Original Research
ajog.org
GYNECOLOGY
Effects of high-intensity training on cardiovascular risk
factors in premenopausal and postmenopausal women
Camilla M. Mandrup, MD; Jon Egelund, MD; Michael Nyberg, PhD; Martina H. Lundberg Slingsby, PhD;
Caroline B. Andersen, MSc; Sofie Løgstrup, MSc; Jens Bangsbo, PhD; Charlotte Suetta, MD, PhD, DMSc;
Bente Stallknecht, MD, PhD, DMSc; Ylva Hellsten, DMSc
BACKGROUND: Menopause is associated with increased risk of
cardiovascular disease and the causal factors have been proposed to be
the loss of estrogen and the subsequent alterations of the hormonal
milieu. However, which factors contribute to the deterioration of cardiometabolic health in postmenopausal women is debated as the
menopausal transition is also associated with increased age and fat
mass. Furthermore, indications of reduced cardiometabolic adaptations
to exercise in postmenopausal women add to the adverse health profile.
OBJECTIVE: We sought to evaluate risk factors for type 2 diabetes and
cardiovascular disease in late premenopausal and early postmenopausal
women, matched by age and body composition, and investigate the effect
of high-intensity training.
STUDY DESIGN: A 3-month high-intensity aerobic training intervention, involving healthy, nonobese, late premenopausal (n ¼ 40) and early
postmenopausal (n ¼ 39) women was conducted and anthropometrics,
body composition, blood pressure, lipid profile, glucose tolerance, and
maximal oxygen consumption were determined at baseline and after the
intervention.
RESULTS: At baseline, the groups matched in anthropometrics and
body composition, and only differed by 4.2 years in age (mean [95%
confidence limits] 49.2 [48.5-49.9] vs 53.4 [52.4-54.4] years). Time
since last menstrual period for the postmenopausal women was (mean
[95% confidence limits] 3.1 [2.6-3.7] years). Hormonal levels (estrogen,
Introduction
The menopausal transition is accompanied by metabolic changes and
increasing prevalence of metabolic syndrome (MetS), which is defined as
copresence of abdominal obesity, hypertension, dyslipidemia, and insulin
resistance.1,2 MetS is associated with
development of type 2 diabetes (T2D)
(relative risk [RR] 5.0), cardiovascular
disease (CVD) (RR 2.35), and all-cause
mortality (RR 1.86),3 and globally it is
Cite this article as: Mandrup CM, Egelund J, Nyberg M,
et al. Effects of high-intensity training on cardiovascular
risk factors in premenopausal and postmenopausal
women. Am J Obstet Gynecol 2017;216:384.e1-11.
0002-9378/$36.00
ª 2016 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.ajog.2016.12.017
follicle stimulation hormone, luteinizing hormone) confirmed menopausal
status. At baseline the postmenopausal women had higher total
cholesterol (P < .001), low-density lipoprotein-cholesterol (P < .05), and
high-density lipoprotein-cholesterol (P < .001) than the premenopausal
women. The training intervention reduced body weight (P < .01), waist
circumference (P < .01), and improved body composition by increasing lean
body mass (P < .001) and decreasing fat mass (P < .001) similarly in both
groups. Moreover, training resulted in lower diastolic blood pressure (P <
.05), resting heart rate (P < .001), total cholesterol (P < .01), low-density
lipoprotein-cholesterol (P < .01), total cholesterol/high-density lipoproteincholesterol index (P < .01), and improved plasma insulin concentration
during the oral glucose tolerance test (P < .05) in both groups.
CONCLUSION: Cardiovascular risk factors are similar in late
premenopausal and early postmenopausal women, matched by age and
body composition, with the exception that postmenopausal women have
higher high- and low-density lipoprotein-cholesterol levels. A 3-month
intervention of high-intensity aerobic training reduces risk factors for
type 2 diabetes and cardiovascular disease to a similar extent in late
premenopausal and early postmenopausal women.
Key words: cardiorespiratory fitness, cardiovascular risk factors,
glucose metabolism, high-intensity exercise, lipids, menopause,
metabolic risk
estimated that 30-55% of postmenopausal women fulfill the diagnostic
criteria for MetS.4 It is debated whether
the increased prevalence of MetS after
menopause is due to hormonal changes,
a normal phenomenon of aging, or a
consequence of gain in weight and fatmass during and after the menopausal
transition.5 It is therefore highly relevant
to evaluate factors associated with MetS
in nonobese premenopausal and postmenopausal women matched by age and
body composition.
