Journal of Psychosomatic Research 149 (2021) 110589

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Journal of Psychosomatic Research

journal homepage: www.elsevier.com/locate/jpsychores

Sex differences in the trajectories to diagnosis of patients presenting with

common somatic symptoms in primary care: an observational cohort study
Aranka V. Ballering a, *, Daan Muijres b, Annemarie A. Uijen b, Judith G.M. Rosmalen a,
Tim C. olde Hartman b
a
University of Groningen, University Medical Center of Groningen, Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), Groningen, the
Netherlands, P.O. Box 30.001, 9700, RB, Groningen, the Netherlands
b
Department of Primary and Community Care, Radboud University Medical Center, Nijmegen, the Netherlands. P.O. Box 9101, 6500, HB, Nijmegen, the Netherlands

A R T I C L E I N F O A B S T R A C T

Keywords: Objective: Little insight exists into sex differences in diagnostic trajectories for common somatic symptoms. This
Common somatic symptoms study aims to quantify sex differences in the provided primary care diagnostic interventions for common somatic
General practice symptoms, as well as the consequences hereof for final diagnoses.
Medically unexplained symptoms
Methods: In this observational cohort study, we used real-world clinical data from the Dutch Family Medicine
Primary care
Network (N = 34,268 episodes of care related to common somatic symptoms; 61,4% female). The association
Sex differences
between patients’ sex on the one hand, and diagnostic interventions and disease diagnoses on the other hand,
were assessed using multilevel multiple logistic regression analyses. Structural equation modelling was used to
estimate a mediation model with multiple parallel mediators to assess whether the fewer disease diagnoses given
to female patients were mediated by the fewer diagnostic interventions female patients receive, compared to
male patients.
Results: Women received fewer physical examinations (OR = 0.84, 95%CI = 0.79–0.89), diagnostic imaging (OR
= 0.92, 95%CI = 0.84–0.99) and specialist referrals (OR = 0.85, 95%CI = 0.79–0.91) than men, but more
laboratory diagnostics (OR = 1.27, 95%CI = 1.19–1.35). Women received disease diagnoses less often than men
for their common somatic symptoms (OR = 0.94, 95%CI = 0.89–0.98). Mediation analysis showed that the fewer
disease diagnosis in female patients were mediated by the fewer diagnostic interventions conducted in women
compared to men.
Conclusion: This study shows that sex inequalities are present in primary care diagnostic trajectories of patients
with common somatic symptoms and that these lead to unequal health outcomes in terms of diagnoses between
women and men. FPs have to be aware of these inequalities to ensure equal high-quality care for all patients.

1. Introduction examinations, diagnostic imaging and specialist referrals when they

Health outcomes are closely related to patients’ trajectories to
diagnosis [1]. A diagnostic trajectory comprises everything a family
physician (FP) does, including diagnostic interventions, to obtain a
diagnosis for a patient’s complaint. Yet, patients’ characteristics,
including their sex, may influence the FPs perception of symptoms and
consequently, patients’ diagnostic trajectories [1].
Diagnostic trajectories for multiple diseases differ between women
and men. A recent study shows that women receive fewer physical
present with cough and/or dyspnoea in primary care than men [2].
Additionally, studies show that a patient’s sex is associated with
different diagnostic trajectories in coronary heart disease (CHD).
Women presenting with symptoms suggestive of CHD in primary care
are less likely to receive physical examinations [3,4]. A similar sex dif­
ference is observed in colorectal cancer, as studies show women have
higher mortality rates and are less often screened than men [5]. How­
ever, a recent study shows that men are less likely to receive an early
diagnosis of dementia than women [6].

* Corresponding author at: Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), Groningen, the Netherlands, P.O. Box 30.001, Internal code
CC72, 9700, RB, Groningen, the Netherlands.
E-mail addresses: a.v.ballering@umcg.nl (A.V. Ballering), Daan.Muijres@radboudumc.nl (D. Muijres), Annemarie.Uijen@radboudumc.nl (A.A. Uijen), j.g.m.
rosmalen@umcg.nl (J.G.M. Rosmalen), Tim.OldeHartman@radboudumc.nl (T.C. olde Hartman).

