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JOURNAL OF WOMEN’S HEALTH

Volume 19, Number 2, 2010


ª Mary Ann Liebert, Inc.
DOI: 10.1089=jwh.2008.1156

Scientific Excellence in Applying Sex- and Gender-Sensitive


Methods in Biomedical and Health Research

1,2
Linda Nieuwenhoven, M.P.H., and Ineke Klinge,
1,3
Ph.D.

Abstract

Despite regulations, the attention paid to sex and gender in biomedical and health research is far from optimal.
Researchers often recognize the importance of incorporating sex and gender issues in general but fail to see the
applicability to their own research. This can have severe consequences and impedes gender equity in healthcare.
More hands-on approaches are needed that stimulate scientists to integrate sex and gender aspects into their
research. The present work is based on the contents of a workshop developed by the authors that serves as such a
hands-on method. It aims at familiarizing a broad range of scientists in the field of biomedical and health research
with the basics of conducting sex- and gender-sensitive research. In addition to clarifying concepts, it serves to
provide a general introduction to sex- and gender-sensitive methods. To this end, challenges in pitfalls conducting
sex- and gender-sensitive research, originally identified in the social sciences, are translated to the practice of
biomedical and health research. Implications and applicability to all areas of biomedical and health research are
shown by providing illustrative examples. Finally, a tool is presented that allows for the detection of sex and
gender bias throughout all phases of the research process and shows how this bias can be overcome through sex-
and gender-sensitive (1) relevance checking, (2) literature search, (3) formulation of research questions and
hypotheses, (4) research methods and sample, (5) data analysis and interpretation, (6) reporting, and (7) conclu-
sions and recommendations.

Introduction It is often a lack of expertise and experience with sex and


gender issues that leads to failure to address them in research.

L ittle by little, sex and gender in research are getting the


attention they deserve. In North America as well as in
Europe, research and research policy organizations are mak-
Evaluating the integration of sex and gender into their latest
research programs, the European Commission (EC) con-
cludes: ‘‘There is a lack of ideas on practical ways of
ing sure that the gap left open by industry, universities, and inte- grating gender into research. [ . . . ] Some project
researchers is starting to fill. Regulations and policies should proposals automatically dismiss the relevance of gender to
ensure that enough women are included in trials, that research the research topic or instruments used, without any analysis
designs account for possible sex differences, and that sex- and of whether it
gender-specific results are reported.1–3 Still, the efforts to in- might be relevant.’’6 Even a willing researcher is no guarantee
corporate sex and gender in research seem to be minimal. for success, however. Of all Swedish public health researchers
Women are included in trials if required, but the subsequent who believed their research to be gender sensitive, only a fifth
data analyses still are sex and gender insensitive.4,5 The role of conducted research that could be labeled as such.9 It, there-
sex and gender is, often mandatorily, considered but poorly fore, happens that although researchers in the field of bio-
understood and ‘‘very weakly addressed.’’6 This causes medical and health research acknowledge the added value
the rate of change to be very slow in spite of legislation and that a sex and gender dimension could bring to their research,
ac- countability frameworks.7 However, to profit from the the lack of familiarity and practice with the topic holds them
health advantages that sex- and gender-sensitive research can back.
offer, as well as to avoid harm, this type of research needs Scientists educated in the field of gender studies have the
to be conducted carefully, regularly, and to the full extent.8 expertise to see how sex and gender may play a role, but a
majority of gender experts are in the social sciences. Articles