Physical exercise increases cardiorespiratory fitness and reduces the risk
of MetS6,7 but the ability of postmenopausal women to respond to
exercise training has been debated.
Some cross-sectional studies suggest
that postmenopausal women have a
reduced fitness level compared to
384.e1 American Journal of Obstetrics & Gynecology APRIL 2017
premenopausal women8,9 and a
blunted response to exercise-induced
central and peripheral cardiovascular
modulations.10 Another study finds
similar beneficial effects of brisk
walking on body composition and
glucose metabolism, irrespective of
menopausal status, in overweight to
obese women11 and a review, investigating the effects of exercise training
in early postmenopausal women,
_ 2max (ranging
found increases in Vo
from 4-32%), diverse effects of exercise on blood pressure (BP) in
normotensive women but a lowering
effect in hypertensive women, as well
as reductions in plasma lipids in dyslipidemic but not in normolipidemic
women.12 However, very few studies
have compared the effect of physical
activity on the risk of MetS in
ajog.org
GYNECOLOGY
Original Research
FIGURE 1
Overall study design of Copenhagen Women Study, menopause
Horizontal timeline and vertical overview of different examinations. This article only includes physiological data.
Mandrup et al. High-intensity training for postmenopausal health. Am J Obstet Gynecol 2017.
premenopausal vs postmenopausal
women. The aim of this study was
therefore to investigate the effect of a
well-controlled high-intensity aerobic
training program on risk factors predisposing to T2D and CVD in nonobese, early postmenopausal women
and to compare the effect of the
training intervention to the effect in
late premenopausal women differing,
on average, only by 4 years of age.
Materials and Methods
Overall study design
The work was carried out as part of the
research program Copenhagen Women
Study (cws.ku.dk) funded by the University of Copenhagen Excellence Program for Interdisciplinary Research.
This article presents data from work
package II where late premenopausal
and early postmenopausal women were
assigned to 3 months of high-intensity
aerobic training, performed as spinning. All participants underwent a health
examination before inclusion as well as
examinations at baseline and after 3
months, comprising physiological, psychological, and sociological tests
(Figure 1). All women participated in the
general tests on day 1 and 2 at baseline
and test day 4 and 5 after 3 months. At
test day 3 (baseline) and 6 (3 months)
specific investigations of either cardiovascular function13 (n ¼ 42 women) or
adipose tissue and skeletal muscle
metabolic function (n ¼ 41 women)
were conducted. This article covers the
results of the general physiological tests,
and all presented outcomes were a priori
defined as secondary outcomes in
clinicaltrials.gov, registration number:
NCT02135575.
Recruitment
Late premenopausal (n ¼ 43) and early
postmenopausal (n ¼ 40) women were
recruited from the Copenhagen area
through newspaper advertisements.
Eligibility was assessed upon first contact by telephone or mail, secondly by
evaluation of an online questionnaire,
and finally at a health examination
(Figure 2). Recruitment was conducted
through 4 rounds from August 2013
through August 2015, and an almost
equal number of premenopausal and
postmenopausal women were recruited
in each round to prevent seasonal and
investigator-dependent variations. All
participants received written and oral
information about the study, including
risks and discomforts associated with
participation, before they gave their
written consent to participate. The
study was conducted according to the
Helsinki Declaration and approved by
the ethical committee in the capital
region of Denmark, protocol no. H-12012-150.
Participants
Inclusion criteria were healthy, sedentary, normal-weight to overweight (body
mass index [BMI] 18.5-30 kg/m2)
women, 45-57 years of age, who were
either late premenopausal (regular
bleeding and plasma estradiol [E2] in the
normal fertile range; follicular phase
0.05-0.51 nmol/L, mid cycle 0.32-1.83
nmol/L, luteal phase 0.16-0.78 nmol/L,
and plasma follicle-stimulating hormone [FSH] <20 IU/L) or early postmenopausal (no bleeding for at least 1
year, E2 <0.20 nmol/L and FSH 22-138
IU/L). Being sedentary was defined as
performing <2 hours of physical activity
per week during the last 2 years, and
the definition was also supported by a
_ 2max <40 mL O2/min/kg. Exclusion
Vo
criteria were smoking, use of hormonal
contraception, excessive alcohol intake,
diagnosis of hypertension or any other
chronic disease, daily intake of medication, or blood samples (screening for
liver, kidney, and bone-marrow function) outside of normal range. Characteristics of the participants are presented
in Table 1.
