Abstract
The Intelligent Genome: What Mediates Adaptation?
Marianne J. Legato, MD, PhD (hon c)1,2
1Emerita Professor of Clinical Medicine, Columbia University 2Adjunct Professor of Medicine, Johns Hopkins
For decades, the historical division between the biomedical community and the scholars of social structure about how the final phenotype is shaped seemed irreducible. It produced particularly heated arguments within the discipline of gender-specific medicine. Clinical investigators insisted that the answers to what shaped function lay almost entirely within our biological sex while anthropologists, sociologists, and even epidemiologists maintained that biomedical investigators were ignoring the powerful impact of the environment on shaping the phenotype, that is, that “maleness” and “femaleness” are profoundly influenced by the environment. The only thing about which both camps agreed was that to separate the individual impact of the two—biology and environment—was an impossible task. It was the Gordian knot of gender-specific medical studies: Before the genomic era, lecture after lecture in conferences like these began with the effort to describe the distinction between ”sex” and ”gender.” With the discovery of the structure of the human genome less than 2 decades ago, a unifying hypothesis began to emerge. The first piece of data was that the human genome was 99.5% identical in all humans and that the actual number of individual genes was much smaller than had been predicted: 20 000 to 25 000 (Human Genome Project) and at a maximum, 46 000 (Stephen Salzberg). How did this explain the enormous variability- and adaptability-of humans both within and across generations? If biological sex is significantly restrictive for the phenotype, how do we explain memory, learning new skills, and adjustment to the world around us? The answer lies in how genes are expressed: their function is modified by actual chemical tags attached to the various components of the genome. These modifications do not change underlying structure, but profoundly modify the way genes are up or down regulated, modify mRNA, and even postranslationally modify protein structure through folding, stabilization, and binding partners. The results are the precisely engineered components of the individual human. Importantly, some of the epigenetic changes in the genome can be inherited by future generations in a sex-specific way. In short, the science of epigenetics knits the once separate findings of social scientists and biomedical investigators into a unified functional whole. We might well consider substituting epigenetic medicine for the term gender-specific medicine, a term that tells a more accurate and complete story and unites the 2 concepts that are no longer separable: sex and gender.
Prioritising Sex and Gender Equity in Health in Europe
Peggy A. Maguire1
1European Institute of Women’s Health, Dublin, Ireland
The European Union can do more to prioritize women’s health in order to improve the health of all, targeting existing gaps and challenges. Action must be taken early and at critical points to ensure health and well-being from preconception to childhood through to old age. Biological and social influences are critical to health. Women face higher rates of diseases, such as in breast cancer, osteoporosis, and autoimmune diseases than do men. Other diseases affect men and women differently, including diabetes, depression, and cardiovascular disease. Women do not present the same for conditions and respond differently to treatment than do men. Strategies must account for these differences. Many factors outside of the health sector—such as socioeconomic status, education, culture, and ethnicity—affect behavior and resource access. Sex and gender have important implications for health-care delivery. Due to women’s reproductive role, their health affects the health of their unborn child and that of future generations. Health care and health systems should be highly responsive to women, but too often fail them. Translating the evidence from sex and gender research into regulatory practice leads to more targeted, safe, and effective opportunities for health and health care. Women are the heaviest medicine users, yet they are underrepresented in research and data. Consequently, the evidence base is weak for women as well as for older people. The Clinical Trials Regulation must be implemented in order to combat the underrepresentation of women in clinical trials. Health-care systems must be supported to systematically and more effectively overcome sex and gender inequities. Treatments must be delivered, responding to differences, such as sex, gender, and age, and adapt treatment to ensure that all people and patients in Europe receive the best available care.
Focusing on Women’s Health: Policies That Work? Experiences From an Austrian Initiative
Beate Wimmer-Puchinger, PhD1, and Sylvia Gaiswinkler, MSc2
1Austrian Association of Psychologists, Vienna, Austria
2Gesundheit Österreich GesmbH, Vienna, Austria
After the highly successful Vienna Women’s Health Program adopted in 1999 by the city parliament as a regional model of good practice, the Austrian Ministry of Women’s Affairs and the Austrian Ministry of Health decided 2014/2015 to develop an Action Plan for Women’s Health on the national level. Goals of the Action Plan mirror the different stages of life: girls and young women, working women, and elderly and old women.
Austrian Women’s Health Action Plan was elaborated by interdisciplinary highly professional expert working groups. The Plan highlights and addresses critical issues of women’s health based on a biopsychosocial view. Following this approach, the goals focus not only on women’s health but furthermore on the social determinants of health such as poverty, equal pay, and gender roles. The Action Plan was adopted by the Austrian parliament and consists of 17 goals and proposes 40 measures on achieving these goals. To ensure the implementation and progress, the departments for health and the departments of women’s affairs of all 9 counties were activated and as “Focal Points” established. These act as coordinating body within the 9 countries. The overall aim of the “Focal Points” is that all over Austria, in the cities as well as countryside, women’s health issues are known, understood, and services for special issues like violence, body images, sexual health, reproductive health, and gender-specific chronic diseases are offered. To advance the process of the implementation, the focal points are establishing regional networks, 3 times a year Focal Point meetings are held to exchange experiences as well as an Austrian “Women’s Health Dialogue” conferences for a broader audience. Summarizing these joint efforts, awareness for women’s health has increased policies as well as in experts and the population. Therefore, it seems to be a model of good practice because it works.
Chronotype, Gender, and Health
Roberto Manfredini1
1Faculty of Medicine, Pharmacy and Prevention, University of Ferrara, Ferrara, Italy
The circadian preference (chronotype) reflects the individual’s internal circadian rhythm that influences the sleep-activity cycle in a 24-hour period. It can be self-assessed by the Morningness-Eveningness Questionnaire (MEQ), identifying Morning-types, Evening-types, and neither-types or Intermediate. Many genes participate in the determination of chronotype, and PERIOD2, a core molecular component of the circadian clock, seems to play active role. However, individual chronotype is not immutable, and varies with age and sex. Eveningness is more frequent in younger subjects, whereas morningness is greater in the advancing age. Men are typically later chronotypes than women before 40, but earlier types after 40. Moreover, environmental cues, for example light in particular, may play an important role. For billion years, the light/dark cycle determined by the sun has regulated the endogenous circadian rhythmicity in almost all life forms. From the XIXth century, the availability of incandescent light sources (ILSs), allowed humans to work over the 24-hour of a day, leading to a “shift-work desynchronization.” Due to many advantages, that is, low energy consume and smaller size screen, light-emitting diodes (LEDs) have replaced ILS, becoming the dominant source for urban lighting and personal domestic devices, that is smartphones, tablets, so on However, the LED-emitted blue light elicits a significant, dose-dependent, suppression of endogenous melatonin, with negative consequences on sleep. Light-at-night (LAN) has an impact on chronotype and health. A growing body of evidence indicates an association between eveningness and health problems, including (i) unhealthy habits and diet, more smoking, and alcohol drinking; obesity, metabolic syndrome, diabetes; (ii) psychological and psychological disorders, impulsivity, anger, depression, and anxiety (especially in women), risk taking behavior, psychopathology and personality traits, and (iii) sleep disorders, later bedtime and wake-up time, irregular sleep-wake schedule, subjective poor sleep, excessive daytime sleepiness and poor sleep quality (especially in women). These findings open new perspectives for prevention.
The Biological Clock and Sleep
Eva S. Schernhammer, MD, DrPH1
1Department of Epidemiology, Center for Public Health, Medical University of Vienna, Vienna, Austria
Virtually all cells follow the 24-hour circadian rhythm of a hypothalamic master pacemaker that evolved in the natural light–dark cycle. Decoding this biologic clock, which is the prime regulator of sleep/wake, culminated in the Nobel Prize in Physiology or Medicine 2017 for the discovery of molecular mechanisms controlling the circadian rhythm. It is now recognized that a strong, unperturbed biologic clock is a hallmark of healthy aging. The introduction of electric light, however, presents unique challenges: Increases in the risk of major chronic disease and mortality have been associated with night work. Further, the ubiquity of light at night implicates potential risk not only for night workers but for everyone. Triggered by the melatonin hypothesis posed by Richard Stevens und Scott Davis in 1986, substantial effort has been put toward deciphering these negative health effects. In 2007, based on convincing evidence from animal research, yet only a limited number of observational studies, the World Health Organization (WHO) classified nightshift work as a class 2A carcinogen (“probably carcinogenic”). A large body of additional evidence has now accumulated, giving rise to a WHO reassessment of the carcinogenicity of night shift work in June 2019. In this presentation, an overview and current status of the accumulated epidemiological evidence is provided, and future directions are discussed.
Biological Clock and Sleep
Riva Tauman1
1Sleep Disorders Center, Tel Aviv Souraski Medical Center, Sackler School of Medicine, Tel Aviv University, Israel
Sleep is important to our health and well-being and is essential to our homeostasis. The regulation of the sleep-wake cycle is governed by the circadian system. The circadian system acts as a “supra-physiological” system that coordinates and regulates many physiological functions on a 24-hour basis including core body temperature, hormone secretion, appetite, and the sleep-wake cycles. Proper organization of circadian rhythms is a key for normal function and disruption to the circadian rhythm leads to adverse consequences. The human circadian system actively synchronizes (entrains) to the 24-hours day via environmental signals (light and darkness). However, the entrainment of the circadian system to the 24-hour cycles is not constant. Differences between individuals in this phase of entrainment is shaped by genotype, environment, gender, and age leading to different phenotypes, known as chronotypes. There are several circadian sleep disorders including: shit work disorder, the relative new disorder called “social jet-lag,” delayed sleep phase syndrome, advanced sleep phase syndrome, irregular sleep-wake rhythm, and non-24-hour sleep-wake rhythm. An overview on these sleep disorders will be provided.
Why so Slow? Content and Context in Gender Medicine
Sabine Oertelt-Prigione1,2, Sarah Hiltner1, Sabine Jenner3, and Jenny Jesuthasan2
1Primary Care Department, Radboud Institute of Health Sciences, Radboudumc, Nijmegen, the Netherlands
2Institute of Legal Medicine, Charité-Universitätsmedizin, Berlin, Germany
3Equal Opportunities Office, Charité-Universitätsmedizin, Berlin, Germany
Although the political and institutional support for sex and gender-sensitive medicine has significantly increased over the last decade, the implementation of its concepts into practice is lagging behind. General knowledge and single best practice examples are available, yet they are not widely adopted. Sex and gender-medicine is an innovative approach to medical research, care, and teaching. Its implementation is a complex change process that questions the underpinnings of traditional androcentric medicine. Given the complexity of the process, its implementation can only be achieved through a systemic approach and the sole production of sex-specific knowledge will not lead to innovation. In this talk, I will briefly discuss 3 examples from the (a) academic, (b) organizational, and (c) societal context to demonstrate how content and context are interlinked. Starting with (a) a focus on sex and gender-sensitive medicine in Europe, I will highlight how the alignment of content, institutional, and sociopolitical context is needed to achieve implementation. I will then proceed to (b) the role of context in the establishment of organizational guidelines against gender discrimination and sexual harassment. Here again, perceived need, pressure groups, and institutional support are essential in mandating lasting institutional change. Last, I will point out (c) the role of context in the development of innovative health-care concepts for vulnerable populations. A detailed need analysis, stakeholder networks, and structural support are mandatory for the implementation of successful social innovations. All 3 examples demonstrate how the presence of innovative content and best practices alone does not suffice to achieve change. Only the alignment of knowledge, perceived need, and political will lead to rapid and effective implementation. Most intriguingly, however, the examples demonstrate that context can be shaped to favor adoption of innovation. These learnings could provide a blueprint to accelerate the implementation of sex and gender-sensitive medicine.
Reducing the Gender Gap in Medical Academic Activities in Japan
Miyuki Katai1
1Department of General and Women’s Medicine, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
According to the latest data released by the Japanese government, the percentage of women medical doctors (MDs) in Japan is 21.1%, which is the lowest among the Organization for Economic Co-operation and Development countries as of 2013. However, in 2016, the ratio of women MDs in their 20s reached 34.6% in Japan, which was the highest among all age groups. As with other occupations, the employment rate of Japanese women MDs shows an “M-shaped curve” due to the decrease in the rate that reflects maternity and childcare leave. According to a survey by the Ministry of Health, Labour and Welfare, the employment rate among women decreases to its lowest point (73%) at the 11th year after licensure (estimated age: 37 years), compared with 89.9% among men in the same age cohort. Although the employment rate increases to over 80% among women in their 50s, it remains lower than that among men of the same age. One way to address this issue is by promoting changes in health policies, the working environment, and established notions about women and childcare. Since around 2006, federal funding in the form of grants and incentives from the Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labour and Welfare has been allocated for activities that promote the career development of women MDs and prevent job abandonment. Furthermore, universities, academic societies, prefectural governments, and the Japan Medical Association and affiliated associations have been working to address these issues. We analyzed female participation in the Japanese Societies of Internal Medicine and Subspecialties. Especially, we conducted a detailed analysis of the Japan Endocrine Society. I would like to introduce the results of this analysis and our efforts to reduce the gender gap in academic activities over the past 10 years.
The 9th Congress of the International Society for Gender Medicine (2019) Sex and Gender in Cardiovascular Medicine
Hiroaki Shimokawa, MD, PhD1
1Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
The importance of sex and gender differences has been emerging in all medical fields, including cardiovascular medicine. In our department, we have been conducting research for sex difference, ranging from basic to clinical and epidemiology research. We have demonstrated the importance of sex differences in ischemic heart disease, heart failure, pulmonary hypertension, arrhythmias, and even disaster medicine. In ischemic heart disease, we demonstrated that Rho-kinase, a molecular switch for vascular smooth muscle contraction, plays a central role not only in vasospastic angina but also in microvascular angina. The long-term prognosis of patients with vasospastic angina is deteriorated when coronary microvascular dysfunction is coexisted, both of which are mediated by Rho-kinase activation. Importantly, the expression of Rho-kinase is markedly suppressed by estrogen and enhanced by nicotine. Indeed, smoking is the strongest risk factor in postmenopausal women. In heart failure, we demonstrated the sex differences in terms of clinical characteristics, transition to symptomatic heart failure, and long-term prognosis. In pulmonary hypertension, it is widely known that the prevalence of the disorder is higher in females than in males, while the long-term prognosis is better in females than in males. We found that sex hormones may be differently involved in the development of pulmonary hypertension and right ventricular dysfunction. In arrhythmias, sex differences are also involved, especially in atrial fibrillation and Brugada syndrome. Finally, in 2011, we experienced the Great East Japan Disaster, where the City of Sendai was the center of the disaster. We found that although all types of cardiovascular diseases and pneumonia were increased in both sexes after the earthquake, post-traumatic stress disorder was associated with increased cardiovascular diseases, especially in female patients, after the earthquake. Thus, sex and gender differences are one of the most important points and therapeutic targets in cardiovascular medicine.
