Women’s health

Women in cardiology have long faced barriers, but their leadership is redefining the field. By turning bias into opportunity and exclusion into inclusion, initiatives such as Women As One are opening doors, advancing equity and shaping a more innovative, representative future for cardiovascular care.

The collective priorities of the rheumatology field represent the lived experience, and therefore diversity of its members. The ‘mould’ of rheumatology, that is, its culture, structures and expectations, was not created for or by women, but women have slowly changed this mould to make space for diverse perspectives.

Far from being a niche concern, women’s brain health is a global issue, affecting more than half of the world’s population. Despite this, the unique aspects of how the female brain adapts, reorganizes and ages, particularly those shaped by hormonal transitions across the lifespan, have not received proportionate attention in research agendas, funding priorities or clinical guidelines.

The modulating influence of biological sex on clinical variability, disease trajectories and treatment response represents a nascent topic in frontotemporal dementia (FTD) research. Recent empirical studies leveraging large-scale consortium data illuminate how biological sex impinges on — and potentially interacts with — variations in clinical symptomatology, pathophysiology and disease trajectory in FTD.

Despite recognized sex-based differences in healthcare requirements, women continue to experience substantial disparities in treatment, diagnosis and research. This ‘gender health gap’ manifests through increased emergency wait times, dismissal of symptoms and inadequate research prioritization. Patient advocacy groups have emerged as powerful forces for change, successfully lobbying governments and raising awareness through social media. Addressing these disparities requires increased research funding, sex-specific study designs, improved medical education curricula and continued patient advocacy.

In this Perspective, Joshua Rubin emphasizes the importance of gender–sex interaction (GSI) differences in cancer biology and clinical parameters to enhance precision medicine. He outlines the challenges and opportunities of integrating GSI effects into personalized oncology and argues that optimal outcomes require extending our current molecular approaches to include family history, life history and individual vulnerabilities in our diverse groups of patients with cancer.

The ways in which people express and define their own sex, gender and orientation are complex. However, these aspects are often relevant for patient care and research, which presents the need for a standardized tool for this purpose. In this Perspective, experts in the field discuss the tools that have previously been developed and propose the use of a new tool — the XYGO wind rose — to enable patients and health-care professionals to better communicate and improve care.

Sex and gender influence the entire healthcare ecosystem of Alzheimer disease (AD). In this Review, Castro-Aldrete et al. present a holistic view of sex and gender in AD, and discuss how these factors affect research and policy efforts to improve AD prevention, diagnosis and treatment.

We spoke with neurologist Esther Bui from Canada about her work to improve neurological health for women.

Although autoimmune rheumatic diseases are more prevalent in women than men, few clinical trials report findings on the basis of sex and gender. Future clinical trials should report sex and gender differences in treatment and safety outcomes in a standardized manner to improve outcomes for all patients.

Pituitary neuroendocrine tumours (PitNETs) exhibit notable sex-related differences, particularly in prolactinomas and corticotroph tumours. Findings from the past 5 years in other cancers suggest that interactions between sex hormones and the immune system, as well as epigenetic modifications specific to sex chromosomes, could influence sex differences in tumour development.

Ovarian cancer comprises a group of malignancies of epithelial origin that have distinct pathogeneses, histologies and prognoses. In this Primer, Scott et al. discuss epidemiology and risk factors, mechanisms, diagnosis and management of ovarian cancer subtypes, and highlight patient quality of life and areas for future research.

Dormant tumour cells that survive initial therapy can awaken years later to seed metastases. New data from a phase II trial indicate that intercepting this dormancy by targeting autophagy and mTOR signalling might prevent breast cancer relapse before it begins, opening a path towards proactive prevention disease recurrence.

The SERENA-6 trial assessed a paradigm-shifting approach to personalized cancer therapy in patients with advanced-stage breast cancer, in which therapy was switched upon the identification of resistance-related mutations in ESR1 in circulating tumour DNA (ctDNA). Herein, we discuss how the results of this trial challenge the standard-of-care management for these patients, in whom therapy changes are otherwise undertaken only after radiographic and/or clinical progression.