1
School for Public Health and Primary Care (Caphri), Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The
Netherlands.
2
National Institute for Health Development, Budapest, Hungary.
3
Centre for Gender and Diversity, Maastricht University, Maastricht, The Netherlands.
313
58 NIEUWENHOVEN AND KLINGE
SCIENTIFIC EXCELLENCE IN BIOMEDICAL AND HEALTH RESEARCH 59
by them often remain at a conceptual level. The distance to the man or the woman should raise these children (gender roles).
practice of life science research is too great, and too few The definition of the words implies that the term, sex, can be
bridges between the two worlds exist. On the other hand, applied to biological male-female differences in both humans
there is quite a body of literature from the fields of gender and and animals but that the sociocultural term, gender, will al-
life sciences alike that identifies the need to integrate the two most exclusively be used for human beings. Unfortunately,
lines of research, although, few move beyond descriptive or the terms sex and gender are sometimes used interchangeably
state-of-the-art articles. In addition, some excellent and de- in the medical literature. To avoid confusion,20 we use them
tailed articles by gendered life scientists serve specific audi- distinctively in this article. We prefer the term, sex- and
ences.10,11 gender-sensitive research, which is used to indicate research
A consequence is that interested life science and health that takes into account the full array of possible influences of
researchers cannot easily find ways and methods to incor- both sex and gender on all phases and aspects of the research.
porate sex and gender issues into their research. A general tool
would have the advantage of broad applicability, but it is Why Conduct Sex- and Gender-Sensitive Research?
exactly this general level, in combination with a lack of
Sex and gender can have a profound influence on health
fa- 12
miliarity with sex- and gender-sensitive research, that can
make it very difficult for researchers to acknowledge that and illness throughout the life span. In order to ensure
sensitivity to sex and gender is relevant to their own research optimal healthcare for both men and women, the differences
as well.6 It is, therefore, essential that general tools be and similarities of their health needs should be considered in
ac- companied by examples that show specific biomedical and health research and subsequently translated
21
applications to
to clinical practice. Wieringa et al. argue that the clinical
different aspects of biomedical and health research.
To this end, we developed a workshop, Scientific Ex- relevance of sex and gender is 3-fold. First, sex and gender can
cellence and Sexy Research. The workshop aimed at famil- help explain the differences in etiology and prognosis of dis-
iarizing scientists in the field of biomedical and health research eases. Even if a condition predominantly affects one sex, it is
with the basics of conducting sex- and gender-sensitive re- exactly the differences between men and women that can lead
search. The workshop was based on previous work and ex- us toward identifying the mechanisms responsible for the
perience by the authors and a literature study focusing on key condition, which facilitates the development of (new) treat-
publications.12–16 It aimed at finding a middle course between ments. Second, sex and gender can modify the outcomes of
introducing general concepts that are of relevance to a wide diagnostic procedures and of preventive and treatment inter-
variety of biomedical and health researchers, on the one hand, ventions. This effect modification will only come to the fore if
8
and the illustration of those concepts with specific examples, carefully designed studies are analyzed by sex. Third, the dif-
on the other, which allows all participants to acknowledge the ferences in health perception and practices of women and men
relevance of such concepts to their own field of research. This may cause differences in health outcomes—a gender issue.
article is an account and elaboration of the contents of the In addition to its clinical relevance, conducting sex- and
workshop and aims at conveying the importance of con- gender-sensitive research can improve the scientific quality of
ducting sex- and gender-sensitive research to a larger audi- a study. In many cases, it is plainly unscientific to leave out
