There is not enough evidence to determine whether testosterone helps with thinking and memory in midlife women, even though it is often prescribed in the UK, according to a UCL study.
Published in Reproduction and Fertility, the review examined five existing studies of women aged 41 to 65 to understand whether testosterone treatment improves thinking and memory in women during and after menopause.
Senior author and Director of the UCL Menopause Mind Lab Professor Aimee Spector (UCL Psychology and Language Sciences) said: “Social media is flooded with claims that testosterone improves memory and brain fog, and we hear of many women taking testosterone specifically to manage these symptoms during the menopause. While there may be some anecdotal evidence for this in perimenopausal women (who are missing from these trials), we cannot claim testosterone improves cognition during menopause without further evidence.
“More research is needed to understand any links between testosterone and brain health.”
The menopause is when a woman’s periods stop due to lower hormone levels. This usually happens between the ages of 45 and 55. Post menopause is the stage of life that begins 12 consecutive months after a woman’s final menstrual period and lasts for the rest of her life.
The menopause transition and post menopause have been associated with cognitive complaints, often described as ‘brain fog’. This includes difficulties recalling words and numbers, misplacing items, trouble concentrating and forgetfulness. It is thought that testosterone levels do not acutely change during menopause but instead begin to decline from a woman’s mid-20s to early 30s.
Researchers reviewed five different studies to determine whether testosterone improved executive function, verbal learning and memory, and visuospatial learning and memory in post-menopausal women.
Many of the study participants were given testosterone while most of the other participants were given a placebo, administered on a daily, weekly or monthly basis for periods ranging between four to 26 weeks. Researchers then compared the effects of cognition between testosterone and the placebo.
The authors conducted a meta-analysis on the results of three of the five studies, which examined a total of 244 women in randomised controlled trials, and they did not find any statistically significant improvements for cognitive function among participants taking testosterone.
Hormone treatments are often used to manage menopause symptoms, but it is unclear whether they help with brain fog. Current guidance from the British Menopause Society and the International Menopause Society only supports testosterone therapy for low libido, and the researchers note its effects on thinking and memory are not well understood.
The researchers say that testosterone prescribing has anecdotally increased across NHS and private clinics in the UK, reflecting growing interest in its role during menopause.
Corresponding author Dr Alexandra Faulkner (UCL Psychology and Language Sciences) said: “Our review found that the available evidence is limited and insufficient to determine the effect of testosterone therapy on cognition in women during the menopause transition and post menopause. This reflects a lack of sufficient evidence rather than evidence of no effect.”
Further research is needed to guide treatment decisions and support women in making informed choices about their care, particularly in women going through the menopause. Future research should also explore how women perceive changes in their thought processes and memory.
Data was included from Australia, Canada, the USA and Sweden to complete this review.
The researchers note that the studies available were limited in number and sample size, with the existing evidence base too small to draw firm conclusions about whether testosterone therapy helps cognitive symptoms during menopause. The findings should not be interpreted as proof that testosterone has no effect on cognition.
But nightly prenatal sleep length may modify this association, exploratory findings suggest
Working night shifts during pregnancy is linked to a heightened risk of neurodevelopmental abnormalities detected by screening in the child by the age of 4, finds research published online in Occupational & Environmental Medicine.
But nightly prenatal sleep length during this period may modify this observed association, exploratory findings suggest.
Night shift work during pregnancy has been associated with unfavourable health outcomes for both mother and child, including neurodevelopmental issues, potentially related to body clock and sleep disturbances, note the researchers.
They therefore wanted to explore the associations between mums’ night shift work and their children’s neurodevelopment and to find out if there are potentially modifiable prenatal factors, such as changes in night shift patterns and sleep duration.
They drew on nationwide survey data for around 100 000 pregnant women from the Japan Environment and Children’sStudy (JECS) who were enrolled between January 2011 and March 2014.
The women were surveyed in the first and second/third trimesters and answered questions about the number of night shifts they worked in a month.
Their responses were divided into 3 groups: no night shifts reported in either survey (27 655 women); night shifts in the first, but not second survey (‘discontinued night shifts’, 1779 women); and night shifts in both surveys (‘continued night shifts’, 2084 women).
Prenatal sleep length was calculated from self-reported bedtime and wake-up times in the second/third trimester. Sleep length was categorised as short if less than 6 hours; moderate if 6–9 hours; and long if 10 or more hours.
Child neurodevelopmental abnormalities at the age of 4 were assessed using a developmental screening tool—the Japanese version of the Ages and Stages Questionnaire, Third Edition (J-ASQ-3).
