Comorbidity and sex differences in functional disorders and internalizing disorders.

OBJECTIVE: In the current exploratory study we estimate comorbidity rates between FDs [fibromyalgia (FM), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and irritable bowel syndrome (IBS)]-and IDs-[major depressive disorder (MDD) and generalized anxiety disorder (GAD)] by using self-reported diagnostic criteria. METHOD: We analyzed data from 107,849 participants (mean age = 49.3 (SD = 13.0), 58.6% women) of the Lifelines Cohort Study. Lifelines is a prospective population-based cohort study in the northeast of the Netherlands. Current IDs were assessed using the Mini-International Neuropsychiatric Interview. Current FM, ME/CFS, and IBS were assessed according to the 2010 American College of Rheumatology criteria, the 1994 Centers for Disease Control and Prevention criteria and the ROME IV criteria, respectively. We estimated tetrachoric correlations between diagnoses and tested for sex differences. Additionally, we estimated the ratio of observed-to-expected frequency for combinations of diagnoses. RESULTS: FDs and IDs are highly comorbid (odds ratios: 3.2-12.6) with associations stronger among men. Participants with at least three disorders/diagnoses were more prevalent than expected by chance. CONCLUSION: Studies that aim to explain sex differences and the comorbidity of specific combinations of IDs and FDs will be an important contribution to understanding the etiology of these conditions.

Gender scores in epidemiological research: methods, advantages and implications.

Sex and gender-related factors are strongly associated with patients' illness trajectories, underscoring their essential role in epidemiological research and healthcare. Ignoring sex and gender in research and health inevitably results in inequities between women and men in terms of detection of disease, preventative measures, and effectiveness of treatment. Historical influences, including ideas of female inferiority and conservative notions of women's health only comprising reproductive health, reinforced the perceived irrelevance of sex and gender to health. Currently, these ideas are largely abandoned and epidemiology is becoming increasingly sensitive to sex. Gender-sensitivity, however, is lagging behind. This is potentially due to lacking knowledge and awareness about the relevance of both sex and gender to health and challenges in operationalizing gender in epidemiological research. Here, we thoroughly discuss the relevance of sex and gender to health, and pay special attention to the time, place, and culture-dependent embodiment of gender. We also discuss the operationalization of gender via composite gender scores in epidemiological studies. We argue to move beyond solely using these. Rather we should consider sex and gender in the initial stages of designing a study, to facilitate relevant, reproducible, and person-centric research.

Family healthcare patterns as a proxy for transgenerational transmission of functional somatic symptoms in early childhood - A longitudinal cohort study.

OBJECTIVE: Functional somatic symptoms (FSS) accumulate within families. Exposure to family patterns of high healthcare use may induce maladaptive symptom coping and thereby potentially contribute to the transgenerational transmission of FSS. This study aimed to uncover associations between parental and child healthcare use during the child's first years of life (age 0-4) and childhood FSS at age 5-7. METHODS: We utilized data from the Copenhagen Child Cohort (CCC2000), a population-based birth cohort. Parent-reported FSS of their 5-7-year-old children were linked to Danish national registry data on parental and child healthcare use (including general practitioner [GP] consultations and hospital contacts) during child age 0-4 years. Logistic regression analyses were performed to investigate longitudinal associations between family healthcare use and child FSS. RESULTS: We found an association between prior parental healthcare use and child FSS at age 5-7 (OR = 1.02, 95% CI [1.01-1.04]). Key sensitivity analyses specifically focusing on GP consultations, revealed modest but statistically significant associations between parental (OR = 1.03, 95% CI [1.02-1.05]) and child (OR = 1.18, 95% CI [1.04-1.34]) GP consultations and impairing FSS at age 5-7. CONCLUSION: Family healthcare use, especially within the general practice, may play a role in the transgenerational transmission of FSS. Early-stage FSS identification and care might be improved through training aimed at GPs. Future research may identify vulnerable families at whom parent-focused interventions for symptom-coping could be targeted. This could potentially contribute to the prevention of transgenerational transmission of FSS.

Persistent physical symptoms: definition, genesis, and management.