https://doi.org/10.1016/j.jpsychores.2021.110589
Received 20 April 2021; Received in revised form 27 July 2021; Accepted 28 July 2021
Available online 31 July 2021
0022-3999/© 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
A.V. Ballering et al.
Although sex differences in the prevalence and longevity of common
somatic symptoms are recognized [7,8], little insight exists into sex
differences in the primary care diagnostic trajectories related to these
symptoms. Most research into diagnostic trajectories focuses on previ­
ously diagnosed disease [9,10] and only the aforementioned study on
respiratory symptoms studied diagnostic trajectories from symptom
presentation to final diagnosis in primary care [2]. Additionally, pre­
vious research into diagnostic trajectories is based on self-reported
outcomes, which are prone to recall bias [11,12].
It is thought that sex differences exist in whether patients receive a
disease diagnosis [13,14], with women’s symptoms remaining more
often unexplained than men’s. However, it remains unknown whether
the primary care diagnostic trajectory associates with symptoms that
remain unexplained. It is pivotal to understand sex differences in diag­
nostic trajectories of somatic symptoms as these may result in sex in­
equalities in healthcare and sex-skewed morbidity or mortality rates
[5,15].
Therefore, this study aims to quantify sex differences in primary care
diagnostic trajectories of patients with common somatic symptoms and
to assess whether potential sex differences in these trajectories are
associated with whether the somatic symptoms are ultimately attribut­
able to a disease (i.e. disease diagnosis) or continue to be symptoms that
cannot be (fully) explained by an underlying disease or bodily abnor­
mality (i.e. symptom diagnosis) [16]. Firstly, we will study the presence
of differences between female and male patients in provided diagnostic
interventions when a patient presents with somatic symptoms in pri­
mary care. Secondly, we will assess whether sex differences exist in
whether the patient receives a disease diagnosis when presenting with
somatic symptoms. Lastly, we will study whether potential differences in
women’s and men’s diagnostic trajectories are associated with patients’
final diagnoses.
2. Methods
2.1. Study design and data collection
In this observational cohort study we used data from the Practice
Based Research Network (PBRN) Family Medicine Network (FaMe-Net),
which includes approximately 32,000 patients and 26 FPs in seven
different primary care practices throughout the Netherlands. Studies
involving FaMe-Net data are exempted from ethical review by the CCMO
(Dutch Central Committee on research involving human subjects). Pa­
tients are extensively informed about the inclusion of their health-
related information in FaMe-Net, and are offered the opportunity to
opt out of FaMe-Net. FaMe-net is embedded in the regular Dutch pri­
mary care system. It is the world’s oldest PRBN and since its inception
patients’ morbidity is systematically registered within an episode of care
(EoC) structure [17]. An EoC is defined as a patient’s health problem
from the first encounter until the last encounter related to that specific
health problem. Within each encounter of an EoC, the FP routinely and
systematically codes the patient’s reason for encounter (RFE), diagnosis
and interventions (including physical examinations, diagnostic tests and
referrals to specialists) according to the International Classification of
Primary Care (ICPC-2). An EoC may start with more than one RFE, but
one final diagnosis is ultimately linked to all encounters within the EoC.
The registered diagnosis of an EoC can be modified anytime when new
insights regarding the patient’s RFE arise. The RFE should be
acknowledged by the patient as a correct description of their demand of
care. The validity of data registration is high, as participating FPs
structurally meet to discuss diagnostic criteria to minimize bias during
registration. Moreover, the automated FP information system recognizes
inconsistencies in registration.
We selected EoC that started on January 1st, 2014 until December
31st, 2018 with at least one common somatic symptom. Contacts within
EoC that continued hereafter were excluded. Face-to-face encounters,
telephone and digital consultations were included within an EoC. The
2
Journal of Psychosomatic Research 149 (2021) 110589
relative distribution of the type of contact was similar among female and
male EoC. We included fifteen RFEs related to twelve symptoms:
headache (ICPC-N01), dizziness (ICPC-N17), heart pain (ICPC-K01),
(lower) back pain (ICPC-L02 and ICPC-L03), nausea (ICPC-D09), muscle
pain (ICPC-L18), shortness of breath/dyspnoea (ICPC-R02), chills (ICPC-
A02), tingling of fingers, feet and/or toes (ICPC-N05), swallowing/
throat problems (ICPC-D21 and ICPC-R21), weakness or general tired­
ness (ICPC-A04), and arm or leg symptoms (ICPC-L09 and ICPC-L14).
These symptoms reflect the contents of the Symptom CheckList-90 So­
matization subscale (SCL-90 SOM) [18], are common [19], and often
remain unexplained [1]. EoCs starting with the same RFE on the same
date within the same patient were excluded (N = 106). We analysed the
EoC that started with more than one RFE related to somatic symptoms
(N = 1605; 4.7%) as an EoC of the first-mentioned RFE.
2.2. Statistical analyses
To assess sex differences in whether a physical examination (ICPC-30
and ICPC-31) was conducted, and whether laboratory diagnostic in­
terventions, including microbiological/immunological testing and
blood tests (ICPC-33 and ICPC-34, respectively), diagnostic imaging
(ICPC-41) and specialist referrals (ICPC-67) were requested when pa­
tients presented common somatic symptoms, we conducted multilevel
multiple logistic regression analyses. Patients’ sex, patients’ age at time
of diagnosis, the number of contacts between patients and FPs during an
EoC, the type of RFE, the type of consults (face-to-face or by phone/
electronic) and the presence of comorbidities at the start of an EoC
(Supplementary Table 1) were included as independent variables; the
diagnostic interventions were included as dependent variable. As EoCs
are nested at the individual level, analyses were clustered at this level.
To exclude that the association between sex and laboratory diagnostics
was explained by women receiving laboratory diagnostics to confirm a
urinary tract infection when presenting (lower) back pain, we conducted
a sensitivity analyses in which EoC starting with (lower) back pain were
excluded. We included sex-by-RFE interaction terms to assess whether
the association between the type of RFE and interventions differed be­
tween female and male patients.
Similar analyses, with disease diagnosis as the outcome, were con­
ducted to assess whether the presence of disease diagnoses in an EoC
that started with somatic symptoms differed between women and men.
A disease diagnosis was operationalized as ICPC≥70, including psychi­
atric ICPC codes. This means that symptoms, followed over time,
evolved in a diagnosed disease. In contrast, a symptom diagnosis was
operationalized as ICPC≤30, in which symptoms followed over time
continued to be symptoms as relevant diagnostic criteria were not met.
For example, a symptom diagnosis is registered for symptoms if during
the whole year no medical diagnosis (i.e. an ICPC≥70) has been regis­
tered as explanation for the symptom.
To assess whether the diagnostic interventions mediated the associ­
ation between sex and disease diagnosis, we used structural equation
modelling to estimate a mediation model with multiple parallel medi­
ators. We used weighted least squares-estimation with 1000 bootstraps.
Because all involved variables were binary, we used a probit link-
function to estimate all regression coefficients and 95%CIs for direct
and indirect paths between sex and final diagnosis. To facilitate easier
interpretation of the probit slopes, we converted the predicted proba­
bilities of the probit model to odds and computed the concomitant odds
ratio [20,21] .
To test whether continuous covariates included in the logistic
regression analyses fulfilled the linearity assumption of multiple logistic
regression we divided the covariates into categories, and assessed
whether the estimates changed monotonically. We found no indication
for multicollinearity as the VIF was <5 in all analyses [22]. The statis­
tical analyses and additional descriptive analyses were conducted in IBM
SPSS Statistics v. 25, except for the mediation analysis, which was
performed in R version 3.5.1, package ‘Lavaan’ version 0.6–5 [23]. We
A.V. Ballering et al. Journal of Psychosomatic Research 149 (2021) 110589