Sex and Gender in Arterial Vascular Stiffness—A Modern Management in Risk Assessment
Ute Seland1 ,2
1Gender in Medicine (GiM), Charité-Universitaetsmedizin Berlin, Germany
2DZHK (German Centre for Cardiovascular Research), partner site, Berlin, Germany
Arterial stiffness is an important component of vascular ageing and a potent cardiovascular disease (CVD) risk predictor. The concept that “early vascular aging” (EVA) is better related to the prognosis of CVE compared to chronological age is rapidly evolving. Methods for assessing vascular ageing, for example, noninvasive measurement of pulse wave velocity (PWV) and augmentation index (AIx), are not yet established in clinical routine practice. Clinical data of 2 main studies will be presented by the author to elucidate the benefit of arterial vascular stiffness measurement for clinical practice both for general practitioners and gynaecologists: The “Berlin Risk Evaluation in Women” study was performed to measure the vascular health of women living in Berlin. The study tested the hypothesis that the measurement of AIx and PWV is useful in addition to that of traditional cardiovascular risk factors when assessing the risk of left ventricular diastolic dysfunction (LVDD). The study data show that the measurement of pathological aortic PWV values ≥ 9.7 m/s predict the risk of LVDD, in addition to the cardiovascular risk factors postmenopausal age and waist circumference > 80 cm. The high prevalence of vascular dysfunction and arterial stiffness (45%) in this female cohort and the high prevalence of LVDD (31.7%) should encourage implementation of aortic PWV measurement to improve cardiovascular-risk assessment. The aim of the sub study of BASE-II was to examine age and sex differences of arterial wave reflection and to estimate associations with endogenous (estradiol)- and exogenous (oral contraceptives [OCP] and postmenopausal hormone therapy [HRT]) sex hormones. Pulse wave velocity and AIx were measured in 590 male and 400 female participants, recruited from 2 age-strata, 22 to 35 years and 60 to 82 years. The findings suggest important sex differences in measures of arterial wave reflection, with a higher mean AIx observed in women compared to men. Oral contraceptives promote the development of hypertension, maybe by increasing the AIx. Suppressed endogenous estradiol levels could be responsible for this increased arterial wave reflection, due to higher vasotonus of the small and medium arteries compared to the non-OCP users. Among postmenopausal women, no associations of HRT with estradiol level and measures of arterial stiffness were observed.
Sex Differences in Immunity and Immune-Mediated Diseases
Elena Ortona1, Maria Luisa Dupuis1, Maria Cristina Gagliardi1, Maria Teresa Pagano1, Katia Fecchi1, and Marina Pierdominici1
1Center for Gender Specific Medicine, Istituto Superiore di Sanità, Viale Regina Elena, Rome, Italy
Immune response differs between women and men at many levels. In general, females mount stronger innate and adaptive immune responses in comparison to males. In particular, women show more effective phagocytosis and antigen presentation, stronger production of inflammatory cytokines, higher absolute number of CD4+ T lymphocytes, higher levels of circulating antibodies, in comparison to men. Genetic, epigenetic, hormonal, and environmental factors contribute to sex differences in immune response. The strong immune response in women, on one hand, appears to be beneficial, leading to the reduction of pathogen load and accelerating pathogen clearance, but, on the other hand, it can be detrimental by causing autoimmune or inflammatory diseases. Accordingly, most autoimmune diseases (eg, rheumatoid arthritis, Sjögren syndrome, primary biliary cirrhosis, antiphospholipid syndrome, systemic sclerosis, multiple sclerosis, and systemic lupus erythematosus) are more prevalent in women than in men and symptoms, disease course, and response to therapy may also differ between males and females. The search for the mechanisms responsible for these differences could lead to the identification of sex-specific diagnostic, prognostic and predictive biomarkers, and to the identification of new therapeutic targets. Our studies focused on estrogen (ER) and vitamin D (VDR) receptors in T cells of men and women. We found that ERβ expression could be considered a marker of disease progression and represents a potential therapeutic target in systemic autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. We also observed that VDR expression is significantly different in T lymphocytes from women and men and its activation significantly inhibited IL-17 and TNF-α production. In conclusion, ER and VDR could represent important biomarkers and therapeutic target in autoimmune diseases opening new perspective in the application of a gender-specific, personalized treatment.
Sex Differences in Invisible Illnesses: Chronic Pain, Fibromyalgia, and Hypermobility Disorders
Katelyn A. Bruno, PhD1, Andrea C. Morales, MD1, Rinald Paloka1, John M. Sousou1, Jenil B. Patel, MD1, Shelby T. Watford1, Anna A. Mease, MPH1, Nicholas A. Courson2, Peter T. Dorsher, MD3, Todd D. Rozen, MD4, Edsel B. Bittencourt, PT2, Lynsey A. Seim, MD5, and DeLisa Fairweather, PhD1
1Department of Cardiovascular Medicine, Mayo Clinic, FL, USA
2Department of Rehabilitation, Mayo Clinic, FL, USA
3Department of Physical Medicine and Rehabilitation, Mayo Clinic, FL, USA
4Department of Neurology, Mayo Clinic, FL, USA
5Department of General Internal Medicine, Mayo Clinic, FL, USA
Recent research suggests that chronic pain conditions like hypermobile spectrum disorder (HSD) and hypermobile Ehlers Danlos syndrome (hEDS), which are considered invisible illnesses, occur fairly often in the population; 255 million or 3.5% people affected worldwide. Based on Mendelian genetics, the sex ratio of hEDS patients is expected to be 1:1, but in fact the disease affects females more than males. Fibromyalgia is an illness associated with chronic pain and estimated to occur in 2% of the population (9:1, W: M). In spite of the large number of patients with these conditions, the pathogenesis of disease remains largely unknown. We performed a retrospective study examining sex and age difference, presence of comorbidities, vitals and labs in around 8000 patients from the Mayo Clinic EMR who were diagnosed with one of these chronic pain condition. We found that HSD, hEDS, and fibromyalgia occur more often in women with hEDS occurring more often in premenopausal women and fibromyalgia occurring more often in postmenopausal women. Comorbidities that were examined include fatigue, migraine, IBS, chronic pain, and depression. We also found that sex differences occur in common comorbidities such as migraines. We found that females with fibromyalgia had more migraines and depression compared to males, whereas males had more fatigue. When we examined comorbidities according to age using age 50 as a surrogate for menopause status, we found that women under 50 were more likely to have migraines while women over 50 were more likely to have hypertension. Knowing common comorbidities and/or vital/lab trends affecting patients could lead to a better understanding of the pathogenesis of disease and lead to better treatment strategies for patients. Our findings highlight the importance of studying sex and age differences in disease and provide insight on factors that may contribute to chronic pain in patients with these conditions.
Blood Sera of Women Affected by Fibromyalgia: An NMR Metabolomics Analysis
Manuela Grimaldi1, Michela Buonocore1, Carmen Ricciardelli2, Arianna Pallavicini2, Paola Sabatini3, Patrizia Amato2, and Anna Maria D’Ursi1
1Department of Pharmacy, University of Salerno, Fisciano, Salerno, Italy
2SerT ASL Salerno Cava dei Tirreni, Italy
3U.O.C Clinical Pathology D.E.A. III Umberto I, Nocera Inferiore, Salerno, Italy
Fibromyalgia syndrome (FMS) is a female prevalent chronic pain disease. Timely diagnosis and accurate monitoring are decisive to improve the accuracy of therapy. In the present work, we present an NMR-based metabolomic study of blood sera of FMS patients. Spectral analyses of samples were conducted using a 600 MHz 1H nuclear magnetic resonance (NMR) spectrometer; data processing and analyses were performed using Bayesil and MetaboAnalyst software. Unsupervised and supervised multivariate analyses distinguished control and FMS patient groups. Sample of patients analyzed versus control according to age and gender led to the identification of a characteristic metabolomic profile that can be a useful tool to classify FMS affected women. Nuclear magnetic resonance based metabolomic analysis confirms to be a suitable tool to explore the metabolite information in order to improve existing medical practice and planning personalized therapies.
Gender and Pain: Theoretical Foundations and Practical Applications
Kateryna Ostrovska1
1The Ukrainian Society for Gender and Anti-Aging Medicine, Dnipro, Ukraine
The gender differences in experience of pain became a burning issue in current years. Women are corroborated to be at a higher risk of chronic pain compared to men and even suffer from more severe aches. Gender divergences in pain perception are hypothesized to be based on the modifying impact of gonadal hormones on the neural substrate. The existing evidence on the distribution of sex hormones and their receptors in the areas of the central and peripheral nervous system engaged with the nociceptive transmission revealed causal pathways. The peculiarities of both personalities: a health-care worker and a patient evidently contribute to gender bias in pain therapy. Various biological, psychological, and social factors (genetics, endogenous opioid system, sex hormones, gender roles, pain relieving models, and catastrophizing) are involved as well. Furthermore, the gender discrepancies in responses to the medicamental and nonmedicamental pain treatment are discovered, whereas the findings may fluctuate in relation to the definite methods of treatment and characteristics of pain. As far as prescribed doses of remedies are calculated on a model of 70 kg weighing man, female patients may be posed at risk of either enlarged therapeutic or adverse effects of the drug. The predispositions are explained by lower mean body weight paralleling a higher average percentage of body fat that leads to elevated average drug concentrations in women in comparison with male patients. The pain management cannot be adjusted in accordance with gender specificity nowadays. Hence, further researches clarifying the mechanisms defining gender differences in pain responses for the purpose of personalized therapy are warranted.
Clinical Feature of Coronary Artery Disease in Japan
Hiroaki Kawano, MD PhD1
1Deptartment Cardiovascular Medicine, Kumamoto University, Kumamoto, Japan
The incidence of angina pectoris in women increases after 60 years of age in Japan as other western countries. Coronary spasm has been reported to play an important role in the pathogenesis of ischemic heart disease in general, including acute coronary syndrome. Approximately 40% of angina pectoris is related to coronary spasm in Japan. Impairment of endothelial function as well as the hypercontractile response of smooth muscle in coronary artery may play an important role the genesis of coronary spasm. A hyperventilation test is a specific test for coronary spastic angina (CSA). Estrogen replacement prevents the hyperventilation-induced attacks in postmenopausal women with CSA. Thus, estrogen may prevent coronary spasm. Even though a lot of perimenopausal women have chest symptoms in Japan, most of those patients do not go to hospital, or do not receive any treatment due to be diagnosed as cardioneurosis or unknown. These facts are not good for women’s health. Internists must be aware of this lapse and need to induce these women that estrogens may be efficacious and effective.
Sex Differences in the Management of Heart Failure
Kotaro Nochioka1, Yasuhiko Sakata1, and Hiroaki Shimokawa1
1Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
Heart failure (HF) is a global pandemic in Asia and Western countries. Sex is an important contributor to the phenotypic heterogeneity of HF. Women with HF are typically older, and more often have hypertension, preserved left ventricular ejection fraction, and less ischemic heart disease as compared with men. The significant underrepresentation of women in clinical trials limits the capacity to evaluate the extent of sex-related differences in HF. The Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study is a multicenter, prospective cardiovascular observational study in Japan (NCT 418 041). Among 4736 consecutive HF patients (mean age, 69 years) in the CHART-2 Study, crude mortality rate was comparable between women and men (52.4/1000 and 47.3/1000 person-year for women and men, respectively, P = .225), but women had a reduced risk of mortality after adjusting for potential confounders (adjusted HR: 0.791; 95% CI: 0.640-0.979, P = .031). The incidence of cardiovascular death, particularly that due to HF, was significantly higher in women than men. We also found sex difference in prognostic importance of statin therapy in patients with history of myocardial infraction (n = 3124): statin therapy was comparably related with reduced incidence of death between both sexes but associated with reduced incidence of HF admission only in men but not in women (men: HR = 0.70, P < .001; women: HR = 0.98, P = .92, P for interaction = 0.07). These observations indicate that consideration of sex differences may provide more precise cares for HF patients. In this session, we will discuss the current insights into management of HF to maximize treatment benefits with a special reference to sex difference.
Multicenter Studies in Japan on Subjective Symptoms and Diagnosis at Internal Medicine in Consideration of Sex, Gender and Age Differences in Medicine
Jinko Yokota1
1Tokyo Women’s Medical University, Health Care Center, Shinjuku-ku, Tokyo, Japan
The General Internal Ambulatory Department plays a very important role in local hospitals and the demand among the inhabitants in Japan. We present hereby the second report where we considered the problem of patients at the Internal Medicine Ambulatory department from the standpoint of sex, gender, and age. This is a cross-sectional retrospective study conducted in the form of a unified medical examination sheet questionnaire. We studied 6 local hospitals/infirmaries near the metropolitan area, presenting us with data of new patients all in the field of internal medicine. Thus, between June 15 and July 15, 2011 (summer period), and between January 16 and February 15, 2012, we collected data from 4424 individuals. Those individuals whose complaints we could analyze we grouped according to sex and gender, age, and encoded according to the Element No 1 of the second edition of International Classification of Primary Care. Of all, 3976 individuals were analyzed, 1335 in summer, 2641 in winter, 46.8% were male, mean age 51.7 ± 19.6 years. A split up according to complaints yielded 43.3% “Respiratory,” which was the highest value followed by “General and unspecified” (35%), “Digestive” (30.9%), ”Neurological” (22.2%), and “Musculoskeletal” (12.1%) in this order. Female patients had significantly more troubles with digestive organs than men. The younger the patients were the more they suffered from locally unspecified troubles (or over the whole body), problems with digestive tract, nerves, and respiratory organs. On the other hand, the older the patients were the more they suffered from circulatory dysfunctions. We studied the complaints of patients at the Ambulatory Departments of community-based hospitals. We are continuing our research about prognoses, diagnostic name, and appropriate treatment at the time of the first examination.
Sex, Hormones and Macrophage Activation in Cardiovascular Disease
Maria Luisa Barcena de Arellano1,2, Sofya Pozdniakova1,2, Celine Christiansen1,2, Anja Kühl3, Istvan Baczko4, Yury Ladilov1,2, and Vera Regitz-Zagrosek1,2
1Institute of Gender in der Medicine, Center of Cardiovascular Research, Charité—Universitätsmedizin Berlin, Germany
2DZHK (German Centre for Cardiovascular Research), Partner site Berlin, Germany
3Research Center ImmunoSciences (RCIS), Charité—Universitätsmedizin Berlin, Germany
4Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary
Development of AI Diagnostic Navigation System (WaiSE) for Women’s Medical Care Assistance
Miyuki Katai1, Jo Kitawaki2, Shigeru BH Ko3, Teiji Nishio4, Koji Oba5, and Mari Hotta Suzuki6
1Department of General and Women’s Medicine, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
2Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
3Department of Systems Medicine, Keio University School of Medicine, Tokyo, Japan
4Department of Medical Physics, Graduate School of Medicine, Tokyo Women’s Medical University, Tokyo, Japan
5Department of Biostatistics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
6Department of Health Services Center, National Graduate Institute for Policy Studies, Tokyo, Japan
Women, especially at perimenopausal phase, often present with a wide range of psychosomatic symptoms. Limited examination time often prevents a final diagnosis from being determined in general clinics. Therefore, women tend to repeatedly visit multiple clinics with nonspecific symptoms. In Japan, an estimation showed 18.8 billion yen spent annually on medical expenses for perimenopausal women. Comprehensive support that focuses on sex, gender, and age differences is desired. Since 2007, Tokyo Women’s Medical University has provided comprehensive women’s medical care based on gender medicine, and diagnoses specific diseases in 27% of women with nonspecific complaints. Therefore, based on our experience with gender medicine, we decided to develop a tool using artificial intelligence (AI) and a chatbot to support interview-taking and diagnosis for women with nonspecific symptoms. In April 2019, we began developing an AI diagnosis navigation system “WaiSE” with support from the Japan Agency for Medical Research and Development (AMED). WaiSE is an application for patients and physicians that incorporates a chatbot system with a diagnostic algorithm based on our clinical experience. In order to elucidate the pathology and establish evidence for appropriate diagnosis and treatment for women’s nonspecific symptoms, we will analyze data from 61 983 medical records of 5241 patients who visited our Women’s Specific Clinic at Tokyo Women’s Medical University over the past 10 years. WaiSE reproduces inquiries of Women’s Specific Clinic experts in dialogue form through an AI chatbot system to organize complaints and guide users to the necessary information for diagnosis. Women can use WaiSE to review information about their chief complaint before attending a clinic and know candidate of disease to be distinguished. They can share that information with physicians in order to get differential diagnoses and treatments. WaiSE is expected to improve patient satisfaction, reduce medical expenses, and help women’s health through more accurate diagnoses.