Persistent physical symptoms (synonymous with persistent somatic symptoms) is an umbrella term for distressing somatic complaints that last several months or more, regardless of their cause. These symptoms are associated with substantial disability and represent a major burden for patients, health-care professionals, and society. Persistent physical symptoms can follow infections, injuries, medical diseases, stressful life events, or arise de novo. As symptoms persist, their link to clearly identifiable pathophysiology often weakens, making diagnosis and treatment challenging. Multiple biological and psychosocial risk factors and mechanisms contribute to the persistence of somatic symptoms, including persistent inflammation; epigenetic profiles; immune, metabolic and microbiome dysregulation; early adverse life experiences; depression; illness-related anxiety; dysfunctional symptom expectations; symptom focusing; symptom learning; and avoidance behaviours, with many factors being common across symptoms and diagnoses. Basic care consists of addressing underlying pathophysiology and using person-centred communication techniques with validation, appropriate reassurance, and biopsychosocial explanation. If basic care is insufficient, targeted psychological and pharmacological interventions can be beneficial. A better understanding of the multifactorial persistence of somatic symptoms should lead to more specific, personalised, and mechanism-based treatment, and a reduction in the stigma patients commonly face.

Factors associated with having previously received a diagnosis of fibromyalgia, chronic fatigue syndrome and irritable bowel syndrome: A cross sectional DanFunD study.

OBJECTIVES: Fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome are highly prevalent conditions and part of the functional somatic syndromes (FSS) diagnosis, that are classified under the unifying umbrella term functional somatic disorder (FSD). Multiple factors are associated with FSD symptom development; However, few studies have explored these associations in relation to the diagnosis status. This study aims to examine associations with a previously received FSS diagnosis from a physician in participants fulfilling the FSD diagnostic criteria in a population-based sample. METHODS: This research employs a comprehensive observational approach using a cross sectional design with data from the DanFunD part two cohort. Information about received FSS diagnoses was obtained from self-reported questionnaires. Participants fulfilling the FSD diagnostic criteria were identified with both self-reported questionnaires and diagnostic interviews. Validated questionnaires were used to assess the examined factors. RESULTS: 1704 cases fulfilled the diagnostic criteria for an FSD according to questionnaires or interviews in the DanFunD study. In participants fulfilling the diagnostic criteria, having previously received an FSS diagnosis by a physician was strongly associated with female sex, negative illness perceptions and poor health-related quality of life for questionnaire and interview-based diagnoses. Less consistent associations were observed for lower socioeconomic status, anxiety, and adverse life events. CONCLUSION: Previously received FSS diagnoses showed associations with multiple factors with a particular strong association with female sex and poor health related quality of life.

Healthcare professionals' views on factors influencing persistent somatic symptoms - ARISE-HCP online survey across countries.

OBJECTIVE: The Health Care Online Survey Europe-Healthcare Professionals (ARISE-HCP) cross-sectionally investigated healthcare professionals' (HCPs) views on healthcare factors influencing the symptom course of persistent somatic symptoms (PSS) across four European countries. METHODS: An online survey was developed for HCPs experienced in PSS care in Germany, Italy, Poland, and the Netherlands. The study employed a mixed-methods approach. Quantitatively, it assessed HCPs' perspectives on training, tools, and consultation times. Qualitatively, it explored their perceptions of healthcare-related factors influencing the PSS symptom course and systemic barriers encountered in treatment and diagnosis. RESULTS: Overall, 258 HCPs participated: 152 from the Netherlands, 46 from Germany, 30 from Italy, and 30 from Poland (67% female, mean age = 47.68 ± 11.64 years). HCPs' views on PSS training, tool adequacy, and consultation time sufficiency differed significantly. Regarding symptom persistence and deterioration, HCPs from Italy and Poland highlighted access-related issues, whereas German and Dutch HCPs focused on care implementation. Across all countries, interdisciplinary collaboration was mentioned as important for symptom improvement. A more holistic approach was advocated, emphasizing the need for comprehensive PSS-focused training and the integration of these practices in care delivery, service coordination, and patient engagement. CONCLUSION: Healthcare factors associated with the course of PSS and systemic treatment and diagnosis barriers varied across different countries, highlighting the importance of considering country-specific factors in managing PSS. Taking tailored measures to enhance multidisciplinary collaboration and HCP education is essential for improving patient outcomes, and sharing knowledge about effective healthcare practices across countries can improve patient care. Future research should focus on identifying systemic barriers to optimal care and developing country-specific interventions.

The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: an individual participant data meta-analysis.

