consistent with definitive evidence in nonhuman primate models exposed to THC, the main psychoactive compound in cannabis.
The related research in animal models included standard prenatal ultrasound and MRI imaging that revealed a detrimental effect on the placenta, in terms of blood flow and availability of oxygen in addition to decreased volume of amniotic fluid.
“These findings tell me as an obstetrician that the placenta is not functioning as it normally would in pregnancy,” Lo said. “When the placenta isn’t functioning well, it can affect the baby’s development and growth.”
Even though cannabis remains a Schedule 1 substance under the federal Controlled Substances Act, Oregon is one of several states that have legalised it under state law for medicinal and recreational use. Lo said she recommends a harm-reduction approach to patients. For those who cannot abstain, she advises them to reduce the amount and frequency of use to help reduce the risk of prenatal and infant complications.
“Even using less can mitigate the risk,” she said. “Abstinence is ideal, but it’s not realistic for many patients.”
An Edith Cowan University (ECU) study has found children born to mothers who experienced gestational diabetes (GDM) during pregnancy are more likely to develop attention-deficient hyperactive disorder (ADHD) and externalising behaviour. The study appears in BMC Paediatrics.
The study used data from 200 000 mother-child pairs across Europe and Australia, and found that in children aged 7 to 10, those born to mothers with gestational diabetes had consistently higher ADHD symptoms.
Children aged 4 to 6 years, born to mothers with gestational diabetes consistently exhibited more externalising problems than those born who didn’t.
“Externalising symptoms are behaviours directed outward. Instead of experiencing depression or anxiety, these children often display hyperactivity, impulsivity, defiance, or aggression,” explained first author Dr Rachelle Pretorius, ECU Honorary researcher.
“Externalising problems frequently coexist with ADHD symptoms and tend to emerge before medical intervention, especially during the early school years,” she added.
“At younger ages, children may exhibit more externalising problems and as the child matures, symptoms or behaviour related to ADHD may become more apparent. ADHD does not have biological markers for diagnosis, making ADHD a disorder that is difficult to detect before symptoms manifest,” said senior author Professor Rae-Chi Huang.
It is still unclear why children exposed to gestational diabetes retained more externalising problems and ADHD symptoms respectively after adjustments.
“However, our findings suggest that these externalising behaviours may decrease over time but could extend into other domains such as neurodevelopment outcomes such as ADHD symptoms.”
Dr Pretorius noted that while the exact mechanics of gestational diabetes influence on child development is still unclear, it is believed that acute and chronic maternal inflammation during pregnancy may influence certain pathways in a child’s brain programming in-utero and contribute to neurodevelopment, cognitive and behaviour outcomes later in life.
“Several studies suggest that the severity of maternal diabetes, associated with maternal obesity, chronic inflammation have a joint impact on the development of autism spectrum disorder and ADHD in children, which is greater than the impact of either condition alone.”