This is made up of 5 domains: communication; gross motor skills; fine motor skills (ability to make small, precise, deliberate movements); problem solving; and personal–social functioning (interpersonal skills, emotional/behavioural development, and awareness of personal boundary/space).
In all, 31,528 mothers who worked in the first trimester and completed the child development questionnaire when their children were 4 years old were included in the analysis.
Some 4189 (just over 13%) of the 4 year olds were classified as high risk of an abnormality in at least one of the five J-ASQ-3 domains: 1210 (4%) for communication; 1599 (5%) for gross motor skills; 1906 (6%) for fine motor skills; 913 (3%) for problem solving; and 1495 (5%) for personal–social functioning.
Compared with the children of mothers who didn’t work night shifts, the children of those who discontinued night shift work were more likely to have developmental screening abnormalities, but only in the fine motor skills domain (24% higher risk).
But the children of mothers who continued night shifts during their pregnancy had higher risks of developmental abnormalities in 3 domains compared with children whose mothers didn’t work night shifts.
These were in the domains of communication skills (29% higher risk); fine motor skills (34% higher risk); and personal–social functioning (31% higher risk).
Only the fine motor skills domain showed a significant association, regardless of whether night shifts were continued or discontinued.
“One possible explanation is that maternal inflammation associated with persistent night work may preferentially affect neural pathways involved in fine motor function,” suggest the researchers.
A separate exploratory analysis showed that the observed association between night shift pattern and the child’s neurodevelopmental risk differed according to how long the mothers slept.
Prenatal sleep duration of 10 or more hours was associated with an 80% heightened risk of abnormalities in any of the 5 domains compared with prenatal sleep length of 6-9 hours.
Long prenatal sleep duration may also reflect underlying fatigue, subclinical depression, inflammation, or anaemia, rather than representing a harmful exposure in itself, suggest the researchers.
This is an observational study, and as such, can’t establish cause and effect. And the researchers acknowledge that they weren’t able to account for shift rotation systems, individual chronotype, workload, exposure to light, or the timing of night shift discontinuation, all of which might have influenced the findings.
But in light of the findings, it may be worth employers considering flexible work schedules for pregnant night shift workers, they say.
Menopause, defined as a year with no periods, marks the end of a woman’s reproductive years. Photo by Ayo Ogunseinde on Unsplash
Across the country’s townships and rural clinics, women are breaking inherited silences to redefine reproductive ageing on their own terms.
In South Africa, women are challenging the silence around menopause, and the expectation to endure it without support.
This is significant because research suggests that some women in South Africa never discuss menopause with a healthcare worker. In a 2017 study of 450 black women in communities near Pretoria, more than three-quarters had never sought medical help for their symptoms, possibly, researchers argue, because of a cultural view of menopause as a positive natural process.
Menopause, defined by the World Health Organisation (WHO) as a year with no periods, marks the end of a woman’s reproductive years. It’s a natural transition brought on as the ovaries stop releasing eggs and oestrogen levels fall, usually between the ages of 45 and 55. Joint and muscle pain, exhaustion, poor memory and hot flushes are among the most common symptoms, but a new review suggests there are up to 72 possible symptoms.
Hormone replacement therapy is the most effective treatment to ease hot flushes, according to South African Menopause Society (SAMS) guidance, but whether it’s the right choice will depend on each person’s medical history and preferences.
After researching women’s perceptions of menopause in Gauteng and North West, researcher Sostina Matina now believes that the limited use of menopause treatments in South Africa’s public healthcare sector should not be mistaken for a rejection of clinical care. Many women, she says, had simply never had their options explained to them.
Xoli Madlala, who experienced menopause early, has made it her personal mission to bring menopause out into the open. She travels across the country, speaking in settings ranging from corporate boardrooms to rural Bible study groups.
Wherever she goes, she says, women of different ages are open to talking about a subject that previous generations were often expected to endure without discussion.
How clinic staff can fuel midlife myths
Midlife women seeking menopause symptom relief are often turned away by health workers, Matina says, especially if they’re experiencing symptoms earlier than usual or as a result of surgery.
“They’ll say ‘it’s just menopause, there’s nothing we can do’,” she says.
The country’s treatment guidelines for clinics and hospitals include menopausal hormone therapy pills that can ease hot flushes and other symptoms. Women who have had a hysterectomy can usually be prescribed pills with only oestrogen. Those with a womb also need to take progestogen because oestrogen on its own can cause the uterine lining to become too thick, which can increase the risk of cancer.