ence of biomedical and health researchers. After clarifying half the population or fail to do subgroup analysis and thereby
terminology, we illustrate why and how sex and gender are miss out on valuable information. Thus, the EC made the
relevant in biomedical and health research. Next, the short- integration of a sex and gender dimension a criterion of sci-
comings of sex- and gender-insensitive research are discussed entific quality in the evaluation of proposals for their research
2
by identifying common pitfalls. To make the knowledge on programs. Furthermore, paying attention to possible sex
sex and gender issues applicable to one’s own research, a step- differences and gender effects in research is an innovative
by-step plan for sex- and gender-sensitive research is pre- enterprise, and its more precise results allow the researcher to
sented that synchronizes sex- and gender-sensitive actions get an edge on colleagues in the field. Last, because of its med-
with the phases of the research process. ical and social consequences, a sex and gender bias in medical
research has ethical implications.22 Increasing the quality and
quantity of evidence on the effect of sex and gender on health
Clarifying Concepts outcomes and healthcare leads to better targeting of medical
For conceptual clarity, it is important to distinguish be- care at the individual level and, thus, to a better chance
tween the terms sex and gender. Scientists in the field of at
gender speak of sex when they refer to male=female differ- improved health. Socially, the aim of ensuring gender equity
ences attributed to biological characteristics, such as chro- in healthcare necessitates consideration of relevant differences
mosomes, physiology, and anatomy, as well as processes at in healthcare policy, including the conduct of clinical
molecular and cellular levels.17–19 Sex is a characteristic, research.
usually dimorphic and related to the XX or XY genotype, al-
though a range of exceptions of people who are chromoso- Sex Differences and Gender Effects
mically different exists. Gender, on the other hand, refers to in Health and Disease
the social and cultural influences that lead to differences be-
tween women and men. It is a process and a Sex differences and gender effects are relevant throughout
continuum: people may develop a strong or less strong biomedical and health research. Some examples in which sex
gender identity and may adhere to perceived gender roles differences plays a role include:
to a different ex- tent. As an example: only women can give Sex differences in the development of the pulmonary
birth to children (sex difference), but it is not biologically system are visible in utero. It has been demonstrated that
determined if the the lungs of the female fetus mature more rapidly, and
60 NIEUWENHOVEN AND KLINGE
surfactant production begins earlier than in male
fetuses.
As a result, female newborns have increased airflow men’s lower frequency of health service use is cultural
rates compared with male newborns and are less likely norms with regard to masculinity and the expectation
to develop respiratory distress syndrome.21,23 that men be strong and not show weakness.36 Less fre-
Healthy women produce three times as much growth quent doctor-patient contact of men compared with wo-
hormone (GH) as men do yet have the same levels of men could lead to underdetection of certain conditions,
insulin-like growth factor-I (IGF-I), suggesting a lower such as osteoporosis, which because of its frequent oc-
responsivity. GH-deficient women thus require higher currence in women, is underdiagnosed in men anyway.
doses of therapeutic recombinant human GH (rhGH)
Some scientists have objected to the distinction between sex
to achieve the same treatment effect as GH-deficient
and gender, fearing that a focus on the one might lead
men.24,25 Also, the changes in body composition
in- to
9
duced by rhGH therapy are more pronounced in men ignorance of the other or that they will be seen in hierarchical
than in women.26 order. To avoid this, the potential roles of both sex and gender,
The incidence and location of gastric cancer vary by sex. as well as their interplay, should always be considered. In fact,
Male=female incidence ratios are generally 1.5–2.5:1 but it is infrequent that only sex or only gender plays a role. In
general, sex and gender work together in influencing health
