Women’s health

In this Review, Kirabo and colleagues discuss the mechanisms that underlie the sex-related differences in salt sensitivity of blood pressure and hypertension, highlighting the implications for research and clinical practice.

Biological sex has a vital role in the pathogenesis of inflammatory bowel disease (IBD). This Review examines sex in IBD pathophysiology and clinical manifestation and provides a frame for improving clinical and preclinical IBD studies by considering sex an essential factor.

Anju Loveridge discusses the Framingham Heart Study report that described the link between diabetes mellitus and cardiovascular disease as well as sex-related differences in cardiovascular disease.

This Review discusses obstacles to health care equity in rheumatic disease, including access to health care and the use of inaccurate language when labelling population groups. The authors also highlight the siloing of biological and epidemiological research in rheumatology. They conclude with recommendations for achieving equitable precision medicine.

The importance of active involvement of people living with diseases in various aspects of medicine, including disease management and follow-up, regulatory issues, health advocacy and clinical research, is increasingly recognized. This Perspective reviews the current status of patient involvement in neurological and other medical research, highlighting the role of patient experts.

Evidence for the effects of sex hormones on inflammation, myelination and neurodegeneration has implications for both cisgender and gender-diverse individuals with multiple sclerosis. Here, the authors summarize what is known about the effects of endogenous and exogenous sex hormones, and they highlight the need for future research inclusive of gender-diverse individuals.

This Review focuses on currently available literature describing sex differences in skeletal muscle metabolism in humans, as well as highlighting current research gaps within the field. These discussions serve as a call to action for sex-balanced research within exercise physiology.

This Review outlines how the effects of steroid hormones on hippocampal neuroplasticity across the adult lifespan differ between the sexes, highlighting the importance of considering sex and steroid hormones in biomedical research.

A strategic dialogue on ‘gender justice in the HIV response’ held at the 25th International AIDS Conference highlighted how bias and discrimination against women and girls in all their diversities disadvantages them in the HIV response. Ending AIDS requires increased participation and leadership by diverse women at all levels of the HIV response.

Immune dysregulation is a main feature of chronic liver disease, whose burden increases worldwide. This Review discusses the influence of biological sex in hepatic immune mechanisms in the context of liver disease and identifies sex disparities in research and therapeutics.

Autoimmune diseases such as systemic lupus erythematosus preferentially affect women, and multiple hypotheses are under investigation to elucidate this phenomenon. Emerging research suggests that multiple pathophysiological mechanisms and pathways are likely involved, including several that involve the X chromosome, but is skewing of X chromosome inactivation one of them?

Amyotrophic lateral sclerosis (ALS) differs considerably in prevalence and manifestation between sexes. This Review summarizes sexual dimorphism in the epidemiology, clinical presentation and disease mechanisms of ALS and explores the role of brain–body interactions in driving sex-dependent pathogenesis.

The under-representation of women in cardiovascular clinical trials persists across participant, clinician and research roles. This gap perpetuates health inequity and hampers the generation, translation and implementation of optimal evidence-based care. Urgent action is needed to address barriers, promote diversity, and ensure inclusive trial design and health-care delivery and dissemination, for more equitable cardiovascular health.

Alzheimer disease has a sex bias: women are twice as likely as men to be affected. Studies have linked elevated follicle-stimulating hormone (FSH) levels to worsened Alzheimer disease pathology and cognitive decline in mice. Exploring the interaction of FSH with APOE4 has uncovered new aspects of Alzheimer disease. The therapeutic potential of FSH and gonadotropin-releasing hormone have also been highlighted.

In this Review, the authors discuss the unique neurological health disparities faced by sexual and gender minority (LGBT+) people. The Review presents clinical considerations alongside language and practice recommendations to promote inclusive care, and highlights the gaps in need of further research.

Sex differences impact various non-reproductive organ cancers, often leading to higher cancer incidence and poorer outcomes in male individuals. In this Perspective article, Xiao, Lee et al. outline the biological factors contributing to sex bias in immuno-oncology, emphasizing the need for future research to offer a fuller understanding of sex disparities in cancer.

