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BioMed Central
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BMC Public Health
Open Access
Study protocol
Design of the sex hormones and physical exercise (SHAPE) study
Evelyn M Monninkhof*
1,2
, Petra HM Peeters
1
and Albertine J Schuit
2
Address:
1
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands and
2
Division of Public
Health and Health Care, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
Email: Evelyn M Monninkhof* - e.monninkhof@umcutrecht.nl; Petra HM Peeters - p.h.m.peeters@umcutrecht.nl;
Albertine J Schuit - jantine.schuit@rivm.nl
* Corresponding author
Abstract
Background: Physical activity has been associated with a decreased risk for breast cancer. The
biological mechanismn(s) underlying the association between physical activity and breast cancer is
not clear. Most prominent hypothesis is that physical activity may protect against breast cancer
through reduced lifetime exposure to endogenous hormones either direct, or indirect by
preventing overweight and abdominal adiposity. In order to get more insight in the causal pathway
between physical activity and breast cancer risk, we designed the Sex Hormones and Physical Exercise
(SHAPE) study. Purpose of SHAPE study is to examine the effects of a 1-year moderate-to-vigorous
intensity exercise programme on endogenous hormone levels associated with breast cancer among
sedentary postmenopausal women and whether the amount of total body fat or abdominal fat
mediates the effects.
Methods/Design: In the SHAPE study, 189 sedentary postmenopausal women, aged 50–69 years,
are randomly allocated to an intervention or a control group. The intervention consists of an 1-
year moderate-to-vigorous intensity aerobic and strenght training exercise programme. Partcipants
allocated to the control group are requested to retain their habitual exercise pattern. Primary
study parameters measured at baseline, at four months and at 12 months are: serum
concentrations of endogenous estrogens, endogenous androgens, sex hormone binding globuline
and insuline. Other study parameters include: amount of total and abdominal fat, weight, BMI, body
fat distribution, physical fitness, blood pressure and lifestyle factors.
Discussion: This study will contribute to the body of evidence relating physical activity and breast
cancer risk and will provide insight into possible mechanisms through which physical activity might
be associated with reduced risk of breast cancer in postmenopausal women.
Trial registration: NCT00359060
Background
Most of the established risk factors for breast cancer, such
as family history of the disease, early age at menarche, late
age at menopause, late age at first childbirth or nulliparity
are not, or not easily, amenable to intervention. Physical
activity is a modifiable lifestyle characteristic that has
been associated with breast cancer risk in various studies
[1-22] and as such a potential means for the primary pre-
vention of breast cancer. A recent review [23] showed
strong evidence for an inverse association between physi-
Published: 4 September 2007
BMC Public Health 2007, 7:232 doi:10.1186/1471-2458-7-232
Received: 2 May 2007
Accepted: 4 September 2007
This article is available from: http://www.biomedcentral.com/1471-2458/7/232
© 2007 Monninkhof et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0
),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
BMC Public Health 2007, 7:232 http://www.biomedcentral.com/1471-2458/7/232
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cal activity and postmenopausal breast cancer, with risk
reductions ranging from 20–80%. For premenopausal
breast cancer, however, the evidence was much weaker. A
recently published large cohort study, EPIC, provides
additional evidence for a protective effect of physical
activity on breast cancer risk [24]. The causal pathway
between physical activity and (postmenopausal) breast
cancer risk, however, is not clear. Several biological mech-
anisms that mediate the relation between physical activity
and breast cancer are suggested. The most prominent
hypothesis is that physical activity affects the hormonal
milieu, including sex steroid hormones and metabolic
profiles [25-28]. The evidence that estrogens contribute to
breast cancer risk is strong and widely accepted. Women
with relatively high levels of estrogens have increased risk
of developing breast cancer [29-32].