Exercise training intervention
The intervention consisted of 3 months
of high-intensity aerobic training (spinning), conducted 3 times/wk for
approximately 1 hour. Two weekly sessions were conducted in our exercise
training facility by instructors from our
research group and in the beginning of
every round, a medical doctor attended
the spinning classes. The sessions
comprised a warm-up, 3 blocks of
APRIL 2017 American Journal of Obstetrics & Gynecology
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Original Research
GYNECOLOGY
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FIGURE 2
Flow diagram of inclusion and exclusion
Participants before and after start of high-intensity aerobic training intervention.
Mandrup et al. High-intensity training for postmenopausal health. Am J Obstet Gynecol 2017.
varying intervals, with multiple periods
of maximum performance, followed by a
cool-down period (Figure 3). The intensity of the training sessions increased
gradually during the 3-month period.
During the sessions, the instructor and
the participants were able to monitor
their own and their peers’ heart rate (HR)
on a big screen, given as a percentage of
their individual maximal HR (HRmax).
One weekly session took place in a local
fitness center. During all training sessions
the participants wore HR monitors (FT2;
Polar, Kempele, Finland).
Measurements and analyses
Anthropometrics were assessed using a
tape measure for hip and waist circumference and a stadiometer for height.
Body composition was assessed by dual
x-ray absorptiometry scanning (Lunar
iDXA; GE Healthcare, Little Chalfont,
United Kingdom) at Department of
Clinical Physiology, Nuclear Medicine,
384.e3 American Journal of Obstetrics & Gynecology APRIL 2017
and Positron Emission Tomography,
Rigshospitalet, Glostrup, Denmark, by
an investigator blinded for menopausal
status. All scans were performed by the
same investigator at baseline and after 3
months. Blood samples were obtained
from the antecubital vein by a BD
Vacutainer system (Becton-Dickinson,
Plymouth, United Kingdom) and
analyzed at Department of Clinical
Biochemistry, Rigshospitalet, Copenhagen, Denmark, by investigators blinded
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TABLE 1
Participant characteristics before and after 3-month high-intensity aerobic training intervention
Premenopausal
Variables
Baseline
Postmenopausal
n
3 months
39
e
38
e
n
Baseline
n
3 mo
38
e
37
e
n
Anthropometrics
Age, ya
49.2 (48.5e49.9)
Height, m
Weight, kg
1.68 (1.66e1.70)
b
53.4 (52.4e54.4)
1.67 (1.65e1.69)
67.7 (65.5e70.0)
38
67.1 (64.9e69.3)
38
66.4 (63.6e69.1)
38
65.8 (62.9e68.7)
37
23.9 (23.2e24.7)
38
23.7 (23.0e24.4)
38
23.7 (22.9e24.4)
37
23.5 (22.6e24.3)
37
80 (78e82)
32
79 (77e81)
32
79 (76e81)
32
78 (76e81)
31
43.5 (42.0e44.9)
38
44.1 (42.7e45.5)
38
42.7 (41.3e44.1)
38
43.2 (41.7e44.7)
37
24.3 (22.8e25.7)
38
23.0 (21.5e24.5)
38
23.6 (21.8e25.5)
38
22.6 (20.6e24.6)
37
35.7 (34.2e37.1)
38
34.1 (32.7e35.6)
38
35.3 (33.7e36.9)
38
33.9 (32.1e35.7)
37
Android fat, %
38.4 (35.8e41.0)
38
36.4 (33.7e39.0)
38
35.9 (32.8e39.1)
38
34.3 (30.9e37.6)
37
b
41.5 (40.0e43.0)
38
39.4 (38.0e40.9)
38
41.9 (40.5e43.2)
38
39.7 (38.1e41.4)
37
BMI, kg/m2b
Waist circumference, cm
b
Body composition
Lean body mass, kgb
Fat mass, kg
b
Fat, %b
b
Gynoid fat, %
Android-gynoid fat ratio
0.92 (0.87e0.98)
38
0.92 (0.86e0.98)
38
0.85 (0.79e0.91)
38
0.85 (0.79e0.92)
37
0.61 (0.28e1.13)
39
0.54 (0.37e0.98)
32
0.04 (0.04e0.32)
38
0.04 (0.04e0.09)
32
8.5 (5.3e16.3)
39
8.3 (5.4e13.8)
32
90.0 (74.2e112.0)
38
79.8 (65.5e103.0)
32
11.4 (8.6e15.2)
39
11.0 (8.0e15.1)
32
38.3 (35.0e41.9)
38
33.8 (30.1e38.1)
32
Hormones
P-follitropin [FSH], IU/L
a,b,c
a,c
P-lutropin [LH], IU/L
Blood pressure
107 (99e117)
39