Sex Differences in Myocarditis and DCM: A Personalized Medicine Approach for Men and Women
DeLisa Fairweather, PhD, FAHA1
1Mayo Clinic, Department of Cardiovascular Medicine, Jacksonville, FL, USA
Heart failure due to nonischemic dilated cardiomyopathy (DCM) contributes significantly to the global burden of cardiovascular disease. Myocarditis is, in turn, a major cause of acute DCM in both men and women. However, recent clinical and experimental evidence suggests that the pathogenesis and prognosis of myocarditis and DCM differs between the sexes. Men have an increased incidence and severity of most cardiovascular diseases including atherosclerosis, myocardial infarction, myocarditis, DCM, and heart failure, with the exception of hypertension, which is higher in women. A recent study found that myocarditis is 3.5 times more common in men than women and DCM, regardless of cause, is around 2 times more common in men. Men are more likely to require a heart transplant following myocarditis and are at increased risk of death compared to women. Animal models have provided valuable information about the mechanisms that lead to more severe myocarditis, DCM, and heart failure in men than women. We recently showed that the biomarker sST2 only indicates risk of heart failure in men under the age of 50 but not in women and not in men over 50. This study highlights the need to examine diagnostic and risk biomarkers and clinical end points according to sex and age. Considering that sex hormones alter gene expression that influences basic organ physiology, the immune response to infection and damage, drug dose effects, and thus symptoms and outcomes of therapy, a personalized approach to medicine that incorporates the sex and age of the patient is essential in order to provide effective health care.
Sex Differences in Mitochondrial Function
Renée Ventura-Clapier1, Jérôme Piquereau1, Vladimir Veksler1, and Anne Garnier1
1Cardiovascular Signaling and Pathophysiology, UMR-S 1180 Inserm, Université Paris-Sud, Châtenay-Malabry, France
Mitochondria are unique organelles present in almost all cell types. They are involved not only in the supply of energy to the host cell but also in multiple biochemical and biological processes like calcium homeostasis, production and regulation of reactive oxygen species (ROS), pH control, or cell death. The importance of mitochondria in cell biology and pathology is increasingly recognized. Being maternally inherited, mitochondria exhibit a tissue-specificity, because most of the mitochondrial proteins are encoded by the nuclear genome. This renders them exquisitely well adapted to the physiology of the host cell. It is thus not surprising that mitochondria also show a sexual dimorphism as that they are also prone to the influence of sex chromosomes and sex hormones. Sexual dimorphism of mitochondria involve mainly oxidative capacities, calcium handling, and resistance to oxidative stress in a tissue-specific manner. In turn, sex hormones regulate mitochondrial function and biogenesis. Estrogens affect mitochondria through multiple processes involving membrane and nuclear estrogen receptors (ERs) as well as more direct effects through signaling pathways. Moreover, estrogen receptors have been identified within mitochondria. Mitochondrial dysfunction is also an important parameter for a large panel of pathologies including neuromuscular disorders, encephalopathies, cardiovascular diseases, metabolic disorders, neuropathies, renal dysfunction and so on. Many of these pathologies present sex/gender specificity. We will discuss the sexual dimorphism of mitochondria from different tissues and how this dimorphism takes part in the sex-specificity of important pathologies, mainly cardiovascular diseases and neurological disorders.
La Pura Women’s Health Resort: Healthy Aging and Well-Being Exclusively for Women
Sabine Fröhlich, MD1
1Medical Director of la pura, Women’s Health Resort, Gars am Kamp, Austria
In the idyllic Gars am Kamp region, la pura presents itself as a site of strength and energy only for women who consider a healthy lifestyle just as important as ambiance. La pura is the only resort just for women in all of Europe. It was founded 2011 and belongs to the VAMED company. Our gender medicine programs have been developed in cooperation with Alexandra Kautzky-Willer, Professor of Gender Medicine and Head of the Division of Endocrinology & Metabolism of the Medical University of Vienna. The Gender Institute in Gars enables sex and gender-based research at La pura. The medical team at la pura consists of general practitioners and specialists for trauma surgery and orthopedics with additional education in osteopathy, FX Mayr medicine, traditional Chinese Medicine, homeopathy, and minimal aesthetic intervention and sports experts as well as psychologists. The nutritional concept at la pura is the GourMed® Cuisine. Valuable regional food products are prepared in a gentle way, using organic and seasonal products. With our medical programs, we focus on prevention of chronic diseases, a healthier lifestyle including individualized healthy nutrition, exercise, and healthy aging and mental health. As well we provide medical help and advice for women-specific problems and female life-phases. We offer detox programs for weight management and the FX Mayr cure for regeneration of the digestive system—all under medical supervision. Our healthy aging program includes 2 epigenetic tests, on the one hand a metabolic panel and on the other hand a biological age panel to find out any predispositions and risks to premature aging. All programs are being perfected continuously based on current evaluation and new knowledge to further improve health and well-being of our female guests.
Inflammaging and Gender Differences
Giovannella Baggio1
1University of Padua, Italian Research Center for Gender Health and Medicine, Padova, Italy
Human aging is characterized by a chronic, low-grade inflammation. This phenomenon has been called inflammaging, defined as the chronic low-grade inflammation which is an important risk factor for morbidity and mortality in the old people. Most if not all age-related diseases have an inflammatory pathogenesis. Gender differences in prevalence/incidence of diseases, clinical manifestations, prevention strategies as well as in pharmacological needs are very important. This may be most dependent on differences in the inflammaging process. Is there a relationship between inflammaging and Frailty? And is there a difference between males and females? Frailty is a state of reduced physiological reserve and increased vulnerability for poor resolution of homeostasis after a stressor event. The male-female health survival paradox may bound to the fact that at any given age females have higher Frailty Index (FI) scores than males. However females live longer than males but with poorer health. In many papers a relationship between frailty and cardiovascular diseases is described with higher incidence but less mortality in females who are more affected by obesity, diabetes, metabolic syndrome, coronary calcifications, carotid plaques. Several papers conclude that biological, behavioural, and social factors underpin sex differences in frailty. However a great importance may be due to different inflammaging processes: women have a lower susceptibility and higher resistance to infection diseases in the first years of life, due to a higher inflammation capacity. However in the adult and late life, the high inflammation reaction of women leads more often to immunological, atherosclerotic diseases, as well as to the so called “degenerative” diseases (as osteoarthritis and dementia). Longevity is a good balance between pro- and anti-inflammatory stimula. And genetic component and great individual variability influences frailty or robustness.
Sex and Gender Specific Phenotypes in Alzheimer’s Disease—the Gateway to Precision Medicine
Maria T. Ferretti1
1Institute for Regenerative Medicine, University of Zurich, Schlieren, Switzerland
Sex differences in neurological and psychiatric diseases, notoriously heterogeneous in biology, clinical presentation and disease progression, have just started to be investigated and their significance is currently debated. In this talk, I will provide an overview of the literature documenting the occurrence and role of sex differences in dementia, with a focus on Alzheimer’s disease. Sex-differences in symptoms, biomarkers, risk factors, and in response to medical intervention will be discussed. Failing to recognize and appropriately consider sex and gender differences might compromise the development and validation of optimal diagnostic and therapeutic tools for highly heterogenous diseases, such as Alzheimer’s. The Women’s Brain Project advocates for more basic and clinical research into this topic, in the context of a precision medicine approach that will benefit both men and women.
Metabolomic Profiles Differentiate Men and Women in Accordance With Metabolic Disease
Miriam Hufgard-Leitner1, Karoline Leitner1, Lena Fragner2, Martin Brenner2, Xiauliang Sun2, Wolfram Weckwerth2, and Kautzky-Willer1
1Department for Endocrinology and Metabolism, Gender Medicine Unit, Medical University of Vienna, Vienna, Austria
2Department for Ecogenomics and System Biology, Vienna Metabolomics Center, University of Vienna, Vienna, Austria
There is evidence that pathophysiology of metabolic syndrome (MetS) differ between men and women. Sixty-six (33 female, 33 male) patients aged 60.3 to 62.5 years with (n = 57) and without (n = 9) MetS, but without diabetes, were included in the study. Each patient performed an oral glucose tolerance test (oGTT). Untargeted metabolomics were measured fasting and 120 minutes after intake of 75 g glucose. Metabolic syndrome was diagnosed by NCEP-ATIII criteria. Branched-chain amino acids (BCAA) and fatty acids (FA) could be selected by a VIP plot for MetS. A coefficients plot showed FA negatively correlated with MetS and BCAA positively correlated. Individual amino acids (AA) were clustered in MetaFA and MetaBCAA. Men had fewer MetaFA than women at time point 0 (LSD Intervals: −0.6 vs 0.5); after 120 minute men had more MetaFA than women (LSD intervals: 0.6 vs −0.4). Women had fewer MetaBCAA at time point 0 (−0.5 vs 0.5) and after 120 minutes (−1 vs 0.9) after oGTT and MetaBCAA dropped, while MetaBCAA in men rose after glucose intake. A boxplot showed that MetaBCAA in women without MetS differed significantly compared to MetaBCAA in women with MetS, whereas no such difference could be shown for MetS in men. Men had less MetaFA than women at time point 0 (−0.7 vs 0.5), after glucose MetaFA increased in men (0.4) but decreased in women (−0.5). Men without MetS had a significant different MetaFA profile than men with MetS, whereas this could not be detected in women. Women without insulin resistance (IR) had significant lower MetaBCAA than women with IR (−1 vs 1); men showed no differences in MetaBCAA regarding IR; women with IR had more MetaBCAA than men with IR (1 vs −0.3). Men with IR had significantly fewer MetaFA than women with IR (−1 vs 1.3). Spearman rank correlations of single AA showed differences in untargeted metabolomics between men and women. These results indicate that metabolomics can distinct (patho)mechanisms of components of MetS that differ between men and women. More detailed analysis and exact requests in homogenous groups are needed.
The Nuclear Membrane Estrogen Receptors Define the Diagnosis and Treatment of Gender Specific Medicine Disease
Edward M. Lichten, MD1
1Wayne State College of Medicine, Birmingham, MI, USA
Gender specific medicine (GSM) no longer is limited to hypothesizing from observations of statistically significant correlation between mankind’s gender and appearance of diseases. Pierdominici’s discovered that loss of the estrogen receptor-beta (ERβ)/estrogen receptor-alpha (ERα) ratio correlated directly with 90% of flairs of Crohn disease. Therefore, researchers and clinicians have a reproducible biomarker that directly links inflammation, hormones, GSM observations, and treatments. Homeostatic ERβ signaling maintains the anti-inflammatory humoral state of IL-6, IL-10, and TNFα. As ERβ is a testosterone receptor, our clinical research directly links loss of bioavailable testosterone in both sexes with loss of ERβ homeostasis and disease. In women with severe endometriosis, the ERβ/ ERα ratio is increased up to 100-fold. Considering endometriosis as a GSM diseases limited to only women, the prescribe anabolic steroids, actions similar to danazol, reset the ERβ/ ERα ratio biomarkers downward. The 2 biomarkers used are bioavailable testosterone (Free Androgen Index) and the ERβ/ ERα ratio. This differs from Crohn disease in which men and women are both affected, yet, remissions have occurred in both sexes with anabolic medications that reset the low ERβ/ ERα ratio, upward. This information has almost unlimited applications: the clinician defines the disease, measures the aforementioned serum biomarkers, and treats the patient in parallel to the in vitro findings from the individual’s T-lymphocytes tissue culture. The ERβ/ ERα ratio and 8 cytokines testing are repeated 8-weeks after various drug therapies. This is the future of precision medicine: direct treatment individually based on in vitro biomarkers. The ERβ/ ERα ratio should be adopted as the biomarker for all GSM research: it separates diseases limited to only women such as endometriosis, breast and ovarian cancer, and directs a new course of understanding and potential future treatments in diseases that affect both sexes.
Large-Scale Screening of Organ-Specific Autoantibodies in Patients With Autoimmune Thyroid Diseases
Porcelli Brunetta1, Civitelli Serenella2, Tabucchi Antonella1, Pini Alessandro1, Cinci Francesca1, Terzuoli Lucia1, Bacarelli Maria Romana2, Cantara Silvia2, Dalmazio Gilda2, Scapellato Carlo1, Castagna Maria Grazia2, and Pilli Tania2
1Department of Medical Biotechnologies, University of Siena, Siena, Italy
2Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
Gender Differences in Osteoporosis
Ginaldi L1, Sirufo M M1, Di Silvestre D1, and De Martinis M1
1Department of Life, Health and Environmental Sciences, University of L’Aquila; Allergy and Clinical Immunology Unit, AUSL 04 Teramo, Italy
Sex Differences in Gastrointestinal Cancers
Anna D. Wagner, MD1, Berna Oezdemir, MD, PhD1, and Sabine Oertelt-Pirigione, MD, PhD2
1Department of Oncology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
2Radboud Institute of Health Sciences (RIHS), Department of Primary and Community Care, Radboud University Medical Center, Nijmegen, the Netherlands
So far, oncology has been largely sex- and gender-blind. However, together with the interest in personalized oncology and our improved understanding of cancer biology, sex differences in cancer epidemiology and distribution of molecular subtypes of various cancer types (eg, gastroesophageal cancer) as well as patient outcome are gaining increasing attention. In addition, recent evidence suggests significant sex differences in efficacy and toxicity of certain chemotherapies, alone or when used in combination with biologicals. The European Society for Medical Oncology (ESMO) is addressing this challenge. After an initial workshop “Gender medicine meets oncology” held in 2018, ESMO created a multidisciplinary task force which will define key research projects to investigate the effect of sex and gender on cancer epidemiology and outcomes, as well as treatment effects and communicate relevant findings at future meetings.