Furthermore, both an early menarche and a late meno-
pause increase risk, probably by increasing lifetime expo-
sure to ovarian hormones [33,34]. Several cross-sectional
studies have shown that an elevated level of physical activ-
ity is associated with 15–25% lower serum concentrations
of estradiol, estrone and androgens in postmenopausal
women, even after adjustment for body mass index [35-
37]. In addition, a positive energy balance has been asso-
ciated with (a) increased levels of active estrogens, (b)
increased levels of unbound estradiol and (c) increased
levels of progesterone [38]. This association can be
explained either directly but also indirectly through accu-
mulation of adipose tissue [39,40]. Compared with nor-
mal-weight postmenopausal women, obese
postmenopausal women have higher blood concentra-
tion of both estrone and estradiol and lower concentra-
tion of sex hormone binding globulin. In
postmenopausal women, increased levels of estrogens
due to peripheral conversion (mainly in fat cells) from
androgens result from increased body fat, particularly
intra-abdominal fat mass. Regular exercise represents an
approach to regulate energy balance and to prevent the
accumulation of adipose reserves and consequently influ-
ence the production of estrogens. Another possible medi-
ator in the relation between physical activity and breast
cancer risk may be insulin (resistance). Several studies
have shown inverse associations between physical activity
and markers for insulin sensitivity independent of body
size [41-45].
So far, one study has reported on the effects of an exercise
intervention on sex steroid concentration among post-
menopausal women. This study observed that a 12-
month moderate-intensity exercise intervention in seden-
tary, overweight women resulted in small but significant
decreases in serum estrogens and androgens. These results
were restricted to women who lost a certain amount of
body fat.
In order to get more insight in the causal pathway
between physical activity and breast cancer risk, we
designed the Sex Hormones and Physical Exercise (SHAPE)
study. This study examines the effect of an exercise inter-
vention on sex steroid hormones and insulin in sedentary
postmenopausal women and investigates if the amount of
total body fat or abdominal fat mediates the effect. If
increase in physical activity has a beneficial effect on the
sex hormone and metabolic profile of postmenopausal
women, it will offer opportunities for breast cancer pre-
vention programs. This paper presents the design and
evaluation plan of the SHAPE study.
Methods/Design
The SHAPE study examines the effects of a 1-year moder-
ate intensity exercise programme on endogenous hor-
mone levels (sex steroid hormones, insulin) associated
with breast cancer among sedentary postmenopausal
women. The study is designed as a single blind, ran-
domised, controlled trial with two study arms.
We chose to include only postmenopausal women
because (a) there is more evidence for an inverse associa-
tion between physical activity and breast cancer risk in
postmenopausal women (b) the incidence of breast can-
cer is greatest in postmenopausal years (c) the major con-
version locus of androgens into estrogens in
postmenopausal women is fat tissue – a reduction in fat
mass through exercise may be more likely to affect the rel-
ative concentrations of estrogens on postmenopausal
women than in premenopausal women (d) there are no
problems associated with measurements of hormones
with timing of the menstrual cycle.
Study population
The SHAPE study includes 189 healthy postmenopausal
women aged 50 tot 69 year, who are sedentary and not
currently using postmenopausal hormone replacement
therapy. Postmenopausal status is defined as not having
menstrual periods for at least 12 months. Being sedentary
is defined as less than 2 hours per week of moderate sport
activity (e.g., tennis, swimming, running, aerobics, fitness,
and volleyball) and not adherent to the international
physical activity recommendation. The international
physical activity recommendation states that every adult
should accumulate 30 minutes or more of at least moder-
ately intense physical activity for at least five days per
week [46,47]. The exclusion criteria (see Table 1) are
based on factors that might interfere with measurement of
endogenous hormones or with the success of the interven-
tion, or that might affect the safety of the participant. We
exclude women with a BMI below 22, because these
women may have estrogen levels below the detectable lev-
els of a laboratory. The study protocol is approved by the
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Medical Ethics Committee of University Medical Centre
Utrecht before the start of data collection.
Recruitment
Participants are recruited through a random selection out
of the female inhabitants aging 50–69 years of the follow-
ing middle sized municipalities in the centre of The Neth-
erlands: Utrecht, Zeist, Bilthoven, Houten, Soest en
IJsselstein. Potential candidates receive an invitation letter
explaining the goal of the study and a short eligibility
questionnaire. Next, the potential candidates are con-
tacted by phone to explain further details and the inclu-
sion criteria list is completed to screen eligibility.
Additionally, interested and eligible women receive writ-
ten study information and are asked to complete and sign
an informed consent form. With the women who return
their informed consent form an appointment for the base-
line visit at our research unit is made. See Figure 1 for the
flow chart of the inclusion of the participants.
Intervention
Eligible women are randomised into an intervention
group or a control group. Randomisation is blocked on
two categories of waist circumference: < 92 cm and ≥ 92
cm (cut-off level is based on the median value reported in
similar women [48]).
