Sex and gender differences in drug treatment: experiences from the knowledge database Janusmed Sex and Gender.

BACKGROUND: Evidence from clinical research indicates that men and women can differ in response to drug treatment. The knowledge database Janusmed Sex and Gender was developed to illuminate potential sex and gender differences in drug therapy and, therefore, achieve a better patient safety. The database contains non-commercial evidence-based information on drug substances regarding sex and gender aspects in patient treatment. Here, we describe our experiences and reflections from collecting, analyzing, and evaluating the evidence. JANUSMED SEX AND GENDER: Substances have been systematically reviewed and classified in a standardized manner. The classification considers clinically relevant sex and gender differences based on available evidence. Mainly biological sex differences are assessed except for gender differences regarding adverse effects and compliance. Of the 400 substances included in the database, clinically relevant sex differences were found for 20%. Sex-divided data were missing for 22% and no clinically relevant differences were found for more than half of the substances (52%). We noted that pivotal clinical studies often lack sex analyses of efficacy and adverse effects, and post-hoc analyzes are performed instead. Furthermore, most pharmacokinetic analyses use weight correction, but medicines are often prescribed in standard doses. In addition, few studies have sex differences as a primary outcome and some pharmacokinetic analyses are unpublished, which may complicate the classification of evidence. CONCLUSIONS: Our work underlines the need of sex and gender analyses, and sex-divided data in drug treatment, to increase the knowledge about these aspects in drug treatment and contribute to a more individualized patient treatment.

Awareness of sex and gender dimensions among physicians: the European federation of internal medicine assessment of gender differences in Europe (EFIM-IMAGINE) survey.

Sociocultural gender is a complex construct encompassing different aspects of individuals' life, whereas sex refers to biological factors. These terms are often misused, although they impact differently on individuals' health. Recognizing the role of sex and gender on health status is fundamental in the pursuit of a personalized medicine. Aim of the current study was to investigate the awareness in approaching clinical and research questions on the impact of sex and gender on health among European internists. Clinicians affiliated with the European Federation of Internal Medicine from 33 countries participated to the study on a voluntary basis between January 1st, 2018 and July 31st, 2019. Internists' awareness and knowledge on sex and gender issues in clinical medicine were measured by an online anonymized 7-item survey. A total of 1323 European internists responded to the survey of which 57% were women, mostly young or middle-aged (78%), and practicing in public general medicine services (74.5%). The majority (79%) recognized that sex and gender are not interchangeable terms, though a wide discrepancy exists on what clinicians think sex and gender concepts incorporate. Biological sex and sociocultural gender were recognized as determinants of health mainly in cardiovascular and autoimmune/rheumatic diseases. Up to 80% of respondents acknowledged the low participation of female individuals in trials and more than 60% the lack of sex-specific clinical guidelines. Internists also express the willingness of getting more knowledge on the impact of sex and gender in cerebrovascular/cognitive and inflammatory bowel diseases. Biological sex and sociocultural gender are factors influencing health and disease. Although awareness and knowledge remain suboptimal across European internists, most acknowledge the underrepresentation of female subjects in trials, the lack of sex-specific guidelines and the need of being more informed on sex and gender-based differences in diseases.

Instant electrocardiogram feedback with a new digital technique reduces symptoms caused by palpitations and increases health-related quality of life (the RedHeart study).

AIMS: Palpitations, particularly common in women, are generally considered benign symptoms rarely caused by clinically important arrhythmias. Nevertheless, palpitations may cause anxiety, depression, and decreased health-related quality of life (HRQOL). This study investigates to what degree palpitations cause symptoms such as anxiety and depression and affect HRQOL in women and whether direct feedback of underlying heart rhythm during palpitations decrease anxiety and depression and increase HRQOL in women. METHODS AND RESULTS: The study included 821 women, age 21-88 years (mean 57 ± 11 years), with symptomatic palpitations recruited using social media. For 60 days, the participants used a handheld electrocardiogram (ECG)-recording device (Coala Heart Monitor) connected to their smartphones. ECG was recorded twice a day and when symptoms were present and was automatically algorithm-interpreted with immediate response to the user. Non-benign arrhythmias were also analysed manually. Questionnaires addressing anxiety and depression-Hospital Anxiety and Depression Scale (HADS), Generalized Anxiety Disorder (GAD-7), HRQOL (RAND-36), and Symptoms Checklist: Frequency and Severity (SCL)-were analysed before and after the data were collected. A total of 101 804 ECG recordings were automatically analysed. In 94%, sinus rhythm or premature atrial/ventricular contraction were recorded; in 6%, atrial fibrillation or supraventricular tachycardia were recorded. Apart from premature ventricular contractions, no ventricular arrhythmias were documented. Anxiety and depression (HADS and GAD-7) decreased (P < 0.001) as did frequency and severity of symptoms, and HRQOL increased in all domains (P < 0.001) at the 2-month follow-up. CONCLUSION: Instant analysis of the ECG with direct response during palpitations decreases symptoms, anxiety, and depression and increases HRQOL in women.