Hormone patches, which deliver hormones through the skin, are not on South Africa’s essential drug list, but they are listed as alternatives if the pills don’t work well for a particular patient or as an alternative when pill stocks are low, which a report by the National Essential Medicines List Committee suggests happens often.
Professor Lineo Matsela, an obstetrician, gynaecologist and president of SAMS, says it’s become common for public sector doctors to write prescriptions for menopausal hormone treatments so that patients can buy them at a private pharmacy.
Over the past three years, however, there have also been sporadic private sector shortages of menopausal hormone therapy treatments.
But access to medicines is only part of the problem, Matina says. Dismissing menopause can also mean the health system could be missing other health risks that can impact women in midlife, a phase that can span about 40% of their lives.
The transition is also associated with bone loss, and the stakes might be slightly higher for women living with HIV. Over five years, a Soweto study found a greater loss of bone-density among women living with HIV compared to those without HIV, though there wasn’t a difference in fractures between the two groups. Researchers didn’t have information on which HIV treatments participants were taking so they couldn’t untangle the effects of HIV itself from the possible impact of tenofovir, which is part of first-line HIV treatment and can contribute to bone loss.
US research suggests there could also be links between HIV, menopause and heart disease and an African study found higher rates of the “bad” kind of cholesterol after menopause regardless of HIV status.
Loss and liberation
People’s experiences of menopause vary widely across countries, cultures and generations.
Women in four rural villages in Limpopo, for instance, described menopause to researchers as a series of losses, of beauty, respect and quality of life even though older people were generally regarded as important veterans who deserve respect regardless of gender.
In some instances, researchers found that elders enforce a culture of silence about menopause. One premenopausal woman explained: “At the girls’ initiation when we were still young, old women told us blood will cease and since then no one ever talked to me about it. That is why I say it is my secret.”
In interviews at two Mamelodi clinics, researchers heard accounts linking pain and weight gain to blood that was no longer flowing out. “I do not know where this blood goes,” one participant said.
In a 2013 discussion of menopause and marriage, theologian Elijah Baloyi described a belief among Tsonga-speaking people that sex after menopause could cause semen to accumulate and a woman’s abdomen to swell.
In Johannesburg’s Soweto township, Matina found many postmenopausal women held beliefs about dirty blood, some saying they withdrew from sexual intimacy entirely or accepted the end of their intimate relationships.
For others, menopause brought liberation from the monthly financial burden of sanitary pads, or elevation to the level of an elder who could commune with ancestors.
Research conducted in South Africa and Zimbabwe suggests that inter-generational support can make all the difference to help women approach the milestone with acceptance.
One woman, who initially worried the changes she was experiencing were signs she could be dying, was calmed by her mother’s reassurance and positive outlook. Another told researchers: “[Menopause] is something I am looking forward to, why, because I am getting old. Yes, if time permits and if God allows it, with life, it’s okay.”
Language mirrors a society’s worldview, and where Western medicine isolated a clinical hormonal deficit, African linguistic traditions instead describe social shifts.
When clinical concepts are translated literally into local languages, they often produce phrases steeped in shame, stigma, or perceived uselessness such as kuguma ura (no longer bearing) in Shona or phelelo maikutlo (the end of one’s feelings) in Setswana.
In response, women may express their bodily changes through idioms and euphemisms, describing hot flushes as fufulelwa or framing the transition socially as ugugile (she has aged), sekhulile (growing older), or into zabogogo (grannies’ stuff).
Because nursing and medical school curricula spend little time on multicultural health communication or the endocrinology of ageing, Matina argues clinic staff frequently misinterpret these cultural expressions or fail to engage with them altogether.
“You know, I don’t know menopause properly… because sometimes people speak in such big English, so you don’t understand it, unless someone explains it to you”, an older woman in Soweto told researchers.
From stigma to selfhood
When researchers set out to learn about midlife health across South Africa and Zimbabwe, they discovered that women want something different from what their public health systems currently offer.
The women described leaving clinics without accessible information and with lingering physical distress or anxiety over health risks.
When asked what would help, participants explicitly requested clear, contextually relevant information so they could understand their bodies and take charge of their own health regardless of their access to more expensive hormone therapies.
The result is a series of question-and-answer booklets co-created with communities, doctors, translators and designers, which reflect the women’s firm rejection of the “old granny” stereotypes.
The participants banned old-fashioned dresses, which they felt aged menopausal women, and insisted on vibrant, modern images of smiling, active women. Also banished were medical jargon and deficit-based translations of “menopause”.