108 (103e118)
38
111 (103e120)
38
107 (99e120)
37
Diastolic, mm Hgb
70 (66e75)
39
70 (66e76)
38
71 (66e79)
38
70 (65e75)
37
d
82 (76e88)
39
82 (78e90)
38
84 (79e92)
38
82 (77e88)
37
e1b
66 (61e72)
38
65 (58e71)
38
64 (59e68)
38
61 (56e66)
37
176 (172e180)
35
175 (172e177)
38
175 (171e180)
36
173 (169e176)
34
Mean arterial pressure, mm Hg
Resting heart rate, beats/min
Maximal heart rate, beats/min
e1b
Data are mean (95% confidence limits). No statistical analysis has been performed for estrogen as most measurements for postmenopausal women were lower than detection limit. In first inclusion round, waist circumference and postintervention analysis of hormonal
levels were not performed, resulting in lower n for those parameters.
BMI, body mass index; FSH, follicle-stimulating hormone; LH, luteinizing hormone.
384.e4
Baseline differences assessed by independent t test: a Statistically significant (P .05) difference between premenopausal and postmenopausal group. Effort of intervention was assessed by 2-way analysis of variance; b Statistically significant (P .05) difference
from baseline to 3 mo; c Statistically significant (P .05) difference between premenopausal and postmenopausal group; d Statistically significant (P .05) interaction between time and menopausal status, meaning that 2 groups responded differently to
intervention.
Mandrup et al. High-intensity training for postmenopausal health. Am J Obstet Gynecol 2017.
Original Research
Systolic, mm Hgd
GYNECOLOGY
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P-estradiol, nmol/L
Original Research
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GYNECOLOGY
for menopausal status. Plasma E2 was
analyzed by competitive electrochemiluminescence
immunoassay
(ECLIA), and FSH and luteinizing hormone were analyzed by sandwich ECLIA
(Cobas 8000, e602 module; F.
Hoffmann-La Roche Ltd, Rotkreuz,
Switzerland). Plasma high-density lipoprotein (HDL)-cholesterol (HDL-C),
low-density
lipoprotein-cholesterol
(LDL-C), total cholesterol, and triglyceride were measured by enzymatic absorption photometry (Cobas 8000, c702
module; F. Hoffmann-La Roche Ltd).
Screening samples, used for evaluation
of liver, kidney, and bone-marrow
function, were analyzed by standard
methods at Department of Clinical
Biochemistry, Rigshospitalet, Copenhagen, Denmark.
FIGURE 3
Graphic illustration of training sessions
Duration and intensity of the high-intensity training intervention.
HRmax, maximal heart rate.
Mandrup et al. High-intensity training for postmenopausal health. Am J Obstet Gynecol 2017.
Oral glucose tolerance test
The participants arrived at the laboratory after an overnight fast and an
intravenous catheter (Vasofix Safety,
20G; B. Braun Melsungen AG, Melsungen, Germany) was placed in an
antecubital vein. Blood was obtained
from the catheter, put into EDTAprecoated tubes, and immediately
centrifuged (Ole Dich Instrumentmakers ApS, Hvidovre, Denmark) at
4000 rpm for 2 minutes, and plasma was
stored at e80 C until analysis. After
oral intake of 82.5 g monohydrate
glucose dissolved in 250 mL of water,
blood samples were collected at 15, 30,
45, 60, 90, and 120 minutes and handled
as described above. Glucose was
assessed by photometric measurement
(Cobas 8000, c702 module), and insulin
and C-peptide were determined by
sandwich ECLIA (Cobas 8000, e602
module).
Calculations
The Matsuda index was calculated as a
surrogate measure of insulin sensitivity
during the oral glucose tolerance test
(OGTT) using the formula14:
BP was measured using an upper arm,
automatic BP monitor (M2 HEM7121-E; Omron, Hoofddorp, The
Netherlands) with the participant in a
supine position, after at least 15 minutes
of rest. The reported values are means of
7 consecutive measurements.