Improving Efficiency of Clinical Studies Using a Total Digital Approach: Prospective Observational Study.

BACKGROUND: In general, most clinical studies have long recruitment periods. Signing the informed consent is particularly time-consuming when the participant must meet physically with the researchers. Therefore, introducing fully web-based techniques with the use of eAuthentication (BankID) and new digital electrocardiogram (ECG) monitoring could speed up inclusion time, increase adherence, and also reach out to more remote regions. OBJECTIVE: The objectives of this study were to explore whether inclusion of a large number of participants could be realized quickly by using a total digital approach both for information and signing of informed consent, along with ECG monitoring and instant feedback on a mobile device. We also explored whether this approach can increase adherence in registration of ECG recordings and answering questionnaires, and if it would result in a more geographically uniform distribution of participants covering a wide age span. METHODS: Women with palpitations were intensively studied over 2 months by means of a handheld ECG monitoring device (Coala Heart Monitor). The device connects to a smartphone or tablet, which allows the participants to obtain the results immediately. Recruitment, study information, and signing the informed consent form with the help of BankID were performed in a completely digital manner. RESULTS: Between March and May 2018, 2424 women indicated their interest in participating in the study. On June 19, 2018, presumptive participants were invited to log in and register. After 25 days, 1082 women were included in the study; among these, 1020 women fulfilled the inclusion criteria, 913 of whom completed all phases of the study: recording ECG using the handheld device, completion of the prestudy questionnaires, and completion of the poststudy questionnaires 2 months after the ECG recordings. The dropout rate was 9%. In total, 101,804 ECG recordings were made. The mean age was 56 (SD 11) years (range 21-88 years) and 35 participants were 75 years or older. The participants were evenly distributed between living in the countryside and in cities. CONCLUSIONS: Total digital inclusion recruitment of 1082 participants was achieved in only 25 days, and resulted in a good geographical distribution, excellent adherence, and ability to reach a vast age span, including elderly women. Studies using a total digital design would be particularly appealing during a pandemic since physical contact should be avoided as much as possible. TRIAL REGISTRATION: ISRCTN Registry ISRCTN22495299; http://www.isrctn.com/ISRCTN22495299.

Takotsubo Syndrome: Finally Emerging From the Shadows?

It is now 30 years since Japanese investigators first described Takotsubo Syndrome (TTS) as a disorder occurring mainly in ageing women, ascribing it to the impact of multivessel coronary artery spasm. During the intervening period, it has become clear that TTS involves relatively transient vascular injury, followed by prolonged myocardial inflammatory and eventually fibrotic changes. Hence symptomatic recovery is generally slow, currently an under-recognised issue. It appears that TTS is induced by aberrant post-ß2-adrenoceptor signalling in the setting of "surge" release of catecholamines. Resultant activation of nitric oxide synthases and increased inflammatory vascular permeation lead to prolonged myocardial infiltration with macrophages and associated oedema formation. Initially, the diagnosis of TTS was made via exclusion of relevant coronary artery stenoses, plus the presence of regional left ventricular hypokinesis. However, detection of extensive myocardial oedema on cardiac MRI imaging offers a specific basis for diagnosis. No adequate methods are yet available for definitive diagnosis of TTS at hospital presentation. Other major challenges remaining in this area include understanding of the recently demonstrated association between TTS and antecedent cancer, the development of effective treatments to reduce risk of short-term (generally due to shock) and long-term mortality, and also to accelerate symptomatic recovery.

Device profile of the Coala Heart Monitor for remote monitoring of the heart rhythm: overview of its efficacy.