Instead, they opted for culturally relevant terms of dignity and strength such as Ubufazi in isiZulu and Sesadi in Setswana, both of which simply mean “womanhood”.
Studies on menopause have always had to cope with the date of the final menstrual period varying enormously, which blurred the data due to the variable onset ages. But a innovative technique finds a distinct ‘physiological cliff’ related to the onset of menopause – and significant changes for a decade and a half preceding it.
To get around the problem of the variable onset age of menopause, researchers made use of a computational method originally used for astronomy and applied it to map large-scale biomedical datasets by anchoring health markers to the final menstrual period.
By analysing hundreds of millions of laboratory tests from two independent populations, scientists uncovered a step-like physiological cliff across endocrine, skeletal, hepatic, renal, and lipid systems that coincides precisely with menopause. These abrupt physiological shifts – which are of course completely absent in male control cohorts – often signal an increased risk of disease and begin more than a decade before menstruation permanently ceases. Furthermore, the analysis demonstrates that menopausal hormone therapy significantly attenuates these abrupt biological disruptions, restoring postmenopausal test trajectories to resemble a smoother continuation of earlier health patterns.
An AI model created by researchers at King’s can detect signs of faulty DNA-repair mechanisms in ovarian cancer cells, potentially enabling a low-cost, widely accessible diagnostic tool.
By analysing tissue images, the model recognised tumours with defective DNA-repair mechanisms, which could help clinicians select treatments that exploit this vulnerability.
We are unlocking information hidden in microscopic images of cancer tissue that could transform how we match patients to treatments. By using AI to reveal defects in DNA repair, we could make precision cancer medicine faster, more affordable and accessible to more women with ovarian cancer, not just in the UK but around the world.
Dr Heba Sailem, Reader in Computational Pathology at King’s College London
The study focused on high-grade serous tubo-ovarian carcinoma (HGSOC). Homologous recombination deficiency (HRD), often arising from BRCA1/BRCA2 or related mutations, impairs DNA-damage repair and increases vulnerability to platinum chemotherapy and PARP inhibitors. HRD is therefore a useful biomarker for treatment selection, but current tests require genomic analysis that is costly and less accessible in resource-limited settings.
In the study, published in Nature Communications and led by Dr Heba Sailem, researchers developed HRDPath. Rather than sequencing DNA, HRDPath analyses high-resolution digital histopathology images. It was trained on images from patients with known genomic HRD status and correctly identified approximately 91% of HRD-positive cases, particularly when multiple images per patient were considered.
HRD-positive tumours showed subtle morphological differences, including rounder nuclei and denser cellular packing in certain regions. Defects in DNA repair therefore appear linked to tissue-architecture changes recognisable by AI but difficult to detect by conventional microscopy.
If validated in larger cohorts, HRDPath could use images already acquired for diagnosis, reducing reliance on expensive genomic testing and widening access to platinum and PARP-inhibitor selection for patients whose tumours are likely to benefit.
Researchers have identified two common drugs that may, when given together during pregnancy, prevent premature births.
The finding comes from a new, Stanford Medicine-led, artificial intelligence-powered technique for screening drugs to prevent early labour. It uses a comprehensive atlas of the immune system, accurate at cell-by-cell level, to create ‘digital twins’ of the immune systems of individual pregnant women for virtual drug testing.
The study, published online 21 October in Science Advances, builds on two decades of Stanford Medicine research on maternal immune shifts during pregnancy. When the immune clock of pregnancy runs too quickly, preterm labour can result.
After screening several possible treatments with the digital twin system, the researchers identified one drug combination that promises to markedly lower the risk of early labour. It shows sufficient potential that researchers are starting a clinical trial.
“We’re on the brink of having a real impact for the treatment of preterm birth, a global health problem that affects 10% of pregnancies worldwide,” said senior study author Dr Brice Gaudilliere. It has been decades since a new pharmacological intervention for preventing preterm birth.
The winning combination was aspirin and lansoprazole. Low-dose aspirin alone has a modest ability to prevent premature birth; lansoprazole is sometimes used in pregnancy for acid reflux.
“In the digital twin system, these two drugs in combination had a large effect on the delay of labour, 15 times higher than aspirin alone,” Gaudilliere said.
Modelling how the immune clock ticks
Although triggers of labour remain incompletely explained, Stanford Medicine research has shown immune signals play a key role. Early in pregnancy the maternal immune system adjusts to tolerate the fetus. Late in pregnancy, immune changes – including a switch toward pro-inflammatory signals – prepare the body for labour. When pro-inflammatory signals activate too soon, early labour can result.