BACKGROUND: Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers). METHODS: Two-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs). RESULTS: Smoking (HRs range 1.04-1.10) and physical inactivity (HRs range 1.01-1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03-1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01). CONCLUSIONS: Smoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.

Strategies to improve implementation of collaborative care for functional disorders and persistent somatic symptoms: A qualitative study using a Research World Café design.

INTRODUCTION: Persistent somatic symptoms and functional disorders (PSS/FD) are often complex conditions requiring care from multiple disciplines. One way of bringing the different disciplines together is through collaborative care. Little is known about the implementation barriers faced and relevant strategies to tackle the barriers in this field. Therefore, using expert knowledge, we aim to develop realistic strategies for dealing with implementation barriers of collaborative care in PSS/FD. METHODS: The Research World Café method is a single-session, expert-based method with multiple focus-groups forming and reforming to answer a set of inter-related questions, under the guidance of moderators. Using this method, participants involved in PSS/FD care across different areas of healthcare in the Netherlands developed several realistic strategies for dealing with ten implementation barriers for collaborative care in PSS/FD that were previously identified in a Delphi study. Strategies were grouped into strategy clusters using a card-sorting task. RESULTS: Thirty-three participants took part, representing ten different disciplines, most commonly physiotherapists, psychologists, and physicians. In total, 54 strategies, identified in response to the ten barriers, were grouped into eight strategy clusters. The strategy clusters were professional education, communication, care coordination, care pathways, joint consults, funding, patient involvement, and prevention. CONCLUSION: We identified a number of useful strategies for dealing with implementation barriers for collaborative care in PSS/FD. Many strategies provided ways to deal with multiple barriers at once. The effects of applying these strategies in collaborative care in PSS/FD will need testing through implementation studies, as well as in other areas needing multidisciplinary care.

Validity and diagnostic overlap of functional somatic syndrome diagnoses.

OBJECTIVE: We present the first study that investigates the validity and the diagnostic overlap of the three main functional somatic syndrome (FSS) diagnoses, i.e. chronic fatigue syndrome (CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS), irrespective of help-seeking behaviour or diagnostic habits, and irrespective of differences in diagnostic thresholds for chronicity or symptom interference. METHODS: This cross-sectional analysis was performed in 89,781 participants of the general-population cohort Lifelines. Diagnostic criteria for CFS (Centers for Disease Control and Prevention), FM (American College of Rheumatology) and IBS (Rome IV) were assessed by questionnaire. Additional items were added to enable studying the effects of differences in thresholds for minimum symptom chronicity (varying from three for FM to six months for CFS and IBS), and symptom interference (required for CFS but not for FM and IBS). RESULTS: The diagnostic criteria were met by 3.1% for CFS, 6.6% for FM, and 5.5% for IBS participants. The number of participants that met criteria for all three diagnoses was 45 times higher than what would have been expected based on chance. After alignment of the chronicity and symptom interference criteria to circumvent differences in diagnostic thresholds, the overlap between diagnoses increased to 152 times. Furthermore, there was a similar pattern of symptom occurrence, particularly for those fulfilling diagnostic criteria for CFS and FM. CONCLUSION: The diagnostic overlap of different FSS was much higher than would be expected by chance, and substantially increased when FSS were more chronic and serious in nature.

Psychological risk factors of somatic symptom disorder: A systematic review and meta-analysis of cross-sectional and longitudinal studies.

OBJECTIVE: Current diagnostic concepts of somatic symptom disorder (SSD) in DSM-5 and bodily distress disorder (BDD) in ICD-11 require certain psychological criteria, but researchers have called for further specification. Therefore, in a first step, this systematic review and meta-analysis aimed to summarize the current evidence on psychological factors associated with SSD/BDD and/or disorder-relevant clinical outcomes such as symptom severity and impairment. METHODS: Psychological factors were systematically searched using Pubmed, Cochrane Library and Psycinfo via EBSCO. Studies providing original data in English or German, after 2009 were included. Cross-sectional, cohort and case-control studies investigating at least one psychological factor in individuals with SSD/BDD in the context of disorder-relevant outcomes were included. RESULTS: Forty-three eligible studies (n = 3760 patients) in SSD (none in BDD) provided data on at least one psychological factor, 37 in case-control format, 10 cross-sectional and 5 longitudinal. Meta-analyses of the case-control studies found patients with SSD to be more impaired by depression (SMD = 1.80), anxiety (SMD = 1.55), health anxiety (SMD = 1.31) and alexithymia (SMD = 1.39), compared to healthy controls. Longitudinal results are scarce, mixed, and require refining, individual studies suggest self-concept of bodily weakness, anxiety and depression to be predictive for persistent SSD and physical functioning. CONCLUSION: This review provides a detailed overview of the current evidence of psychological factors in relation to SSD/BDD. Future studies on SSD and BDD should include under-studied psychological factors, such as negative affect, fear avoidance, or emotion regulation. More longitudinal studies are needed to assess the predictive value of these factors.