Women in the intervention group participate in a com-
bined endurance and strength training programme over a
period of 12 months. The programme is organised in a
way to optimise fat loss. The goal of the intervention pro-
gramme is to have participants exercise at least 3 times per
week (i.e. twice in a supervised group session and once
individual) and to reach a training stimulus in each per-
son. In general, implementation of the exercise goals is
done slowly, to reduce chance of injury and to increase
participants' adherence and sense of accomplishments.
Group Exercise
Twice a week the participants of the intervention group
meet for an exercise session of one hour. Each group
includes about 15–20 women. A qualified sports instruc-
tor facilitates the standardised group sessions according to
a protocol. Group exercise takes place in six fitness centres
located in the subjects' home town. Classes start with a
10-minute warming up: e.g. exercise to music routines
and walking. Then the training is continued with moder-
ate-to-vigorous level of aerobic exercise on 60 – 85% of
the age-predicted maximum heart rate. The maximum
heart rate is established as 220 minus the person's age in
years. The participants receive heart rate monitors to con-
trol their training intensity. The training session ends with
25 minutes strength exercises and 5 minutes cooling
down. The sport instructor registers the attendance of the
subjects. Since it is important that the group exercise ses-
sions are conducted uniformly in all centres, all instruc-
tors who participate in the SHAPE study are instructed
extensively. In addition, the study coordinator (EM) per-
forms several monitor visits per exercise group to control
adherence to the protocol.
Previous experience showed that group exercises are pre-
ferred by Dutch women of this age and are better adhered
to in the short and long term [49]. However, for budgetary
and practical reasons also an individual exercise session is
included.
Flow chart of the inclusion of the SHAPE participantsFigure 1
Flow chart of the inclusion of the SHAPE participants.
Invitation letters mailed to
women aged 50-69 y
n= 6200
Response to invitation letter
n=1799
Subject information mailed to
eligible women
n=310
Invited for baseline visit
n=208
Randomised
n=189
Intervention group
n=96
Control group
n=93
Screened on eligibility criteria
by phone
n=1360
Not eligible n=1046
Refused to participate n=4
Refused to participate
n=102
Not eligible n=19
Most important reasons:
- high blood glucose
- low BMI
- physically active
lifest
y
le
Table 1: Exclusion criteria of the SHAPE study
< 12 months since last menses
Use of hormone replacement or oral contraceptives in past 6
months
Active life style
Morbidly obese (BMI > 40)
BMI < 22
Currently on or planning to go on a strict diet
Ever diagnosed with breast cancer
Diagnosis of other types of cancer in the past 5 years
Diabetes mellitus or other endocrine related diseases
Disorders or diseases (locomotor, optical, neurological, mental)
that might impede the participation in the exercise programme
Alcohol or drug abuse
Maintenance use of corticosteroids
Use of beta blockers
Smoking
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Individual Exercise
Once a week the participants are asked to perform an indi-
vidual home-based exercise session. They receive instruc-
tions during the group sessions. The home-based exercise
programme consists of 30 minutes brisk walking or
cycling with an intensity of moderate-to-vigorous inten-
sity (60–80% of maximal heart rate). Afterwards, the
women record the type and duration of their activity in an
exercise log, together with the mean heart rate during the
training and the BORG-score (6–20) for exertion [50].
Control group
Participants in the control group are requested to retain
their habitual exercise pattern. They also receive newslet-
ters. Although some control subjects may decide to
increase their level of physical activity, we believe that it is
unlikely that they will sustain in a similar level as the
intervention group. Level of physical activity is measured
frequently to monitor changes in physical activity (PASE
questionnaire) during the course of the intervention.
Outcomes and measurements
The study participants visit the research unit of the Julius
Center at baseline, after 4 months and at the end of the
study (See table 2). To evaluate the effects of the exercise
intervention and potential confounding factors, data are
collected in several ways, i.e., by blood samples, physical
examination and questionnaires. Socio-demographic
information, reproductive factors, smoking information,
past physical activity and medical history is collected by a
self-constructed questionnaire at baseline only. Besides
blood sampling, anthropometric measurements includ-
ing dual-energy x-ray absorptiometry (DEXA) and ultra-
sound of the abdomen, blood pressure measurements
and a submaximal exercise test is performed each visit.
Also, medication use is assessed each visit. Furthermore,
habitual physical activity and diet are assessed at baseline
and at the end of the study. Level of physical activity is
assessed every four months to investigate changes during
the intervention period in both groups either in person or
by phone.