The new system, SIMCO (simulated immune modelling of clinical outcomes), uses AI and machine-learning to integrate extensive data on immune-cell behaviour during pregnancy.
Researchers collected blood samples from pregnant women and exposed immune cells to multiple drugs. “We measured responses from a quarter of a billion cells, training the algorithm on a massive single-cell dataset,” Gaudilliere said.
“A digital twin has the prerequisite that you understand a biological system very well,” said co-lead author Dr Jakob Einhaus, postdoctoral scholar at Stanford Medicine. “The digital twin represents the complexity and connections in the immune system.”
Einhaus shares lead authorship with graduate students Peter Neidlinger and Olivier Fondeur, and with Dr Masaki Sato (now at the National Center for Child Health and Development, Tokyo).
Longitudinal data from 63 pregnancies were integrated to link cell-behaviour patterns to clinical outcomes and capture inter-patient variability. The algorithm predicts individual immune-cell responses to drugs and, from limited patient data (e.g., a small blood sample), the likely clinical effect on the immune clock of pregnancy.
“You’re making the prediction for one individual based on knowledge of millions of single cells from dozens of patients,” Einhaus said.
Common medications may delay delivery
After validating that SIMCO forecasts time to labour, the team evaluated nine pregnancy-safe drug regimens identified via a drug-repurposing pipeline developed by a group led by Dr Marina Sirota (University of California, San Francisco). Multiple digital-twin copies compared treated versus untreated scenarios for each individual.
The model strongly predicted that the aspirin–lansoprazole combination would delay labour. “Our findings suggest that salicylic acid [aspirin] and lansoprazole act synergistically … this synergy may enhance their immunomodulatory effect,” the investigators write.
Folic acid also delayed immunological progression toward labour. “We’re giving folic acid for spina bifida prevention, but maybe, unknowingly, we’re also helping the maternal immune system adapt to pregnancy,” Einhaus said.
The model indicated specific immune-signal changes: for the aspirin–lansoprazole combination, processes supporting pregnancy continuation are enhanced while those triggering labour are inhibited.
Because the model captures patient variation, it can identify likely responders and non-responders, potentially allowing smaller, more efficient trials restricted to predicted responders.
The combination delayed labour onset in an animal model of inflammatory pregnancy; FDA approval was obtained for a human trial.
Children whose mothers received opioid prescriptions during pregnancy have a higher rate of hospital admission in childhood than unexposed children, including unexposed siblings, according to a new study published October 13th in the open access journal PLOS Medicine by Dong Keon Yon of Kyung Hee University College of Medicine, South Korea, and colleagues.
Over recent decades, opioid prescriptions and doses have risen in clinical practice, and a considerable proportion of pregnant women are exposed to these drugs. In the US, for example, data has shown that 14-22% of women filled a prescription for opioids during pregnancy. Prenatal opioid exposure may disrupt infant development and immune system function, but prior studies have had limitations such as confounding factors, limited sample sizes, or restricted follow-up durations.
In the new study, researchers used nationwide health insurance data on mothers and children in South Korea, following a cohort of 2,928,186 children born between 2010 and 2017 for up to 14 years. Children were classified as prenatally exposed to opioids if their mothers received two or more opioid prescriptions during pregnancy, and were compared both with unexposed children and with their own siblings.
Children with prenatal opioid exposure had a 28% higher rate of hospital admission than unexposed children (adjusted incidence rate ratio 1.28, 95% CI 1.28-1.29). The association was smaller but still significant when comparing siblings (aIRR 1.08, 95% CI 1.07-1.10). The effect was also dose-dependent, with higher maternal opioid doses associated with higher admission rates (aIRR 1.19 for low-dose exposure versus 1.40 for high-dose exposure). The elevated admission rates spanned several causes, including infections and respiratory, gastrointestinal and genitourinary conditions, with the association strongest up to five years of age.
“These findings suggest the need for additional postnatal health checks for those born to mothers with opioid prescriptions during pregnancy,” the authors write. “However, these findings should be interpreted with caution, as the study relied on electronic health records, which may not reflect actual use of medication, and unmeasured factors shared within families may still partly explain the observed associations.”
Dong Keon Yon, MD, PhD (co-corresponding author) states, “In a nationwide cohort of nearly three million Korean children, those whose mothers received two or more opioid prescriptions during pregnancy had about a 28% higher rate of hospital admission, most notably for infections and respiratory illness in the first years of life. The risk rose with higher opioid doses and longer prescriptions, which points to a possible biological effect—but when we compared siblings within the same family, the association shrank considerably, so shared family factors clearly explain part of what we see.”