VO2-max
Maximal oxygen consumption was
assessed during an incremental bicycle
ergometer protocol (839E; Monark
Exercise AB, Vansbro, Sweden) using
an
automated
online
system,
measuring breath-by-breath pulmonary oxygen uptake and carbondioxide production (Oxycon Pro,
Intramedic,
Gentofte,
Denmark).
Before the test, the bicycle ergometer
and the Oxycon Pro were calibrated
and the saddle and handlebars were
adjusted to fit the participant. HR
monitor (Team2 Transmitter, Polar)
was placed, and the mask was fitted.
The participant was informed about
the test, told to remain seated during
the entire test, and to keep a pace of
60-70 rpm. Before the test was started,
there was an 8-minute warm-up period
with a workload of 50 W. The test
workload started at 50 W and was
increased by 25 W every minute, until
exhaustion. The test was approved if 2
of 3 criteria were fulfilled: plateau in
_ 2 despite an increasing workload,
Vo
respiratory exchange ratio >1.1, and
HR >90% of predicted value, calculated as 220 minus age in years. The
maximal watt load was registered at the
end of the test.
Statistical methods
Statistical calculations were performed
using software (SAS Enterprise Guide
7.1; SAS Institute Inc, Cary, NC).
Descriptive statistics for parametric
data are given as means (95% confidence limits) and for nonparametric
data as median (25th-75th percentile).
Baseline comparisons were made using
independent t tests. The effects of
menopausal status and exercise
10;000
Matsuda index ¼
fasting glucose
mg
dL
fasting insulin
384.e5 American Journal of Obstetrics & Gynecology APRIL 2017
mU
mL
mean glucose
mg
dL
mU0:5
mean insulin mL
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GYNECOLOGY
Original Research
TABLE 2
Training adherence for 3-month high-intensity aerobic training intervention
Percentage of time spent in each interval of HRmax, %
Training sessions
Group
Total
Premenopausal (n ¼ 38)
37 (35e39) 54 (53e54)
2 (1e2) 7 (6e8)
26 (24e29) 23 (21e24) 26 (23e28) 14 (11e16) 1 (1e2)
Postmenopausal (n ¼ 37) 38 (36e39) 53 (51e54)
1 (1e2) 7 (6e9)
26 (22e29) 23 (21e25) 27 (24e31) 13 (10e16) 1 (1e2)
Length, min <61%
61e70% 71e80%
81e85%
86e90%
91e95%
96e100%
Data are mean (95% confidence limits). Equal number, length, and intensity of training sessions.
HRmax, maximal heart rate.
Mandrup et al. High-intensity training for postmenopausal health. Am J Obstet Gynecol 2017.
training were assessed using a 2-way
repeated measures analysis of variance.
Alpha was set to 0.05.
Results
A total of 43 premenopausal and 40
postmenopausal
women
were
included, but 4 (3 premenopausal and
1 postmenopausal) women were
excluded in the run-in period, as it was
not possible to schedule the test days.
Time since last menstrual period for
the postmenopausal women was
(mean [95% confidence limits] 3.1
[2.6-3.7] years). There were a few
dropouts in each group, but only 1 due
to low adherence to the training
intervention (Figure 2). Data from a
participant who was later excluded due
to pregnancy and 1 who was excluded
due to low training adherence were
included in the baseline analyses. At
_ 2max test was not
baseline, 1 Vo
approved due to subjective exhaustion
_ 2. At 3 months, 2
before plateau of Vo
tests were not included: 1 due to anemia and 1 test was not performed due
to logistic difficulties. No adverse
events occurred in response to the
high-intensity training.
High-intensity aerobic training
intervention
The 2 groups of premenopausal and
postmenopausal
women
adhered
equally well to the training intervention, as assessed by total training sessions, duration of the sessions, and
exercise intensity during the sessions
(Table 2).
_ 2max
Vo
At baseline, there was no difference in
_ 2max between premenopausal and
Vo
postmenopausal women (Figure 4, A).
After the training intervention, the premenopausal
and
postmenopausal
_ 2max by
women had increased their Vo
8.8% and 9.4% (P < .001), respectively.
Nonresponders were observed in both
groups (Figure 5).
Maximal watt load
We observed no group difference in
maximal watt load at baseline and both
groups increased wattmax by 13.2% (P <
.001) (Figure 4, B).