maintained a two-sided alpha-value of p < 0.004 corrected for multiple
testing.
3. Results
3.1. Study population and incidence rates of common somatic symptoms
We identified 34,268 unique EoC that started with 46,898 RFEs. In
total, 9690 (28.3%) EoC started with more than one RFE. An overview of
the study population is given in Table 1.
Fig. 1 shows that heart pain and chills were equally presented by
women and men; other symptoms were more frequently presented by
women than men. The most prevalent symptoms in both sexes were
weakness/general tiredness, (lower) back pain, swallowing/throat
symptoms, and arm or leg symptoms. In total, 21,031 (61.4%) female
EoC and 13,327 (38.6%) male EoC were found, translating into a total of
266.4 (95%CI = 263.3–269.5) and 174.8 (95%CI = 172.1–177.5) EoC
related to somatic symptoms per 1000 patient years in women and men,
respectively (Supplementary Table 2).
3.2. Sex differences in diagnostic interventions
3.3. Sex differences in final diagnoses
Table 3 shows that women have 0.94 times the odds (95%CI =
0.89–0.98) of men to receive a disease diagnosis, when they present with
somatic symptoms in primary care, adjusted for their age, number of
contacts within an EoC, type of consult and RFE and comorbidities. In
heart pain we found the largest sex difference in receiving a disease
diagnosis as final diagnosis: women had 0.56 times the odds (95%CI =
0.37–0.84) compared to men to receive a disease diagnoses. Supple­
mentary Table 4 provides the sex-stratifed final diagnoses most
commonly given for somatic symptoms.
3.4. Mediation effects of interventions on the association between sex and
disease diagnoses
Table 4 shows that the association between sex and disease diagnoses
(i.e. the direct effect) is no longer statistically significant (OR = 1.02;
95%CI = 0.99–1.06), whereas the total effect was statistically significant
(OR = 0.94; 95%CI = 0.93–0.98). Diagnostic interventions, except for
diagnostic imaging, at least partly explain the association between sex
and final diagnosis. Supplementary Fig. 5 shows the probit regression
coefficients.

