Abstract
‘As an instrument for presenting the most important advances in research on sex and gender, and for discussing their clinical relevance, Women's Health will serve an important role in a movement that gained momentum two decades ago in the USA.’
As an instrument for presenting the most important advances in research on sex and gender, and for discussing their clinical relevance, Women's Health will serve an important role in a movement that gained momentum two decades ago in the USA. The women's health movement led to the establishment of the Office of Research on Women's Health (ORWH) at the National Institutes of Health (NIH), where it serves as a focus for policy and research leadership, and collaboration. Whereas policy and research funding often resides with institutions, translation of the results of these policies and funded research studies into healthcare depends heavily on peer-reviewed biomedical journals.
Since the establishment of the ORWH in September 1990 and the subsequent strengthening of NIH policies requiring the inclusion of women in clinical research, a substantial expansion of science-driven initiatives in women's health has occurred, with an increased emphasis on comprehensive, interdisciplinary approaches to research. The ORWH, from its position as the focal point for women's health research within the Office of the Director of the NIH, has worked in concert with the institutes and centers of the NIH, and the biomedical and healthcare communities, to formulate an agenda for research on women's health issues. The initial agenda, published in 1992, included but went beyond concepts of reproductive health to address the health status of women across the lifespan and the differences between populations of women.
Early progress deepened our scientific understanding of sex and gender differences and similarities in the etiology, diagnosis, progression, treatment, health outcomes and prevention of many conditions that affect both women and men. For example, there has been progress in identifying and understanding the role of various metabolic enzymes in causing sex differences in pharmacodynamics. Studies using combinations of neuron anatomy and behavioral techniques have identified sex differences in the manifestations of brain disorders and the influence of reproductive endocrine disorders in both women and men. Many researchers now examine sex and gender, socioeconomic, racial and ethnic differences when studying the incidence, mortality, and prevention of cancers and other diseases. Research is increasingly defining the effects of hormones on the biological, genetic, environmental and behavioral aspects of health.
From progress, new concepts emerge; from the advances resulting from the initial research agenda, a revised agenda for research on women's health was developed. In 1996 and 1997, the ORWH convened a series of national scientific workshops and public hearings to revise the agenda for women's health research. Basic, clinical, and social scientists, healthcare providers, educators, and representatives from community organizations and advocacy groups formulated recommendations regarding areas of continuing or emerging scientific interest in need of further research, and strategies to take advantage of these opportunities. The resulting report, Agenda for Research on Women's Health for the 21st Century, [101] reflects the contributions and efforts of more than 1500 participants.
A persistent concern was the need to establish consistency in the medical literature of the use of the terms ‘sex’ and ‘gender.’ The recent Institute of Medicine report, Exploring the Biological Contributions to Human Health: Does Sex Matter? [1] provides clarification of these terms in its discussions of differences between males and females: the word ‘sex’ is used when differences are primarily biological in origin and may be genetic or phenotypic (genetic or physiological characteristics of being male or female), whereas ‘gender’ is used when referring to responses to social and cultural influences based on sex.
Recent advances
Today clinicians benefit in their practice from documented findings on sex and gender differences in health and disease.
Urinary incontinence and dysfunction
Urinary dysfunction, which has a female-to-male ratio of 2:1, most commonly results from deficits of urine storage in women, associated with risk factors related to the female pelvic anatomy and physiology, in contrast to bladder outlet obstruction in men.
HIV/AIDS
Manifestations and progression of HIV/AIDS are distinct in women, who represent an estimated 30% of new infections. Although the initial viral load in women may be significantly lower than in men, both sexes develop AIDS at the same rate. These sex differences are significant in determining HIV treatment guidelines.
Response to pain
Responses to both pain and pain therapies differ between men and women, although whether this difference is related to sex-based (physiological) mechanisms of the brain, gender (psychosocial) factors, or both, has not yet been clearly defined. Women are more likely to have a lower pain threshold and lower tolerance for pain than men; however, data also suggest that women are more likely to be inadequately treated. Furthermore, the effects of some analgesics have also been found to vary with sex, a striking example being κ-opioids, which are much more effective in women.
‘Today, clinicians benefit in their practice from documented findings on sex and gender differences in health and disease.’
Type 2 diabetes
Prevalence and care of type 2 diabetes differ between the sexes. Type 2 diabetes is more prevalent in women than men, especially in those over the age of 65, resulting in an increased risk for coronary heart disease and other comorbid conditions. Clinicians must consider prevention strategies and counseling for women across the lifespan, including prevention of risk factors such as obesity, management of pregnancy, and possible complications of depression.
Heart disease
Heart disease is now recognized as the most common cause of death of both women and men in the USA; however, women may have different clinical presentation, outcomes, and responses to interventions compared with men.
Major depression & dysthymia
These disorders affect approximately twice as many women as men and other mental disorders, such as anxiety disorders, anorexia nervosa and bulimia nervosa, are predominant in women. Sex differences in drug pharmacokinetics can influence the required antidepressant dosages in women, in addition to other factors such as age and pregnancy. Biopsychosocial gender issues must also be considered in the clinical approach to the management of depression and other mental illnesses.
Menopausal hormone treatment
Hormone treatment has been demonstrated to be effective for a number of the symptoms of menopause but the assumption that it prevents heart disease was disputed by the results of the estrogen–progestin clinical trial arm of the Women's Health Initiative.
