Obesity is linked to dysregulated cellular energetics in neoplastic and non-neoplastic cells in the tumour microenvironment. Here, Brown discusses the interdependence of metabolic pathways of oestrogen production in breast tissue and the obesity-related mechanisms that promote breast cancer growth.
Research into women’s health has suffered from historical neglect and lack of funding. This is reflected in, for example, the bias against women’s experiences in the medical field and the lack of inclusion of the female sex in preclinical and clinical studies. While this situation is steadily improving, research into health conditions that affect women requires continuous and ongoing attention to keep improving lives. These health conditions can affect cisgender, transgender, intersex, and/or non-binary people with female-specific organs and hormonal cycles.
This regularly updated collection of articles published in the Nature Reviews journals provides in-depth discussions of recent research and medical advances in fields covering women’s health in the broadest sense. Topics covered include sexual function, sexual and reproductive health, pregnancy and childbirth, breast and gynaecological cancers, as well as organ-specific diseases and conditions that exclusively, predominantly or differentially affect people with female-specific organs and hormonal cycles.
Breast and gynaecological cancers
Aberrant signalling of ERBB family members plays an important role in tumorigenesis and in the escape from antitumour immunity in multiple malignancies. This Review discusses the mechanisms by which this signalling affects antitumour immune responses and the potential application of immune-genome precision medicine in this context.
Risk-adapted approaches to breast cancer prevention and screening could potentially be more effective than universal approaches, which have important limitations. In this Consensus Statement, representatives of the European Collaborative on Personalized Early Detection and Prevention of Breast Cancer (ENVISION) discuss the current state of breast cancer risk prediction, risk-stratified prevention and early detection strategies, and their implementation. They also present the ENVISION recommendations on priorities for future research in each of these areas with the aim of stimulating and guiding risk-adapted breast cancer prevention and screening programmes.
This Review presents the evidence for the role of risk factors in breast cancer incidence and their inclusion in risk estimation tools as a step towards precision prevention to specifically target those women at increased risk for appropriate risk-reducing interventions.
TRM cells have a role in peripheral immune surveillance in several organs. The presence of TRM cells in the immune infiltrate is also associated with improved outcomes in patients with several solid tumour types, and these cells might have a role in the response to immune checkpoint inhibitors. In this Review, the authors describe the available date on the role of TRM cells in patients with breast cancer
The female reproductive tract (FRT) harbours a site-specific microbiome. When dysbiosis of the FRT occurs, altered immune and metabolic signalling might lead to gynaecological cancer. In this Review, the authors discuss how dysbiosis could lead to malignancy and how cancer and its treatment can, in turn, affect the FRT microbiome. Finally, they consider how modulation of the microbiome might prove useful in improving responsiveness to cancer treatment and quality of life in women with gynaecological cancers.
HER2-targeted therapy has greatly improved the outcomes of patients with HER2-positive breast cancer, with a range of agents now approved or in late-stage clinical development. In the era of precision medicine, efforts are being made to further improve patient outcomes by personalizing HER2-targeted treatment regimens, primarily though escalation or de-escalation of therapy according to the disease biology. In this Review, the authors provide an overview of the current landscape of HER2-targeted therapy and discuss the evidence supporting such tailored therapeutic strategies.
Breast cancer is the most frequent malignancy in women worldwide. Patients are managed on the basis of the key molecular and histological features underpinning their disease and its stage. This Primer discusses these issues, covering both early and advanced disease.
Endometrial cancer is histologically and molecularly complex, and effective clinical strategies for aggressive forms of the disease are needed. This Review discusses the identification and potential use of molecular features of endometrial cancer for early detection, treatment and risk stratification.
Women with early-stage oestrogen receptor (ER)-positive (ER+) breast cancer remain at risk of distant recurrence for at least 15 years after discontinuation of 5 years of standard endocrine therapy. The authors of this Review discuss the epidemiology and mechanisms underlying late recurrence and examine several models used for risk prognostication and for estimating the presence of minimal residual disease.
This Opinion article highlights how activating mutations in the gene encoding oestrogen receptor-α (ERα), a major driver in breast cancer, undermine structural features of wild-type ERα that maintain the ‘off-state’ in the absence of oestrogens, thus making ERα constitutively active and endocrine-therapy resistant.
To efficiently prevent cancers associated with human papillomavirus (HPV) infection, especially cervical cancer, effective vaccines and high vaccination coverage are required. This Review provides insight into virological, immunological and strategical progress in HPV vaccines as well as implementation and potential advances.
Pregnancy, postpartum period and breastfeeding
This Primer by Dimitriadis and colleagues summarizes the risk factors, mechanisms, diagnosis and treatment of recurrent pregnancy loss.
The management of viral hepatitis in the setting of pregnancy requires special consideration. This Review examines each hepatitis virus individually to address the effect of pregnancy on the natural history of infection and how the viral infections influence maternal and infant outcomes, including mother-to-child transmission.