Table 2 shows that women have 0.84 (95%CI = 0.79–0.89) times the 4. Discussion
odds of men to receive a physical examination during their EoC,
adjusted for age, number of contacts within an EoC, type of consult and This study identified sex differences in the diagnostic trajectories of
RFE, and comorbidities. Also, female patients received fewer diagnostic patients presenting with somatic symptoms in primary care. We found
imaging and specialist referrals than their male counterparts. In that women present themselves more often with somatic symptoms than
contrast, we found that women were more likely to receive laboratory men, and that men are more likely to receive a physical examination,
diagnostics than men (OR = 1.27, 95%CI = 1.19–1.35). We found an diagnostic imaging and specialist referrals than women, whereas women
unadjusted OR of 1.28 (95%CI = 1.21–1.35) and an adjusted OR of 1.20 received more laboratory diagnostics. This is the first study that shows
(95%CI = 1.12–1.28) in sensitivity analyses that excluded EoC related to that the fewer disease diagnoses given to women are mediated by the
(lower) back pain. fewer diagnostic interventions that are performed in women.
In models in which we included sex-by-RFE interaction terms we
found that the associations between the type of RFE and diagnostic 4.1. Strengths and limitations
imaging or a specialist referral did not differ between women and men.
However, a significant interaction term (OR = 0.33, 95%CI = Our study had several strengths. First, the FaMe-Net database holds
0.13–0.81) showed that women were less likely to receive a physical rich, valid and accurate primary care data of a large patient cohort.
examination when presenting chills. Moreover, significant interaction Participating FPs frequently discuss coding and the inherent warning
terms showed that women were more likely to receive laboratory di­ system in the FP information system resulted in no indication of missing
agnostics if they presented with vertigo/dizziness, (lower) back pain and data in our cohort. Additionally, we used the RFE to define symptoms,
weakness/general tiredness than men (OR = 1.91, 95%CI = 1.43–2.56; which is an accurate measure, as the RFE is not interpreted by the FP
OR = 1.69, 95%CI = 1.26–2.26; OR = 1.46, 95%CI = 1.14–1.88, [24].
respectively). Analyses stratified per RFE are shown in Supplementary We acknowledge several limitations of our study as well. First, the
Table 3. patients’ full medical history was unknown to the researchers. Second,
the adjustment for comorbidities included cardiovascular diseases, res­
Table 1 piratory diseases and malignancies, which is non-exhaustive. Both the
Overview of the study population. patient’s full medical history and comorbidities could have affected FPs’
Characteristic Women Men p-value clinical decision making process and final diagnosis. Further research
should investigate whether FPs value medical history and comorbidities
Patients, N (%) 10,541 7915 (42.9)
(57.1) similarly in female and male patients. Also, we could not include
Patient yearsa, N (%) 78,954 75,734 possible effect modifiers in our analyses, for example the patient’s so­
(52.3) (47.7) cioeconomic status or ethnicity, and the FP’s working experience and
New EoC, N (%) 21,031 13,237
sex [25], as these data were unavailable.
(61.4) (38.6)
Age in years, Mean (SD) 43.4 (23.1) 42.3 (23.9) <0.001b
Notably, especially the FP-patient sex concordance is important in
Number of encounters per EoC, Median 1.0 (1.0, 1.0 (1.0, 0.053c patients’ diagnostic trajectories. For example, female physicians are
(IQR) 2.0) 2.0) more inclined to deliver female preventive procedures, such as a Pap-
EoC with comorbidities at the start, N 8282 (39.4) 5295 (43.7) 0.271d smear [25,26]. Patients, irrespective their sex, are also more assertive
(%)
and demanding towards female FPs than towards male FPs. Therefore,
Cardiovascular disease 5741 (27.3) 3827 (28.9) 0.001d
Asthma and/or COPD 3106 (14.8) 1998 (15.1) 0.427d patients may request more interventions from female FPs [27]. Thus, if
Malignancies 1684 (8.0) 979 (7.4) 0.038d more female than male FPs are included in our study, the results may be
a skewed towards more diagnostic interventions, especially in female
The cumulative years the included patients were at risk for an incident
common somatic symptom. patients.
b
Independent t-test;
c
Mann-Whitney U test;
d
Chi-Square test

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A.V. Ballering et al. Journal of Psychosomatic Research 149 (2021) 110589

Fig. 1. Incidence of common somatic symptom, stratified by sex.

