Gender-specific preventive medicine & women’s health in our „longer-life society”

>> Studies in recent years have increasingly examined differences between men and women in terms of health and disease. A comparatively higher incidence of overdose and increased adverse drug reactions in women due to proven physiological differences in drug bioavailability, metabolism, and excretion is just one of many examples of the need to identify gender-specific differences in drug treatment (Ankowitsch et Rieser 2014 2). A gender-specific approach must also be given greater focus in cardiovascular diseases: In stable angina pectoris, the interpretation of non-invasive diagnostics is less reliable in women, which is why guidelines in this area also require gender-specific recommendations. The number of acute coronary syndromes has increased significantly in recent years, especially among younger women – despite a lack of awareness of this problem among both patients and physicians.
These examples illustrate that measures for the diagnosis and treatment of diseases, as well as for prevention, are not always equally effective and/or necessary for men and women. This applies not only to aspects of disease development and progression, but also to modifiable risk factors such as lifestyle and gender-specific care needs.
It is therefore particularly important to place the topic of gender-specific prevention at the center of scientific research in the coming years, particularly depending on epidemiological developments based on relevant analyses.

Knowledge transfer/training and further education
The focus is not only on generating new insights, but also on implementing existing knowledge into the training, continuing education, and continuing medical education of the medical profession. While the topic of gender-specific disease developments and preventive medicine is now receiving more media attention, it is by no means a given that gender-specific aspects are specifically incorporated into patient care. Furthermore, gender-specific topics are too rarely addressed in medical training, continuing education, and continuing medical education, and there is a lack of appropriate practical implementation. For example, depending on the epidemiological morbidity constellation, specific information, education, and coaching programs for women and men are far from being an integral part of clinical or practice-oriented healthcare (Amelung et Chase 2014 3).
Objective
As part of a collaborative project between the Research Institute for Women's Health at the University Hospital of Tübingen and the University Women's Hospital of Heidelberg, the Institute for General Practice and Interprofessional Care at the University Hospital of Tübingen, and the AOK Baden-Württemberg, the aim is to generate preventive medical findings on gender-specific differences in diseases at different stages of life, with a focus on women's health, based on a biopsychosocial approach using routine data. The aim of the project is to identify which disease courses, including those related to age decades, exhibit gender-specific differences and where gender-specific disease prevention can be targeted. While considering limitations, the analysis of anonymized insured data can make a valuable contribution to this, as appropriate strategies could be developed for specific target groups.
Using analyses of relevant gender-diverse
The current findings on morbidity constellations are intended to confirm or refute existing hypotheses and generate new ones in order to develop practical care and prevention concepts. These findings will be incorporated not only into teaching but also into basic, continuing, and further education for both physicians and other healthcare professionals. Diseases based on epidemiological developments will be taken into account, including those with corresponding risk categories, such as high-risk patients with diabetes mellitus and/or coronary heart disease and/or kidney disease, etc., which occur in only one or both sexes. The overarching goal of the project is to give greater consideration to gender-specific and gender-specific prevention and the promotion of gender-specific health in healthcare than has previously been the case.
methodology
The interdisciplinary, primary care provider-centered care and the specialist contracts of the AOK Baden-Württemberg provide a guiding framework for the research questions to be developed. They address chronic diseases comprehensively, evidence-based, and biopsychosocially oriented, as well as non-pharmacological counseling where corresponding over-, under-, and mistreatment are described in the specialist literature.2 This applies, among other things, to musculoskeletal, cardiovascular, and nephrological (so-called delayed progression) diseases, as well as interdisciplinary care for mental disorders and shared decision-making through the promotion of health literacy.

Project process
The overall project will be divided into content-related subprojects, each of which will be carried out collaboratively, but with a lead from one of the partners. A joint approach will be agreed upon in the first project phase. Figure 1 illustrates the defined steps.
Due to the lack of central patient registries in the Federal Republic of Germany, routine data analyses have gained significant importance in recent years as an alternative or supplement to empirical studies in the medical field. Corresponding data are available from statutory health, pension, and accident insurance providers. These data are primarily used for billing purposes, but can be used in anonymized form for scientific evaluations beyond their original purpose, subject to compliance with applicable data protection regulations (Zeidler et Braun 2011 4). Advantages here include the availability of large data sets and the possibility of analyzing cross-sectoral care processes longitudinally.

Basics of epidemiology and disease burden according to service utilization based on AOK routine data analyses
When interpreting the results, it should be noted that they were collected for purposes other than scientific ones (Zeidler et Braun 2011 4). Descriptive analyses of outpatient care for the insured members of the AOK Baden-Württemberg, with over 4.5 million people, refer to population-related age groups and gender distributions with corresponding allocation of diagnoses, where applicable also to the treating general practitioner/specialist/psychotherapist, medication and other, for example, behavioral therapy measures. Figures are available for diseases that can be described by an ICD code and for which the insured person has claimed a GKV benefit. Risk factors such as obesity, smoking or alcohol consumption have so far been coded less reliably, whereby diseases such as COPD (chronic
obstructive lung diseases) are already more than 90% attributable to chronic nicotine abuse.
The comparison should also take into account, among other things, the health reports from the Robert Koch Institute and its analyses (www.rki.de) as well as the reports and care analyses from the Scientific Institute of the AOK for all AOKs (www.wido.de).
When analyzing the data and interpreting the results, the aforementioned principles and their limitations are taken into account and discussed.
Hypotheses and preliminary results
The first focus of this cooperation project is the overarching topic of „nephrology“ with a focus on chronic kidney diseases (ICD-10 N 18.- according to www.dimdi.de).
In this context, the Institute of General Practice is investigating whether gender-specific differences exist with regard to various outcomes (disease progression, cardiovascular events, hospitalization, mortality) and risk factors for their occurrence. Sociodemographic and, where applicable, lifestyle factors will be taken into account, as will existing comorbidities, medication use, and various aspects of care. One goal of this initial study is to determine the incidence of CKD among AOK Baden-Württemberg insured persons between 2011 and 2018 and to identify gender-specific differences, for example, with regard to prescribing and referral behavior or other preventive aspects. Furthermore, the longitudinal study will examine the associations between gender and various outcomes. Specifically, the following questions will be answered using regression analyses:
1. Are there differences between men and women regarding the following outcomes: mortality, cardiovascular events, progression of renal failure to end-stage renal disease, and hospitalization?
2. Are different factors (including lifestyle, sociodemographics, health factors) associated with different outcomes in men and women?