Drug-Utilization Pattern of Non Small Cell Lung Cancer Patients Related to Gender at the University Hospital of Siena, Italy
Spini Andrea1,2,3, Salvo Francesco3, Roberto Giuseppe4, Ciccone Valerio1, Pascucci Alessandra2, Rosellini Pietro2, Francini Edoardo5, Donnini Sandra1, Gini Rosa2, and Ziche Marina1,2
1Università degli studi di Siena, Siena, Italy
2Azienda Ospedaliera Universitaria Senese, Siena, Italy
3Université de Bordeaux, Bordeaux, France
4Agenzia Regionale di Sanità della Toscana, Firenze, Italy
5Università “La Sapienza”, Roma, Italy
Lung cancer is the third most commonly occurring cancer in females. Non-small cell lung cancer (NSCLC) represents about 85% of all cases of lung cancer. Recently, treatment guidelines for NSCLC have changed due to the introduction of new drugs for patients with advanced stage of the disease. The aim of the study was to analyze the treatment patterns of patients diagnosed with NSCLC between 2009 and 2017 at the University Hospital of Siena (UHS), focusing on gender difference in drug utilization. Patients with NSCLC diagnosis were identified by records in the pathology registry (PR) of UHS. Pathology registry data of NSCLC patients were anonymized and linked to the administrative health-care database of Tuscany region. Advanced stage patients were defined as those without surgical intervention (NO-SUR patients). A total of 2003 NSCLC patients were identified. There was a statistically significant upward trend (P = .0177) in the incidence in women, rising from 25% in 2009 to 38% in 2017. The average age of patients was 69 years and 45.3% were aged between 50 and 69 years; NO-SUR were the 57.1% of the study cohort (n = 1144). This cohort was divided in elderly, aged ≥ 70 years (n = 587), and young patients, aged 18 to 69 years (n = 557). In the 6 months following the index date, the percentage of subjects who received both immunotherapy and target therapy was higher among young patients, 5.9% vs 1.7% and 13.1% vs 11.1%, respectively and increased from 2.8% to 28.2% in young patients (P < .001) and from 1.4% to 6.9% in elderly patients between 2015 and 2017. In this cohort, the proportion of women increased. Data will be presented on the pattern of drug utilization and outcome in relation to gender. Real-world data on the pattern of drug utilization provide important information for clinician and health provider both in terms of appropriateness and economic sustainability of care.
X-Chromosome-Linked miR-548am-5p Is a Key Regulator of Mitochondria-Mediated Apoptosis and Is Implicated in XX and XY Cell Disparity
Paola Matarrese1, Paolo Tieri2, Simona Anticoli1, Barbara Ascione1, Maria Conte3,4, Claudio Franceschi5, Walter Malorni1,6, Stefano Salvioli3,4, and Anna Ruggieri1
1Center for Gender Specific Medicine, Istituto Superiore di Sanità, Rome, Italy
2National Research Council, Rome, Italy
3University of Bologna, BO, Italy
4Interdepartmental Centre “L. Galvani”, Bologna, Italy
5Neurological Sciences Institute Bologna, Italy
6University of Tor Vergata, Rome, Italy
The relevance of sex dimorphism in cell response to stress has previously been investigated by different research groups. It has been reported that, under the same stressing conditions, XY cells easier undergo cell death in comparison with XX cells that easier undergo cytoprotection by autophagy. This dimorphism could be due, at least in part, to regulatory elements such as microRNAs (miRs). In order to point out miR expression differences, we took advantage of specialized databases to identify X chromosome-encoded miRs potentially escaping X chromosome inactivation (XCI). One of these, the MiR-548am-5p, was found as a potential XCI escaper. This MiR is also deeply related to cell fate paths. We found that experimentally induced overexpression of miR548am-5p in XY cells by lentivirus vector transduction decreased apoptosis susceptibility, whereas its downregulation in XX cells enhanced apoptosis susceptibility. These data suggest that miR identified with this approach, miR548am-5p, can account, at least in part, for sex-dependent differences observed in the susceptibility to mitochondria-mediated apoptosis of human cells. More in general, these results also underscore the relevance of X chromosome-encoded miRs escaping XCI in cell pathology and the possible key roles of epigenetic mechanisms in determining XX and XY cell fate disparity.
Global Health and Gender Education: A Multidisciplinary Approach
Serenella Civitelli1 and Alessandra Viviani2
1Department of Medical, Surgical and Neurological Sciences, University of Siena, Italy
2Department of Political and International Sciences, University of Siena, Italy
Global Health is a concept that apply to the vision of health and disease as a result of many factors related to biological or individual characteristics but also to social, economic, and environmental conditions. Introducing gender issues in educational programs for health professionals may be useful but global health may be improved only through a multidisciplinary commitment aimed at creating a wider gender perspective about access to health care, decent work, and representation in political and economic decision-making processes. In the Global Gender Gap Index 2018, Italy ranks 82nd out of 144 Countries and 118th in economic participation and opportunity subindex. “Gender equality” is the fifth out of 17 goals of the UN 2030 Agenda for Sustainable Development. Based on the premises that global health inequalities cannot be overcome by simply focusing on medical field but that an encompassing cultural change is needed, a group of teachers of different Departments (Law, Social sciences, Medicine) of the University of Siena decide to run the first comprehensive educational program addressed to students, both graduated and undergraduated, and to University and Municipality staff. Following presentations of statistics, scientific data and academic research in various disciplines, students were invited, also through non formal education tools, to openly discuss about their beliefs, feelings, and ”unconscious” gender stereotypes to enhance their critical thinking skills. The exams’ results of the pilot course held in May demonstrate students’ increased interest and understanding of the multiple levels of gender issues and the need for gender mainstreaming in all fields of social life.
Focus Gender—Medical Students Gender Specific Perception and Attitudes Towards Burdens of the Everyday Student Life
Steiner-Hofbauer Verena1, Capan Melser Mesküre1, and Holzinger Anita1
1Medizinische Universität Wien, Research Unit für Curriculumentwicklung, Wien, Austria
The aim of this study was to investigate whether female and male medical students perceive burdens differently and whether students of both sexes assess their capability to stand performance pressure differently. In 2017, second (n = 424, 53% female) and sixth (n = 161, 46.6% female) year students at the medical university of Vienna were surveyed using a fully structured questionnaire. In second year, female students felt significantly more often that they could not measure up to study requirements than male students (87.5% vs 94.4%). Performance pressure was perceived as major problem by male (45.5%) and female (50.9%) students, while in sixth year the number was only half as high than in second (24%, 18.4%). In sixth year, significantly more female than male students were complaining about competition between students (33.3% vs 8%). Half of the students shared the view that there is no difference between men and women in the capability to deal with performance pressure. Most of the other half state that men are superior to women in handling performance pressure. In both groups, significantly more male than female students were convinced that they are superior to the other sex in handling performance pressure. Perception of problems is similar in male and female students. While in objective assessments, female students perform equally to male students they consider themselves less competent and are more inclined to doubt their capability.
Gender Integration in the Pregraduate Medical Curricula: A Swiss Perspective
Alexina Legros-Lefeuvre1, Virginie Schlüter1, Joëlle Schwarz1, and Carole Clair1
1Gender and Medicine Unit, Department of Training, Research and Innovation, Center for Primary Care and Public Health (Unisanté), University of Lausanne, Switzerland
Integrating a Gender Perspective into Core Curriculum of Medical Students
Serenella Civitelli1, Rosa D’Amico1, Brunetta Porcelli2, and Piersante Sestini1
1Department of Medical, Surgical and Neurological Sciences, University of Siena, Italy
2Department of Medical biotechnologies, University of Siena, Italy
Integrating gender issues into curriculum and underlining the influence of gender in personal and professional choices is necessary to promote gender equality in medicine. Several years ago, an optional course on Gender Medicine was run at the University of Siena on request of a teacher who aimed to raise awareness about the influence of gender on health and illness, choice of specialization, professional and social relationships. Following students’ interest, “Gender health” was then introduced into the second year core curriculum as a module within the Integrated Course of “Medico-scientific methodology, human sciences and health promotion.” A gender perspective was applied in reviewing the medical literature, discussing the role of women in the history of medicine and surgery and the concept of gender as a determinant of health and a topic of scientific relevance. The final examination consisted of a written paper on the treated topics with a free-form reflection. Afterward, according to the Faculty policy, all students must fill out an online anonymous, semistructured satisfaction questionnaire. In all, 658 students (404 F; 254 M) attended the MSSUP from 2016 to 2019 and most of them stated their satisfaction with the course as a whole. The module of “Gender Health” received the highest rating in all 3 years (4.8 in a 5 level scale). Students of both sexes declared great interest for gender issues that were referred to as relevant for their clinical practice and social commitment. Young people have a desire to learn and fertile minds. Persons in leadership positions have to be engaged to introduce a gender perspective in formal education. Competent and gender sensitive teachers are important as well. All staff and educators have to become aware of scientific relevance of gender differences to integrate such knowledge in every class and discipline.
A Conceptual Framework: Gender Medicine Versus Gender of Medicine
Gamze Aktuna, MD1
1Hacettepe Universitesi, Halk Sagligi Enstitüsü, Sihhiye, Cankaya, Ankara, Turkiye
In this study, the physicians’ opinions about “Gender of Medicine” and ”Gender Medicine” were evaluated from the answers of the survey question conducted for physicians and medical faculty students. Over the years, the effects of gender on medicine became more observable. It has been possible for women to be involved in the medical profession just in the last centuries. Like women, LGBT+ individuals also experience various problems in medical practice. On the other hand, in every step of medical practices Gender Medicine Vision’s significance is a crystal-clear fact. In this descriptive study, the universe is the physicians in Turkey; sample size is not calculated and purposive and snowball sampling methods were used. Through social media and communication tools, open access online questionnaire was shared and volunteers answered. This study conducted via the last question which is “In your opinion, what is the difference between ‘Gender of Medicine’ and ‘Gender Medicine.’” Of all, 908 people participated in the questionnaire, and the 2 conceptual frame, from the view of semantics, inference and differences were discussed with the coding of answers. As a result of coding, few main themes were revealed as Medicine is a little Man growing with patriarchy, doctor’s sexual identity versus Patients’. The main outcome point of this research is that physicians may differ in their perception of the gender of their own professional discipline and knowledge of “Gender Medicine” that may shed light on the future of medical practices.
Reflexivity on Gender Bias in Clinical Practice: A Tool for Medical Education Implemented in Switzerland
Joëlle Schwarz1, Elisa Geiser1, and Carole Clair1
1Gender and Medicine Unit, Department of Training, Research and Innovation, Center for Primary Care and Public Health (Unisanté), University of Lausanne, Switzerland
The Medical School of Lausanne, Switzerland, includes a gender medicine theoretical teaching that aims at “fixing the knowledge” on sex and/or gender differences in medicine. In 2019, a pilot project was introduced to integrate reflexivity on the influence of gender in clinical practice. The aim was to raise students’ awareness on gender bias and the potential effect on patients’ management. Reflexivity is the ability to critically reflect on and assess one’s own presuppositions and social experiences that shape one’s perceptions and actions. By reflecting on one’s gender perceptions, the hypothesis is that gender bias (gender stereotyping [treating men and women differently but not clinically relevant] or gender blindness [treating men and women equally when clinical differences exist]) may be reduced in clinical practice. During their internship, medical students discuss the case management an encountered clinical case with a chief resident, in small groups. A gender lens was introduced whereby students are asked to discuss the case considering potential gender bias, with support from a gendered medicine expert. In a second step, students are asked to fill an online reflexivity sheet, presenting their discussed clinical case and reflecting individually on potential gender bias and lessons learned. Their assessment is commented and validated by a gendered medicine expert. Topics discussed in groups and in reflexivity sheets can be grouped in different categories: the relevance and use of epidemiological data (gender difference in disease prevalence) for patient management; medical knowledge on evidence-based gender differences, by pathology; gender bias at different steps of a consultation: anamnesis (gender stereotypes assessing psychosocial background); clinical exams (influence of gender on clinician-patient interactions); differential diagnosis (driven by evidence-based or stereotyped-gender differences); treatment (gender differences in pain management). Reflexivity is a powerful tool to raise awareness on one’s own gender perceptions and potential bias that may impact clinical practice.
The Relevance of Hidden Curriculum in Health Professional Formation
Serenella Civitelli1, Ferretti Fabio1, Anna Coluccia1, Roberto Gusinu2, and the Gender Health and Medicine Group of the University Hospital of Siena3
1Department of Medical, Surgical and Neurological Sciences, University of Siena, Italy
2Santa Maria alle Scotte University Hospital of Siena, Siena, Italy
3University Hospital of Siena, Siena, Italy
Gender Medicine in the Programs of the Italian Public Institutions: The Role of FNOMCeO
Teresita Mazzei1, Filippo Anelli2, and Franco Lavalle3
1Florence Medical Council and FNOMCeO Gender Medicine Committee, Italy
2FNOMCeO President, Rome, Italy
3Bari Medical Council and FNOMCeO Gender Medicine Committee, Italy
Health and Gender Medicine: a Cutting-Edge Formative Experience Promoted by the University of Florence
Michela Cirillo, MSc1, Linda Vignozzi2, Domenico Prisco1, Teresita Mazzei3, and Cinzia Fatini, PhD1
1Department of Experimental and Clinical Medicine, University of Florence, Italy
2Department of Experimental Clinical and Biomedical Sciences “Mario Serio”, University of Florence, Italy
3Department of Health Sciences, University of Florence, Italy
Gender Medicine Multimedia Library: An Apulian Experimental Project
Anna Maria Moretti1, Orazio Valerio giannico2, and Annavita Perrone3
1GISeG and GVM Santa Maria Hospital, Bari, Italy
2Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
3Director of the Library and Institutional Communication Section of the Apulia Regional Council, Bari, Italy
The main objectives of this structure are:
develop knowledge of gender issues and undertake health education initiatives
promote scientific and research activities
carry out training programs for professional development and ongoing training
correctly inform citizenship of related issues through the use of correct information dissemination channels
construct a qualified gender point of view on the set of pathologies affecting women and men
highlight the centrality of the “gender approach” in medicine.
Reporting of Sex-Specific Outcomes in Trials on Cardiovascular Disease: Where Is the Progress?
M. M. Schreuder, BSc1, E. Boersma, PhD2, M. Kavousi, MD3, L. E. Visser, PhD3, J. W. Roos Hesselink, MD2, J. Versmissen, MD1, and J. E. Roeters van Lennep, MD1
1Department of Internal Medicine, Division Vascular Medicine, Erasmus MC, Rotterdam, the Netherlands
2Department of Cardiology, Erasmus MC, Rotterdam, the Netherlands
3Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands
Sex-specific analyses on efficacy and safety.
Role of Endometriosis in Defining Cardiovascular Risk in Women: An Interdisciplinary Approach of Gender Medicine
Michela Cirillo1, Maria E. Coccia2, Tiziana Ciarambino3, Francesca Rizzello2, and Cinzia Fatini1
1Department of Experimental and Clinical Medicine, University of Florence, Italy
2Center for Assisted Reproductive Technology, Division of Obstetrics and Gynecology, Careggi University Hospital, Florence, Italy
3Department of Internal Medicine, Hospital of Marcianise, ASL Caserta, Italy
Sex Differences in Prognostic Impacts of Serum Uric Acid Levels in Heart Failure—Insights From the CHART-2 Study
Takahide Fujihashi1, Yasuhiko Sakata1,2, Kotaro Nochioka1,2, Hajime Aoyanagi1, Shinsuke Yamanaka1, Hideka Hayashi1, Takashi Shiroto1, Koichiro Sugimura1, Jun Takahashi1, Satoshi Miyata3, and Hiroaki Shimokawa1,2,3
1Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
2Big Data Medicine Center, Tohoku University, Sendai, Japan
3Department of Evidence-Based Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
Prognostic impacts of serum uric acid levels (Cox proportional hazard model).