Table 2 Table 3
Associations between sex and the interventions conducted during an EoC. Associations between sex and receiving a disease diagnosis when presenting
Intervention Number of EoC (%) OR (95%CI)a
common somatic symptoms in primary care, stratified per RFE.
EoC with disease OR (95%CI)a
Female Male EoC Unadjusted Adjustedb
diagnoses,
EoC
N (%)
Physical 16,052 10,876 0.79 0.84
RFE Female Male Unadjusted Adjustedb
examination (78.5) (82.1) (0.75–0.84) (0.79–0.89)
EoC EoC
Laboratory 5649 2875 1.33 1.27
diagnostics (26.9) (21.7) (1.26–1.40) (1.19–1.35) Headache 858 506 0.99 0.99
Diagnostic 1264 (6.0) 951 (7.2) 0.83 0.92 (39.9) (40.2) (0.86–1.14) (0.85–1.14)
imaging (0.76–0.90) (0.84–0.99) Dizziness 629 365 0.84 0.86
Specialist 2160 1611 0.83 0.85 (35.3) (39.3) (0.72–0.99) (0.73–1.01)
referrals (10.3) (12.2) (0.77–0.89) (0.79–0.91) Heart pain 60 (17.8) 93 0.54 0.56
a (28.8) (0.37–0.77) (0.37–0.84)
Odds ratios reflect women compared to men.
b (Lower) back pain 596 360 1.21 1.20
Adjusted for the patients’ age at time of diagnosis, number of contacts in an (17.1) (14.5) (1.05–1.40) (1.03–1.39)
EoC, presence of comorbidities at the start of an EoC, type of consult and the type Nausea 295 114 0.88 0.87
of RFE. (32.7) (35.5) (0.68–1.15) (0.66–1.15)
Muscle pain 50 (15.5) 51 0.65 0.65
(22.0) (0.42–1.00) (0.41–1.02)
4.2. Comparison with existing literature
Shortness of breath 1240 933 0.87 0.92
(59.0) (62.5) (0.76–0.99) (0.80–1.06)
In line with previous studies, we found women to present more so­ Chills 35 (52.2) 40 0.68 0.71
matic symptoms in primary care than men [28,29]. We also found (61.5) (0.34–1.37) (0.32–1.60)
Tingling fingers, feet 149 101 0.98 0.96
women to receive fewer diagnostic interventions, except for laboratory
and/or toes (40.8) (41.4) (0.70–1.36) (0.68–1.35)
diagnostics, when presenting common somatic symptoms in primary Swallowing/throat 1821 1108 1.11 1.21
care. Our results are in line with a recent study that assessed patients’ symptoms (60.0) (57.5) (0.99–1.25) (1.06–1.36)
diagnostic trajectories in primary care for respiratory complaints: this Weakness/general 698 440 0.78 0.77
study found that women receive fewer physical examinations, diag­ tiredness (18.9) (23.0) (0.68–0.89) (0.67–0.89)
Arm and/or leg 1039 813 0.91 0.89
nostic imaging and specialist referrals than men when presenting with
symptoms (37.3) (39.5) (0.81–1.03) (0.79–1.00)
cough and/or dyspnoea [2]. Additionally, previous studies assessing the Total 7470 4924 0.93 0.94
management of CHD found similar sex differences in the conduct of (35,5) (37.2) (0.89–0.97) (0.89–0.98)c
physical examinations and specialist referrals [4,30,31]. One study, in a
Odds ratios reflect women receiving a disease diagnosis (either psychiatric
contrast, found a higher diagnostic test ordering in primary care in men or somatic) compared to men.
for CHD-related symptoms [3]. However, this study did not distinguish b
Adjusted for the patients’ age at time of diagnosis, number of contacts in an
between diagnostic imaging and laboratory diagnostics. EoC, presence of comorbidities at the start of an EoC and type of consult.
Our finding that women are more often diagnosed with a symptom c
Adjusted for aforementioned factors and type of RFE as well.
diagnosis than men is in line with earlier literature [32]: a previous
study found that women have 0.82 (95%CI = 0.74–0.88) times the odds previous study included, for example, constipation and sleep distur­
of men to receive a disease diagnosis for their somatic symptoms [1]. bances, whereas the current study did not include these symptoms.
The difference in strength of the association between female sex and a Similarly, a recent study found an incidence rate ratio of 0.70 (95%CI =
disease diagnosis compared to the current study may be partly due to the 0.54–0.91) for receiving a disease diagnosis for somatic symptoms in
different symptoms that were assessed in the previous study. The