Introduction: Several handheld thumb ECG devices for on-demand recording of heart rhythm have become available lately. These can be used both by health-care providers and purchased by laypersons for private use.Area covered: This profile describes the Coala Heart Monitor. This device differs from other handheld ECG monitors in three aspects: 1) it records both thumb and chest ECGs, 2) it uses both RR-dispersion and P-wave morphology for detecting atrial fibrillation, and 3) in synchronization with the chest ECG, it also records heart sounds presented as a phonocardiogram making measurement of systolic time intervals possible. The sensitivity and specificity for detecting atrial fibrillation are high. The use of systolic time interval in patients with heart failure has so far not been evaluated.Expert opinion: The increasing use of long-term prescribed and privately owned handheld ECG devices for on-demand recording of heart rhythm will most probably cause a paradigm shift in arrhythmia diagnostics. Coala Heart Monitor´s use of both chest and thumb recordings as well as analyzing both RR-dispersion and P-wave morphology may offer an advantage in diagnosing atrial fibrillation.

Personality Traits in Patients with Myocardial Infarction with Nonobstructive Coronary Arteries.

OBJECTIVE: The purpose of this study was to describe type A behavior pattern and trait anger in patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) and compare them with patients with coronary heart disease and healthy controls. Type A behavior pattern and anger have been linked to coronary heart disease in previous studies. This is the first study to assess type A behavior pattern and trait anger in MINOCA patients. METHODS: One hundred MINOCA patients, consecutively recruited during 2007-2011 at 5 coronary care units in Stockholm, were matched for sex and age to 100 coronary heart disease patients and 100 healthy controls. All participants completed the Bortner Rating Scale to quantify type A behavior pattern and the Spielberger Trait Anger Scale to quantify anger 3 months after the acute event. RESULTS: MINOCA patients' Bortner Rating Scale score was 70.9 ± 10.8 (mean ± SD) and Spielberger Trait Anger Scale score was 14 (12-17) (median; interquartile range). Coronary heart disease patients' Bortner Rating Scale score was 70.5 ± 10.2 and Spielberger Trait Anger Scale score was 14 (12-17). Healthy controls' Bortner Rating Scale score was 71.9 ± 9.1 and Spielberger Trait Anger Scale score was 13 (11-16). CONCLUSION: We found no significant differences in Bortner Rating Scale score and Spielberger Trait Anger Scale score among MINOCA, coronary heart disease patients, and healthy controls, regardless of whether total scores, subscales, or cutoffs were used to classify type A behavior pattern and trait anger. However, we cannot exclude the existence of an occasional episode of anger or mental stress in relation to the coronary event. This is the first study to assess type A behavior pattern and trait anger in patients with MINOCA, and future studies need to confirm the current findings before any firm conclusions can be made.

Coronary artery disease in post-menopausal women: are there appropriate means of assessment?

The recognition of sex differences in cardiovascular disease, particularly the manifestations of coronary artery disease (CAD) in post-menopausal women, has introduced new challenges in not only understanding disease mechanisms but also identifying appropriate clinical means of assessing the efficacy of management strategies. For example, the majority of treatment algorithms for CAD are derived from the study of males, focus on epicardial stenoses, and inadequately account for the small intramyocardial vessel disease in women. However, newer investigational modalities, including stress perfusion cardiac magnetic resonance imaging and positron emission tomography are providing enhanced diagnostic accuracy and prognostication for women with microvascular disease. Moreover, these investigations may soon be complemented by simpler screening tools such as retinal vasculature imaging, as well as novel biomarkers (e.g. heat shock protein 27). Hence, it is vital that robust, sex-specific cardiovascular imaging modalities and biomarkers continue to be developed and are incorporated into practice guidelines that are used to manage women with CAD, as well as gauge the efficacy of any new treatment modalities. This review provides an overview of some of the sex differences in CAD and highlights emerging advances in the investigation of CAD in post-menopausal women.

Prevalence of Anxiety and Depression Symptoms in Patients with Myocardial Infarction with Non-Obstructive Coronary Arteries.