Daylight Saving Time and Circulatory Deaths: Are There Differences By Sex? Data From the Veneto Region of Italy
Roberto Manfredini1, Rosaria Cappadona1, Ruana Tiseo1, Fabio Fabbian1, Alfredo De Giorgi1, Giulia Capodaglio2, and Ugo Fedeli2
1Faculty of Medicine, Pharmacy and Prevention, University of Ferrara, Italy
2Epidemiological Department, Veneto region, Padua, Italy
Some years ago, a study by the Karolinska Institutet first reported an association between daylight saving time transitions and an increased frequency of acute myocardial infarction (AMI) after the spring shift, and the effect was somewhat more pronounced in women than in men. A recent meta-analysis by our group, based on the available further studies, did not find differences by sex. We aimed to verify this observation in Veneto, a large region of North-Eastern Italy, with a total population of about 4 900 000 inhabitants. We performed a retrospective analysis on the regional archive of mortality records, years 2000 to 2015. For death classification, we utilized the ICD-9 and ICD-10 categories used in standard reports of mortality statistics. The number of deaths observed in each of the 7 days after the spring and the autumn shift (posttransitional weeks) was compared with the mean number of deaths registered in the corresponding week-day of the 2 weeks before and the 2 weeks after the posttransitional week (reference period). During the study period, a total of 10 387 circulatory deaths were registered in the Spring and Autumn posttransitional weeks. No overall excess mortality was found in the posttransitional weeks with respect to the reference period in both Spring and Autumn. When analyzing the day-of-week pattern of mortality on total population, although a statistically significant excess of deaths (P = .011) was observed on Tuesday only after the Spring post-transitional week, no differences by subgroups by sex were found. This study provides further confirmation of the existence of a modest, but significant, excess of death on the first days of the week, only after the Spring shift but with no differences by sex subgroups. It is likely that phase advance, sleep deprivation, and disruption of circadian rhythms could play some role, but these mechanisms need further investigation.
Gender Differences of an Impact of Variant Mitochondrial Dehydrogenase Type2 Genotype in Patients With ST-Elevated Myocardial Infarction
Toshifumi Ishida1, Yuji Mizuno2, Yuichiro Arima1, Eisaku Harada2, Takayoshi Yamashita1, Koichiro Fujisue1, Seiji Takashio1, Eiichiro Yamamoto1, Satoru Suzuki1, Kenji Sakamoto1, Koichi Kaikita1, Kentaro Oniki3, Junji Saruwatari3, Seiji Hokimoto4, Hirofumi Yasue2, and Kenichi Tsujita1
1Department of Cardiovascular Medicine, Faculty of Life Science, Graduate School of Medical Sciences, Kumamoto University, Japan
2Division of Cardiovascular Medicine, Kumamoto Kinoh Hospital, Kumamoto Aging Research Institute, Japan
3Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Japan
4Division of Cardiovascular Medicine, Kumamoto City Ueki Hospital, Japan
Relationship Between Uric Acid, Renal Dysfunction, and Left Ventricular Remodeling in Hypertensive Women
Akiko Yoshikawa, MD1, Shuichi Hamasaki, MD2, Satoko Ojima, MD1, and Mitsuru Oishi, MD1
1Department of Cardiovascular Medicine and Hypertension, Graduate School of Medicine and Dental Sciences, Kagoshima University, Kagoshima, Japan
2Department of Cardiology, Kagoshima City Hospital, Kagoshima, Japan
Sex Differences and Real World Registry in a Cryptogenic Ischemic Stroke via Patent Foramen Ovale
Shigefumi Fukui1, Shunsuke Tatebe1, Ryo Konno1, Yosuke Terui1, Haruka Satoh1, Saori Yamamoto1, Kotaro Nochioka1, Kimio Satoh1, Koichiro Sugimura1, and Hiroaki Shimokawa1
1Department of Cardiovascular Medicine, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Japan
It was shown as robust evidence in a multicentre, randomized, open-label trial that device closure of a patent foramen ovale (PFO) significantly reduces recurrent ischemic strokes compared to medical therapy alone. Therefore, it is expected that the specified PFO occluder will be soon reimbursed also in Japan following the United States. In addition, a recent meta-analysis of those randomised controlled trials revealed that device closure was more beneficial in men, implying the sex differences in a cryptogenic ischemic stroke via PFO. However, the Risk of Paradoxical Embolism (RoPE) score, which currently guides the decision of which patients benefit from PFO closure, includes only age, hypertension, diabetes, a history of stroke, smoking, and type of stroke, but not sex. On the other hand, we have shown in the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 Study that 19.4% of the patients with stage C/D chronic heart failure complicated stroke at baseline. However, the systematic collaboration by stroke specialists and cardiologists has been absent in our hospital, in evaluating the etiology, demographics, and treatment options of stroke associated with heart disease. Recently, we have established the Brain-Heart Team with the stroke specialists in our hospital. Now, we are planning to expand our Brain-Heart Team to the high volume centres of strokes in the whole Tohoku District, to establish multicenter, real world registry of a cryptogenic ischemic stroke. In this session, we would like to discuss the impact of the sex differences in a cryptogenic ischemic stroke and PFO closure by introducing our real world registry.
Capillaroscopic Alterations in the Phenomenon of Raynaud in Men and Women
Sirufo MM, De Martinis M, Ginaldi L1
1Department of Life, Health and Environmental Sciences, University of L’Aquila; Allergy and Clinical Immunology Unit, AUSL 04 Teramo, Italy
Raynaud phenomenon (RP) is a pathological condition of vasospasm in response to cold or emotional stimulation, affecting the extremities, mainly the fingers. Clinically, it is characterized by 3 successive phases: the white (ischemic) phase, the cyanotic (deoxygenation) phase, and the red (reperfusion) phase. Raynaud phenomenon is often secondary to autoimmune diseases, exhibiting typical microvascular alterations. In the absence of diseases able to cause it, RP is called primitive (PRP). Primitive Raynaud phenomenon is present in 5% to 20% of women and 4% to 14% of men, and due to its clear prevalence in women it is traditionally considered a gender pathology. The naifold videocapillaroscopy (NVC) is an in vivo noninvasive instrumental technique easily repeatable, which allows to study in real time the morphological and functional characteristics of microcirculation. The purpose of our study is to verify whether there are gender specific capillaroscopic alterations in patients having PRP. We evaluated 434 subjects affected by PRP, observed in the last year at the outpatient NVC service of our Allergology and Clinical Immunology division. Three hundred-thirty were females (mean age 45 years ± 6,1 DS) and 96 were males (48 ± 4,3 years DS). Patients affected by autoimmune pathologies, as well as smokers or those with a history of exposure to ionizing radiation or chemicals capable of inducing a secondary RP, were excluded from the study. No significant gender differences were found in the NVC patterns observed: 148 (43.7%) females and 46 (47.91%) males had a normal NVC pattern (high skin transparency, absence of morphological abnormalities, uniformity of diameter and distribution of the capillaries, hairpin capillaries arranged in a parallel fashion to each other), whereas 190 (56.21%) females and 50 (52.08%) males exhibited an abnormal nonspecific NVC pattern (microvascular abnormalities without findings suggestive of scleroderma, and characterized by lack of morphological homogeneity of capillaries, presence of tortuous capillaries, ectasia of the efferent tract of the loops). The PRP, even though it is a patology that affects the females more than men, doesn’t exhibit gender-related differences in the characteristics and distribution of capillaroscopic patterns.
Human Induced Pluripotent Stem Cells as Alternatives to Animal Models For Studying Sex Differences
Judith Lechner1, Georg Kern1, Elisabeth Feifel1, Anja Wilmes2, Paul Jennings2, and Gerhard Gstraunthaler1
1Div. Physiology, Medical University of Innsbruck, Innsbruck, Austria
2Molecular and Computational Toxicology, Faculty of Science, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
Sex and sex hormones affect all the cells in the body resulting in different susceptibility to cellular stressors and disease development. Researchers engaged in basic research and preclinical studies are increasingly challenged by regulatory bodies, major funding agencies, and highly ranked journals to also include sex as a biological variable into their study designs. At present, these requirements are mostly met—if at all—through animal experimentation. Besides concerns about how well the human system is represented by animals, there is also an ethical problem. This is addressed by regulations to promote the principles of refinement, reduction, and replacement (3Rs) of animal experimentations (eg, Directive 2010/63/EU). Great efforts are addressed worldwide to the development of alternative methods to animal testing. However, in vitro models for researching and testing of sex differences are not in the focus. Human induced pluripotent stem cells (hiPSC) generated from human somatic cells present a new trajectory to develop novel and ethically acceptable in vitro model systems for studying sex differences. The cells can be differentiated into any cell type of the body. Cell culture conditions during reprogramming, stem cell propagation and differentiation need to be adapted in order to establish valid models for researching sex as a biological variable in vitro using hiPSC. We have developed a differentiation protocol for renal proximal tubular like cells from hiPSC. Currently, we work on refining the model to allow studying sex differences. For this purpose, hiPSCs derived from males and females are treated with different combinations of sex hormones during the differentiation process. Human induced pluripotent stem cells-derived models are expected to provide improved preclinical data avoiding problems arising from species differences between animals and humans and allowing to account for the genetic variability among the human population and sex differences.
“Effect of Gender on Hypoglycemia’s Risk and Worse Clinical Outcome Among Diabetic Patients Admitted to Internal Medicine Departments.”
Elena Barbagelata1, FlavioTangianu2, Imma Ambrosino3, Tiziana Ciarambino4, Cecila Politi5, and “F.A.D.O.I. Giovani Group”
1UOC Medicina Interna, ASL 4 Chiavarese, Genova, Italy
2UOC Medicina Interna, ASST Settelaghi, Ospedale Luini Confalonieri, Luino, Italy
3Geriatria, ASL Ba DSS 13, Bari, Italy
4UOC Medicina Interna, ASL Caserta, Ospedale Clinicizzato di Marcianise, Caserta, Italy
5UOC Medicina Interna, P.O.“F. Veneziale”, Isernia, Italy
Sex and Gender in Complex Systems
Peter Klimek1,2
1Section for Science of Complex Systems, CeMSIIS, Medical University of Vienna, Vienna, Austria
2Complexity Science Hub Vienna, Vienna, Austria
With the accumulation of large amounts of data, a new predictive, personalized and data-driven approach to medicine has emerged. It has become clear that most chronic disorders emerge from concerted interactions of multiple genetic, metabolic, social, or lifestyle-related risk factors. In this talk, we will demonstrate how the theory of Complex Systems offers a novel methodological toolkit to understand how these different factors and their interactions impact patient health in a sex- and gender-specific way. Heterogeneous health-related data sets can often be quantified by means of networks that record individual risk factors (from molecular to societal levels) and their interactions in different diseases. For instance, we will show how males and female build their social networks in different ways and how the structure of these networks determines their susceptibility to disorders such as obesity or depression. Using administrative data from an entire country over several years, we find that males and females show highly distinctive patterns in the way in which their health typically changes over the course of their life which allows the identification of “typical male or female”-associated longitudinal disease trajectories. Furthermore, we show how network approaches can be used to gain insight into sex-specific adverse drug events and the extend to which males and females differ in their health-care utilization. In conclusion, sex and gender shows highly complex interactions with other disease risk factors across multiple domains, ranging from the very small (molecular level) to the very big (institutional configuration of the healthcare system). Novel methodological approaches are needed for a more stringent consideration of gender differences in (chronic) diseases and to contribute to better targeted prevention, more patient-oriented and more efficient therapeutic approaches.
Sex and Gender Differences in Antihyperglycemic Treatment
Alexandra Kautzky-Willer1,2
1Clinical Division of Endocrinology and Metabolism, Gender Medicine Unit, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
2Gender Medicine Institute, Gars am Kamp, Austria
Type 2 diabetes mellitus and associated complications are an increasing problem worldwide in both sexes and go along with reduced quality of life and life expectancy. Therefore, optimal therapy is essential and should consider biological factors including age and sex as well as psychosocial factors and gender issues. However up to now sex and gender have no impact in most clinical guidelines and decisions. Nevertheless side effects of drugs as well as choices and preferences of and adherence to therapies differ between men and women. Gender sensitive programs to promote healthy lifestyle should be accompanied by personalized pharmacological therapy considering complications, sexual function, individual expectations and fears, and social environment. Antihyperglycemic drugs differ in regard to their risk of cardiorenal complications, hypoglycemia, effects on weight and possibly associations to risk of fractures and certain cancers. Metformin is the first choice for both men and women and appears to be particularly effective in women with previous gestational diabetes and obese men and women. Overall women have higher risk of hypoglycemia on insulin therapy. However, normal weight appears to relate to higher risk of hypoglycemia in both sexes on basal insulin therapies. Due to higher risk of stigmatization of obese women, weight loss is even more important for women, favouring SGLT2 inhibitors or GLP-1 analogues; thus GLP-1 analogues were more often prescribed to obese women than men. SGLT2 inhibitors reduce cardiovascular events and hospitalizations due to heart failure and progression of renal disease in both sexes. However they are associated with a higher risk of urogenital infections and ketoacidosis in women compared to men. Pioglitazone associates with increased risk of bone fractures, particularly in postmenopausal women. During pregnancy, insulin is still the first choice therapy. Overall women seem to have lower success of antihyperglycemic therapies despite having more from drug side effects. Most clinical studies still include more men than women and do not stratify data analysis by sex. Taking into account sex and gender in diabetes management could contribute to more personalized better care in the future.
Sex Differences in the Cardiovascular Consequences of Type 2 Diabetes
Judith G. Regensteiner, PhD1
1Judith and Joseph Wagner Chair in Women’s Health Research, Center for Women’s Health Research, Office of Women in Medicine and Science, Aurora, CO, USA
By 2017 estimates, diabetes mellitus affects 425 million people—approximately 90% to 95% have type 2 diabetes and the number is rising. The cardiovascular (CV) consequences of type 2 diabetes are overall worse in women than men across the life span. These disparities include: (1) increased CV mortality, (2) increased CV morbidity, and (3) lower rates of CV risk factor control. These sex differences appear partly related to biological factors, though there are also disparities in provider level prescribing patterns and patient-level adherence patterns. This talk will take a life span approach to describing these sex differences in CV outcomes, starting with children exposed to gestational diabetes in utero, and including those diagnosed with type 2 diabetes during youth, in midlife, and in later life, respectively. The major goal of this talk is to highlight research gaps that must be addressed to better understand how to potentially redress these sex differences. I also will summarize clinical opportunities to improve these disparities.