4
A.V. Ballering et al. Journal of Psychosomatic Research 149 (2021) 110589

Table 4
Parallel mediation effects of interventions on the association between female sex
and final diagnosis for all RFEs.
OR (95%CI)a,b
Intervention Indirect effect Direct effect Total effect
Physical examination 0.96
(0.94–0.97)
Imaging 1.01 (1.00–1.01)
Laboratory 0.96
diagnostics (0.95–0.97)
Specialist referral 0.98
(0.98–0.99)
Total 0.91 1.02 0.94
(0.90–0.93) (0.99–1.06) (0.93–0.98)
a disease than women when consulting the FP for somatic symptoms,
Odds ratios reflect women compared to men.
b which justifies the sex difference in diagnostic interventions. Therefore,
Adjusted for patient’s age at time of diagnosis, number of contacts in an EoC,
presence of comorbidities at the start of an EoC and the type of RFE.
women compared to men in a Latino and Asian American patient pop­
ulation [33]. Possibly, ethnic diversity interacts with sex, resulting in an
excess of symptom diagnoses in women.
It is argued that many factors interact and form a complex interplay
that could partially explain the sex differences we found in interventions
and final diagnoses. First, it is known that women report more numerous
and varied somatic symptoms [7,34], possibly due to biological sex
differences in the central processing of sensory information [35].
Second, women visit their FP more often and earlier in their symp­
tom trajectory than men [36]. The heightened bodily vigilance of
women and their familiarization with primary care is thought to lower
the threshold of seeking care for somatic symptoms [37,38]. In contrast,
masculine gender stereotypes, for example stoicism about symptom
reporting [28,39], may delay male healthcare-seeking behaviour. Due to
the relatively early female healthcare-seeking behaviour, women pre­
sent with less typical symptoms of disease and consequently receive
fewer specialist referrals and diagnoses.
Third, sex differences in communication styles could contribute to
the sex difference in performed diagnostic interventions: women’s
communication is more subjective, talkative and polite, whereas men’s
communication is thought to be more demanding, rational and
straightforward [40].
Fourth, we found that women receive more laboratory diagnostics.
The higher likelihood of requesting laboratory diagnostics for female
patients could be an attempt to reassure the patient, as uncertainty
about symptoms is more often reported in women [3,41,42]. However,
FPs also request laboratory diagnostic tests to mitigate their own diag­
nostic uncertainty [43,44], which is thought to be higher in female
patients. Notably, sex differences in diagnostic uncertainty are mainly
investigated for CHD-related symptoms [3,45]; to our knowledge no
studies investigated sex differences in diagnostic uncertainty in common
somatic symptoms. Additionally, laboratory diagnostics are an easily
conducted and accessible intervention to rule out underlying conditions
related to common somatic symptoms that are more frequent in women,
for example urinary tract infections and anaemia.
Last, FPs’ prejudices could also promote sex differences in diagnostic
trajectories. For example, it is argued that physicians more readily as­
sume somatization in women [46] and offer fewer interventions to
women. FPs’ state that they feel that their unconscious presumptions
about gender and sex affect their clinical decision making process in a
way that may disadvantage one sex over the other [37].
4.3. Conclusions and implications for research and practice
This study shows that sex inequalities exist in the diagnostic trajec­
tories of patients presenting somatic symptoms in primary care. How­
diagnostic trajectories are not necessarily the golden standard: possibly
males are overmedicalized in comparison to females. The sex differences
in diagnostic interventions may also be due to a differing probability for
final diagnoses between women and men. Men receive disease diagnoses
more frequently than women. On the one hand, this could be attribut­
able to a higher detection rate of diseases in men as they receive more
diagnostic interventions. Ultimately, this may be a vicious circle:
increased use of diagnostic interventions in male patients leads to a
higher detection rate of diseases in men compared to women. Conse­
quently, the male rate of disease diagnoses increases, followed by an
increased probability of FPs ordering more diagnostic interventions, as
FPs base their actions on guidelines and personal experience. On the
other hand, men may have a truly higher a priori chance of underlying
further research could focus on whether women and men equally benefit
from diagnostic interventions. Additionally, an experimental vignette-
based study in which the vignette differs in patient’s sex that asks FPs
to suggest diagnostic interventions for the patient with a common so­
matic symptom may provide insights into sex differences, and reasons
behind these, in diagnostic interventions suggested by FPs [47].
Clinically this study suggest that the fewer diagnostic interventions
in women may result in fewer disease diagnoses. Thus, if additional
research shows that men and women equally benefit from diagnostic
interventions in terms of receiving a disease diagnosis, FPs should be
aware of the negative impact of the underuse of diagnostic interventions
in female patients.
Funding
This work was supported by the ZonMw Gender and Health program
(849200013).
Declaration of Competing Interest
The authors have no competing interests to report.
Supplementary data.
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.jpsychores.2021.110589.
References
[1] P.F. Verhaak, S.A. Meijer, A.P. Visser, G. Wolters, Persistent presentation of
medically unexplained symptoms in general practice, Fam. Pract. 23 (4) (2006)
414–420.
[2] J.M. Groeneveld, A.V. Ballering, Boven Kv, Akkermans RP, Olde Hartman TC, Uijen
AA. Sex differences in incidence of respiratory symptoms and management by
general practitioners, Fam. Pract. 37 (5) (2020) 631–636.
[3] S. Arber, J. McKinlay, A. Adams, L. Marceau, C. Link, A. O’Donnell, Patient
characteristics and inequalities in doctors’ diagnostic and management strategies
relating to CHD: a video-simulation experiment, Soc. Sci. Med. 62 (1) (2006)
103–115.
[4] J.B. McKinlay, C.L. Link, K.M. Freund, L.D. Marceau, A.B. O’Donnell, K.L. Lutfey,
Sources of variation in physician adherence with clinical guidelines: results from a
factorial experiment, J. Gen. Intern. Med. 22 (3) (2007) 289–296.
[5] S.E. Kim, H.Y. Paik, H. Yoon, J.E. Lee, N. Kim, M.K. Sung, Sex- and gender-specific
disparities in colorectal cancer risk, World J. Gastroenterol. 21 (17) (2015 May 7)
5167–5175.
[6] N. Sourial, I. Vedel, C. Godard-Sebillotte, J. Etches, G. Arsenault-Lapierre, S.
E. Bronskill, Sex differences in dementia primary care performance and health
service use: a population-based study, J. Am. Geriatr. Soc. 68 (5) (2020)
1056–1063.
[7] A.V. Ballering, I.J. Bonvanie, T.C. Olde Hartman, R. Monden, J.G.M. Rosmalen,
Gender and sex independently associate with common somatic symptoms and
lifetime prevalence of chronic disease, Soc. Sci. Med. 253 (2020) 112968.
[8] A.V. Ballering, K.J. Wardenaar, T.C. olde Hartman, Rosmalen JGM, Female sex and
femininity independently associate with common somatic symptom trajectories,
Psychol. Med. (2020) 1–11.

ever, it remains unknown whether these inequalities are justified.