Pre-eclampsia and fetal growth restriction are diseases of pregnancy that arise from disorders of placental development. This Review discusses healthy development of the placenta and considers disease mechanisms, biomarkers and diagnosis of pre-eclampsia and fetal growth restriction.
In this Review, Roos-Hesselink and colleagues describe how the physiological adaptations during pregnancy can induce cardiometabolic complications or an exacerbation of existing cardiometabolic disease, and discuss the epidemiology, pathophysiology, diagnosis and management of cardiometabolic diseases acquired or presenting during pregnancy, including hypertensive disorders, gestational diabetes mellitus, thromboembolic disorders and peripartum cardiomyopathy.
Neuromyelitis optica spectrum disorders (NMOSD) are a type of neurological autoimmune disease characterized by attacks of CNS inflammation. In this Review, the authors discuss the relationship between pregnancy outcomes and NMOSD disease activity, and outline potential treatment approaches.
Successful pregnancy requires changes to the immune system to enable tolerance of the growing fetus. In this Review, the authors discuss how these immunomodulatory mechanisms contribute to the phenomenon of pregnancy-related improvement of rheumatoid arthritis.
This Primer provides a comprehensive review of the current state of basic science and clinical knowledge on nausea and vomiting of pregnancy, and its extreme form hyperemesis gravidarum. Directions to focus on for future study are also discussed.
Gestational diabetes mellitus (GDM) is the most common complication in pregnancy and has short-term and long-term effects in both mother and offspring. This Primer discusses the definitions of GDM, diagnosis and management of the disease and areas requiring further research.
Pregnancy can affect the underlying disease and vice versa, and drug therapy may need to be altered before, during and after pregnancy. With careful planning, monitoring and treatment, most women with inflammatory rheumatic diseases can have successful pregnancies.
Women with pre-existing diabetes mellitus are at increased risk of complications during pregnancy. This Review outlines the latest management strategies that have been designed to reduce this risk, including diet and pharmacotherapy options.
In a new study, the risk of new mental illness postpartum was significantly increased in women with IBD, and specifically in those with Crohn’s disease. Disturbingly, the risk of a substance disorder was also elevated in these women. The findings highlight that disease management during pregnancy is challenging and requires a multidisciplinary approach.
Pre-eclampsia is associated with substantial maternal and fetal morbidity and mortality worldwide. Here, the authors discuss the epidemiology, pathogenesis and current and future treatment of pre-eclampsia with a focus on the role of angiogenic imbalance.
Postpartum psychiatric disorders comprise postpartum depression and anxiety, which are relatively common, and the rare but more severe postpartum psychosis. This Primer by Meltzer-Brody and colleagues reviews the mechanisms underlying the development of postpartum psychiatric disorders and the approach to diagnosis and treatment of these disorders.
Chronic kidney disease (CKD) is associated with an increased risk of adverse pregnancy outcomes. Here, Wiles et al. discuss fertility issues, contraception, important comorbidities, drugs commonly used in nephrology and the effect of dialysis provision in the context of CKD. Advances in biomarkers for CKD and pre-eclampsia are also presented.
Sex-related differences in disease
This Perspective highlights the evidence from basic and translational research that genetic sex influences multiple factors that can contribute to cancer development and treatment responses, and suggests that including genetic sex considerations in treatments for patients with cancer will improve outcomes.
This Review provides insight into sexual dimorphism in adipose tissue distribution and substrate metabolism in adipose tissue, skeletal muscle and liver, as well as the underlying mechanisms. The effects of these sex differences on cardiometabolic health are outlined and the potential for developing sex-specific prevention and treatment strategies is discussed.
The effects of sex steroids (oestrogens, androgens and progesterone) on immune responses contribute to the sex bias in autoimmune rheumatic diseases in complex ways. Targeting these effects could hold potential for treating patients with autoimmune rheumatic diseases.
Inflammatory bowel disease (IBD) has different manifestations and associated risk factors between the sexes. This Review explores the sex-based differences in presentation and management of IBD, as well as insights into sex-based differences in pathogenesis and underlying mechanisms inferred from basic research.
Historically, preclinical pain research has been dominated by studies in male subjects. Jeffrey Mogil describes recent trends towards the inclusion of male and female subjects in research and the subsequent identification of qualitative sex differences in the mechanisms of pain processing.
Urinary tract infections: microbial pathogenesis, host–pathogen interactions and new treatment strategies
In this Review, Klein and Hultgren discuss recent advances in our understanding of the interplay between pathogens and the host during urinary tract infections, and how the insights into host–pathogen interactions and pathogenesis are guiding the development of antibiotic-sparing therapeutics.
Results from a prospective study by Santema and colleagues suggest that women with heart failure and reduced ejection fraction might need lower doses of standard heart failure drugs than men. However, this conclusion was formed on the basis of data from a small proportion of the population studied and might only be relevant to participants taking β-blockers.