differ according to cancer location.27 Whereas
and health outcomes. Krieger states: ‘‘Not only can gender
gastric cancer in women develops mostly in the lower
relations influence expression—and interpretation—of bio-
part of the stomach (distal gastric cancer), it develops in
logical traits, but also sex-linked biological characteristics can,
the up- per part of the stomach (proximal gastric cancer)
in the in some cases, contribute to or amplify gender differentials in
13
majority of men. The reasons for the sex differences in
location are still unknown.28 Although gendered life- health.’’ To illustrate:
style factors (smoking, drinking, nutrition) contribute par- Sex plays a role in the acquisition of HIV=AIDS through
tially to the development of gastric cancer, it has been biological and physiological factors that make male-to-
suggested that the relationship between smoking and female compared with female-to-male transmission more
alcohol and gastric cancer is mediated by sex.29,30 likely in unprotected vaginal intercourse. At the same
In- fection with the Helicobacter pylori bacterium, a time, a gender power imbalance may lead to a lesser abil-
proposed risk factor for gastric cancer, is also suggested ity of the woman compared with the man to negotiate
to have a differential impact on the development of condom use.13 Female injection drug users have
gastric cancer in males and females.30,31 Because also
etiology, underlying biological processes, and clinical been shown to have a higher risk of acquiring an HIV
outcomes are hypoth- esized to be different in infection than their male counterparts because of gender
proximal and distal gastric cancer, this will have differences in injecting practices related to sharing and
therapeutic implications.32 cleaning behaviors.38
The risk of hypospadias, a urethral birth defect in males,
Although some tend to believe that for some areas of life
is increased by maternal exposure to certain toxins. Be-
science research a sex and gender dimension is taken suffi-
cause exposure to such agents is highest among hair-
ciently into account when paying attention to sex differences,
dressers, gender influences the risk of exposure through
it is a mistake to use sex as a proxy for gender.7 Attention to 13
gender effects might require different analyses than those the gender segregation of the workforce.
needed for dealing with sex differences. Whereas sex is Because of their interplay, it is not always easy to distin-
es- sentially biological, gender is a lens used to analyze guish between the roles of sex and gender. For example, bone
factors that extend to behavioral, social, societal, and mass development is related to body weight and exercise.
sometimes even political levels. To make sure an analysis The current thin ideal for girls and weightbearing exer-
includes the rele- vant factors that together account for cises commonly performed by boys (gender) lead to a differ-
gender effects can, therefore, be a wholly different ent weightbearing impact on the bones of females compared
enterprise. The potential im- pact of gender effects on health with males, contributing to differences in bone mass in males
is highly significant because behaviors, power relations, and and females (sex). Also, it is fairly difficult to determine the
environments (among others) all have an impact on health relative influences of biological factors on the development of
but can differ between men and women. Some examples melanoma because of different social practices of men and
include: women, for example, with regard to clothing styles and lev-
12
Gender influences environmental factors. In
occupational
health research, job segregation by sex can lead to Men make less use of health services than women,
dif- ferential exposure rates to different occupational particularly in primary care. A common explanation of
hazards, such as toxic chemicals, ergonomic demands,
accident risk, and psychosocial stressors.33,34
Gender mediates risk perception. Men and women
ex- press different levels of concern about the same
risks, attribute different meanings to them, and also
perceive different risks.35 It therefore cannot be
assumed that men’s and women’s perception and fear
of diseases, treatment, and health outcomes are the
same, which is likely to have consequences for health-
promoting and
help-seeking behavior and noncompliance rates.
els of sun exposure.