Some gender-specific differences in prevalence, progression, and mortality are already known from the literature (Correro et al. 2018, 5). Accordingly, women are more likely to develop chronic kidney disease than men (Correro et al. 2018, 5; Hill et al. 2016, 6). However, the disease progresses more rapidly in men, and the incidence of end-stage renal disease is higher than in women (Correro et al. 2018, 5; Gallieni et al. 2012, 7). Men and women also differ with regard to the initiation of renal replacement therapy, for example, dialysis, with men receiving dialysis more frequently and earlier than women (Correro et al. 2018, 5; Neugarten et Golestaneh 2019, 8). Identifying patients at high risk for rapid progression to end-stage renal disease (ESRD) is challenging due to heterogeneity in etiology and comorbidities. Established risk scores and formulas have so far been developed primarily with patients from nephrology units (Tangri et al. 2016, 9). Data on patients from general practice or from Germany are lacking or have been conducted with selected patient cohorts (Herget-Rosenthal et al. 2013, 10; Herget-Rosenthal et al. 2006, 11).
The aim of this sub-project is therefore to provide targeted prevention and intervention recommendations tailored to the respective target group based on the different risk constellations identified in this way and to develop concepts for how these can be implemented in practice and also in continuing education and training.
The Department of Women's Health, in cooperation with the Heidelberg University Women's Hospital, is investigating the incidence of chronic kidney disease and cardiovascular and cerebrovascular events in women with hypertensive disorders of pregnancy. In addition to modifiable risk factors and comorbidities, parameters affecting the child are also taken into account.
Hypertensive disorders occur in 8% of all pregnancies, contribute to 20–25% of perinatal mortality, and are the leading cause of maternal death in Europe (S2k Guideline on Hypertensive Pregnancy Disorders 2019 12; Kühnert 2016 13). Preeclampsia is of particular importance: 10–15% of all maternal deaths are related to preeclampsia/eclampsia, and it is responsible for at least 70,000 maternal deaths per year worldwide (Lo Jo et al. 2013 14). In clinical practice, there is a clear overlap with other or similar clinical manifestations of placental dysfunction, such as IUGR (intrauterine growth retardation).
Since there is currently no causal treatment for eclampsia/preeclampsia, the focus is on reducing maternal and fetal morbidity and mortality through prevention, early detection, risk stratification, and detection of signs of clinical manifestations. Management of this condition during pregnancy should, as far as possible, be evidence-based, interdisciplinary, and performed in a Level 1 clinic (S2k Guideline on Hypertensive Pregnancy Disorders 2019, 12; Buemi et al. 2004, 15). Women who have experienced any form of preeclampsia in general, and especially those who have experienced a severe form of preeclampsia, show a significantly increased risk of developing cardiovascular, cerebrovascular, or nephrological disease after several years (Wu et al. 2014 16; Vikse et al. 2008 17; Lykke et al. 2009 18; Auger et al. 2017 19; Cunningham et al. 2018 20). This risk was also influenced by the presence of obesity and diabetes.
A uniform aftercare concept does not currently exist. An extensive literature review has revealed that recommendations for aftercare and follow-up after preeclampsia vary considerably between individual national guidelines regarding the initiation, content, and target group of aftercare (Bro Schmidt et al. 2017 21).
In Germany, too, there is currently a lack of a structured care concept for women with preeclampsia during pregnancy. Recommendations for prevention mainly relate to medication-related aspects, such as taking aspirin in a subsequent pregnancy (Rolnik et al. 2017 22; Rolnik et al. 2017 23), lifestyle-related advice and/or education.
One goal of this subproject is to develop a regulated, step-by-step aftercare concept based on the insights gained from the data analyses regarding risk constellations for the development of further disease aspects in women after preeclamptic pregnancy. Furthermore, suggestions will be derived as to how this concept can be incorporated into the care of affected women and where it can be integrated into training, continuing education, and continuing education.
outlook
Modern women's health has long since transcended the medical field of somatic gynecology: it is interdisciplinary and at the center of gynecological, sociocultural, and societal interest (Wallwiener et al. 2016, 24). This shifts the focus to women's transitional and life phases in their heterogeneous living environment. In terms of research, this means a call for increased research on gender-specific morbidity trends, health care epidemiology, and preventive medicine.
The practical implementation of the respective research results is conceivable in different formats depending on the topic in question (e.g. training courses, workshops, health promotion programs, patient information).
Interprofessional aspects and digital formats (e.g. use of online tools) should be included where possible and appropriate according to the evidence-based state of knowledge.
In a further step, which is no longer the subject of this project, these gender-specific prevention programs must be implemented and evaluated.