FIGURE 4
_ 2max) and maximal watt load (Wattmax)
Maximal oxygen consumption (Vo
_ 2max and B, Wattmax for premenopausal and postmenopausal women at baseline (light green/blue) and after high-intensity aerobic training
A, Vo
intervention (green/blue). zDifference from baseline to 3 months, P .05.
Mandrup et al. High-intensity training for postmenopausal health. Am J Obstet Gynecol 2017.
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GYNECOLOGY
Blood pressure
At baseline, no difference between the
groups in systolic or diastolic BP,
mean arterial pressure, or resting HR
was observed (Table 1). After training,
both groups had lowered their diastolic BP (0.3% and 4.6% for premenopausal and postmenopausal
group, respectively) (P < .05) and
their resting HR (mean [95% confidence limits] 2.0 [3.7-0.4] beats/min
for both groups) (P < .001). For systolic BP and mean arterial pressure a
significant interaction between the 2
groups was found as the postmenopausal women had a lower
systolic BP after the intervention,
while the premenopausal women had
a slight elevation (nonsignificant
changes).
Lipids
At baseline, the concentrations of total
cholesterol (P < .001), LDL-C (P ¼ .01),
and HDL-C (P < .001) differed between
the premenopausal and postmenopausal
women (Table 3). The training intervention reduced total cholesterol (P <
.001), LDL-C (P < .001), and the total
cholesterol/HDL-C index (P < .001)
in both premenopausal and postmenopausal women. No significant
change in triglyceride level was observed
after training.
Body composition
At baseline, we did not find any differences in body composition between the
premenopausal and postmenopausal
women (Table 1). After the training
period, both groups had experienced a
decrease in weight, BMI, and waist
circumference (P < .01). Additionally,
both groups had similar reductions in fat
mass (P < .001), fat percentage (P <
.001), android fat percentage (P < .001),
and gynoid fat percentage (P < .001),
with no change in android-gynoid fat
ratio. Lean body mass increased in both
groups (P < .001).
OGTT
Fasting glucose was similar for the premenopausal
and
postmenopausal
women at baseline and no changes were
seen after the intervention (Table 3).
Likewise, the total glucose load during
an OGTT expressed as area under the
curve was similar between groups and
unchanged after the intervention
(Figure 6). No difference was seen in
fasting insulin at baseline, but the
training intervention entailed a decrease
in the fasting insulin level across groups
(P < .05). However, the postmenopausal
women had a better response to the
training intervention as they had lower
fasting insulin: 27% compared to 3% in
the premenopausal women (P < .05 for
interaction). The total insulin concentration (area under the curve) during the
OGTT was lowered after the intervention in both groups (P < .05) (Figure 6),
which was also reflected by the increase
in Matsuda index after the intervention
(P < .05). No difference was seen between groups in the C-peptide concentration either in the fasting state or
during glucose stimulation at baseline or
after the intervention.
Comment
This study evaluated the effects of
menopause and high-intensity aerobic
training in late premenopausal and early
postmenopausal women on cardiovascular and metabolic risk factors in a
controlled and unique study design with
narrow inclusion criteria for age (45-57
years) and BMI (18.5-30 kg/m2) to avoid
confounding from those parameters.
The main finding of the study was that
3 months of high-intensity aerobic
training induces substantial beneficial
effects on aerobic fitness and a number of
risk factors in middle-aged women and
that the postmenopausal women experienced the same positive adaptations to
training as premenopausal women.
Study strengths and limitations
A strength of our study is that the
exercise training intervention was
highly controlled with continuous
monitoring and supervision, resulting
in optimal compliance. To avoid confounding factors such as obesity,
smoking, and chronic disease when
observing the effect of menopausal
status on training response, we had
narrow inclusion criteria. This led to a
study population more healthy than
384.e7 American Journal of Obstetrics & Gynecology APRIL 2017
FIGURE 5
Individual training response
Change in maximal oxygen (O2) consumption.
Mandrup et al. High-intensity training for postmenopausal
health. Am J Obstet Gynecol 2017.
the general population, and thereby
reducing the generalizability of our
study. However, since moderateintensity exercise has been shown to
reduce BP in hypertensive early postmenopausal women, and the cholesterol level in dyslipidemic early
postmenopausal women,12 it seems
likely that also less healthy postmenopausal women would benefit
from high-intensity training to reduce
cardiovascular risk factors. A selection
bias may have been introduced, as the
women who volunteered to participate
were motivated to be physically active.