Exploring Underlying Biological Mechanisms


of Sex Differences
Sex- and gender-sensitive health research is most easily
associated with the detection of health differences between
men and women, for example, through epidemiology or
clinical outcomes. It is also because this step is perhaps most
obvious that in recent years, considerable attention has been
given to the differences and similarities between females and
males at the societal level, on the one hand, and at the level of
the whole organism, on the other.12 The scope of sex- and
gender-sensitive research has historically been limited. But
although it might have been most clear-cut to explain
sex
differences by focusing on genetic differences in insensitive. Paying attention each other, the problems she
the reproductive system, the metabolism that are likely to to sex and gender in identifies are (still) very
role of sex hormones have interact with sex.21 research counts as relevant for biomedical and
to be considered outside of More pharmacogenomic something extra, which health research. Clearly, if
their repro- ductive research is needed that might or might not be healthcare and health
functions. Their influence addresses such issues as taken into consideration, policies are based on
has been major in some the role of sex de- pending on time, research that has
nonreproductive health chromosomal differences budget, and good will of significant reliability and
matters, such as on pharmacokinetics, the the researcher. Even validity problems, the
cardiovascular dis- ease, mechanisms of sex effects something as basic as the consequences can be major.
asthma, and on gene ex- pression, and collection of sex- To increase awareness, we
osteoporosis.21,23,37,39 the genetic, molecular, and disaggregated statistics is discuss three of these main
Indeed, to be able to cellular basis of ac- tion of not routine. Because old pitfalls: overgeneralization,
provide tailored and pharmacological agents that habits die hard, sex- and sex and gender insensitivity,
adequate healthcare to men are known to have gender-insensitive ways of and double standards.
and women alike, differential effects in men and doing research are passed
researchers must begin to women.41 Even at this level, on to a new generation of
‘‘see women’s entire bodies scientists. To be able to O
the influence of gender
v
as different from men’s.’’40 should not be dismissed. avoid sex and gender bias,
e
It is necessary to start Gender roles researchers will have to act.
r
exploring the precise can, for example, determine In her book on nonsexist
g
mechanisms and dietary habits, smoking, and research methods,
e
explanations that can al- cohol consumption, and Eichler14 iden-
n
account for the sex thereby influence the tifies common pitfalls e
differences in patterns, environment to which related to sex and gender r
course, and treatment genetic factors might issues that may bias research, a
response that are revealed respond differently.43 with less reliability and l
at the population level. For validity as a result. i
example, the NIH Office of Although the book was z
I
Research on Women’s written from the a
g
Health (ORWH)41 lists the n perspective of the social t
need for studies of o sciences and although the i
chromosomal, genetic, r pitfalls are closely related o
gonadal, and phenotypic i and, therefore, not always n
sex in vitro or in animal n conceptually distinguishable
Overgeneralization takes
models, the need for g from
place when only one sex is
systemic and cellular stud- ied but the data are
modeling of biological S presented as if they were of
pathways and systems e general (rather than sex-
related to women’s health, x specific) applicability.
and the need for mapping
Overgeneralization can take
etiological mechanisms that
a many different forms, the
can shed a light on sex
n most serious of which is
differences in cellular,
d over- general data
tissue=organ, physiological,
interpretation. One sex is
and immune re- sponses
to environmental and G studied, but the results are
infectious agents. Even—or e interpreted as if they were
exactly—at these levels we n applicable to both sexes.
may not presume men and d For example, the American
women to be the same. e Heart Association
‘‘Every cell has a sex. r recommended as- pirin
Whether a cell contains an therapy to high-risk adults
To protect the potentially
XX or an XY chromosome to reduce the incidence of
childbearing woman and in
may have an impact on coronary heart disease
the belief that accepted the
every- based on a number of trials
male as a model for the
thing from regulation of in which only 20% of the
human species (which, at
gene expression in a cell the same time, meant that subjects studied were
line to the efficacy or toxicity the complicated hor- monal women. Recent sex- specific
of a pharmaceutical in meta-analyses, however,
cycles could be ignored),
living human.’’42 showed that aspirin therapy
sex and gender have been
Genomics and ignored in biomedical and reduces the risk of a
pharmacogenomics enable myocardial infarction in
health research for a very
new approaches to identify men only, whereas the risk
research populations long time.44,45 Even today,
of an ischemic stroke is
according to biological vari- it appears that the
lowered only in
ables, such as the rates of standard way of doing
research is sex and gender women.46 The
drug metabolism and other
recommendation should, n
therefore, only have s
applied to men and in fact e
was harmful to women n
because the use of aspirin s
increases the risk of i
bleeding events. t
Overgeneralization can i
also pervade language, v
such as i
when sex-specific terms are t
y
used for purposes that are
ge- neric, for example, by Sex and gender
using he or man when, in insensitivity occurs when
fact, both sexes are meant. A sex and gender are not
questionnaire might contain addressed in the research,
the following question: If a although they are related to
doctor tells you smoking is the research content. This
bad, do you believe him? can take several forms. First,
Not only is it wrongly studies may fail to report the
implied that a doctor is sex of the research subjects
neces- sarily a man, thus altogether. When it is not
reinforcing stereotypes, but mentioned in the title or
also the answer might just abstract, but closer scrutiny
be different if it said ‘‘her’’ of text and tables allows us
because of different to determine the sex of the
patient-doctor subjects, this is a form of
interactions.47 Second, overgeneralization. When
overgeneral language there is no mention of sex at
occurs when generic terms all in the article, however, it
are used for all-male of all- is impossible to even
female groups, for example, establish if
when the wording single overgeneralization took
parents is used to indicate a place. To date, multiple
group of single mothers examples of such studies
only. Such undifferen- tiated can be found in respected
as humans, healthy journals (e.g., a recent article
volunteers, patients, in JAMA fails to mention the
consumers, and families sex
should always be specified. of the subjects
Preferably, the title of a completely49). This can
publication should reflect the easily be avoided by
sex composition of the adhering to the rules for
research population. For an nonsexist language. Even
extensive guide on how to if no human subjects are
avoid sexist involved, the sex of
language, see the APA research subjects in animal
Publication Manual trials should be noted and
Task Force.48 since every cell has a sex,
also the origin of the
(cellular) material used.18
S
e
x