BACKGROUND: Myocardial infarction with non-obstructive coronary arteries is a working diagnosis for several heart disorders. Previous studies on anxiety and depression in patients with myocardial infarction with non-obstructive coronary arteries are lacking. Our aim was to investigate the prevalence of anxiety and depression among patients with myocardial infarction with non-obstructive coronary arteries. METHODS: We included 99 patients with myocardial infarction with non-obstructive coronary arteries together with age- and sex-matched control groups who completed the Beck Depression Inventory and the Hospital Anxiety and Depression Scale (HADS) 3 months after the acute event. RESULTS: Using the Beck Depression Inventory, we found that the prevalence of depression in patients with myocardial infarction with non-obstructive coronary arteries (35%) was higher than in healthy controls (9%; P = .006) and similar to that of patients with coronary heart disease (30%; P = .954). Using the HADS anxiety subscale, we found that the prevalence of anxiety in patients with myocardial infarction with non-obstructive coronary arteries (27%) was higher than in healthy controls (9%; P = .002) and similar to that of patients with coronary heart disease (21%; P = .409). Using the HADS depression subscale, we found that the prevalence of depression in patients with myocardial infarction with non-obstructive coronary arteries (17%) was higher than in healthy controls (4%; P = .003) and similar to that of patients with coronary heart disease (13%; P = .466). Patients with myocardial infarction with non-obstructive coronary arteries and takotsubo syndrome scored higher on the HADS anxiety subscale than those without (P = .028). CONCLUSIONS: This is the first study on the mental health of patients with myocardial infarction with non-obstructive coronary arteries to show that prevalence rates of anxiety and depression are similar to those in patients with coronary heart disease.

Sex differences in spontaneous reports on adverse drug events for common antihypertensive drugs.

PURPOSE: To explore sex differences in spontaneously reported adverse drug events (ADEs) for antihypertensives in routine care. METHODS: A cross sectional analysis combining number of reports from the national pharmacovigilance database with data from the Swedish Prescribed Drug Register, from 2005 to 2012 for ACE inhibitors (ACE-I) and angiotensin receptor blockers (ARB), with or without thiazide, diuretics (thiazides, potassium-sparing agents, sulfonamides, aldosterone antagonists), selective betablockers, and dihydropyridine calcium-channel-blockers (DHPs). The total number of reports was adjusted to exposed patients and dispensed DDDs among women and men. Dose exposures, co-medications, and co-prescriptions were also analyzed. RESULTS: In women, a higher prevalence of ADE-reports was seen in ACE-I (odds ratio, OR 1.21; 95% CI 1.09-1.35), ACE-I-combinations (OR 1.61; 1.44-1.79), ARB-combinations (OR 2.12; 1.47-3.06), thiazides (OR 1.78; 1.33-2.39), diuretics and potassium-sparing agents (OR 1.62; 1.22-2.17), and DHPs (OR 1.40; 1.17-1.67), with a potential linkage to dose exposure. For aldosterone antagonists, we observed a higher prevalence of ADE reports in men (OR 0.75; 0.59-0.97) but without any sex difference in dose exposure. CONCLUSIONS: This ecological study of reported ADEs showed a higher prevalence of reports in women in six out of ten groups of antihypertensive drugs, and this may potentially be linked to dose exposure. Aldosterone antagonists was the only group with a higher prevalence of ADE-reports in men with a similar dose exposure between women and men.

Correction to: Sex differences in drugs: the development of a comprehensive knowledge base to improve gender awareness prescribing.

CORRECTION: Unfortunately, after publication of this article [1], two errors were noticed. The names of Linnéa Karlsson Lind and Karin Schenck-Gustafsson were formatted incorrectly, attributing incorrect elements to the Given and Family names. Further to this, a reference in Fig. 1 was missing. The line reading, "Fig. 1 shows the working process and each step is explained in more detail below" should instead read, "Fig. 1, modified from Nörby et al. [2], shows the working process and each step is explained in more detail below".

Recording a diagnosis of stroke, transient ischaemic attack or myocardial infarction in primary healthcare and the association with dispensation of secondary preventive medication: a registry-based prospective cohort study.