Although we used men as reference category in our analyses, male

5
A.V. Ballering et al.
[9] F. Crea, I. Battipaglia, F. Andreotti, Sex differences in mechanisms, presentation
and management of ischaemic heart disease, Atherosclerosis 241 (1) (2015)
157–168.
[10] M. de Jong, R.C. Vos, R. de Ritter, C.J. van der Kallen, S.J. Sep, M. Woodward, et
al., Sex differences in cardiovascular risk management for people with diabetes in
primary care: a cross-sectional study, BJGP Open 3 (2) (2019 Jul 23), https://doi.
org/10.3399/bjgpopen19X101645. Print 2019 Jul.
[11] A.E. Thompson, Y. Anisimowicz, B. Miedema, W. Hogg, W.P. Wodchis, K. Aubrey-
Bassler, The influence of gender and other patient characteristics on health care-
seeking behaviour: a QUALICOPC study, BMC Fam. Pract. 17 (1) (2016) 38.
[12] I. Armstrong, N. Rochnia, C. Harries, S. Bundock, J. Yorke, The trajectory to
diagnosis with pulmonary arterial hypertension: a qualitative study, BMJ Open 2
(2) (2012 Apr 18) e000806-000806. Print 2012.
[13] O. Gureje, G.E. Simon, T.B. Ustun, D.P. Goldberg, Somatization in cross-cultural
perspective: a World Health Organization study in primary care, Am. J. Psychiatry
154 (7) (1997 Jul) 989–995.
[14] C. Gijsbers van Wijk, A. Kolk, W. van Den Bosch, H. Van Den Hoogen, Male and
female morbidity in general practice: the nature of sex differences, Soc. Sci. Med.
35 (5) (1992) 665–678.
[15] S. Halvorsen, J. Eritsland, M. Abdelnoor, C. Holst Hansen, C. Risoe, K. Midtbo, et
al., Gender differences in management and outcome of acute myocardial
infarctions treated in 2006-2007, Cardiology 114 (2) (2009) 83–88.
[16] J.K. Soler, I. Okkes, Reasons for encounter and symptom diagnoses: a superior
description of patients’ problems in contrast to medically unexplained symptoms
(MUS), Fam. Pract. 29 (3) (2012 Jun) 272–282.
[17] H. Luijks, K. van Boven, T. olde Hartman, A. Uijen, C. van Weel, H. Schers, Making
visible what is intuitively known by family physicians. Capturing core value of
family medicine in structured data, J. Am. Board Fam. Med. 34 (4) (2021)
709–723 [Manuscript in press].
[18] W.L. Zijlema, R.P. Stolk, B. Löwe, W. Rief, P.D. White, J.G.M. Rosmalen, How to
assess common somatic symptoms in large-scale studies: a systematic review of
questionnaires, J. Psychosom. Res. 74 (6) (2013) 459–468.
[19] A. Acevedo-Mesa, J.N. Tendeiro, A. Roest, J.G.M. Rosmalen, R. Monden, Improving
the Measurement of Functional Somatic Symptoms With Item Response Theory,
Assessment 1073191120947153 (2020).
[20] K. Imai, L. Keele, D. Tingley, T. Yamamoto, Unpacking the black box of causality:
Learning about causal mechanisms from experimental and observational studies,
Am. Polit. Sci. Rev. 105 (4) (2011) 765–789.
[21] Y. Rosseel, Software for Mediation Analyses, Available at: http://www.da.ugent.be
/cvs/pages/en/Presentations/Presentation%20Yves%20Rosseel.pdf;, 2013.
Accessed October, 2, 2020.
[22] J. Miles, Shevlin M. Collinearity, Applying Regression and Correlation: A Guide for
Students and Researchers, Sage, 2001, pp. 126–135.
[23] Rosseel Y. Lavaan, An R package for structural equation modeling and more.
Version 0.5-12 (BETA), J. Stat. Softw. 48 (2) (2012) 1–36.
[24] K. van Boven, A.A. Uijen, N. van de Wiel, S.K. Oskam, H.J. Schers, W.J.
J. Assendelft, The diagnostic value of the patient’s reason for encounter for
diagnosing cancer in primary care, J. Am. Board Fam. Med. 30 (6) (2017) 806–812.
[25] S. Vinker, I. Kvint, R. Erez, A. Elhayany, E. Kahan, Effect of the characteristics of
family physicians on their utilisation of laboratory tests, Br. J. Gen. Pract. 57 (538)
(2007 May) 377–382.
[26] K.D. Bertakis, R. Azari, Patient gender and physician practice style, J. Women’s
Health 16 (6) (2007) 859–868.
[27] J.A. Hall, D.L. Roter, Do patients talk differently to male and female physicians?: A
meta-analytic review, Patient Educ. Couns. 48 (3) (2002) 217–224.