Due to ethical considerations a nontraining control group was not
included in the study design, as our
primary objective was to evaluate differences in training response between
premenopausal and postmenopausal
women.
The high intensity of our training
intervention may be pivotal to the
beneficial effects of exercise as moderateintensity exercise training did not
improve the plasma lipid profile in
nondyslipidemic, early postmenopausal
women.12 Other studies, concluding that
estrogen is essential for exercise-induced
improvements in risk factors for CVD,
consisted of moderate-intensity walking
interventions with HR between 50-65%
_ 2max.15,16 Earlier, we
and 65-80% of Vo
showed that floorball training, also
classified as high-intensity exercise,
_ 2max among
caused an increase in Vo
postmenopausal women.17 Which also
implies that intense exercise training
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TABLE 3
Glucose metabolism and lipids
Premenopausal
Variables
Baseline
Fasting glucose, mg/dL
Fasting insulin, pmol/L
f
b,c,d,f
Fasting C-peptide, pmol/L
f
Postmenopausal
N
3 mo
n
Baseline
n
3 mo
n
95.1 (87.6e98.4)
38
93.5 (91.0e97.1)
38
93.0 (89.9e97.5)
37
92.8 (86.1e97.1)
37
46.6 (33.7e59.0)
36
45.2 (33.3e57.9)
37
40.7 (32.2e64.4)
37
31.9 (24.5e45.0)
37
617 (506e705)
36
610 (487e719)
37
536 (477e689)
37
515 (455e636)
37
Oral glucose tolerance test
Glucose, AUC, mg/dL * 103f
3b,f
Insulin, AUC, pmol/L * 10
C-peptide, AUC, pmol/L *10
Matsuda index
3f
b,f
14.5 (12.1e16.7)
34
14.7 (12.6e16.6)
35
13.9 (12.7e15.5)
35
13.9 (12.6e16.5)
35
34.5 (29.7e41.9)
36
32.6 (28.6e41.9)
37
32.3 (25.9e44.6)
37
31.3 (24.7e40.0)
37
249 (208e280)
34
238 (207e288)
35
252 (200e300)
35
251 (209e286)
35
6.0 (4.5e7.2)
34
6.3 (4.7e7.8)
35
6.7 (4.5e9.1)
35
7.9 (5.4e9.7)
35
188 (179e197)
37
184 (175e192)
37
218 (209e227)
37
212 (204e220)
36
111 (102e120)
37
105 (97e112)
37
126 (118e134)
37
123 (114e131)
36
64 (59e68)
37
67 (61e72)
37
77 (72e83)
37
79 (73e84)
36
37
71 (61e97)
37
75 (59e97)
37
69 (59e93)
Lipids
LDL-cholesterol, mg/dL
a,b,c,e
HDL-cholesterol, mg/dL
a,c,e
f
Triglycerides, mg/dL
Total/HDL-cholesterol ratiob,f
74 (57e96)
3.1 (2.4e3.6)
37
2.7 (2.3e3.3)
37
2.8 (2.5e3.2)
37
2.7 (2.4e3.1)
36
36
AUC, area under the curve; HDL, high-density lipoprotein; LDL, low-density lipoprotein.
384.e8
Original Research
Baseline difference assessed by independent t test: a Statistically significant (P .05) difference between premenopausal and postmenopausal group. Effect of intervention was assessed by 2-way analysis of variance; b Statistically significant (P .05) difference
from baseline to 3 months; c Statistically significant (P .05) difference between premenopausal and postmenopausal group; d Statistically significant (P .05) interaction between time and menopausal status, meaning that 2 groups responded differently to
intervention; e Parametric data are presented as mean (95% confidence limits); f Nonparametric data are presented as median (25the75th percentile).
Mandrup et al. High-intensity training for postmenopausal health. Am J Obstet Gynecol 2017.
GYNECOLOGY
APRIL 2017 American Journal of Obstetrics & Gynecology
Total cholesterol, mg/dLa,b,c,e
Original Research
GYNECOLOGY
ajog.org
FIGURE 6
Oral glucose tolerance test (OGTT)
Area under curve for glucose, insulin, and C-peptide during OGTT. Data are given as median and 25th-75th percentile. zDifference from baseline to 3
months, P .05.
Mandrup et al. High-intensity training for postmenopausal health. Am J Obstet Gynecol 2017.
384.e9 American Journal of Obstetrics & Gynecology APRIL 2017
ajog.org
provides an effective stimulus for central
cardiovascular adaptations.