Blood samples
Blood samples (30 ml per visit) are drawn between 9.00
and 11.00 AM after an overnight fast in order to determine
serum concentrations of estradiol (total, free), estrone,
estrone sulfate testosterone, androstenedione, insuline,
glucose and sex hormone binding globulin. Blood sam-
ples are stored at -70°C. All samples from an individual
subject are analysed in the same batch since the batch-to-
batch variation can be higher than any woman's likely
change in hormones over the year [51]. Serum estrogens,
androgens, insulin and sex hormone binding globuline
(SHBG) are determined by use of commercially available
double-antibody radioimmunoassay kits.
The laboratory "Stichting Huisartsenlaboratorium Oost"
in Velp [52] performs all assays.
Physical examination
Anthropometry
Body weight and height (to the nearest 0.5 kg and 0.5 cm
respectively) are measured while the subjects wear light
clothes and no shoes using an analogue balance (SECA)
and wall-mounted tape measure.
Body fat distribution is measured by the waist- and hip
circumference. Waist circumference (to the nearest 0.1
cm) was measured standing at the midway between lower
ribs and iliac crest. Hip circumference (to the nearest 0.1
cm) was measured standing over the buttocks. All meas-
urements were taken in duplicate and averaged. Total
body fat and body fat percentage are determined by using
a whole-body DEXA scan (Lunar, Prodigy™). A whole
body scan analyses body composition according to a
three-compartment model: fat mass, lean tissue, and bone
mineral content. The standard soft tissue analysis is per-
formed using software supplied by the manufacturer.
Total body fat is estimated for each subject in kilograms.
Intra-abdominal fat is measured by abdominal ultra-
sound assessment (Acuson Aspen, Siemens). The ultra-
sound measure comprises the distance between the
peritoneum and the lumbar spine at three predefined
places. All measurements are performed longitudinally
from one line over the abdomen halfway between the
lower rib and iliac crest.
Blood pressure
Blood pressure is measured with an automatically tonom-
eter (OMRON M4) after participants have been sitting
quietly for at least five minutes.
Fitness
Fitness is measured by the maximal oxygen uptake (VO
2
max). VO
2
max is determined by a submaximal cycle test:
the Fit Test programme on a Life Fitness cycle ergometer.
The theory of the test is based on the Ästrand Rhyming
Protocol [53], in which, a submaximal heart rate at a
known workload is used to predict maximal aerobic
capacity. The participants wear light clothing and a heart
rate monitor. Prior to each test, the seat height of the cycle
ergometer is adjusted for near full extension of the sub-
ject's leg while pedalling and is kept the same during the
whole study. Before the start of the test, weight, age and
gender is entered in the programme. Additionally, a resist-
ance level that suits the subject is chosen. Guidelines for
the resistance level have been specified in the manual of
the manufacturer. During the test, the subject pedals for 5
minutes using a relatively consistent cadence. The subject
should exercise with an intensity of 60 – 85% of the age-
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predicted maximum heart rate (220 – age). Towards the
end of the 5 minutes, the programme measures the heart
rate via telemetry. Once a steady heart rate reading is
acquired, the programme calculates a VO
2
max estimate
based on the subject's weight, age, gender, selected resist-
ance, and steady-state heart rate. After the test, the subject
pedals without resistance for 2 minutes to cool down.
To assess reproducibility of the Fit Test, we tested 25 vol-
unteers twice with an average period of 2.0 ± 1.5 days
between the tests. Group means and standard deviations
of the first and second VO
2max
measurement were almost
identical: 38.9 ± 6.5 ml/kg/min versus 38.8 ± 6.5 ml/kg/
min, respectively. The test-retest reliability (i.e. Pearson's
correlation coefficient) was 0.993 (P < 0.001). Other reli-
ability indexes (i.e. Intraclass Correlation Coefficient,
Standard Error of Measurement and Smallest Detectable
Difference) were respectively 0.993, 0.532 ml/kg/min and
1.475 ml/kg/min. This reproducibility study showed that
the Fit Test is a reproducible measure of submaximal work
capacity.
Questionnaires/interviews
A self-constructed questionnaire (general questionnaire)
is used to assess level of physical activity, diet, socio-
demographic variables, smoking history, medical history
and reproductive factors.