Stroke and Dementia (Invited Speech)
Mia von Euler, MD, PhD1, Zupanic E1, Garcia-Ptacek S Kåreholt I1, Religa D1, Kramberger MG1, Norrving B1, Winblad B1, Eriksdotter M1, and Von Euler M1
1Neurology Karolinska Institutet, Stockholm, Sweden
Stroke and dementia are common causes of death and acquired functional disability for both men and women. For ischemic stroke and intracerebral hemorrhages, the incidence is higher in men up to the age of 85 years when it becomes more common in women. For subarachnoidal bleeding the incidence is higher in women. Stroke can lead to cognitive impairment and dementia itself is associated with a 3 to 7 fold higher risk of stroke. Although the risk factors for stroke and dementia are similar in men and women, the impact may vary. Effect of acute reperfusion treatment and pharmacological prevention seems similar between men and women but access to treatment has shown varied results. In a registry-based longitudinal cohort study on differences between men and women with ischemic stroke with and without prestroke dementia, we compared reperfusion treatment and outcomes. Using data from the Swedish Dementia and Stroke Registries 2010 to 2014, we identified patients with dementia and acute ischemic stroke (765 women, 592 men) and compared them with matched nondementia subjects (3838 women, 2917 men) regarding reperfusion treatment and outcomes at 3 months (death, residency and modified Rankin Scale score [mRS]). Of those surviving hospitalization, more women than men with dementia had a poor outcome, had institutional care or home help (P < .001). When adjusting for age, dementia, and stroke severity (determined by level of consciousness) odds ratio was higher for women for a poor outcome, mRS 3-6, at 3 months (odds ratio [OR]: 1.60, 95% confidence interval [CI]: 1.42-1.81), lower for death 1 year after stroke (OR: 0.876, 95% CI: 0.78-0.98), and higher for higher level of assisted living (OR: 1.30, 95% CI: 1.15-1.47). For death 1 year after stroke, there was no difference between men and women if dementia was not included in the analysis while worse living conditions and poor functional level remained in women.
Carotid Surgery in Men and Women
Rebecka Hultgren1
1Patientområde Kärlsjukdomar, Fd. Kärlkirurgiska Kliniken, Karolinska Universitetssjukhuset, Stockholm Aneurysm Research Group, STAR, MMK, Karolinska Institutet, Stockholm, Sverige
Strong evidence based on multicenter RCTs support the benefit of vascular interventions in selected patients with significant stenosis of their internal carotid artery in order to decrease the risk of a subsequent fatal neurological event. The indication of surgical treatment should be correlated to the degree of stenosis, which have rendered debate, but consensus is that intervention should not be performed in men or women below 50%. However, as for all surgical procedures other factors strongly contribute in the preoperative work-up evaluation, and influences eligibility, such as age, ongoing medication, morphology of arteries. The selection for patients actually subjected to be evaluated for a vascular intervention does influence the possibility to in-depth analyze relevant sex-and gender differences. The presentation will cover the most recent reported findings in the field in vascular treatment for carotid stenosis, endovascular and open, and also present contemporary outcome data.
Arrhythmias in Women and Men
Karin Schenck-Gustafsson1
1Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
Recent research has revealed sex-difference in the appearance of rhythm disturbances as well as differences in the pathophysiology, symptoms, and treatment. Atrial fibrillation especially in elderly women, increases the risk of stroke as well as death and cardiovascular outcomes more in women than in men. Women have also been undertreated both with invasive treatment like ablation as well as with drug treatment. Atrial fibrillation is the most common sustained arrhythmia in adults and carries a risk of significant morbidity and mortality, especially an increased risk of stroke. Many of these patients experience palpitations, however not all of them. Also other treatable arrhythmias like supraventricular tachycardias for example atrio-nodal reentry tachycardia might induce palpitations and are important to detect as well as malignant ventricular arrhythmias. Independant of etiology, heart palpitations can cause anxiety, worry, depression, reduced quality of life, and more so in women than in men. Atrial fibrillation is uncommon below the age of 50 years but the prevalence increases by age and in ages older than 85 years it could be as high as 25% to 30%. It is well-known that women have more symptoms than men of palpitations and also of anxiety disorders and poorer quality of life. Studies also indicate sex-difference in adverse drug reactions like antiarrhythmic drugs, for example, women being more sensitive to long QT prolonging drugs. The aim of the on-going Swedish study Red Heart is to evaluate if instant analysis and feed back of underlying heart rhythm during palpitations reduces symptoms, anxiety, depression, and increases the quality of life. We informed about the study in connection with our yearly women’s heart campaign in 20 cities. Recruitment also took place via social websites. For the first time we used a new form of eAuthentication via BankID when getting the informed consent of the study from the participants. During the first weeks in May 2018, totally, 2387 women reported interest to participate. Of these, the first 1132 were invited and finally 913 were included. The women who completed the study were between 21 and 88 years. Coala Heart Monitor was used by the participants and thumb and chest electroencephalography were recorded twice a day and at symptoms during 60 days. The system uses a well-validated algorithm to analyze heart rhythm and is connected to the user’s smartphone and provides immediate response to the user. Questionnaires addressing symptoms like anxiety, depression, HRQOL were analyzed before and after the study period. In the great majority of episodes causing symptomatic palpitation in women, the underlying arrhythmia was benign. However, in 5% previously undiagnosed atrial fibrillation or supraventricular tachycardia were found. These women were referred to a doctor. Among the participating women, 75% had palpitations more than once a week, 66% had contacted a doctor because of the symptoms. Notably 40% of the women experienced that they were not taken seriously by the health-care system when they seek help. Much more information will come out from our study and in the follow-up we will also include men. In total over 280 000 registrations were monitored making this study probably the largest arrhythmia study in women in the world.
Sexual Function, Gender Role, and Sexual Preference in Females with Classical Versus Nonclassical Congenital Adrenal Hyperplasia
Marie-Helene Schernthaner-Reiter1#, Sabina Baumgartner-Parzer1#, Hans Christian Egarter2, Kathrin Kirchheiner3, Michael Krebs1, Alexandra Kautzky-Willer1, Anton Luger1, Michaela Bayerle-Eder1
1Clin. Div. of Endocrinology and Metabolism, Dept. Internal Medicine III, Medical University of Vienna, Vienna, Austria
2Clin. Div. of Gynecologic Endocrinology and Reproductive Medicine, Dept. of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria
3Dept. of Radiotherapy, Medical University of Vienna, Vienna, Austria
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is an autosomal recessive disease caused by mutations in the CYP21A2-gene. The severity of the mutations is mirrored by a wide spectrum of different biochemical (hyperandrogenism, hypocortisolism) and phenotypic (virilization, hirsutism) symptoms. The present cross-sectional cohort analysis aimed to evaluate sexual function, gender identification, and partner preference in classic (C-CAH) versus nonclassic CAH (NC-CAH). Depending on their pheno- and genotype (determined by Sanger sequencing and MLPA), 35 female patients with CAH were divided into 2 groups: classic CAH (severe deficiency, salt-wasting or simple virilizing, n = 17) and NC-CAH (n = 18). Sexual function and sexual distress, gender role and sexual satisfaction were assessed using established questionnaires (FSFI, FSDS, BSRI) and visual analogue scales. Phenotype (as defined by signs of hyperandrogenism) was assessed clinically (Ferriman-Gallwey score) as well as with the ovulatory function index. Moreover, sexual function was separately analyzed in the context of clinical signs of androgenization in women with (n = 13) and without acne (n = 22). Women with NC-CAH had significantly lower orgasm scores, a trend toward lower sexual function with higher sexual distress and biochemical evidence of hyperandrogenism (higher DHEA-S, lower SHBG). Presence of acne in all patients was related to lower sexual function and higher sexual distress. These findings stress the importance of early diagnosis and therapy initiation particularly in patients with NC-CAH.
Cardiometabolic Effects of Cross Sex Hormone Therapy in Transgender Patients
Lana Kosi Trebotic, MD1, Carola Deischinger, MD1, Anita Thomas, BSc1, Ivica Just-Kukurova, PhD2, Siegfried Trattnig, MD2, Ulrike Kaufmann, MD3, and Alexandra Kautzky-Willer, MD1
1Division of Endocrinology and Metabolism, Department of Internal Medicine III, Gender Medicine Unit, Medical University of Vienna, Vienna, Austria
2Centre of Excellence, High-Field MR, Department of Radiodiagnostics, Medical University of Vienna, Vienna, Austria
3Department for Obstetrics and Gynaecology, Medical University of Vienna, Vienna Austria
3Siemens AG Healthcare, Vienna, Austria
The Contribution of the Italian National Institute of Health on Transgender Health
Marina Pierdominici1, Matteo Marconi1, Maria Luisa Dupuis1, Luciana Giordani1, Carmela Santangelo1, Angela Ruocco2, Maria Teresa Pagano1, Paola Matarrese1, and Walter Malorni1, Alessandra Carè1
1Center for Gender Specific Medicine, Istituto Superiore di Sanità, Rome, Italy
2National Center for Rare Diseases, Istituto Superiore di Sanità, Rome, Italy
Email marina.pierdominici@iss.it
Transgender people are a medically underserved population in both primary and specialist care settings. Moreover, despite the growing interest of the scientific community in transgender health, this subject remains understudied. Unavailability of realistic estimates of transgender prevalence, limited data on general health status and the long-term effects of gender affirming hormone treatment and surgical interventions are among the main problems to be solved in terms of transgender health research. Nowadays, in Italy, as across much of the world, we do not know exactly how many transgender people there are, their health status and the services they need. This hinders a suitable health planning by policy makers and an appropriate activity by the Italian National Institute of Health (NIH). Additionally, given the probable size of transgender population (at least 500 000 people) and the large range of health-care needs, it is crucial that health-care providers could be trained in transgender health care. It is urgently warranted to fill all these gaps to provide an appropriate evidence-based prevention and care for people. To this aim, the Center of Gender Specific Medicine at the Italian NIH is creating a close network of collaborations among public health institutes, policy makers, health-care providers, and transgender communities. Different projects including research, medical training with specific courses, and communication campaigns directed to citizens have been performed and launched. Two studies aimed at evaluating the size of transgender people and their health status, respectively, are undergoing. We consider of great relevance the part of our project dealing with communication/information of the citizens with the creation of the first institutional web site on legal and health information dedicated to the transgender population. These activities could represent a first step toward a more inclusive health policy aimed at improving the interplay between transgender people and the health-care system.
Making Sense of Sex Differences in the Brain; a Whole-Body Approach
Geert J. de Vries1
1Neuroscience Institute and Department of Biology, Georgia State University, Atlanta, GA 30303, USA
This presentation will play with three interrelated ideas. First, there are sex differences in all organs in the body; the brain is no exception. Second, sex differences in the body forge sex differences in the brain. Third, sex differences in the brain serve 2 roles: to prevent as well as to cause sex differences in behavior and physiology. The consequences of these ideas for the role of the brain in health and disease will be discussed using sex differences in vasopressin function as an example.
Sex Differences in The Molecular Regulation of Memory: Implications for the Development of Sex-Specific Treatments for Memory Dysfunction
Karyn Morrione Frick, PhD1
1Department of Psychology, University of Wisconsin-Milwaukee, WI, USA
Estrogens play a key role in the etiology and symptomatology of psychiatric illnesses (eg, depression, anxiety) and neurodegenerative diseases (eg, Alzheimer disease). Thus, understanding exactly how estrogens regulate cognitive and emotional processes is essential to developing the next generation of therapeutics to treat conditions such as these for which women are at greater risk. However, estrogens modulate cognitive and brain function not only in females but also in males, so a thorough understanding of how estrogens mediate cognition requires knowledge of the mechanisms through which it acts in both sexes. Although we have learned much in recent years about the molecular mechanisms through which estradiol mediates memory consolidation in female rodents, considerably less is known about estrogenic regulation of memory processes in males. This talk will first summarize my laboratory’s work in female mice identifying molecular mechanisms in the dorsal hippocampus necessary for estradiol to enhance memory consolidation and promote hippocampal and neocortical dendritic spine density. Next, our recent work examining how estradiol regulates memory consolidation in male mice will be described, including data suggesting significant sex differences in the cell-signaling mechanisms underlying estradiol-induced memory enhancement. Finally, the implications of these findings for developing sex-specific treatments for memory dysfunction will be considered.
Women’s Brain Health and Aging
Nicole J. Gervais1 and Gillian Einstein1,2,3
1Department of Psychology, University of Toronto, Toronto, Ontario, Canada
2Rotman Research Institute, Toronto, Ontario, Canada
3Tema Genus, Linköping University, Linköping, Sweden
Growing evidence implicates ovarian hormones in maintaining brain health in women as they age. Following menopause, 17β-estradiol (E2) and progesterone levels decline, and this loss has an impact on women’s cognition, and brain structure. Such effects are exacerbated following oophorectomy prior to spontaneous menopause, which is associated with accelerated cognitive decline and a 2-fold higher risk of dementia. Reduced sleep quality and increased sleep-disordered breathing is also associated with oophorectomy, which can worsen the cognitive effects of early hormone deprivation. Estradiol-based hormone therapy maintains cognitive function and in some instances, sleep quality in menopausal women. However, few studies have investigated benefits in women with an oophorectomy. In this presentation, we present our recent work on cognition, brain structure, and sleep in middle-aged women with a BSO. Forty-six BRCA 1/2 mutation carriers with a BSO prior to the age of 51 and 25 age-matched premenopausal controls were recruited. Participants with a BSO were stratified based on whether they were currently taking estradiol therapy (BSO+E2; n = 22) or had no history of hormone therapy use (BSO; n = 24). Participants completed a neuropsychological test battery, underwent a high-resolution T2-weighted structural magnetic resonance imaging scan (3T Siemens Prisma), and an at-home polysomnography recording for sleep staging and sleep-disordered breathing analysis. Results revealed that BSO is associated with lower memory performance, reduced hippocampal volume and increased sleep fragmentation, but only among those not taking E2. These findings demonstrate adverse effects of early hormone loss on sleep and brain health, which is prevented by E2 use. The importance of these results to understanding the role of ovarian hormones in promoting sleep, memory, and brain health as women age will be discussed.
Cardiac Symptoms and Menstruation: A Risky period? The Cycle Study I
MM Schreuder1, M Sunamura2, A Maassen van den Brink3, M Kavousi4, E Boersma4, and JE Roeters van Lennep1
1Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands
2Department of Cardiology, Franciscus Gasthuis, Rotterdam, the Netherlands
3Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus Medical Centre, Rotterdam, the Netherlands
4Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands
Percent of Women reporting palpitations or (atypical) Angina Pectoris.