Development of Gender Non-Contentedness During Adolescence and Early Adulthood.

Adolescence is an important period for the development of gender identity. We studied the development of gender non-contentedness, i.e., unhappiness with being the gender aligned with one's sex, from early adolescence to young adulthood, and its association with self-concept, behavioral and emotional problems, and adult sexual orientation. Participants were 2772 adolescents (53% male) from the Tracking Adolescents' Individual Lives Survey population and clinical cohort. Data from six waves were included (ages 11-26). Gender non-contentedness was assessed with the item "I wish to be of the opposite sex" from the Youth and Adult Self-Report at all six waves. Behavioral and emotional problems were measured by total scores of these scales at all six waves. Self-concept was assessed at age 11 using the Global Self-Worth and Physical Appearance subscales of the Self-Perception Profile for Children. Sexual orientation was assessed at age 22 by self-report. In early adolescence, 11% of participants reported gender non-contentedness. The prevalence decreased with age and was 4% at the last follow-up (around age 26). Three developmental trajectories of gender non-contentedness were identified: no gender non-contentedness (78%), decreasing gender non-contentedness (19%), and increasing gender non-contentedness (2%). Individuals with an increasing gender non-contentedness more often were female and both an increasing and decreasing trajectory were associated with a lower global self-worth, more behavioral and emotional problems, and a non-heterosexual sexual orientation. Gender non-contentedness, while being relatively common during early adolescence, in general decreases with age and appears to be associated with a poorer self-concept and mental health throughout development.

Quality indicators for collaborative care networks in persistent somatic symptoms and functional disorders: a modified delphi study.

BACKGROUND: Care for persistent somatic symptoms and functional disorders (PSS/FD) is often fragmented. Collaborative care networks (CCNs) may improve care quality for PSS/FD. Effectiveness likely depends on their functioning, but we lack a straightforward quality evaluation system. We therefore aimed to develop quality indicators to evaluate CCNs for PSS/FD. METHOD: Using an online three-round modified Delphi process, an expert panel provided, selected and ranked quality indicators for CCNs in PSS/FD. Recruited experts were diverse healthcare professionals with relevant experience in PSS/FD care in the Netherlands. RESULTS: The expert panel consisted of 86 professionals representing 15 disciplines, most commonly physiotherapists, psychologists and medical specialists. 58% had more than 10 years experience in PSS/FD care. Round one resulted in 994 quotations, which resulted in 46 unique quality indicators. These were prioritised in round two and ranked in round three by the panel, resulting in a final top ten. The top three indicators were: "shared vision of care for PSS/FD", "pathways tailored to the individual patient", and "sufficiently-experienced caregivers for PSS/FD". CONCLUSIONS: The identified quality indicators to evaluate CCNs in the field of PSS/FD can be implemented in clinical practice and may be useful in improving services and when assessing effectiveness.

Psychosocial factors, health behaviors and risk of cancer incidence: Testing interaction and effect modification in an individual participant data meta-analysis.