Biomarkers of vascular function
change rapidly after menopause suggesting a strong influence by the hormonal milieu17 but the impact of
menopause on the development of
essential hypertension has been debated.
Longitudinal observational studies such
as the Melbourne Women’s Midlife
Health Project18 and the Study of
Women Across the Nation5 indicate that
increasing age and not postmenopausal
status causes hypertension in contrast to
cross-sectional findings.19 The current
result of similar BP levels in the 2 groups
of women at baseline does not support
an influence of estrogen; however, in a
previous publication we showed that
vascular function is impaired and intravascular BP is higher in postmenopausal
compared to premenopausal women in a
subgroup of the same women.13 However, importantly, 3 months of exercise
training was found to normalize vascular
function in the postmenopausal women.
The differences in the lipid profile at
baseline is somewhat consistent with the
literature, as we observed that the LDL-C
concentration was highest in the postmenopausal women.1,20 However, HDLC was also higher in the postmenopausal
compared with the premenopausal
women in accordance with our earlier
observations17 but in disagreement with
most other observations.1 It may be
speculated that the balance between the
more antiatherogenic HDL2 levels and
the less antiatherogenic HDL3 levels
differed in the 2 groups, as menopause
has been associated with decreases in
HDL2 and increases in HDL3.1 Physical
exercise is generally associated with an
increase in HDL-C,21 but like previous
findings in postmenopausal women22 no
change was observed in our study after
the intervention. The observed traininginduced reductions in LDL-C, total
cholesterol, and the total cholesterol/
HDL-C index, which is a valid predictor for CVD in women,23 contrasts
conclusions from STRRIDE24 and a
meta-analysis from the American Heart
Association (2015) stating that there is
no effect of moderate- or vigorousintensity exercise training on LDL-C
GYNECOLOGY
concentrations.6 Apparently, highintensity aerobic training can entail
lowering of LDL-C and presumably the
amount, regularity, and intensity of the
exercise are important for the healthrelated effects.
The matching body compositions
between premenopausal and postmenopausal women at baseline are not
consistent with observations in the
literature, showing that menopause is
associated with increased abdominal and
total adipose tissue.25,26 Nevertheless, we
observed similar reductions in fat mass
and fat percentage in premenopausal
and postmenopausal women after the
intervention despite previous indications that menopause decreases the
ability to oxidize fat during exercise.27
In contrast to previous observations,
where exercise did not improve glucose
homeostasis or insulin secretion in
postmenopausal women,28 we find an
intact ability to reduce the plasma insulin response to an OGTT in early postmenopausal women. Interestingly,
plasma C-peptide did not decline, suggesting that the decrease in insulin concentration was due to higher peripheral
clearance of insulin rather than a
decrease in secretion.29,30
Clinical implication
Adverse metabolic changes appear in
more than one third of postmenopausal
women. In this study we show that even
in postmenopausal women without cardiovascular risk factors, substantial
health improvements can be achieved by
only 3 months of exercise training,
thereby lowering the risk of T2D and
CVD beyond weight loss. This knowledge is of importance for recommendations on physical activity for prevention
and treatment of lifestyle-related diseases
in middle-aged women. The clinical
challenge is to motivate postmenopausal
as well as premenopausal women to
perform high-intensity aerobic training
n
and to adhere to an active lifestyle.
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Author and article information
From the Departments of Biomedical Sciences
(Drs Mandrup and Stallknecht; Ms Andersen; and
Ms Løgstrup) and Nutrition, Exercise and Sports
(Drs Egelund, Nyberg, Lundberg Slingsby, Bangsbo, and
Hellsten), University of Copenhagen; and Department of
Clinical Physiology, Nuclear Medicine, and Positron
Emission Tomography, Rigshospitalet, Glostrup
(Dr Suetta), Denmark.
Received Oct. 14, 2016; revised Dec. 6, 2016;
accepted Dec. 16, 2016.
This study was supported in part by: University of
Copenhagen Excellence Program for Interdisciplinary
Research; Danish Ministry of Culture Research Council
(TKIF2011-014); and Overlæge Johan Boserup og Lise
Boserups Legat. The funding sources had no involvement
in the study design, collection, analysis, or interpretation
of data, nor in the writing process.
The authors report no conflict of interest.
Corresponding author: Camilla M. Mandrup, MD.
camillam@sund.ku.dk