Priorities for future research
The future will bring many more advances in scientific understanding. In 2005, the research priorites of the ORWH describe many research opportunities in terms of overarching themes, specifically: lifespan, sex/gender determinants, health disparities/differences and diversity, and interdisciplinary research. The priorities signify approaches and areas in which the ORWH wishes to stimulate and encourage research on women's health, the advancement of women in biomedical research careers, and the support of both women and men in conducting research on women's health, and sex and gender factors in wellness and disease. There is a growing emphasis on the importance of interdisciplinary collaboration in research to provide a synergy of different disciplines and specialties to address scientific and clinical issues in women's health, thereby providing a framework for a more integrative process of healthcare for women.
Basic, translational, behavioral and clinical research, including the elucidation of sex/gender differences, is currently of particular interest in studies of women's health and their application to clinical practice in a number of areas. These are listed in Box 1.
Studies of chromosomal, genetic, gonadal and phenotypic sex in laboratory models.
Etiologic mechanisms to elucidate sex differences in cellular, tissue/organ, physiological and/or immune responses to environmental and infectious agents.
Cellular and molecular studies of the mechanism of action and effects of complementary and alternative medicines and dietary supplements in the treatment of conditions or diseases that differentially affect women.
Studies of the pathogenesis of diseases that differentially affect women, including those affecting behavior and the endocrine, musculoskeletal, autoimmune, urologic, cardiovascular, ophthalmic, and neurobiological systems.
Clinical trial methodology, including ethical issues and study design specific to women, novel recruitment strategies, and novel statistical analysis methodology.
Mental health studies of the incidence, severity, and treatment of depression and addictive, mood, cognitive and anxiety disorders, including physical and physiological stressors.
Studies of the effects of caregiving on the health of the caregiver and the effects of the multiple and competing societal roles of women on their health and that of their families.
Studies of the behavioral correlates that affect the selection and advancement of women's careers in biomedical sciences.
Studies involving agents for the optimization of menopausal symptom relief.
Studies of the role of the menstrual cycle in disease initiation, course, treatment and response to treatment.
Studies of the effect of pregnancy and the post partum period on disease.
Prevalence and validation of sex differences in the diagnosis and treatment of disorders and diseases differentially affecting men and women.
Development of interventions for specific diseases that have enhanced clinical presentation in women, including, but not limited to, diseases of the metabolic, endocrine, autoimmune, urologic, ophthalmic, oral, reproductive, musculoskeletal, neurological and cardiovascular systems.
Advancement of our understanding of complex integrative syndromes such as chronic fatigue syndrome and temporomandibular joint disorders.
Studies of reproductive disorders such as malignant and benign tumors, especially uterine leiomyomas, and pelvic floor disorders.
Two areas of special interest for current women's health research are prevention and treatment of disease, and the interaction of sex and genetics as determinants of biological processes. There are many specific examples, discussed in Boxes 2 and 3.
For prevention and treatment of disease
Research to identify and validate biomarkers of disease pathogenesis and risk and their applications, including the development of novel tools to enhance disease prevention, early detection and treatment.
Studies into the impact of nutrition, hormones, exercise, weight patterns including obesity and eating disorders, tobacco use, alcohol and drug abuse, and violence on health.
Research on reproduction, from menarche, to pregnancy, to the menopausal transition, with regard to the susceptibility to, and protection from, diseases and conditions.
Studies of the factors which are involved in disease initiation and progression, in order to develop effective preventive and curative strategies.
Development, testing and validation of preventive and curative strategies for conditions and diseases, including but not limited to sexually transmitted diseases, cancer, coronary artery disease, stroke, obesity, musculoskeletal disorders, addictions, and chronic multisystem diseases.
Studies of the effect of biological, behavioral, cultural, social, economic, educational and environmental factors on susceptibility to, or protection from, diseases and response to treatment.
Interaction of sex and genetics and pharmacogenomics
Determination of sex differences that may modify the role of known gene defects or polymorphisms in diseases.
Effect of phases of the menstrual cycle, hormones, pregnancy, and menopause on genetic penetrance of disease.
Mechanism of sex effects on gene expression.
Genetic, molecular and cellular basis of action of pharmacologic agents known to have differential effects in women and men.
Studies of the interaction of environmental exposures and genetic polymorphisms in diseases common in women.
Role of genes known to be differentially expressed in women in the incidence, course and response to treatment of common diseases.
Impact of sex on genetic differences underlying pharmacokinetics, pharmacodynamics, drug efficacy and their adverse effects.
Development of novel methods of analysis to assist in discerning interactions of sex and genes in mechanisms of disease initiation, course and response to treatment.
Importance of age, sex, and gene interactions in diseases affecting women.
Genetic polymorphisms that modify the action of diet, drugs, or toxins during pregnancy on the mother and child.
Differences in gene expression occurring during the prenatal period, during puberty or pregnancy and later in life.
Critical issues addressed in the revised research agenda for the twenty-first century include the delineation of strategies to overcome barriers of carrying out research recommendations and translating research outcomes into healthcare practice. An additional issue is the importance of incorporating research priorities and new advances in knowledge into the education and training of the next generation of biomedical investigators and healthcare providers. To accomplish these goals, we must address not only sex and gender analyses and population differences in research design, but also report the findings in the medical literature. Investigators, research administrators and the editorial staffs of print and electronic journals must collaborate in this effort. The publisher of Women's Health is providing an opportunity for the research and clinical communities to do just that. The inauguration of Women's Health is a sign that there is a substantial amount of relevant research to report, and is an important instrument in translating the results of this research into standards of healthcare practice and improving the health status of women.