A scientist’s personal journey through breast cancer underscores the urgency for greater empathy in research and healthcare, a patient-centred approach to data dissemination, and more comprehensive, streamlined support for early-career researchers navigating health crises.

In this Review, the authors discuss key clinical trials and therapeutic advances that have informed the current treatment landscape for cervical cancers of all stages, including refinement of surgical management approaches, the establishment of chemoradiotherapy, and the integration of anti-angiogenic agents, immune-checkpoint inhibitors and antibody–drug conjugates.

The DESTINY-Breast06 trial investigated earlier and broader use of trastuzumab deruxtecan in patients with metastatic hormone-receptor-positive breast cancer, and demonstrated improvements in progression-free survival over standard chemotherapy. These data provide a meaningful advance; however, this strategy might not be right for all patients, and careful consideration is recommended before blanket use.

Although ovarian cancer is considered an immunoreactive disease, moderate to no efficacy has been shown in the trials testing immune-checkpoint inhibitors in these patients performed thus far. The authors of this Review summarize these results and propose a systematic classification of ovarian cancer based on CD8⁺ T cell immunophenotypes that, integrated with genetic data, can enable the design of tailored therapeutic approaches, including adoptive cell therapy and novel immunotherapy combinations.

Endometrial cancer is the commonest gynaecological cancer in economically developed countries, and both the incidence and mortality continue to increase. This increasing prevalence highlights the need for novel treatment approaches that will improve patient outcomes. In this Review, the authors describe the epidemiology and standard-of-care treatment approaches for patients with endometrial cancer, as well as highlighting the importance of understanding tumour biology and incorporating this knowledge into better-informed treatment strategies for specific subgroups of patients.

Patients with advanced-stage hormone receptor-positive (HR⁺) breast cancer typically receive first-line treatment with anti-oestrogen-based agents, often combined with a CDK4/6 inhibitor, although resistance remains common. The authors of this Review discuss how a variety of novel endocrine therapies together with tumour molecular profiling could shape the future therapeutic landscape for these patients.

In this Review, Harris et al. summarize the dynamic changes of the immune breast tumour microenvironment (TME) that take place during disease progression and in response to treatment, and outline emerging therapies to target the immune TME in patients with breast cancer.

Lessons from the prevention of cervical cancer, the first cancer type deemed amenable to elimination, can provide information on strategies to manage other cancers. Infection with human papillomavirus (HPV) causes virtually all cervical cancers and an important proportion of other cancer types. The authors of this Review discuss the epidemiology of HPV-associated cancers and the potential for their elimination, focusing on the cofactors that could have the greatest effect on prevention efforts and health equity.

Ovarian cancer, accounting for 4.7% of cancer deaths in women in 2020, remains highly prevalent globally. Nonetheless, owing to changes in environmental exposures, the approach to preventive measures and disease classification, both incidence and mortality have been declining in economically developed countries since the early 2000s. Conversely, parts of Asia and eastern Europe have seen increases in the incidence of ovarian cancer over this period of time. In this Review, the authors summarize the epidemiology of ovarian cancer, including the roles of the various risk factors and the potential for prevention.

The year 2024 brought continuing research in the crucial field of adiposity-related health and polycystic ovary syndrome (PCOS). Although PCOS is considered a heterogeneous condition with regards to diagnostic criteria, complications and management, current research is advancing our understanding of the presentation and metabolic features of PCOS, as well as the benefits of lifestyle management.

Polycystic ovary syndrome (PCOS) is characterized not only by reproductive symptoms and hyperandrogenism but also by metabolic abnormalities, such as insulin resistance and obesity. This Review discusses the evidence of metabolic disorders in PCOS and for understanding PCOS as a metabolic disease.

The authors review the effect of chronic kidney disease (CKD) on female and male fertility and pregnancy outcomes. They also discuss the risk of pregnancy-associated CKD progression and the potential effect of maternal or paternal CKD on the offspring.