Habitual-, occupational- and physical activity in the past
The general physical activity questionnaire includes the
Voorrips questionnaire measuring habitual activity in eld-
erly subjects [54] and questions concerning occupational
physical activity and activity in the past. The Voorrips
questionnaire includes household activities, sporting
activities and other physically active leisure activities.
Altogether it leads to an overall activity score. In the ques-
tionnaire, the respondents are asked to report habitual
physical activities of the last year. Items on household
activities are questions with four to five possible ratings
from active to inactive. Sports and other activities are
asked as type of activity, hours per week spent on it, and
period of the year in which the activity is normally per-
formed. All activities are classified according to work pos-
ture and movements. An intensity code, originally based
on Bink et al [55], is used to classify each activity.
Recent physical activity
The PASE (Physical Activity Scale for the Elderly) ques-
tionnaire [56] measures occupational, household and lei-
sure- related activities over a 1-week period. This
questionnaire includes 12 categories of physical activity
and records the frequency of participation in these activi-
ties over the preceeding 7 days. Scoring procedures were
derived from motion sensor counts, physical activity dia-
ries and a global activity self-assessment [56]. The PASE
generates a single composite score of physical activity that
ranges from 0 – 400. We modified the PASE slightly by
adding additional answer categories for the duration of
the activities. We divided the category "less than 1 hour"
into "less than 30 minutes", "30–45 minutes" and "45
minutes – 1 hour" in order to compare the activity level of
the participants with the international recommendations
for prevention of obesity. The calculation of the PASE
score is modified accordingly.
Diet
Daily caloric intake, percent daily calories from fat, per-
cent daily calories from carbohydrates and proteins is
determined by a food frequency questionnaire [57,58].
The questionnaire consists of 74 items. The questionnaire
is completed by the participants at home and subse-
quently checked by a dietician at the research unit.
Table 2: Time schedule of the measurements in the SHAPE study
Measurement Time (months)
-0.5 01234 5678 9101112
Blood sampling √√√
Anthropometry √√√
Ultrasound abdomen √√√
Whole body DEXA scan √√√
Blood pressure √√√
Submaximal exercise test √√√
Medication use (internet database) √√√
General questionnaire# √
Physical activity questionnaire √ √
Past week activity questionnaire √√√√
Food frequency questionnaire √ √
Exercise programme (intervention only) √√√√√√√√√√√ √ √
Exercise logs (intervention only) √√√√√√√√√√√ √ √
# General questionnaire includes demographic information, reproductive factors, smoking information and medical history
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Medication use
Medication use is asked each visit and registered by use of
an internet database. This database is based on the current
available medications and uses ATC codes.
Statistical analysis
All randomised subjects will be analysed according to the
intent-to-treat principle. The intention-to-treat principle
will assess the intervention effect based on assigned treat-
ment at the time of randomisation regardless of adher-
ence. Demographics and baseline characteristics will be
reported descriptively. We will assess whether life style
factors that are potentially related to hormone levels
might have changed differentially between exercisers and
controls, including alcohol use and caloric intake. Differ-
ences between the treatment groups in primary and sec-
ondary efficacy parameters will be analysed by repeated
measurement analyses in SAS and 95% confidence inter-
vals will be calculated. We will also assess effect modifica-
tion by change in intra-abdominal (and total body fat)
and, among exercisers only, by adherence levels.
Discussion
In this paper, we present the rationale and design of the
SHAPE trial which aims to get more insight in the biolog-
ical mechanism underlying the observed effect between
physical activity and breast cancer risk.
The success of the study will depend to a large extent on
adherence to the exercise protocol. Factors that enhance
adherence to exercise programmes in The Netherlands are
group exercise (in stead of individual), a varied pro-
gramme and a regular instructor [59]. We incorporated all
three factors in the SHAPE study as much as possible.
First, group exercise comprises the most important part of
the total exercise programme. Second, the aerobic compo-
nent of the exercise programme can be varied to a large
extent by the sport instructors. The strength exercises,
however, are highly standardised and repetitive which
might be less challenging for the women. We choose for
this type of strength training for two important reasons: 1)
to decrease the risk of injury and 2) since this type of
strength training is most optimal to increase muscle mass.
Third, we opt for regular instructors for all training groups
during the follow-up period, however, in practice there
may be some changes during the year. Additional proce-
dures that we use to enhance adherence are: personal
feedback, use of exercise logs and newsletters.