Next-generation, oral selective oestrogen receptor degraders (SERDs) have been shown to improve outcomes in patients with advanced-stage oestrogen receptor (ER)-positive, HER2-negative breast cancer, particularly those with acquired ESR1 mutations. Now, the proteolysis-targeting chimera (PROTAC) SERD vepdegestrant, which induces ER degradation directly rather than indirectly, has also demonstrated efficacy in this setting, raising questions over the optimal choice and sequencing of treatments.

Rising rates of early-onset oestrogen receptor-positive (ER⁺) breast cancer in women without genetic risk suggest a shift in disease biology. Endocrine-disrupting chemicals (EDCs) may accelerate tissue ageing, destabilize epigenetic regulation and impair immune surveillance. Chronic and cumulative EDC exposure may induce field cancerization in the breast, warranting urgent attention from researchers, regulators and public health leaders.

Many women ≥75 years of age continue to undergo screening for breast cancer despite a lack of evidence supporting this practice. Evidence from the past 5 years suggests rising rates of breast cancer diagnosis in this age group without a corresponding increase in survival — either because the tumour itself is biologically indolent or because life-limiting comorbidities render a biologically aggressive tumour unlikely to further reduce life expectancy. Here, we review what we know, and what we do not know, about screening and overdiagnosis of breast cancer in women ≥75 years of age and build a case for active monitoring for selected screen-detected breast cancers in this population.

In this Journal Club, Dimple Notani discusses a study that demonstrates a tumour suppressive function of the androgen receptor in oestrogen receptor-positive breast cancer.

Premenopausal women aged <40 years diagnosed with oestrogen receptor-positive early-stage breast cancer have disproportionately poorer outcomes relative to older women. The authors of this Review propose a biology-driven approach to challenge the conventional sequencing of chemotherapy and endocrine therapy in this population.

Surgical menopause occurs in premenopausal women who undergo radical cystectomy with bilateral oophorectomy to treat bladder cancer. This Review discusses the pathophysiology of surgical menopause in these patients and highlights current strategies to mitigate associated symptoms and long-term health risks.

Sexual pleasure has often been overshadowed by a focus on dysfunction and reproduction in sexual medicine, particularly in urology. In this Review, the authors discuss the need for multidisciplinary approaches to address the diverse experiences and needs of individuals across their lifespan, and how integrating pleasure into research, clinical practice, sexuality education and public health initiatives could enhance well-being, intimate relationships and overall quality of life.

Oestrogen levels change after menopause and with weight gain above the normal BMI category, both of which can affect breast cancer risk and outcomes. This Review explores the current understanding of these associations.

In addition to having health benefits for those who perform it, exercise might alter parental physiology in ways that support metabolic function in offspring. In this Review, the authors discuss animal studies and data from human study participants that show how exercise affects the placenta, breast milk and sperm in ways that improve offspring health.

Whole-exome sequencing and single-cell technologies are providing unprecedented insights into adenomyosis, uncovering a complex phylogenetic relationship between eutopic and ectopic endometria and identifying prolactin signalling as a possible pathogenic factor. However, these advances contrast with the failure of a clinical trial for a DRD2 agonist, which underscores the formidable translational challenges.

Physiological changes in female individuals during the menopause transition influence cardiometabolic health and type 2 diabetes mellitus (T2DM) incidence. T2DM prevention programmes during midlife among individuals who are at high risk are cost effective but, we suggest, could be enhanced by consideration of the menopause transition and other sex-specific differences in T2DM prevention strategies.

Oestrogen is a key regulator in many metabolic processes, particularly in adipose tissue. This Review discusses the role of oestrogen in adipose tissue metabolism and its wider implications for systemic metabolic health.

Over the past two decades, polycystic ovary syndrome (PCOS) has been redefined from a symptom-based condition to a biologically complex disorder with distinct genetic, developmental and phenotypic features. Translating these advances into precision diagnostics, early interventions and equitable care is essential to improve outcomes.