Literature about prostate cancer in transgender women is growing, but many questions remain unanswered. Unique challenges exist in the identification of transgender women that can slow or even impair research advances in this field. Reframing our thinking about the identification of this population is imperative to help advance both research and clinical care.

Women are under-represented in surgery and are particularly subject to the intrinsically gendered practice of pimping in the clinical learning environment. The potential downstream effects of this continued practice have considerable implications on gender disparities within surgical disciplines.

Premature ovarian insufficiency (POI) is defined as the loss of normal ovarian activity before the age of 40 years, and is a cause of infertility and endocrine dysfunction in women. This Primer outlines the epidemiology and pathophysiology of POI, including associated gene variants, and discusses diagnosis, management and quality of life for women with POI.

In this Review, Timm, Russell and Hultgren provide an overview of the bacterial and host factors contributing to the development of urinary tract infections, and they highlight new treatment strategies currently under development.

Definitions of sexual arousal dysfunction in the International Classification of Diseases use sex-specific binaries that omit the erectile basis of arousal in females. To provide equitable health care for all people with erectile dysfunction, these definitions must be de-gendered.

Inflammatory and fibrotic responses to polypropylene mesh led to the withdrawal of this practice for treatment of stress urinary incontinence and pelvic organ prolapse in women in some countries. Improved material testing has been urged. We report poor responses of polypropylene mesh to repeated mechanical distension and macrophage interrogation. These results from preclinical in vitro testing show the potential of this approach for testing and improving materials before their introduction into the clinic.

Polycystic ovary syndrome (PCOS) is a major public health problem affecting ~11–13% of women worldwide. In this Primer, Stener-Victorin et al. review the epidemiology and pathophysiology of PCOS and highlight the latest advances in the diagnosis and management of this syndrome.

Ectopic pregnancy is defined as the implantation of a developing pregnancy outside of the endometrial cavity of the uterus and is the leading cause of early-pregnancy maternal mortality. This Primer summarizes the epidemiology, pathophysiology, diagnosis and management of ectopic pregnancy.

This Review outlines the complex actions of metformin in metabolic regulation, providing a plausible basis for its benefits in the management of gestational diabetes mellitus. The authors also critically evaluate the safety profile of metformin use during pregnancy in patients with gestational diabetes mellitus.

Mother-to-child transmission of hepatitis B virus remains a mode of transmission in high-burden regions where there are gaps in antenatal screening, limited hepatitis B virus birth-dose vaccination and variable access to antiviral prophylaxis. Policymakers, governments and relevant stakeholders must ensure equitable access to necessary interventions to achieve elimination targets.

Pregnancy involves immune system suppression to protect the fetus, making it a valuable model for understanding cancer immune tolerance. Recently in Cell, Yu et al. identified B7-H4 as a common immune tolerance checkpoint in both tumours and the placenta.

The ability of prenatal cell-free DNA sequencing to incidentally detect occult maternal malignancies was first documented over a decade ago, yet coordinated follow-up of pregnant people who receive these results is still lacking in many countries. Here we provide a call to action for oncologists to become more involved in diagnosing and managing these cases.

This Review describes the luteal phase of natural menstrual cycles and in vitro fertilization (IVF) cycles. The authors highlight the need for luteal phase support during IVF, outlining various luteal phase support regimens, mechanisms for luteal phase deficiency and potential biomarkers of endometrial receptivity.

This Review discusses how the maternal gut microbiome in pregnancy influences the developing immune system and proposes avenues for future research.

The concurrence of cancer and pregnancy can pose complex medical, psychosocial and ethical issues. In this Comment, Varella and Partridge present approaches to the treatment of cancer during pregnancy, with a focus on patient preferences, patient and fetal risks, and team-based management.

Ureteral stents are useful devices for urological management in pregnancy. However, stent encrustation occurs in up to 13% of patients and is related to increased indwelling time. Stent encrustation can be harmful for both the mother and the fetus, increasing their morbidity and mortality. Thus, whether prevention or cure is more cost effective is pertinent.