This Perspectives article, written on behalf of the participants of the NIDDK Workshop on ‘Sex and the Kidneys’, considers opportunities for clinical, basic and translational research into sex differences in renal disease as well as the potential tools and resources needed to conduct this research.
Understanding the fundamental impact of sex and gender on human health and disease is crucial for optimizing precision medicine. In this Review, Khramtsova, Davis and Stranger discuss the roles of sex in the genetics of complex traits, including genomic evidence for sex-dependent genetic architecture, models and molecular mechanisms of sexually differentiated phenotypes and implications for health care.
In this Review, Ferretti et al. discuss the evidence for sex-related differences in Alzheimer disease symptoms, progression, risk factors and treatment, and consider how understanding sex differences is crucial in developing precision medicine.
Alcohol use and 'social' drinking are increasing among the young and particularly in women. However, gender equity does not extend to the risk of alcohol-associated liver disease and alcoholic hepatitis, which are increased and often caused by as little as half as much cumulative alcohol consumption in women compared with men.
Here, four leading researchers discuss key considerations related to women's kidney health, including specific risk factors, the main challenges and barriers to care and policies and systems that could be implemented to improve the kidney health of women and their offspring.
The authors present sexual dimorphism at the molecular, cellular and tissue level and suggest that it contributes to differences in disease onset, susceptibility, prevalence and treatment responses in hypertension and cardiovascular disease. Several factors that confer relative cardioprotection in women are discussed, including biological age, sex hormones, sex chromosome complement and lifestyle.
A growing body of research indicates that sex and gender-specific differences exist in the mechanisms and epidemiology of chronic kidney disease (CKD). Here, the authors describe current understanding of gender and sex differences in the epidemiology, treatment and outcomes of CKD, as well as the possible underlying causes.
Sexual function, female biology and ageing
Devices designed to enhance and diversify sexual pleasure are useful in clinical practice; however, many taboos still seem to exist and the scientific literature on the prevalence, application and effectiveness of sexual devices for therapeutic use is sparse. In this Review, Dewitte and Reisman discuss the clinical use of sex toys and sexual devices, as well as sexually explicit media, across a variety of indications to expand individual and partnered sexuality and to treat sexual difficulties.
The COVID-19 pandemic has undoubtedly put a strain on relationships. For some couples, lockdown has meant long periods of separation, whereas for others, lockdown has resulted in months of isolation together. In this Viewpoint, three experts consider the effects of the pandemic on relationships and suggest ways in which lockdown can become a positive experience for couples making love in the time of corona.
Postoperative sexual function is most often unchanged or improved after treatment of pelvic organ prolapse. Nevertheless, some women experience sexual disorders and/or de novo dyspareunia after repair. Patient counselling is emerging as an important step before surgical prolapse repair.
Rheumatologists lack guidance on how to manage the reproductive health of their patients, and communication to patients on reproductive health issues is an unmet need. New guidelines from the ACR provide support in the counselling of both female and male patients on the different aspects of their reproductive life.
This Primer by Bergeron and colleagues summarizes the epidemiology, mechanisms, diagnosis and treatment of vulvodynia, a condition that is characterized by pain in the vulva.
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in premenopausal women. Here, Héctor F. Escobar-Morreale reviews the newest advances and limitations of current knowledge regarding PCOS and provides principles for the diagnosis and management of women with PCOS.
In this timeline, the authors describe the evolution of the use of polypropylene mesh in female pelvic floor surgery. They detail how the material properties of mesh relate to the occurrence of complications and discuss approaches to developing new materials and tissue engineering techniques.
Subfertility affects one in six couples worldwide and is associated with emotional distress and reduced quality of life. This Primer by Farquhar and colleagues discusses the causes, diagnosis and treatment of female subfertility.
Sexual arousal in women comprises two components: genital arousal and subjective arousal. For some women, genital arousal enhances subjective arousal; for others, the two types of arousal are desynchronous. In this Review, Meston and Stanton describe the mechanisms and the relationship between genital and subjective arousal and consider how they assist in diagnosis and treatment of sexual arousal dysfunction and development of treatments for female sexual arousal dysfunction.
Endometriosis is a common inflammatory disease associated with pelvic pain and infertility and is characterized by the presence of tissue outside the uterus that resembles endometrium. This Primer describes the pathogenesis of the condition and the current outlook for future research.
Labiaplasty is attracting increasing attention in the media and in online forums. How to manage a request for this surgery is controversial, and the indications for and outcomes of labiaplasty have not yet been systematically assessed. In this Review, Özer and colleagues discuss our current knowledge of this surgery.
In this Review, the authors describe the symptoms of menopause and their physiological basis, highlighting emerging data on how ethnicity and individual factors influence symptom incidence and prevalence and how certain symptoms might predict future health risks.