a
n
d

g
e
n
d
e
r

i
A second form of sex and gender insensitivity occurs when exercise stress test is less accurate in women than in men, it
data are collected from both sexes, but the analysis ignores has long been used to detect heart abnormalities in both sexes.
this.4,5 Eichler states that this may ‘‘severely limit the utility of Likewise, it took researchers and medical specialists some
any findings and may, in fact, hide some of the most impor- time to determine that balloon angioplasty, a procedure in
tant aspects of a phenomenon.’’14 As an example which narrowed blood vessels are widened by means of in-
using information from Mickalide,50 Figure 1 depicts the serting and inflating a balloon in the vessel, required different
relation- ship between income and being overweight (defined balloon sizes for men and women.54 Sex and gender sensi-
as 20% above desirable body weight for height). The line tivity is essential in pharmacological research as well, where
for both sexes supports the widely acknowledged inverse sex differences in weight, size, body composition, and cell
relation- ship between income and being overweight. metabolism influence the required dose.
However, a sex- disaggregated analysis corrects this
assumption, showing it to be the mean of two opposite trends
Double standards
for men and women. The only way to prevent such errors is
to routinely analyze data by sex and only after it has shown to When the same or identical situations, traits, or behaviors
be empirically insignificant, collate the data.14 Obviously, are treated or evaluated differently on the basis of a person’s
a sex-disaggregated analysis requires sufficient power sex, double standards are being used. Detection is difficult
because results might otherwise be misleading.51 because double standards are often presented in an indirect
In addition to the sex of the subject, a sex- and gender- manner, as is the case when behaviors or situations are labeled
sensitive study also considers the sex of the investigator and differently for different sexes. For example, when women
the different interactions that might stem from different and men experience the same symptoms of heart disease,
subject-investigator combinations.
52
For example, it was women’s symptoms are three times more likely to be at-
found that pain tolerance of research participants rises with tributed to emotional rather than physical causes.54 When
experimenters of the opposite sex and that having a female their cardiovascular symptoms are recognized, women are
investigator increased pain intensity.53 For animals, investi- also less likely than men to receive treatment.39
gator effects have not been clearly identified but are believed Double standards are present not only in clinical practice
to occur and could be related to differences in the way female but in research as well. Different instruments, methods, or
and male researchers sound, smell, and handle the animals.18 requirements are sometimes used for men and women when
Although it will not always be possible to take the sex of the there is no indication that this is biologically or socially nec-
investigator into account in the study design, reporting essary.14 For example, although paternal drug exposure could
should explicitly mention their sex in relevant cases, and lead to fetal harm, contraceptive requirements for entry into
possible effects should be considered,14 especially when more clinical trials focus on women only.55 Prudence is also called
than one researcher is involved. for when gathering demographic data of research partici-
Sex and gender insensitivity in research can have great pants, for example, when the socioeconomic status of a child is
consequences for establishing criteria and protocols for diag- measured in terms of education of the father or male guard-
nosis or treatment of conditions. For example, although the ian, and only in his absence, by the education of the mother or

FIG. 1. The relationship between family income and being overweight.