Despite affecting 30–50% of sexually active women, female sexual dysfunction (FSD) goes undiagnosed and untreated in many women owing to the stigma associated with sexual health, insufficient awareness and restricted access to specialized medical care. In this Review, experts in the field discuss the treatments currently available to treat FSD — including hypoactive sexual desire disorder, female sexual arousal disorder, female orgasmic disorder and female genitopelvic pain disorders — and consider the new approaches that are currently in development.

There are complex interactions between physical changes during the menopause transition and mental health and wellbeing. In this Review, Thurston et al. integrate these interactions and outline behavioural approaches to managing menopausal symptoms and related mental health concerns.

Bacterial vaginosis is a vaginal microbiome disorder that is associated with serious obstetric and gynaecologic complications and negative effects on quality of life. In this Primer, Bradshaw et al. review the epidemiology, pathophysiology, diagnosis and management of bacterial vaginosis, discuss its effects on quality of life and highlight areas for research.

Menopause affects human health and quality of life. This Review focuses on the effects of menopause and hormonal replacement therapy on gastrointestinal and liver disease, discusses osteoporosis in this context and identifies gaps in clinical research.

This article outlines evidence pointing to an important contribution of endocrine-disrupting chemicals to increasing rates of female reproductive disorders such as abnormal puberty, impaired fertility, premature menopause or polycystic ovarian syndrome reported over the past half a century.

Growing evidence links menopause to the risk of Alzheimer disease (AD) in women, but the effect of menopause hormone therapy (MHT) on this risk remain unclear. Two new studies illuminate how menopause and MHT influence synaptic health and tau pathology, offering new insights into sex-specific mechanisms and MHT timing considerations in AD risk.

Emerging pharmaceuticals that target metabolic and endocrine dysfunctions in polycystic ovary syndrome are transforming treatment paradigms. This article covers innovative drugs, including glucagon-like peptide 1 receptor agonists, sodium–glucose cotransporter 2 inhibitors, kisspeptin, neurokinin 3 receptor antagonists and artemisinins, exploring their mechanisms and potential to advance care for this disorder.

Healthy fetal and placental development depends upon the availability of appropriate nutrients and levels of oxygen, as well as optimal metabolism. In this Review, the authors discuss how metabolism affects feto–placental development by controlling several key mechanisms, including epigenetic changes and post-translational modification of key proteins.

Perinatal mood and anxiety disorders affect one in five women during pregnancy and up to one year postpartum and are a strong predictor of perinatal suicidality. In this Review, Singla et al. provide an overview of evidence-based psychotherapies for perinatal depression, anxiety, post-traumatic stress and suicidality and describe their underlying mechanisms.

Urinary incontinence is highly prevalent during pregnancy and in the postpartum period. This Review provides an overview of this prevalence, discussing potential mechanisms and risk factors underlying this phenomenon. The importance of preventive measures and treatment options to ameliorate the extent and the effects of urinary incontinence during this stage of life is also highlighted.

In this Review, Marques and colleagues discuss the evidence regarding the effects of parental diet on the health of offspring, with a focus on how changes to the gut microbiome alter epigenomic responses in the offspring.

Immediate attention is paramount for addressing the escalating prevalence of severe insulin resistance during pregnancy. A collaborative and multidisciplinary approach involving clinical care, public health initiatives and advanced technologies is essential for enhancing care, improving maternal and fetal outcomes, and mitigating long-term metabolic risks.

Intrahepatic cholestasis of pregnancy is the most common pregnancy-related gestational liver disease, manifesting typically during the third trimester of pregnancy with pruritus and elevated serum bile acids. In this Primer, Dajti et al. discuss the epidemiology, pathophysiology, diagnosis and management of intrahepatic cholestasis of pregnancy.

Pregnancy-associated acute kidney injury is a risk factor for maternal and fetal morbidity and mortality and a driver of health inequity worldwide. This Consensus Statement from the Acute Disease Quality Initiative provides recommendations on the causes, diagnosis, management and follow-up of pregnancy-associated acute kidney injury.

Placenta accreta is a major complication of pregnancy that occurs when part of the placenta fails to separate normally from the uterus at delivery. In this Primer, Jauniaux et al. discuss the epidemiology, pathophysiology, diagnosis, current management options and future research areas.