Women’s health

In this Review, Lam and colleagues evaluate the current literature on sex-related differences in treatment responses in patients with heart failure and highlight potential approaches for tailored therapies and the need for sex-specific evaluation of treatment efficacy and safety in future research.

Immune responses to pathogens and self-antigens show sex-based differences, with female individuals generally more susceptible to autoimmunity and male individuals more vulnerable to infections. In this Review, the authors explore the role of hormones and genetics in shaping immune responses, and discuss genetic and epigenetic contributions to altered X-linked gene expression that affect immune responses.

Oxidative stress and reactive oxygen species contribute to the pathophysiology of interstitial cystitis/bladder pain syndrome through their effects on molecular pathways. Here, the authors discuss these pathways, animal models of interstitial cystitis/bladder pain syndrome and treatment options for the disease.

In this Comment, Berna Özdemir summarizes the evidence for greater drug toxicity in female patients and emphasizes the need for increased awareness of sex differences at all stages of drug development to establish sex-specific anticancer treatment strategies.

Sex differences in immune cell function and immune responses affect the development and outcome of diverse diseases. Here, the authors review current understanding of sex differences in immunity. They describe the key mechanisms that mediate sex differences in immune responses and discuss the functional relevance of such differences for immune-related diseases.

Improved understanding of kidney disease from a sex- and gender-specific perspective is needed to improve patient care. Here, the authors discuss differences in the epidemiology, management and outcomes of acute kidney injury, chronic kidney disease and kidney failure in men and women.

In this Review, Franck Mauvais-Jarvis discusses how adaptive selection during evolution could have shaped sex differences in energy partitioning, adipose tissue function and distribution, and glucose homeostasis. He also discusses the hormonal and genetic mechanisms that underlie these sex differences and their implications for metabolic disease and sex-based precision medicine.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) has been the focus of an increasing number of studies in the past decade. In this Review, Tavella and colleagues detail the prevalence and clinical presentation of MINOCA, describe the mechanisms underlying the syndrome, and summarize the sex-specific and ethnicity-specific differences in the clinical features, pathophysiological mechanisms, treatment and prognosis of MINOCA.

A new study indicates that although men and women are equally likely to experience cognitive impairment after acute ischaemic stroke, there are sex differences in particular cognitive domains. Whether these differences are directly linked to biological sex is uncertain, as many factors, including age and pre-stroke factors, could contribute to cognitive outcomes.

This Review summarizes our current understanding of sex differences in renal fluid and electrolyte transporters, based primarily on studies in rodents. The authors describe the physiological consequences of these differences, based on information from experimental studies and from model predictions, and discuss the differential impact of sex on transporter regulation by hormones, diet and acid–base status.

Bladder cancer outcomes are considered worse for women than for men, whereas incidence is three to four times higher in men than in women. Understanding biological phenomena and health-system factors driving these differences is essential to improve outcomes and develop novel treatment approaches.

The importance of incorporating factors related to sex and gender in all aspects of research is increasingly recognized. Kidney disease pathophysiology, presentation, response to therapy and outcomes differ by sex and gender, but these factors are often not considered in basic and clinical studies. It is time for nephrology to catch up.

Burnout is prevalent among urologists and leads to increased medical errors and decreased career satisfaction. Lack of access to mental health care and long work hours contribute to burnout in urologists; however, gender bias in the workplace, mistreatment and balancing family life responsibilities specifically predispose women urologists to burnout.

Here, Sven Bölte and colleagues consider the effects of sex and gender on neurodevelopmental conditions. They discuss the available epidemiological, behavioural, neurobiological and endocrinological evidence and highlight the importance of further research in this area.

The discovery of ERBB2 as a gene frequently amplified and/or overexpressed in breast cancers and of its product HER2 as a biomarker has spurred the development of various targeted therapies. As a result, the prognosis of patients with advanced-stage HER2-positive breast cancer has greatly improved in the past decades. The authors of this Review describe the development of the current treatment landscape for these patients and discuss how to address resistance to further improve outcomes.

Cyclin-dependent kinase (CDK) 4/6 inhibitors in combination with endocrine therapy have become the standard-of-care therapy for patients with advanced-stage hormone receptor-positive breast cancer. However, this success has created several challenges, such as the need to better understand resistance to these agents and develop novel therapies accordingly. Here, the authors provide an update on the clinical activity of the established CDK4/6 inhibitors along with a summary of ongoing research efforts attempting to address the new challenges created by the success of these agents.

Ovarian carcinoma is a highly heterogeneous tumour type, both spatially and temporally. As a consequence, these carcinomas are often associated with poor outcomes. Ovarian carcinoma comprises various subtypes with distinct complex molecular features. The authors of this Review discuss the molecular, cellular and anatomical heterogeneity of ovarian carcinoma, and outline the current and future treatment strategies for this malignancy.

Evidence indicates an elevated risk of type 2 diabetes mellitus after breast cancer treatment, particularly for endocrine therapy. This Review outlines the evidence for adverse metabolic effects of endocrine therapies in humans. Potential mechanisms, informed by preclinical research, for the increased risk of type 2 diabetes mellitus are discussed.

Although selective antagonism of oestrogen receptor signalling in breast cancer has been one of the most successful therapeutic approaches in oncology, resistance is a major clinical challenge. In this Review, Will et al. explore mechanisms of oestrogen-receptor-α-targeted therapeutic resistance and strategies to overcome it.

Planning for a pregnancy in patients receiving adjuvant endocrine therapy following a diagnosis of hormone receptor (HR)-positive early stage breast cancer is challenging. Recent data from the POSITIVE trial provide reassuring prospective evidence that a temporary interruption of endocrine therapy for women with HR-positive breast cancer who are trying to conceive can be considered safe in the short term for selected patients.