female guardian. Double Assessment (GIA) protocol confronted with the Step 2. Literature Search
standards can play a role developed in 2001 as a short effects of this research
in daily life. The design, results, and
in data interpretation as tool to analyse the sex and
Gender and sex discussion of prior studies
well, when identical gender sensitivity of
differences on this and existing literature will
responses are coded European research
research topic have often give indications about
differentially according to projects.17 It was completed
already been the nature, scope, and
sex. and extended by including
documented in the direction of sex differences
The way in which results important issues identified
literature. and gender effects and
are phrased in reporting in the literature since. The
identify areas that still need
may also lead to double step-by-step plan helps to In all instances, sex or to be explored. Moreover,
standards. The combination identify where sex and gender or both then deserve gath- ering information
man and wife, for example, gender issues can be of further consideration until about to what extent sex
designates the man by his relevance in research proven otherwise. The only and gender have been taken
sex but the woman by her projects. It can be used possible ex- ceptions are into account in past research
marital status.48 Another while writing a research conditions that are unique to gives us material for
example is that medical proposal or during the one sex. For condi- tions comparison and allows us to
literature often speaks of research process to monitor that occur in both sexes, assess the quality of our
atypical symptoms when the im- plementation of a looking for sex differences current efforts to include
discussing women’s sex and gender dimension might give clues to the sex and gender. Our efforts
symptoms signaling a heart along the way. It can also responsible mechanisms of to include sex and gender
attack; by the implication serve as a tool for reviewing
that his symptoms are action, especially when they are adequate when we
a peer’s research. are much more prevalent in
typical, the man is taken as include differences that
one of the sexes. were identified as relevant
a norm.21 Double standards S
also occur when women are before. If there are known
t
routinely described in the e differ- ences that we fail to
passive mode and men in p address in our current
the active mode. These study, relevant aspects are
gender stereotypes are missed. This might be
1
reinforced even at the level because a lack of resources,
.
of the cell: biology has but such decisions have to
created the image of the be substantiated. If our
passive egg cell waiting for R research addresses or
the competing, active sperm e identifies new,
to fertilize it, although given l undocumented sex or
the life expectancy of both e gender differences, it is
v
sex cells, it happens more innovative. Sex and gender
a
often that sperm cells are differences re- main to be
n
waiting for the egg cell to studied when they have not
c
come.56 e been documented to date,
and are not addressed in
Considering Sex and our current research. This
C should be noted in the
Gender in all Research
h
Phases discussion or
e
recommendations.
The pitfalls described c
It may take some practice
can apply to all kinds of k
to develop a search strategy
research practices. Although
Sex and gender are most that identifies the full range
their detection might require
likely of relevance to a of sex and gender
some dili- gence, there is
study when: differences that have been
almost no study involving
documented. The most
humans or animals to which The project involves
straightforward method is to
they are not relevant. Some human subjects.
combine the name of a
research phases are more The project uses human
condition or biomedical
prone to being influenced cells, tissues, or other
research topic with MeSH
by certain pitfalls, specimens or animal
terms, such as sex factors and
however, and throughout tissues or cells that
sex characteristics, or text
the research process, other serve as a model for
words, such as gender
sex- and gender- human biology or
differences and sex
insensitive practices might physiology.
differences. For a more
occur. The project aims at
extensive search strategy,
A step-by-step plan is modifying, changing,
see the article by Wieringa
offered here that indicates or developing (health)
et al.21 In basic life sciences
the main sex and gender policies that have a
research, it might be more
issues to consider in each direct or indirect impact
reward- ing to use search
stage of research. The on human beings.
terms signaling sex-specific
checklist is based on the It is expected that
features on, for example, the
early Gender Impact humans will be
cellular or hormonal level possible to collect sex-
(e.g., estrogen recep- tors), disaggregated data?
which are dependent on the Is it necessary to
field of research. validate an instrument
that is being
Step 3. Research developed for both
Questions and Hypotheses sexes?
Research questions and
hypotheses should indicate
how sex and gender can be
of relevance.
The research questions
should reflect the
sex(es) of the
population under
investigation. To
preclude overgen-
eralization, terms that
do not specify the sex,
such as subjects or
patients, should be
avoided; use a specific
term like female
subjects instead.
Furthermore, research
questions should not
assume that the
research popula- tion is
homogeneous if the
results may differ for
women and men.
If it is not documented
if and how sex
differences and gender
effects can influence
the results, a separate
ques- tion aimed at
investigating this can
have great added
value. The inclusion of
gender hypotheses
allows for a description
of the direction of the
expected outcomes.
Carefully phrased
research questions
and hypotheses should
avoid setting males as
a standard.