[28] A.J. Barsky, H.M. Peekna, J.F. Borus, Somatic symptom reporting in women and
men, J. Gen. Intern. Med. 16 (4) (2001) 266–275.
Journal of Psychosomatic Research 149 (2021) 110589
[29] K. Hunt, J. Adamson, C. Hewitt, I. Nazareth, Do women consult more than men? A
review of gender and consultation for back pain and headache, J. Health Serv. Res.
Policy 16 (2) (2011) 108–117.
[30] C. Clerc Liaudat, P. Vaucher, T. De Francesco, N. Jaunin-Stalder, L. Herzig,
F. Verdon, et al., Sex/gender bias in the management of chest pain in ambulatory
care, Women Health 14 (2018), 1745506518805641.
[31] R.J. Chakkalakal, S.M. Higgins, L.B. Bernstein, K.L. Lundberg, V. Wu, J. Green, et
al., Does patient gender impact resident physicians’ approach to the cardiac exam?
J. Gen. Intern. Med. 28 (4) (2013) 561–566.
[32] A.J. Dirkzwager, P.F. Verhaak, Patients with persistent medically unexplained
symptoms in general practice: characteristics and quality of care, BMC Fam. Pract.
8 (1) (2007) 33.
[33] S. Evangelidou, A. NeMoyer, M. Cruz-Gonzalez, I. O’Malley, M. Alegria, Racial/
ethnic differences in general physical symptoms and medically unexplained
physical symptoms: investigating the role of education, Cult. Divers. Ethn. Minor.
Psychol. 12 (2020 Mar).
[34] J.E. Brush Jr., H.M. Krumholz, E.J. Greene, R.P. Dreyer, Sex differences in
symptom phenotypes among patients with acute myocardial infarction,
Circulation: Cardiovasc. Quality Outcomes 13 (2) (2020), e005948.
[35] O.A. Alabas, O.A. Tashani, M.I. Johnson, Gender role expectations of pain mediate
sex differences in cold pain responses in healthy Libyans, Eur. J. Pain 16 (2) (2012)
300–311.
[36] Serpe C. Somatization, Disorder and gender, editor, in: K.L. Nadal (Ed.), The SAGE
Encyclopedia of Psychology and Gender, SAGE Publications, 2017, pp. 1606–1610.
[37] D. Loikas, L. Karlsson, M. von Euler, K. Hallgren, K. Schenck-Gustafsson, Rahmner
P. Bastholm, Does patient’s sex influence treatment in primary care? Experiences
and expressed knowledge among physicians–a qualitative study, BMC Fam. Pract.
16 (2015) 137.
[38] C.A. Nathanson, Illness and the feminine role: A theoretical review, Soc. Sci. Med. 9
(2) (1975) 57–62.
[39] A. MacLean, H. Sweeting, K. Hunt, ‘Rules’ for boys,‘guidelines’ for girls: Gender
differences in symptom reporting during childhood and adolescence, Soc. Sci. Med.
70 (4) (2010) 597–604.
[40] D.L. Roter, J.A. Hall, Y. Aoki, Physician gender effects in medical communication:
a meta-analytic review, JAMA 288 (6) (2002) 756–764.
[41] K.E. Lutfey, C.L. Link, L.D. Marceau, R.W. Grant, A. Adams, S. Arber, et al.,
Diagnostic certainty as a source of medical practice variation in coronary heart
disease: results from a cross-national experiment of clinical decision making, Med.
Decis. Mak. 29 (5) (2009 Sep) 606–618.
[42] A.J. Barsky, E.J. Orav, D.W. Bates, Somatization increases medical utilization and
costs independent of psychiatric and medical comorbidity, JAMA Psychiatry 62 (8)
(2005) 903–910.
[43] M. Michiels-Corsten, N. Donner-Banzhoff, Beyond accuracy: hidden motives in
diagnostic testing, Fam. Pract. 35 (2) (2018) 222–227.
[44] T. van der Weijden, M.A. van Bokhoven, G.J. Dinant, C.M. van Hasselt, R.P. Grol,
Understanding laboratory testing in diagnostic uncertainty: a qualitative study in
general practice, Br. J. Gen. Pract. 52 (485) (2002 Dec) 974–980.
[45] S. Bösner, Haasenritter Jö, M.A. Hani, H. Keller, A.C. Sönnichsen, K. Karatolios, et
al., Gender bias revisited: new insights on the differential management of chest
pain, BMC Fam. Pract. 12 (1) (2011) 45.
[46] E.N. Chapman, A. Kaatz, M. Carnes, Physicians and implicit bias: how doctors may
unwittingly perpetuate health care disparities, J. Gen. Intern. Med. 28 (11) (2013)
1504–1510.
[47] B. Claréus, E.A. Renström, Physicians’ gender bias in the diagnostic assessment of
medically unexplained symptoms and its effect on patient–physician relations,
Scand. J. Psychol. 60 (4) (2019) 338–347.