Jiseung Kang, PhD (co-corresponding author), adds, “Because opioids in South Korea are obtained almost entirely by prescription, our data let us examine prescribed opioid exposure in pregnancy unusually cleanly, and following nearly three million children for up to 14 years gave us the statistical power to look at dose, timing, and specific causes of admission separately. The consistency of the pattern across all of these analyses is what makes the finding hard to dismiss.”
Hyeon Jin Kim, MS (joint first author) states, “Our message is not that pregnant women should never receive opioids—for some, pain relief is essential. It is that opioids in pregnancy should be prescribed at the lowest effective dose for the shortest time, and that children born after such exposure may benefit from closer routine health checks, particularly in infancy when the risk was highest.”
Yesol Yim (joint first author) notes, “What surprised us most was how quickly the association faded as children grew older. The excess risk was clearest in the first year of life and had largely disappeared after age five. That pattern suggests a window of vulnerability in early infancy rather than a lifelong effect – and it is a window in which pediatric follow-up can make a real difference.”
Contrary to popular belief, the postmenopausal ovary is not defunct.
In a new, paradigm-shifting study of ovaries from 28 women, scientists at Northwestern University and the Buck Institute for Research on Aging found that in the decades after menopause the ovary remains biologically active and continues to remodel with age, showing increased inflammation and changes in tissue structure. The study also identified a molecular link between ovarian ageing and cancer.
The study was published on 14 October in Aging Cell.
“In the ovary, we reach a point of no return with respect to fertility in which it’s no longer producing eggs, and I would venture to say most people assume those ovaries are just sitting there doing nothing, similar to the appendix,” said co-corresponding author Francesca Duncan (associate professor of reproductive science in medicine, Northwestern University Feinberg School of Medicine; associate professor in residence, Buck Institute). “But that’s what makes this study very different.”
The findings challenge the notion that the ovary is an innocent bystander after reproduction ends, raising questions about whether it could play a more active role in ageing and chronic disease in women.
“The ovary is not just a reproductive organ,” said co-corresponding author Birgit Schilling (professor and director of the Mass Spectrometry Center, Buck Institute). “It really influences how somebody ages because it speaks to all these other organs, such as the brain, and also to the bone, and women after menopause experience often a lot of bone problems. So, we think there is a connection between all these organs.”
Women now routinely live for decades after menopause, making it increasingly important to understand what the ovary is doing during this long post-reproductive period, Duncan said.
“Is the ovary the canary in the coal mine in women?” said Duncan. “Could ageing in the ovary set off a cascade of changes that continues throughout the body as women get older?”
Duncan’s group previously found similar evidence of continued remodelling in postmenopausal ovaries of mice. When she embarked on that research and the current study in humans, she expected to see very little activity in the postmenopausal ovary.
“I was predicting that if we took a 50-year-old ovary, a 60-year-old ovary, a 70-year-old, an 80-year-old ovary, they would all look exactly the same, have no eggs, and basically be non-functional,” Duncan said. “The fact that across species we’re seeing this gives us confidence that this isn’t just some random event, but something truly meaningful is happening in the biology.”
What remains unknown is exactly what the ovary is doing after menopause and whether those changes are beneficial or harmful, Duncan said.
“Our data points to progressive ageing features in which the ovary appears to lose its original identity and ends up doing something different,” Duncan said. “We do not yet know if there’s ever a point in a woman’s life when this organ is no longer beneficial and it’s actually harmful. These results really point to the need to ask this question.”
To characterise the changes, Schilling’s team – spearheaded by Buck Institute staff scientist Mark Watson – used advanced proteomic technologies to analyse 5,812 protein groups in normal ovarian tissue from postmenopausal women aged 50 to 75.
Human ovarian tissue is difficult to obtain, making the 28 ovaries an unusually valuable collection. By focusing exclusively on women within a relatively narrow 25-year age range after menopause, the researchers examined molecular changes that continue during the postmenopausal years. The technology allowed examination of thousands of proteins across every sample and identification of patterns using multiple statistical approaches.
Those analyses showed that the ovary continues to change well after its reproductive life ends.
Ovaries from younger postmenopausal women had more proteins involved in maintaining cells and tissue structure, while older ovaries had more proteins associated with inflammation, immune activity and the ongoing breakdown and rebuilding of the extracellular matrix. The differences were most pronounced between ovaries from women in their 50s and those from women 70 and older.