Gender Differences in The Risk Factors Associated With Atherosclerosis By Carotid Intima-Media Thickness, Plaque Score And Pulse Wave Velocity
Satoko Ojima1, Takuro Kubozono1, Shin Kawasoe1, Takeko Kawabata1, Masaaki, Miyata1, Hironori Miyahara2, Shigeho Maenohara2, and Mitsuru Ohishi1
1Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
2JA Kagoshima Kouseiren Medical Health Care Center, Kagoshima, Japan
Sex Differences in Patients with Non-ST-Elevation Myocardial Infarction in Japan: A Report from the Miyagi AMI Registry
Koichi Sato, MD1, Jun Takahashi, MD1, Kiyotaka Hao, MD1, Yasuhiko Sakata, MD1, and Hiroaki Shimokawa, MD1
1Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
Pulmonary Embolism and Gender: An Observational Study
Tiziana Ciarambino1, Ombretta Para2, Cecilia Politi3, Orazio Giannico4, and Anna Maria Moretti4
1Department of Internal Medicine, Hospital of Marcianise, ASL Caserta, Italy
2Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
3Department of Internal Medicine, Hospital of Isernia, F. Veneziale, ASREM, Italy
4President of GISeG, Italian Group of Health and Gender
European Physicians’ Awareness of the Difference Between Sex and Gender: the Imagine Survey
Valeria Raparelli, MD, PhD1,2, Marco Proietti, MD3,4, Ewelina Biskup, MD5,6, and Alberto Maria Marra, MD7,8
1
Department of Experimental Medicine, Sapienza University of Rome, Italy
2Center for Outcomes Research and Evaluation, Research Institute, McGill University Health Centre, Montreal, Quebec, Canada
3IRCCS - Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy
4Department of Internal Medicine and Medical Specialties, Sapienza-University of Rome, Rome, Italy
5Shanghai University of Medicine and Health Sciences | Shanghai, PRC
6Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Basel, Switzerland
7IRCCS SDN Research Institute, Naples, Italy
8Centre for Pulmonary Hypertension, Thoraxclinic at Heidelberg University Hospital, Heidelberg, Germany
Sex and gender shape health status through dynamic interaction, therefore the integration of sex and gender in research and clinical approach is mandatory and it drives toward a personalized medicine and equality in health care. On this basis, the European Federation of Internal Medicine built up the Internal Medicine and Assessment of Gender differences in Europe (IMAGINE) working group. The first phase of the IMAGINE framework was conceived to assess the awareness of the Internal Medicine community on sex and gender dimension in approaching clinical and research questions. Therefore, among December 2017 and March 2018, an online short survey was run among European internists clinicians. Briefly, the first 3 questions aim to assess the knowledge on terminology (sex vs gender) and the awareness of factors specifically related or not to sex and gender dimensions. The fourth question explores the perceived knowledge on sex and gender differences in major diseases within the field of internal medicine. The fifth and sixth questions point out if physicians checked clinical guidelines for the presence of recommendations specifically tailored according to sex and whether they are aware of the low rate of women’s enrolment in clinical trials. Finally, the seventh question is targeted to the identification the high-priority topics for internal medicine community in terms of knowledge in a sex- and gender-perspective. Preliminary results of IMAGINE survey (>1000 participants) will be presented.
Gender Score Construction Based on Retrospective Data Analysis in the Berlin Aging Study II (BASE-II)
A. Tauseef Nauman, MPH1,2,3, Nicholas Alexander, MPH, PD1,2,3, Friederike Kendel5, Johanna Drewelies7, Gert G. Wagner8, Denis Gerstorf.PD7, Ilja Demuth4,9, Louise Pilote6,3, Vera Regitz-Zagrosek1,2,3
1Institute for Gender in Medicine, Charité—Universitätsmedizin Berlin, Germany
2CCR Berlin, Germany
3DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany
4Medical Clinic for Endocrinology, Biology of Aging group, Charité—Universitätsmedizin Berlin, Germany
5Institute of Medical Psychology, Charité—Universitätsmedizin Berlin, Germany
6Department of Medicine, McGill University, Montreal Canada
7Dept. of Psychology, Humboldt-Universität zu Berlin, Germany
8SocioEconomic Panel at the German Institute for Economic Research (DIW), Germany
9Berlin-Brandenburg Center for Regenerative Medicine (BCRT), Charité University Medicine Berlin, Germany
Sex and gender are distinct constructs that require complex measurement. As intercultural differences may be an important factor in capturing the construct “gender,” we aimed to re-construct a gender score (GS) comparable to the index published by L Pilote (APS 2015) in a retrospective analysis of the Berlin Aging Study BASE-II in 2009-2014 for 1869 participants aged above 60 years. From the psychosocial and gender-related (identity, roles, relations, institutionalized gender) variables we selected 13 with focused on data available in more than 65% of cases. Our approach was divided in 3 steps: GS development, GS calculation, and GS application. For step 1 all 1869 cases were used and 9 out of 13 selected variables were identified by PCA and LR that contributed to a GS that separated women and men. A correlation analysis of 13 selected variables was conducted and in any significantly correlated pair of variables, one of the variables was removed. However, we retained all the 13 variables. These 13 variables were loaded onto 6 components in PCA analysis. Any variable, loading equally high on 2 components was removed at this step. The 13 identified variables from the PCA were used to perform the logistic regression analysis. Nonsignificant variables were removed one by one in a descending order of their P value (.05). The 9 most significant variables for the sex as an outcome variable were extracted. The coefficients of the final logistic regression were used to calculate the GS (0-100). The procedure enabled us to construct a gender score in a retrospective manner from available study variables. Gender score distribution was significantly different between women and men. In future analyses, we will examine the validity of the score by linking differences in gender with psychosocial, medical, and cognitive data and by comparison with a prospectively assessed gender score.
How to Measure Gender? Developing a Context-Specific Gender Index to Improve Health Research in Switzerland
Joana Le Boudec1, Joëlle Schwarz1, and Carole Clair1
1Department of Training, Gender and Medicine Unit, Research and Innovation, Center for Primary Care and Public Health (Unisanté), University of Lausanne, Switzerland
The Going-FWD (Gender Outcomes International Group: to Further Well-being Development) Project"
Valeria Raparelli, MD, PhD, Maria Trinidad Herrero, Elizabeth O. Johnson, Alexandra Kautzky-Willer, Karolina Kublickiene, Colleen M. Norris, and Louise Pilote
In summary: Personalized medicine approach is increasingly appreciated in clinical research, where the need for analysis of already collected data requires a proper definition of variables and measures included. Therefore, when including gender, the existing lack of a standardized gender measure poses challenges which might be mitigated via application of a systematic multistep approach currently suggested and currently tested by our multidisciplinary team. Understanding of how sex and gender-related factors impact NCDs will help to improve clinical- and patient-related outcomes with potential to tailor future interventions with a sex- and gender-specific approach.
Described Differences Between Men and Women Regarding Antiretroviral Drugs for Treatment of HIV
von Euler M1,3, Jaran Eriksen1, Karlsson-Lind L4 and Schenck-Gustafsson K3,5
1Department of Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden
2Department of Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Stockholm, Sweden
3Department of Medicine, Centre for Gender Medicine, Karolinska Institutet
4Department of Digital Health and Care, The Health and Medical Care Administration, Region Stockholm, Stockholm, Sweden
5Department of Medicine, Cardiac Unit, Karolinska University Hospital, Stockholm, Sweden
In the data base Janusmed Sex and Gender (janusinfo.se/genus/in-english) evidence-based medical knowledge on sex and gender aspects on drug treatment has been gathered into a searchable tool. In 25% of the included medical drugs included in the data base, information on sex and/or gender differences are lacking. Antiretroviral drugs for treatment of HIV is one of the therapeutic areas covered. These drugs are often used over a long period of time and in different phases of the reproductive life of both men and women. We hypothesized that sex/gender differences were studied and reported more compared to other drug classes. The following search string was used in PubMed: (“Sex Factors”[Mesh] OR “Sex Characteristics”[Mesh] OR sex[Title] OR gender[Title] OR “sex difference*” OR “gender difference*” OR “based on sex” OR ”based on gender”) AND «antiretroviral substance» In all, 18 drugs were included. No information on sex or gender differences were found for one (5.5%) of the substances (cobicistat). For 13/18 (72%) of the included drugs the identified literature indicated no clinically relevant sex differences while in 4 (22.5%) sex differences were identified. The most important being nevirapine where the increased risk of hepatotoxicity and skin reactions need to be considered particularly in women/girl as the risk is higher in female compared to male patients. For several of the nucleoside analogues the risk of adverse reactions such as lactic acidosis and severe hepatomegaly with steatosis are more common in women. More data on sex differences are published regarding antiretroviral drugs for treatment of HIV. The difference mainly concerns an increased risk of some specific adverse reactions more common in women.
Utilization of Antiepileptic Drugs in Men and Women with Stroke
Linnéa Karlsson Lind1 and Mia von Euler2
1Department of Digital Health and Care, Health and Medical Care Administration, Region Stockholm, Sweden
2Department of Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden
Stroke is a common cause of epileptic seizures in adults. However, treatment of patients with poststroke epilepsy is challenging since high-level evidence-based guidelines are lacking. Whether or not antiepileptic drugs (AEDs) should be used is therefore controversial. The aim of the present study was to investigate which AEDs are used in men and women with stroke in a nationwide population. All adults (
The Diagnosis of Osteoporosis in Statin-Treated Women and Men is Dose-Dependent
Leutner Michael1, Matzhold Caspar2,3, Bellach Luise1, Deischinger Carola1, Harreiter Jürgen1, Thurner Stefan2,3,4,5, Klimek Peter2,3, and Kautzky-Willer Alexandra1
1Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Unit of Gender Medicine, Medical University of Vienna, Vienna, Austria
2Section for Science of Complex Systems, CeMSIIS, Medical University of Vienna, Spitalgasse, Austria
3Complexity Science Hub Vienna, Josefstädter Straße 39, 1080 Vienna, Austria
4Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM 85701, USA
5IIASA, Schlossplatz 1, A-2361 Laxenburg, Austria
Differences in Discontinuation of Statin Treatment in Women and Men With Advanced Cancer Disease
Helena Bergström1, Elsa Brånvall2,3, Maria Helde-Frankling1,2, and Linda Björkhem-Bergman1,2
1Department of Neurobiology, Care Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Blickagången, Huddinge, Sweden
2ASIH Stockholm Södra, Palliative Home Care and Hospice Ward, Bergtallsvägen, Älvsjö, Sweden
3Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
Statins are often discontinued in patients with advanced cancer since the net effect of treatment is considered negative. However, guidelines concerning discontinuation of statin treatment are lacking. The aim of this study was to investigate any differences in time of discontinuation of statin treatment between men and women with advanced cancer disease. Medical records from 195 deceased patients with palliative cancer from a previous study cohort were reviewed. Patients treated with statins 2 years before death were identified as “statin users.” The time of discontinuation of statin therapy was identified and correlated to time of death. Only patients with incurable cancer disease at time of statin discontinuation were included in the analysis. Fifty-four patients were identified as statin users, 29 women and 25 men. The average time span between discontinuation of statin treatment and time of death was significantly longer in women than in men, 10 months compared to 4 months (P < .01), with a range of 1 to 24 months among women and 1 to 12 months for men. All patients died due to cancer disease. More men than women had a history of stroke or cardiac infarction (P = .02). There were no differences in age, socioeconomic factors, or survival time from study inclusion between men and women. There was no difference in self-assessed quality of life (QoL) between statin users who had discontinued statin treatment and those who are still on treatment. Men generally assessed their QoL lower than women in this study (P = 0.03). Statin treatment was discontinued earlier in women than in men with advanced cancer disease, and discontinuation was not associated with any negative effects. However, the results need to be confirmed in larger studies before any firm conclusions can be drawn. Future studies will elucidate if early statin discontinuation is safe in both men and women with advanced cancer disease.
Gender Violence: A Study of Awareness Implementation at the University Hospital of Ferrara, Italy
Rosaria Cappadona1, Roberta Capucci1, Camilla Paganelli1, Monica Rizzati1, Fabio Fabbian1, Roberto Manfredini1, Greco P1, Maria Aurora Rodriguez Borrego2, and Pablo Jesus Lopez Soto2
1University of Ferrara, faculty of Medicine, Pharmacy and Prevention, Ferrara, Italy
2Department of Nursing, University of Cordoba, Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain
Gender violence represents international public health burden. However, there is limited knowledge of epidemiological data in Italy. Thus, we decided to perform a study with the following aims: (1) collecting epidemiological data aimed at assessing implementation of the guideline protocol “Care and treatment for women victims of gender violence” developed by the University Hospital of Ferrara (year 2013) according to the Istanbul Convention on Violence against Women, (2) developing an integrated approach between health-care professionals and police officers in case of gender violence. Data were extracted from the reports of women referring to the emergency room (ER) for gender violence, University Hospital of Ferrara, Italy, years 2008 to 2016. The final total sample included 1955 women, average: 217 cases/year. Women were predominantly Italian, aged between 26 and 60 years. In details, 94% of cases involved assault and battery as gender violence; 3.1% involved sexual assault, 2.9% had no precise data, since women omitted any description of the violence. In 2.6% of cases, women victims of gender violence were pregnant. The abuser was more often the victim’s partner, followed by former-partner/relative, and identity remained unknown in 1.7% of cases. Repeated violence occurred in 318 (16.3%) cases. The introduction of the above quoted Guideline Protocol led to improvements in the regional network of services for women victims of gender violence. Furthermore, the training for health professionals improved awareness and quality of delivered care. The ER clinical notes were more accurate in reporting details about type and frequency of violence episodes, allowing considerable improvement in the clinical practice. Finally, in cases of gender violence, the number of yellow tags, according to the triage codifying system, increased, and information exchange between hospital health-care professionals and police officers significantly improved.
Gender Related Violence: An Observational Study
Tiziana Ciarambino2, Ilenzia Sanzo2, Ilaria Boccagna2, Carla Iuliano1, Raffaella Ferrucci1, Filomena Maietta1, Giuseppina Quintili1, Laura Leoncini3, Cecilia Politi1 and Mauro Giordano1
1Health Direction, Hospital of Marcianise, ASL Caserta, Italy
2Women’s Space Association, Project REVIVAL (Right Environment to protect women victims of violence at each level)
3Department Internal Medicine, Hospital of F. Veneziale, ASREM, Italy
Connecting Midwives and Violence Prevention Institutions—One Step in Fighting Violence Against Women
Siller Heid1, Pittl Manuel2, Zenzmaier Christoph2, Perkhofer Susanne2, Hochleitner Margarethe3, and König-Bachmann Martina4
1Medical University of Innsbruck, Gender Medicine Unit, Innsbruck, Austria
2Health University of Applied Sciences Tyrol, Innsbruck, Austria
3Gender Medicine Unit, Medical University of Innsbruck, Innsbruck, Austria
4Department for midwifery, Health University of Applied Sciences Tyrol, Innsbruck, Austria
Violence against women (VAW) is an ongoing concern in health care. It encompasses domestic violence, but also other types of violence only or disproportionally often affecting women. Constant improvements are made to provide best possible support for women affected by VAW. Reducing barriers in accessing violence prevention institutions and knowledge about referral possibilities are important aspects when caring for women affected by VAW. Three qualitative studies with 15 midwives, 21 midwifery students, and 11 representatives of violence prevention institutions, respectively, were conducted by using either interviews or focus groups. These studies were conducted in one part of Austria. Findings showed that there is still a disconnection between these professionals in particular regarding pregnant women. It was also found that midwives who had received training in VAW and younger midwives and midwifery students were more open to including VAW. Continuous care was an important concern in interviews. This is also reflected in the midwives’ role as guided guides. Violence prevention institutions reported that only very few pregnant women contacted them. By combing the findings of all 3 studies, a disconnection between all actors in the field of VAW appeared. Therefore, the so-called meet and greets were developed and will be implemented in autumn/winter 2019. Thereby, midwives, professionals (psychologist and psychotherapists), and representatives of violence prevention institutions will constitute a support network for each other in fighting VAW. Setting up small networks in several areas in Tyrol, Austria, is expected to reduce barriers and increase access to support.