Depression, anxiety and other psychosocial factors are hypothesized to be involved in cancer development. We examined whether psychosocial factors interact with or modify the effects of health behaviors, such as smoking and alcohol use, in relation to cancer incidence. Two-stage individual participant data meta-analyses were performed based on 22 cohorts of the PSYchosocial factors and CAncer (PSY-CA) study. We examined nine psychosocial factors (depression diagnosis, depression symptoms, anxiety diagnosis, anxiety symptoms, perceived social support, loss events, general distress, neuroticism, relationship status), seven health behaviors/behavior-related factors (smoking, alcohol use, physical activity, body mass index, sedentary behavior, sleep quality, sleep duration) and seven cancer outcomes (overall cancer, smoking-related, alcohol-related, breast, lung, prostate, colorectal). Effects of the psychosocial factor, health behavior and their product term on cancer incidence were estimated using Cox regression. We pooled cohort-specific estimates using multivariate random-effects meta-analyses. Additive and multiplicative interaction/effect modification was examined. This study involved 437,827 participants, 36,961 incident cancer diagnoses, and 4,749,481 person years of follow-up. Out of 744 combinations of psychosocial factors, health behaviors, and cancer outcomes, we found no evidence of interaction. Effect modification was found for some combinations, but there were no clear patterns for any particular factors or outcomes involved. In this first large study to systematically examine potential interaction and effect modification, we found no evidence for psychosocial factors to interact with or modify health behaviors in relation to cancer incidence. The behavioral risk profile for cancer incidence is similar in people with and without psychosocial stress.

Symptom profiles and their risk factors in patients with post-COVID-19 condition: a Dutch longitudinal cohort study.

BACKGROUND: To improve research and care for patients with post-COVID-19 condition more insight into different subtypes of post-COVID-19 condition and their risk factors is urgently needed. We aimed to identify risk factors of post-COVID-19 condition in general and for specific symptom profiles. METHODS: This study is based on data collected within the Lifelines Coronavirus disease 2019 (COVID-19) cohort (N = 76 503). Mean pre- and post-SARS-CoV-2 infection symptom scores were compared to classify post-COVID-19 condition. Latent Profile Analysis was used to identify symptom profiles. Logistic and multinomial regression analyses were used to examine the association between demographic, lifestyle and health-related risk factors and post-COVID-19 condition, and symptom profiles, respectively. RESULTS: Of the 3465 participants having had COVID-19, 18.5% (n = 642) classified for post-COVID-19 condition. Four symptom profiles were identified: muscle pain, fatigue, cardiorespiratory and ageusia/anosmia. Female sex was a risk factor for the muscle pain and fatigue profiles. Being overweight or obese increased risk for all profiles, except the fatigue profile. Having a chronic disease increased the risk for all profiles except the ageusia/anosmia profile, with the cardiorespiratory profile being only significant in case of multimorbidity. Being unvaccinated increased risk of the ageusia/anosmia profile. CONCLUSIONS: Findings from this study suggest that Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger different pathophysiological mechanisms that may result in different subtypes of post-COVID-19 condition. These subtypes have shared and unique risk factors. Further characterization of symptom profiles and quantification of the individual and societal impact of specific symptom profiles are pressing challenges for future research.

Depression, anxiety, and the risk of cancer: An individual participant data meta-analysis.

BACKGROUND: Depression and anxiety have long been hypothesized to be related to an increased cancer risk. Despite the great amount of research that has been conducted, findings are inconclusive. To provide a stronger basis for addressing the associations between depression, anxiety, and the incidence of various cancer types (overall, breast, lung, prostate, colorectal, alcohol-related, and smoking-related cancers), individual participant data (IPD) meta-analyses were performed within the Psychosocial Factors and Cancer Incidence (PSY-CA) consortium. METHODS: The PSY-CA consortium includes data from 18 cohorts with measures of depression or anxiety (up to N = 319,613; cancer incidences, 25,803; person-years of follow-up, 3,254,714). Both symptoms and a diagnosis of depression and anxiety were examined as predictors of future cancer risk. Two-stage IPD meta-analyses were run, first by using Cox regression models in each cohort (stage 1), and then by aggregating the results in random-effects meta-analyses (stage 2). RESULTS: No associations were found between depression or anxiety and overall, breast, prostate, colorectal, and alcohol-related cancers. Depression and anxiety (symptoms and diagnoses) were associated with the incidence of lung cancer and smoking-related cancers (hazard ratios [HRs], 1.06-1.60). However, these associations were substantially attenuated when additionally adjusting for known risk factors including smoking, alcohol use, and body mass index (HRs, 1.04-1.23). CONCLUSIONS: Depression and anxiety are not related to increased risk for most cancer outcomes, except for lung and smoking-related cancers. This study shows that key covariates are likely to explain the relationship between depression, anxiety, and lung and smoking-related cancers. PREREGISTRATION NUMBER: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=157677.

Discordance between Adolescents and Parents in Functional Somatic Symptom Reports: Sex Differences and Future Symptom Prevalence.