OBJECTIVES: The aim of this study was to explore whether recording in primary care of a previously recorded hospital diagnosis was associated with increased patient utilisation of recommended medications. DESIGN: Registry-based prospective cohort study. SETTING AND PARTICIPANTS: 19 072 patients with a hospital discharge diagnosis of transient ischaemic attack (TIA), stroke or acute coronary syndrome from hospitals in Stockholm County 2010-2013 were included in the study. MAIN OUTCOME MEASURE: The outcome of the study was medication dispensation as a marker of adherence to recommended medications. Adherence was defined as having had at least two filled prescriptions in the third year following hospital discharge. RESULTS: Recording a diagnosis was associated with higher utilisation of all recommended medications with the exception of antihypertensives in patients with TIA. The differences between the groups with and without a recorded diagnosis remained after adjusting for age, sex, index year and visits to private practitioners. Dispensation of antithrombotics was high overall, 80%-90% in patients without a recorded diagnosis and 90%-94% for those with a diagnosis. Women with recorded ischaemic stroke/TIA/acute coronary syndrome were dispensed more statins (56%-71%) than those with no recorded diagnosis (46%-59%). Similarly, 68%-83% of men with a recorded diagnosis were dispensed statins (57%-77% in men with no recorded diagnosis). The rate of diagnosis recording spanned from 15% to 47% and was especially low in TIA (men 15%, women 16%). CONCLUSION: Recording a diagnosis of TIA/stroke or acute coronary syndrome in primary care was found to be associated with higher dispensation of recommended secondary preventive medications. Further study is necessary in order to determine the mechanisms underlying our results and to establish the utility of our findings.

Sex and Gender Differences in Thromboprophylactic Treatment of Patients With Atrial Fibrillation After the Introduction of Non-Vitamin K Oral Anticoagulants.

To examine sex differences in thromboprophylaxis in patients with atrial fibrillation before and after the introduction of non-vitamin K oral anticoagulants, we performed a cross-sectional registry study based on anonymized individual-level patient data of all individuals with a diagnosis of nonvalvular atrial fibrillation (International Classification of Diseases, Tenth Revision code I48) in the region of Stockholm, Sweden (2.2 million inhabitants), in 2011 and 2015, respectively. Thromboprophylaxis improved considerably during the period. During 2007 to 2011, 23,198 men and 18,504 women had an atrial fibrillation diagnosis. In 2011, more men than women (53% men vs 48% women) received oral anticoagulants (almost exclusively warfarin) and more women received aspirin only (35% women vs 30% men), whereas there was no sex difference for no thromboprophylaxis (17%). During 2011 to 2015, 27,237 men and 20,461 women had a diagnosis of atrial fibrillation. Compared with the earlier time period, a higher proportion used oral anticoagulants (71% women vs 70% men), but fewer women ≥80 years received anticoagulants (67% women vs 72% men), more women received aspirin (15% women vs 13% men), and fewer women had no thromboprophylaxis (15% women vs 17% men). Patients with co-morbidities potentially complicating oral anticoagulant use used more oral anticoagulant in 2015 compared with 2011. The sex differences observed in 2011 with fewer women using oral anticoagulants had disappeared in 2015 except in women 80 years and older and in patients with complicated co-morbidity.

Effect of Myocardial Infarction With Nonobstructive Coronary Arteries on Physical Capacity and Quality-of-Life.

Patients with myocardial infarction with nonobstructive coronary arteries (MINOCA), including Takotsubo syndrome (TS), are considered to have a better survival compared with those with coronary heart disease (CHD). Studies of patients with MINOCA measuring physical and mental function including matched control groups are lacking. The aim of this study was to determine the physical capacity and quality of life in patients with MINOCA. One-hundred patients with MINOCA along with TS (25%) were investigated from 2007 to 2011. A bicycle exercise stress test was performed 6 weeks after hospitalization and QoL was investigated by the Short Form Survey 36 at 3 months' follow-up. Both a healthy and a CHD group that were age and gender matched were used as controls. The MINOCA group had a lower physical capacity (139 ± 42 W) compared with the healthy control group (167 ± 53 W, p <0.001) but better than the CHD control group (124 ± 39 W, p = 0.023). Patients with MINOCA had lower physical and mental component summary scores compared with the healthy controls (p <0.001) and lower mental component summary (p = 0.012), mental health (p = 0.016), and vitality (p = 0.008) scores compared with the CHD controls. In conclusion, the findings of this first study on exercise capacity and QoL in patients with MINOCA showed both physical and mental distress from 6 weeks to 3 months after the acute event similar to CHD controls and in some perspectives even lower scores especially in the mental component of QoL.

Threats or violence from patients was associated with turnover intention among foreign-born GPs - a comparison of four workplace factors associated with attitudes of wanting to quit one's job as a GP.