“When we analysed the data in multiple different statistical ways, what became clear across all these methodologies is that the ovary was not stagnant,” Schilling said. “In fact, over the decades, there were quite dramatic differences in terms of some proteins’ levels would go up with age and some proteins’ levels would go down, which tells us this organ is quite dynamic.”
The ageing ovaries also showed some of the same molecular patterns seen in cellular senescence.
The findings build on a discovery Duncan’s lab made a decade ago. In 2016, the lab was the first to report that as ovaries age they become increasingly inflamed, fibrotic and stiff. Because cancer cells can thrive in collagen-rich, stiff environments, the scientists have been investigating whether these age-related changes could make the ovary more hospitable to cancer cells.
The new study provides a molecular view of that remodelling process later in life. As postmenopausal ovaries aged, proteins involved in maintaining tissue structure declined, while proteins involved in inflammation and reshaping the tissue environment became more prominent.
Although all the ovarian tissue in the study appeared normal and cancer-free, some proteins previously associated with ovarian cancer were more abundant in ageing ovaries, with the strongest signal among women in their 60s. The finding does not mean the ovaries were cancerous or precancerous, but suggests healthy ovarian ageing and ovarian cancer share some biological processes.
“It’s not that all postmenopausal women get ovarian cancer, but we know that that fibrotic inflammatory environment is certainly an environment that cancer cells prefer to home in on,” Duncan said. “This is all consistent with the idea that the ageing ovary is a potential third hit for ovarian cancer, with the first hit being genetic and the second hit being environmental. So can we target the ageing ovary therapeutically to lower the risk of ovarian cancer, or can we develop novel biomarkers of ovarian cancer?”
The findings do not answer whether healthy ovaries should ever be removed after menopause. Rather, they raise new questions about how the biological activity of the postmenopausal ovary might influence women’s health systemically and whether the observed changes contribute to disease or are features of normal ageing.
The benefits of the HPV vaccine may extend beyond protection against cancer. In a study published in The BMJ, researchers at Karolinska Institutet found that women who had been vaccinated against HPV were less likely to experience several pregnancy and childbirth complications, particularly preterm birth.
HPV (human papillomavirus) is the leading cause of cervical cancer. HPV infection and treatment of cervical cell changes have also been associated with an increased risk of certain pregnancy complications. A new study has investigated the link between the HPV vaccine and complications such as preterm birth, premature rupture of membranes, babies being small for their gestational age, stillbirth, and neonatal mortality.
The study is based on Swedish registers and covers 624 713 pregnancies among first-time mothers aged 16 to 35 between 2006 and 2023. Of these women, 92 620 had received the quadrivalent HPV vaccine prior to becoming pregnant, providing protection against four common types of HPV.
Stronger link when vaccinated at a younger age
Women who had been vaccinated before pregnancy consistently had a lower risk of the studied complications, particularly preterm birth. Compared with unvaccinated women, they were around five per cent less likely to give birth prematurely and around 15 per cent less likely to give birth very prematurely.
“We also observed that the associations were stronger among women who had been vaccinated before the age of 17,” says Zhongsong Zhang, doctoral student at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. “This is consistent with previous findings that the HPV vaccine provides the best protection against HPV-related disease when administered at a younger age.”
A large register-based study
Although the researchers took into account several factors that could have influenced the results, as this was an observational study, it was not possible to conclude that the lower risk was caused by HPV vaccination. Nevertheless, the study covered a large number of women from the Swedish population over a long period of time.
“Even a relatively small reduction in the risk of preterm birth can be significant at a population level, given that HPV vaccination is administered to millions of young people worldwide,” says Jiayao Lei, assistant professor at the same department at Karolinska Institutet. “Our results suggest that the benefits of HPV vaccination may extend beyond cancer prevention to include the reduction of complications that can arise during pregnancy and childbirth.”
The study was carried out in collaboration with researchers at the University of Gothenburg, Sahlgrenska University Hospital and the Norwegian Institute of Public Health. Funding for the research came from the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare, the Swedish Cancer Society, Karolinska Institutet and ALF grants, among others. See the scientific article for information on any conflicts of interest.
A recent BBC report described women posing as men to get hold of testosterone gel, hoping to improve their menopause symptoms, because female testosterone products are not easily available to them. But why is the appetite for this predominantly male hormone exploding and are there risks involved?