It is also of utmost importance that the control group is
compliant with the study protocol, e.g., retaining their
habitual lifestyle pattern. Women who are randomised to
the control group might be disappointed about the
assignment and may take up exercise or change their diet.
We monitor the level of physical activity of all participants
with questionnaires in order to get insight in the actual
amount of physical activity and potential cross-over
between both treatment arms. Changes in diet are moni-
tored by a food frequency questionnaire.
Six fitness centres and fourteen instructors participate in
the SHAPE study. Although the exercise protocol is stand-
ardised as much as possible, the attitude and experience of
the instructor might influence the actual performance of
the participants. In the analysis, we will explore whether
outcomes of participants within the same sporting centre
are correlated (intracluster correlation). If there is evi-
dence for intracluster correlation, we will account for this
in the analysis.
Because of the stringent in and exclusion criteria, the par-
ticipants of the SHAPE study comprise a selected group of
postmenopausal women. This type of preselection will
not affect the validity of the study (no selection bias)
because randomisation is aimed to ensure comparability
of intervention and control group but it may limit the gen-
eralisability. For example, since we exclude lean women
and women not using hormone replacement therapy, the
results might not be generalised to these groups of
women.
So far, one study (PATH study) has been published on the
effects of exercise interventions on sex steroid concentra-
tion in women [60]. The PATH study observed that a 12-
month moderate-intensity exercise intervention in seden-
tary, overweight, postmenopausal women resulted in sig-
nificant decreases in serum estrogens and androgens.
These results were restricted to women who lost body fat,
e.g., among women who lost > 2% of body fat, serum
estradiol and testosterone concentrations fell by 13.7%
and 10.1 % between baseline and 12 months in exercisers
compared with a increase of 4.7% and a decrease of 1.6%
in controls, respectively [61,62]. Two other controlled
physical activity intervention studies in postmenopausal
women are under way. These are the ALPHA trial (Alberta
Physical Activity and Breast Cancer Prevention Trial) [63]
and The NEW Trial (Nutrition and Exercise for Women)
[64]. The Alpha trial examines the effect of a 12-month
aerobic exercise intervention compared with a usual sed-
entary lifestyle on several biomarkers of breast cancer risk
in 330 sedentary postmenopausal women. The NEW trial
is a 4-arm trial examining the effects of diet and exercise
induced weight loss on biomarkers of breast cancer risk in
503 sedentary postmenopausal women randomly
assigned to dietary weight loss alone, exercise alone, die-
tary weight loss plus exercise, or usual lifestyle control.
Together, these results will shed important light on bio-
logical mechanisms by which physical activity influences
breast cancer risk. These studies may also give information
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about the type of exercise needed for breast cancer risk
reduction.
In summary, this paper shows the rationale and design of
the SHAPE study. The SHAPE study aims to unravel the
mechanisms underlying the association physical activity
and breast cancer risk. Furthermore, this study evaluates
the feasibility of delivering an exercise programme for
postmenopausal women.
Abbreviations
BMI, Body Mass Index; DEXA, Dual-Energy X-ray Absorp-
tiometry; SHBG, Sex Hormone Binding Globulin;
VO
2
max, Maximum Oxygen Uptake; ATC, Anatomical
Therapeutic Chemical Classification System
Competing interests
The author(s) declare that they have no competing inter-
ests.
Authors' contributions
EMM, PHMP and AJS designed the study, participated in
the coordination of the study and writing of the article. All
authors provided comments on the draft and have read
the paper.
Acknowledgements
First, we would like to thank all participating women. Furthermore, we
gratefully acknowledge Manon de Leeuw, Anneloes van Diemen, Claire
Nollen, Karin Menninga, Lizeth Vendrig, Lara Heuveling, Jose Drijvers, Joke
Metselaars and Fien Stern for their contribution to the inclusion and follow-
up of the SHAPE participants. We would like to thank the following sport
centres for their participation in the SHAPE study: Healthclub Fysio Physics,
IJsselstein; Better Bodies Health Club, Bilthoven and Zeist; Maxfit Europe,
Houten; Body Business, Utrecht; Physiotherapy Center Basten-Kries,
Soest. Finally, we would like to thank all sport instructors for their dedica-
tion to the SHAPE study.
The trial is sponsored by the Dutch Cancer Society (Project number: UU
2003-2793).
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