Systemic therapies for early-stage disease have been tested in clinical trials for decades. The authors of this Review provide an overview of the evolution of (neo)adjuvant trials from the pre-genomic to the post-genomic era, focusing on design, end points and biomarkers that, together, could enable the delivery of more personalized treatment.

Clinical trials of immunotherapies have so far failed to demonstrate efficacy in high-grade serous ovarian cancers. Here, Kandalaft et al. classify high-grade serous ovarian cancers into distinct immunophenotypes that might account for these failures and could also provide a rational basis for tailored immunotherapy in the future.

The pathophysiology of endometriosis is underpinned by a complex interplay of inflammatory processes that are responsible for the local and systemic effects of the condition. Recent studies delve further into this inflammatory interplay; using animal models, they identify potential therapeutic tools and remind us to look beyond the endometriotic lesions.

Key papers on the role of nutrition and metabolic cues in puberty timing were published in 1963, and there have been many advances in this field in the subsequent 60 years. This Review discusses the latest advances in basic and translational sciences underlying the nutritional and metabolic control of pubertal development.

Over the past decade, the focus on modelling the human endometrium and its cyclical transformations has intensified, driven in part by the lack of notable progress in treating endometrial diseases. Gnecco and collaborators now unveil a cutting-edge endometrial organoid culture using synthetic hydrogels with endometrial niche peptides and epithelial and stromal cells.

The menopausal transition period, which begins with irregular menstrual cycles and ends with the final menstrual period, is associated with an increase in cardiovascular risk. In this Review, Mehta and Manson describe the metabolic and cardiovascular changes that occur during the menopausal transition period and summarize the evidence on the use of targeted interventions to slow the progression of atherosclerosis.

Most women experience vasomotor symptoms during menopause, which considerably affect their quality of life. While vasomotor symptoms can be substantially reduced with menopausal hormone therapy, many women are unable or choose not to take hormone therapy. Now, studies have demonstrated that neurokinin 3 receptor antagonists have a level of effectiveness against vasomotor symptoms that is similar to that of hormone therapy.

Menopause can increase the risk of diabetes mellitus, while existing diabetes mellitus can cause early menopause. This Review discusses the interaction of diabetes mellitus and the menopause, including therapeutic management strategies for both conditions.

Chronic kidney disease (CKD) is highly prevalent in women in perimenopause and menopause. Both CKD and menopause affect several important pathologies, such as cardiovascular disease (CVD) and bone mineral disease. More research is needed to better understand the relationships between menopause, CKD, CVD and bone disease.

The urological workforce in the United States is substantially affected by inequitable abortion access across the nation. Female residency applicants avoid states with restrictive laws, and women urologists residing in these states are considering leaving. The urological community needs to invest in advocacy to protect the health of their members.

Findings from the largest longitudinal study (315 participants) on psychosocial functioning in transgender or nonbinary youth after 2 years of gender-affirming hormone (GAH) therapy were recently published in New England Journal of Medicine. At a time of heightened politicization of this treatment, this study adds to the growing literature that demonstrates benefits of GAH therapy for transgender youth.

A transcriptomic analysis of endometriosis and comparison tissues has been conducted, revealing a rich and complex catalogue of single-cell-based expression data. This resource is an invaluable building block towards single cell profiling at scale, aiding research into endometriosis pathogenesis and new ways of diagnosing and treating the disease.

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.

Motherhood in humans is associated with numerous neurobiological adaptations. In this Review, Servin-Barthet et al. focus on the interplay among pregnancy-related hormones, brain plasticity and maternal behaviour and aim to provide a roadmap for future investigations.

This Review discusses the physiological and neurological mechanisms that drive altered eating behaviours in pregnancy, including food cravings, food aversions and changes in sensory perception, and the implications for the long-term health of the gestational parent and offspring.

In this Review, Gaillard and Jaddoe describe how maternal cardiovascular disorders, occurring before and during pregnancy, can influence cardiovascular health in the offspring from embryonic life until adulthood. Furthermore, the authors highlight critical periods for cardiovascular adaptations, including preconception, early pregnancy and infancy, and how the events occurring during these periods can have an effect on future cardiovascular health.

The treatment landscape of inflammatory bowel disease (IBD) is constantly evolving, including among pregnant women and those who wish to become pregnant. This Review provides a detailed update on the management of patients with IBD during pregnancy and breastfeeding.

Conversations around pregnancy and parenting in medicine are increasingly important, especially as the number of women in medical training increases. Common challenges are experienced by women during pregnancy, parental leave, return to work and lactation, and policy suggestions can be offered to support doctors and surgeons who want to expand their families.

Any processes that impair kidney development in the developing fetus can have lifelong adverse consequences for renal health. Here, the authors discuss the effects of preterm birth and/or intrauterine growth restriction on kidney development and the impact of these exposures on the later development of chronic kidney disease.

Immune dysregulation contributes to the pathogenesis of preeclampsia. Here, the authors examine the role of immune cells and mediators in driving the oxidative stress and endothelial dysfunction that characterize this hypertensive disorder of pregnancy.

Fetal alcohol spectrum disorders (FASD) are characterized by neurodevelopmental impairment with or without facial dysmorphology, congenital anomalies and poor growth. This Primer discusses the epidemiology, pathophysiology, diagnosis and treatment of FASD.

Pre-eclampsia is a life-threatening disease of pregnancy and a leading cause of maternal and neonatal morbidity and mortality. This Primer by Dimitriadis and colleagues summarizes the epidemiology, mechanisms, diagnosis and treatment of pre-eclampsia, and discusses patient quality of life and open research questions for this condition.