Gender Differences in Dentists’ Working Practices and Job Satisfaction in Germany
Christiane Gleissner1, Nina Düchting1, Ulrike Uhlmann1, and James Deschner1
1Department of Periodontology and Restorative Dentistry, University Medical Centre, Johannes Gutenberg-University, Mainz, Germany
There has been a steady increase in the proportion of women among dentists over the last 30 years. Female dentists have been shown to work fewer hours per week and take longer career breaks, raising concerns about maintaining community-based dental care in the future. This pilot study aimed to compare the working practices, family life, and job satisfaction of male and female dentists. The study was a web-based 50-item survey on sociodemographic data, working situation, work–life balance, family life, and income. Of this, 1500 dentists were contacted by mail using the database of the local state chamber of dentists. One hundred eighty-nine questionnaires (93 M, 96 F; 44.5 ± 12.0 years) were eligible for analysis which included χ2 and Mann-Whitney U test, Spearman-correlation, and linear-regression analysis. Of this, 71.0% of the men and 37.9% of the women owned their own practice, 4.3% of the men and 46.3% of the women worked as employees. The mean number of working hours per week was 51.1 for males and 42.1 for females; 26.7% of the men and 49.4% of the women were childless. The mean number of children was 1.2; males had more children than females; 66% of the women’s partners worked full time, but only 24% of the men’s; 30% of the women (men: 7.5%) reported that their income had decreased after a career break for child rearing. Women’s average income before taxes was significantly lower than men’s. Mean job satisfaction for males was 12.6 and 11.9 for females (P < .05). Job satisfaction of males was determined by “burden” and “income,” whereas “number of persons living in the household” determined job satisfaction of females. Male and female dentists differ in their working and family situations; this affects their job satisfaction. Such differences should be addressed in order to improve and maintain community-based dental care.
Masculinity Is Associated With Male Medical Students’ Discomfort With Regard to Asking Patients About Sexual Health Issues
Nikola Komlenac, PhD1, and Margarethe Hochleitner, MD1
1Gender Medicine Unit, Medical University of Innsbruck, Innsbruck, Austria
Factors contributing to physicians’ or medical students’ discomfort with addressing patients’ sexual health have rarely been addressed. The current study analyzed whether masculine gender role conflict (GRC), next to the often cited factor of knowledge, was associated with male students’ comfort with regard to asking future patients about sexual health issues. A cross-sectional questionnaire study was conducted at an Austrian medical university with 164 male medical students (mean age = 24.4 years, SD = 2.4). Students’ self-perceived knowledge of sexual health, how prepared they felt about this topic and their comfort with regard to asking future patients about sexual health issues were assessed. The Gender Role Conflict Scale—Short Form was used to assess GRC. Male students reported being more comfortable about asking male patient groups than female patient groups (Ps < .040). Male students who indicated difficulty with expressing affection towards men were more likely to report being uncomfortable about asking patients overall, male patient groups, and elderly female patients (ORs > 1.6, Ps < .020). Furthermore, male students who felt distress when showing emotions were more likely to report being uncomfortable about asking adult female patients (OR = 1.6, P = .012). Knowledge was positively associated with comfort about asking patients overall and female patient groups (ORs > 2.3, Ps < .037). The current study shows that it is not enough to convey facts and skills in order to increase male medical students’ comfort in dealing with patients’ sexual health issues. Male students should be made aware of gender role norms that influence such conversations, and the discussion of strategies for overcoming the barriers set by these norms should be part of sexuality education.
Mistreatment and Incivility at the Medical University of Innsbruck—Focusing on Muslim Students
Gloria Tauber1, Heidi Siller1, Silvia Exenberger2, and Margarethe Hochleitner1
1Medical University of Innsbruck, Gender Medicine Unit, Innsbruck, Austria
2Medical University of Innsbruck, Medical Psychology, Innsbruck, Austria
The study focuses on mistreatment and incivility in medical students at the Medical University of Innsbruck (MUI). Mistreatment and incivility includes subtle sexist and racist remarks and lack of regard and was found to affect more often marginalized and minority groups (eg, migrants, women, sexual minorities, etc). In Austria, Europe, 8% of the population is estimated to be Muslim. The objectives of this study were to investigate whether women and minority groups experience more incivility and might compensate this experience with more persistence and ambition regarding their career compared to men and majority students. In a pilot study, Muslim medical students (n = 35) filled in a questionnaire on resilience, incivility, and career orientation in the workplace. A non-Muslim control group of 42 medical students was recruited to compare findings on resilience, incivility, and career orientation. Findings show that Muslim students experience significantly more often incivility than the control group, but no gender differences were found regarding incivility. Muslim students also reported a significantly greater orientation toward careers, which was not connected to incivility. Contrary to our expectations, women at the MUI do not report incivility more often than do men, but Muslim students report more often incivility than non-Muslim students. This study elucidates the need to detect mechanisms of which aspects are intersecting and experienced as uncivil and mistreating and how this influences the career orientation. Long-term studies to see the impact of incivility and careers in minority and majority groups would be interesting and important.
Sex and Gender Specific Aspects in the Development of Post Stroke Depression and ITS Effects on Neuro-Rehabilitation Success
Jürgen Harreiter1, Ulrich Schneeweiss1, Wolfhard Klein2, Hermann Moser2, and Alexandra Kautzky-Willer1,3
1Gender Medicine Unit, Division for Endocrinology and Metabolism, Department of Medicine III, Medical University Vienna, Vienna, Austria
2Neurological Therapy Center Gmundnerberg, VAMED, Austria
3Gender Medicine Institute, Gars am Kamp, Austria
Worldwide stroke is one of the most common causes of death. Survivors are often dependent on assistance in their daily life activities. Beside the personal fates, the resulting economic burden to health-care systems is high. Effective rehabilitation programs increase the quality of life and reduce the economic burden by lowering the costs for continuing care. Considering the individual needs of every patient is a basic requirement for a successful rehabilitation process. The examination of sex- and gender-specific differences in rehabilitation shall contribute to the further improvement in the rehabilitation processes. This retrospective study included 1593 stroke patients who underwent neurorehabilitation from 2010 to 2015. The change in the Barthel Index during rehabilitation was chosen as marker for the rehabilitation effect. A linear regression model was used to examine the influence of sex and multiple confounders on the rehabilitation effect as well as on the occurrence of depression and pain. The age was comparable between sexes (male: 68.2 ± 11.9 vs female: 69.3 ± 13.6 years). At admission, women had lower Barthel Index (m = 84.7 ± 23.8; f = 79.9 ± 25.9; P < .001). Parameters affecting the change of Barthel index significantly were age, time since stroke and Barthel Index on admission. Pain level on admission, sex, and depression was not associated with the rehabilitation effect. However, female sex, high pain levels, and low Barthel Index on admission were significantly associated with depression. Women suffered more frequently (male = 226/34.6%; female = 205/44.3%; P < .001) from pain and additionally were indicating higher pain levels (male = 1.6 ± 2.4; female = 2.0 ± 2.6; P = .002), which was associated with depression. Men and women have beneficial effects of neurorehabilitation, but factors associated with female sex (low Barthel Index on admission, pain) impact the rehabilitation effect in a negative way. Women are at higher risk for depression, as well as indicate pain more frequently and in higher intensity.
Malnutrition Influence and Outcome in Cardiovascular Rehabilitation: Pilot Study
A. Guttmann1, S. M. Hörsit-Kollmann2, C. Prenner2, A. Deutsch2, M. Kristoferitsch2, A. Krautsack2, E. Wappl2, W. Kullich3, B. Thauerer3, and J. Strametz-Juranek2
1Medical University Graz, Graz, Austria
2Sonderkrankenanstalt—Rehabilitationszentrum Bad Tatzmannsdorf, Austria
3Ludwig Boltzmann Institut fu¨r Arthritis und Rehabilitation, Department fu¨r Rehabilitation Saalfelden, Austria
Cardiovascular diseases are the leading cause of death worldwide. Modern medicine increases the number of elderly and old patients in stationary rehabilitation. Malnutrition, weight loss, sarcopenia, and low protein levels are associated frequent falls, which, in combination with high age, count as independent risk factor for cardiovascular diseases. The aim of this pilot study was to evaluate the efficiency of cardiovascular rehabilitation treatments in elderly and old patients and the influence of a purposeful screening and treatment for malnutrition on the outcome. All patients underwent AKE-screening, blood sampling, BIA, SPPB, and the 6MWT at start and at the end. To calculate the total energy demand of our patients, we used our gender-specific energy calculator. In stationary rehabilitation on ward a total of 31 people (19 female, 12 male) took part in the study. Thirteen patients had a risk of malnutrition, 18 already were malnutritioned. Patients with a risk of malnutrition were randomized 2 groups. The test group and all malnutritioned patients got daily a nutritional supplement with high protein levels. All participants of both study groups showed improvements in their physical ability like the 6MWT (A: 233.11 m ± 81 m to 294.6 m ± 76.7 m; P = .002) and the SPPB (A: 6.25 ± 2.26 to 10.9 ± 1.66; P = .002). Results of 6MWT (211.7 m ± 56.9 m to 280 m ± 54.7 m; P = .001) and SPPB (5.62 ± 1.99 to 10.57 ± 1.9; P = .015) in the test group increased significantly compared to the control group. Malnutrition is a primary issue in rehabilitation. Elderly and old people benefit from rehabilitation. Malnutrition significantly affects treatment outcome and aims of cardiovascular rehabilitation. Targeted interdisciplinary treatment of malnutrition goes along with a significant improvement of muscle strength, walking speed and balance, important for fall prophylaxis, and cardiovascular outcome.
Sex Related Differences in Major Depression in an Austrian Sample: Evidence for the Necessity of Gender Specific Treatment
Karin Schwalsberger1,2, Bernd Reininghaus1,2, Nina Dalkner2, Laura Antonia Lehner1, Alexandra Rieger2, and Eva Reininghaus2
1Therapiezentrum Justuspark, Bad Hall, Austria
2Department of Psychiatry and Psychotherapeutic Medicine, Medical University of Graz, Graz, Austria
The preponderance of depression in women appears to be a universal and substantial finding. A woman is about 1.7 times more likely to have unipolar affective disorder than a man. Aim of this study was to investigate sex sex-related differences in unipolar affective disorders. Differences between men and women regarding sociodemographic variables, symptoms, medical treatment, and comorbidities were examined and multiple explanations for the differences were discussed. The data of 695 patients of a rehabilitation clinic in Austria were analyzed. Of the 695 patients, 465 were admitted with the diagnosis of major depression and therefore were included in the study. Different (neuro-) biological and psychological parameters were compared at the beginning and at the end of a 6-week rehabilitation period between women and men. Men and women showed no differences in depressive symptom severity; however, anxiety was significantly higher in women. Male individuals showed a significantly higher body mass index than women, and in line with that, cardiovascular diseases were more frequent in men. Women on the contrary displayed a significantly higher rate of thyroid dysfunctions. There was no significant difference in the number of psychotropic substances taken. Not only are women almost twice as often affected by depression than men, the chronic disease affects the male and female body and mind in a different way. Men have a stronger vulnerability of the cardiovascular system, women seem to have a hormonal imbalance (thyroid gland), which could explain the higher rate in anxiety, since thyroid dysfunction and anxiety have been found to be highly correlated. These gender-specific differences need to be taken in to account in the treatment of major depression to improve the psychological and physiological well been of the patients.
Gender Gap in Diagnosis of Depression More Prevalent in Type 2 Diabetes Mellitus Patients than Non-Diabetics in Austria
Deischinger Carola1, Dervic Elma2,3, Kosi-Trebotic Lana1, Kautzky Alexander4, Klimek Peter2,3, and Kautzky-Willer Alexandra1
1Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Gender Medicine Unit, Medical University of Vienna, Waehringer Guertel, Vienna, Austria
2Section for Science of Complex Systems, CeMSIIS, Medical University of Vienna, Spitalgasse, Vienna, Austria
3Complexity Science Hub Vienna, Josefstädter Straße, Vienna, Austria
4Department of Psychiatry and Psychotherapy, Division of Social Psychiatry, Medical University of Vienna, Waehringer Guertel, Vienna, Austria
Lack of Gender-Specific Knowledge on How Psychological Factors Contribute to Pre-Hospital Delay After Myocardial Infarction
Sophie H. Bots1, Karlijn B. Rombouts1, Hajo W. Boersma1, Mark C. H. de Groot2, Saskia Haitjema2, and Hester M. den Ruijter1
1Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
2Laboratory of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
Women suffering from myocardial infarction (MI) wait longer to contact medical services than men, while quick treatment is crucial to reduce permanent cardiac damage. Traditional gender roles may affect health-care-seeking behaviour by defining gender-specific socially acceptable behavior. Faced with the same medical emergency, women and men may thus act differently according to their internalized gender role. However, this has not yet been fully elucidated. We performed a systematic review of the literature to evaluate whether the effects of psychological factors on prehospital delay differ between women and men and validated our findings in a pilot study. Our search of PubMed and Embase returned 3634 unique articles, of which 92 were eligible for full-text screening and 11 (published between 1998 and 2018) were included. These articles included 2624 patients (30% women) and covered the psychological factors denial (n = 3), anxiety (n = 6), embarrassment (n = 3), and fear (n = 6), with some articles covering multiple factors. Half of the evaluations (9/18) only reported factor prevalence by gender. Some results suggested that denial increased delay (n = 1, 161/533 women), anxiety decreased delay (n = 2, 120/328 women), and embarrassment and fear had no effect on delay (n = 1, 96/194 women) in both genders. Others showed that anxiety decreased delay only in men (n = 1, 36/98 women) or only in women (n = 1, 162/619 women), while embarrassment and fear increased delay only in men (n = 1, 24/134 women). We screened the electronic health record (EHR) of 100 men and 104 women admitted to the University Medical Center Utrecht with an ST-elevation MI. With the exception of embarrassment as delay reason for one woman, psychological factors were not mentioned in the EHR. Psychological factors seem to affect prehospital delay after an MI similarly in both genders, but limited data question the validity. Large standardized studies with proportionate numbers of women are needed to draw final conclusions.
Real Men Don’t Cry—Gender Differences in Coping With Cancer
Anahita Paula Rassoulian1
1Medical University of Vienna, Vienna, Austria
“Real men don’t cry,” “talking about fear and sorrows are only for women”—do these and similar prejudices still exist today? Men and women handle life challenges differently. They differ in the way they perceive challenges, communicate, in their social relationships, and in the way, they deal with major challenges, such as cancer and disease. Despite medical progress cancer is still a life-threatening disease and throws a person’s views on life into disarray. Studies indicate that depression and anxiety are highly prevalent in patients with cancer and that gender plays an important role in the way patients cope and communicate with their oncologist, family, and friends. By providing patient-centered care, we would benefit from acknowledging and talking about gender issues and gender differences concerning how male and female patients cope with their cancer disease—what it means to them, how they deal with it in their daily life, and how it influences their personal life and relationships. Interviews with male and female patients with cancer show a clear tendency toward gender differences in coping with cancer. The results do not support any stereotypes of male and female behavior or social structures—but it mirrors the real life of human beings! And yes, real men do cry!