Testosterone is usually thought of as the defining male hormone. It is linked to puberty, muscle development and reproductive function. But this overlooks an important biological reality. Women also produce testosterone, and it plays important roles throughout the body.
Although blood concentrations are typically about ten to 15 times lower than in men, testosterone remains biologically active in women.
Women make testosterone in their ovaries and adrenal glands, and the body also makes it by changing other hormones in fat, skin and muscle. Some of this testosterone is then used to make oestradiol, the main form of oestrogen in women of reproductive age.
But testosterone is not simply an oestrogen reservoir. It also acts directly on tissues throughout the body, including the bones, muscles, heart and blood vessels, and the brain. This has led researchers to look more closely at how testosterone may affect women’s health.
Similar to men, testosterone declines gradually across the reproductive lifespan, although patterns vary between individuals. This fall begins well before menopause, and unlike oestrogen, it doesn’t fall sharply at menopause as the ovaries decline.
Measuring how far it’s fallen is its own problem. Female levels are so low that routine blood tests have historically struggled to measure them reliably, making it hard to precisely define “normal” concentrations.
So why are increasing numbers of women interested in testosterone therapy after menopause?
What the evidence says
Because testosterone is known to influence sexual desire, one of its most studied uses in women is for hypoactive sexual desire disorder (HSDD) – persistent low sexual desire that causes distress.
A 2019 meta-analysis of 36 randomised trials found that carefully dosed testosterone can improve sexual desire and satisfaction in some postmenopausal women. International clinical guidelines recognise testosterone therapy as an evidence-based treatment for HSDD, the only condition in women for which there is enough clinical evidence to recommend testosterone therapy.
Sexual desire is shaped by relationships, stress, fatigue and mental health as much as by any single hormone. Testosterone is one input among several rather than a master switch.
Beyond sexual desire, high-quality clinical trial evidence in women is largely absent. But this does not necessarily mean testosterone has no broader influence on women’s health.
Randomised trials are the best way to establish whether a treatment causes a particular effect, but they cannot capture everything that happens in everyday medical practice. Patients may have other health problems or take several medicines, making it harder to know whether an improvement is due to testosterone or something else.
Testosterone is not a replacement for standard menopause hormone therapy. When it is prescribed, it is usually alongside oestrogen – and sometimes progesterone. Some women report that even after their conventional HRT (hormone replacement therapy) has been optimised, they still do not feel that their symptoms are fully addressed, and that adding testosterone makes a noticeable difference.
Women and doctors using testosterone in routine menopause care report improvements beyond sexual function. A recent UK study of 510 women at a specialist menopause clinic found that after four months on testosterone gel, women reported improvements in mood, cognitive symptoms and libido. These findings are interesting, but do not prove that the testosterone treatment caused these changes.
Real-world evidence should not replace randomised trials, but neither should the absence of large trials mean that these observations be simply dismissed. Instead, they can help identify effects worth testing in the clinical trials that are still needed.
A market that’s only just catching up
The evidence for using testosterone in women is strongest for sexual desire, but products made specifically for women have been much slower to arrive. In the US, for example, there’s still no approved testosterone product for women.
Of the three major sex hormones produced by the ovaries, oestrogen and progesterone have widely licensed products for women. Testosterone has been much slower to follow, with female-specific products still limited in many countries. This is despite evidence that testosterone can be used safely in women when given at doses designed to keep levels within the physiological female range.
International guidelines have recognised the lack of suitable products for women and called for testosterone treatments designed specifically for them. The issue is now receiving attention from regulators. In September 2026, the US Food and Drug Administration held a public workshop examining evidence gaps and the need for future drug development in this area.
Australia has led the way with Androfeme, a testosterone cream, being formally registered in 2020, specifically for female use. The UK granted it a marketing authorisation in July 2025, but it is not yet routinely available through the NHS.
The workaround has been men’s gel, measuring out a tenth of a sachet by eye. This is a less precise way to deliver a hormone for which the therapeutic dose is so small. If too much is applied, testosterone can rise above the desired range, increasing the likelihood of side-effects, such as acne and increased facial or body hair.
More importantly, evidence on the long-term safety of testosterone in women remains limited, particularly for heart disease, stroke and breast cancer, because trials have generally been short and often excluded women at higher risk of these conditions.
Demand continues to climb despite these uncertainties. NHS prescriptions to women in England rose roughly tenfold between 2015 and 2022, and in the US, testosterone prescribing has almost tripled over the past decade. The need for licensed female-specific testosterone products cannot be ignored, not just to improve access but to allow testosterone in women to be studied with the same scientific rigour it deserves.