OBJECTIVE: General practitioners (GPs) are crucial in medical healthcare, but there is currently a shortage of GPs in Sweden and elsewhere. Recruitment of GPs from abroad is essential, but foreign-born physicians face difficulties at work that may be related to turnover intention, i.e. wanting to quit one's job. The study aims to explore the reasons to why foreign-born GPs may intend to quit their job. DESIGN: Survey data were used to compare four work-related factors that can be associated with turnover intentions; patient-related stress, threats or violence from patients, control of work pace, and empowering leadership, among native-born and foreign-born GPs. These work-related factors were subsequently examined in relation to turnover intention among the foreign-born GPs by means of linear hierarchical regression analyses. The questionnaire consisted of items from the QPS Nordic and items constructed by the authors. SETTING: A primary care setting in a central area of Sweden. SUBJECTS: Native-born (n = 208) and foreign-born GPs (n = 73). RESULTS: Turnover intention was more common among foreign-born GPs (19.2% compared with 14.9%), as was the experience of threats or violence from patients (22% compared with 3% of the native-born GPs). Threats or violence was also associated with increased turnover intention. Control of work pace and an empowering leadership was associated with reduced turnover intention. PRACTICE IMPLICATIONS: The organisations need to recognise that foreign-born GPs may face increased rates of threats and/or violence from patients, which may ultimately cause job turnover and be harmful to the exposed individual.

Gender differences in Reasons for Sickness Presenteeism - a study among GPs in a Swedish health care organization.

BACKGROUND: It is common that physicians go to work while sick and therefore it is important to understand the reasons behind. Previous research has shown that women and men differ in health and health related behavior. In this study, we examine gender differences among general practitioners who work while sick. METHODS: General practitioners (GP's) working in outpatient care in a Swedish city participated in the study (n = 283; women = 63 %; response rate = 41 %). Data were obtained from a large web-based questionnaire about health and organization within primary care. Two questions about sickness presenteeism (going to work while sick) were included; life-long and during the past 12 months, and five questions about reasons. We controlled for general health, work-family conflict and demographic variables. RESULTS: Female physicians reported sickness presenteeism more often than male physicians. Work-family conflict mediated the association between gender and sickness presenteeism. Women reported reasons related with "concern for others" and "workload" more strongly than men. Men reported reasons related with "capacity" and "money" more strongly than women. These differences are likely effects of gender stereotyping and different family-responsibilities. CONCLUSIONS: Gender socialization and gender stereotypes may influence work and health-related behavior. Because sickness presenteeism is related with negative effects both on individuals and at organizational levels, it is important that managers of health organizations understand the reasons for this, and how gender roles may influence the prevalence of sickness presenteeism and the reasons that female and male GPs give for their behavior.

Does patient's sex influence treatment in primary care? Experiences and expressed knowledge among physicians--a qualitative study.

BACKGROUND: Biological and sociocultural differences between men and women may play an important role in medical treatment. Little is known about the awareness of these differences among general practitioners (GPs) and if they consider such differences in their medical practice. The aim of this study was to explore GPs' perception of sex and gender aspects in medical treatment. METHODS: We conducted five focus group discussions (FGDs) with 29 physicians (mainly GPs) in Sweden. A discussion guide with semi-structured questions was used. All FGDs were audio-recorded and transcribed word-by-word. Data were analysed through inductive thematic analysis with no predetermined categories. RESULTS: Three main categories emerged from the data. The first category emphasised GPs' experiences of sex and gender differences in diagnosing and assessment of clinical findings. Medical treatment in men and women was central in the second category. The third category emphasised GPs' knowledge of sex differences in drug therapy. CONCLUSIONS: The GPs stated they had little knowledge of sex and gender differences in drug treatment, but gave multiple examples of how the patient's sex affects the choice of treatment. Sex and gender aspects were considered in diagnosing and in the treatment decision. However, once the decision to treat was made the choice of drug followed recommendations by local Drug and Therapeutics Committee, which were perceived to be evidence-based. In the analysis we found a gap between perceived and expressed knowledge of sex and gender differences in drug treatment indicating a need of education about this to be included in the curriculum in medical school and in basic and specialist training for physicians. Education could also be a tool to avoid stereotypical thinking about male and female patients.