Step 4.
Research
Methods and
Composition
of Research
Population
Methods should
preferably be sex and
gender sensitive and allow
for gathering of sex-
disaggregated data.
Is it substantiated why
women or men are
included or excluded?
Is it necessary or
Is the existing pregnancy or differences and C
instrument being used menopause. similarities most effec- o
validated for both Reproducing existing tively be used to n
sexes? If not, should it stereotypes without positively affect patient c
still be used for both scientific ground. outcomes and improve l
sexes? health and healthcare? u
12
s
Step 6. Reporting i
Step 5. Data Analysis o
and Interpretation A sex- and gender-
sensitive study does not n
A study includes both guarantee sex- and gender- s
men and women because sensitive reports. Applying In the introduction to
it ac- knowledges that a gender lens during or after her book on nonsexist
results of one sex might writing will reveal: research methods, Eichler14
not apply to the other; begins by quoting a passage
there is a recognition that If pitfalls were
avoided. from Abbott’s novel Flatland,
results might differ between in which entities living in a
the sexes. It logically If sex or gender
differences are two-dimensional world
follows that those potential cannot seem to grasp the
differences should be visualized in the tables,
figures, and notion of a third dimension.
investigated through a sex- The two-dimensional world
disaggregated analysis. A conclusions.
If it is considered seems logical and complete
joint analysis might hide as it is, and the characters
opposing trends. Only if whether the results
will differently affect cannot imagine the concept
proven irrelevant, sex and of and need for an
gender can be left out. women and men, for
additional dimension. We
example, in a clinical
Sex can be included in might be experiencing a
setting.
a study in many similar situation in life
If results and
different ways, and the sciences research, where
conclusions about gender
choice will have a great and sex out- biased re-
impact on the analysis. search practices of long ago
comes are reported
Is it merely a prognostic even if the results are carried on, and the
factor or also an effect indicated they did not added value of sex and
modifier?57 have an impact. The gender is not always
Does it need to be underreporting of noticed. However, there is a
controlled for, or will negative sex and gender whole new world to explore.
this obscure in- findings is caused by Sex and gender differences
teresting findings? the researcher and not are relevant to biomedical
Does a certain the result of editorial and health research in many
research question or decisions!44 ways, and it is a challenge
design call for sex- for life science researchers to
disaggregated models, step out of their two-
Step 7. Conclusions and dimensional world by
or are dummy
Recommendations adding a sex and gender di-
variables better suited?
58
Gender is less easy A complete gender mension to their research
to reduce to variables analysis ends with the activities. Such a challenge
that can be included in formulation of was, for example, taken up
a statistical analysis, but recommendations and by the EU-funded project
its explanatory power implications for clinical GenderBasic, which resulted
can be enormous. practice and future in 10 state-of-the-art
To analyze sex research. reviews on integrating sex
differences using and gender aspects in
Is it necessary that methodologies of basic,
subgroup analyses, the
future research on this clinical, and
statistical power must
topic further public health research.59
be large enough.
investigate the role of More initiatives are needed
Sex- and gender- gender or sex? to ensure
insensitive research may How can information research that is innovative
lower the quality of the data on sex differences be and of high quality so
analysis and interpretation translated into that healthcare and policies
by, for example: preventive, diagnostic, based on the results will
and therapeutic be better, fairer, and more
Taking men as a
practice? effective.
norm.
How can the new
Pathologizing normal
knowledge about and
female biological understanding of
processes, such as A
biological sex c
k c
n e
o s
w
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