Functional somatic symptoms, i.e., physical complaints that cannot be sufficiently explained by an objectifiable biomedical abnormality, become increasingly more prevalent in girls than in boys during adolescence. Both parents and adolescents report more functional somatic symptoms in girls, but their reports correspond only limitedly. It remains unknown whether parent-adolescent discordance contributes to the higher symptom prevalence in girls. This study investigated parent-adolescent discordance in reported functional somatic symptoms throughout adolescence, examined the longitudinal association of parent-adolescent discordance with symptom prevalence in early adulthood and focused on sex differences in these processes. Participants included 2229 adolescents (50.7% female) from four assessments (age 11 to 22 years) of the TRAILS population cohort. Parents and adolescents reported significantly more symptoms in girls than in boys during adolescence. Variance analyses showed that throughout adolescence, parents reported fewer symptoms than girls self-reported and more than boys self-reported. Regression analyses using standardized difference scores showed that lower parent-report than self-report was positively associated with symptom prevalence in early adulthood. Polynomial regression analyses revealed no significant interaction between parent-reported and adolescent self-reported symptoms. Associations did not differ between boys and girls. The findings show that lower parent-reported than self-reported symptoms predict future symptom prevalence in both sexes, but this discordance was more observed in girls. The higher functional somatic symptom prevalence in girls might be partly explained by parental underestimation of symptoms.

How to Ensure Inclusivity in Large-Scale General Population Cohort Studies? Lessons Learned with Regard to Including and Assessing Sex, Gender, and Sexual Orientation.

Despite recent advances in the measurement of sex, gender, and sexual orientation in large-scale cohort studies, the three concepts are still gaining relatively little attention, may be mistakenly equated, or non-informatively operationalized. The resulting imprecise or lacking information hereon in studies is problematic, as sex, gender, and sexual orientation are important health-related factors. Omission of these concepts from general population cohort studies might dismiss participants' identity and experiences and pushes research on sexual or gender minority populations toward purposive sampling, potentially introducing selection bias. It also reinforces the unintentional notion of irrelevance of these concepts to health research, ultimately disadvantaging sexual and gender minority populations. Similarly, a lack of uniform measures on sex, gender, and sexual orientation hampers multi-cohort studies in which data from multiple studies are combined, facilitating increased statistical power. This paper discusses the encountered pitfalls and lessons learned on including and assessing sex, gender, and sexual orientation in large-scale general population cohort studies, exemplified by the Dutch Lifelines Cohort Study. Additionally, we propose hands-on strategies on how to operationalize these concepts in an inclusive manner that is useful for large-scale general population cohort studies.

Sex and gender differences in primary care help-seeking for common somatic symptoms: a longitudinal study.

OBJECTIVE: Women are reported to consult general practitioners (GPs) more frequently than men. However, previous studies on sex differences in help-seeking behavior for somatic symptoms do not distinguish between sex and gender, do not account for sex differences in presented symptoms, and are frequently conducted in clinical settings, automatically excluding non-help seekers. Therefore, we aim to assess the independent associations of sex and gender with primary care help-seeking for somatic symptoms in the general population. DESIGN AND SETTING: Records from the longitudinal population-based Lifelines Cohort Study were linked to routine electronic health records from GPs. SUBJECTS: Participants reporting new-onset common somatic symptoms. MAIN OUTCOME MEASURES: Associations between sex and gender, operationalized via a novel gender-index, with primary care help-seeking for somatic symptoms and differences in the strength of the association between gender and help-seeking for somatic symptoms between women and men. RESULTS: Of 20,187 individuals with linked data, 8325 participants (67.5% female; mean age = 44.5 years [SD = 12.9]) reported at least one new-onset somatic symptom. Hereof, 255 (3.1%) consulted the GP within 6 weeks of symptom onset. Female sex was positively associated with consulting the GP (OR = 1.78; 95%CI = 1.13-2.80), whereas feminine gender was not (OR = 0.67; 95%CI = 0.39-1.16). The latter association did not differ in strength between men and women. More paid working days are negatively associated with help-seeking (OR = 0.95; 95%CI = 0.91-0.98). CONCLUSIONS: The results suggest that female sex rather than feminine gender is associated with primary care help-seeking behavior for somatic symptoms. Nevertheless, clinicians should be aware that gender-related variables, such as mean paid working days, may be associated with help-seeking behavior.