Breast size increment during pregnancy and breastfeeding in mothers with polycystic ovary syndrome: A follow-up study of a randomised controlled trial on metformin versus placebo

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DOI: 10.1111/j.1471-0528.2012.03449.x · Source: PubMed
Abstract
Please cite this paper as: Vanky E, Nordskar J, Leithe H, Hjorth-Hansen A, Martinussen M, Carlsen S. Breast size increment during pregnancy and breastfeeding in mothers with polycystic ovary syndrome: a follow-up study of a randomised controlled trial on metformin versus placebo. BJOG 2012;119:1403–1409. Objective To study the significance of breast size increment in pregnancy, and the impact of metformin during pregnancy on breastfeeding in women with polycystic ovary syndrome (PCOS). Design A follow-up study of a randomised controlled trial (the PregMet study). Setting Eleven secondary care centres. Population Women with PCOS during pregnancy and postpartum. Methods Women with PCOS were randomised to treatment with metformin or placebo from the first trimester to delivery. Questionnaires were sent to 240 participants 1 year postpartum: 186 responded. Main outcome measures Pre-pregnancy and late-pregnancy brassiere size and breastfeeding patterns were registered, and androgen levels were measured in the mothers. Results No difference in breast size increment and breastfeeding were found between the placebo and metformin groups. Breast size increment correlated positively with the duration of both exclusive and partial breastfeeding, whereas body mass index (BMI) correlated negatively with the duration of partial breastfeeding. Dehydroepiandrostenedione-sulphate (DHEAS), testosterone and free testosterone index (FTI) in pregnancy did not correlate with breast size increment or duration of breastfeeding. Women with no change in breast size were more obese, had higher blood pressure, serum triglycerides and fasting insulin levels, and had a shorter duration of breastfeeding compared with those with breast size increment. Conclusions Metformin and androgens had no impact on breastfeeding. Women with PCOS who had no breast size increment in pregnancy seem to be more metabolically disturbed and less able to breastfeed.
Breast size increment during pregnancy and
breastfeeding in mothers with polycystic ovary
syndrome: a follow-up study of a randomised
controlled trial on metformin versus placebo
E Vanky,
a,b
JJ Nordskar,
b
H Leithe,
b
AK Hjorth-Hansen,
c
M Martinussen,
a,b
SM Carlsen
d,e
a
Department of Obstetrics and Gynecology, St Olav’s Hospital, Trondheim University Hospital, Trondheim, Norway
b
Institute for Laboratory
Medicine, Children’s and Women’s Health, Norwegian University of Science and Technology, Trondheim, Norway
c
Medical Faculty,
University of Debrecen, Debrecen, Hungary
d
Unit for Applied Clinical Research, Institute for Cancer Research and Molecular Medicine,
Norwegian University of Science and Technology, Trondheim, Norway
e
Department of Endocrinology, St Olav’s Hospital, Trondheim
University Hospital, Trondheim, Norway
Correspondence: Dr Eszter Vanky, Department of Obstetrics and Gynecology, St Olavs Hospital, University Hospital of Trondheim,
Olav Kyrres gt 16, 7006 Trondheim, Norway. Email eszter.vanky@ntnu.no
Accepted 10 June 2012. Published Online 25 July 2012.
Objective To study the significance of breast size increment in
pregnancy, and the impact of metformin during pregnancy on
breastfeeding in women with polycystic ovary syndrome (PCOS).
Design A follow-up study of a randomised controlled trial (the
PregMet study).
Setting Eleven secondary care centres.
Population Women with PCOS during pregnancy and
postpartum.
Methods Women with PCOS were randomised to treatment with
metformin or placebo from the first trimester to delivery.
Questionnaires were sent to 240 participants 1 year postpartum:
186 responded.
Main outcome measures Pre-pregnancy and late-pregnancy
brassiere size and breastfeeding patterns were registered, and
androgen levels were measured in the mothers.
Results No difference in breast size increment and breastfeeding
were found between the placebo and metformin groups.
Breast size increment correlated positively with the duration
of both exclusive and partial breastfeeding, whereas body
mass index (BMI) correlated negatively with the duration of
partial breastfeeding. Dehydroepiandrostenedione-sulphate
(DHEAS), testosterone and free testosterone index (FTI) in
pregnancy did not correlate with breast size increment or
duration of breastfeeding. Women with no change in breast
size were more obese, had higher blood pressure, serum
triglycerides and fasting insulin levels, and had a shorter
duration of breastfeeding compared with those with breast size
increment.
Conclusions Metformin and androgens had no impact on
breastfeeding. Women with PCOS who had no breast size
increment in pregnancy seem to be more metabolically disturbed
and less able to breastfeed.
Keywords Androgens, breast size increment, breastfeeding, met-
formin, polycystic ovary syndrome, pregnancy.
Please cite this paper as: Vanky E, Nordskar J, Leithe H, Hjorth-Hansen A, Martinussen M, Carlsen S. Breast size increment during pregnancy and breast-
feeding in mothers with polycystic ovary syndrome: a follow-up study of a randomised controlled trial on metformin versus placebo. BJOG 2012;119:
1403–1409.
Introduction
Polycystic ovary syndrome (PCOS) is a common condition,
and is associated with reduced fertility; however, most
women with PCOS become pregnant and give birth.
1,2
Except for one case report and one pilot study,
3,4
little has
been reported about PCOS and breastfeeding. For years,
the clinical impression has been that fewer women with
PCOS were breastfeeding, and in a small pilot study we
found support for this observation.
4
After performing a
larger randomised controlled trial (RCT) on metformin
versus placebo in pregnant women with PCOS,
5
we thought
it important to investigate whether treatment with metfor-
min in pregnancy could have any impact on breastfeeding.
ª 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology ª 2012 RCOG 1403
DOI: 10.1111/j.1471-0528.2012.03449.x
www.bjog.org
Maternal medicine
A large number of observational studies have been pub-
lished about the possible health effects of breastfeeding,
both for the mother and the child.
6–8
In particular the
positive effects of breast milk on the incidence of child-
hood obesity and diabetes have been stressed.
9
Factors or
reasons for breastfeeding or not breastfeeding have mostly
been attributed to maternal age and education level, socio-
economic situation and smoking habits.
10
Lately, obesity
has been associated with a low breastfeeding rate.
11–14
The
metabolic and hormonal determinants for the ability to
breastfeed have not yet been studied to a great extent. As
there seems to be a large proportion of women with PCOS
struggling with and failing to breastfeed, the question
emerged: what makes some women breastfeed easily and
others not? Which clinical, metabolic or hormonal factors
can be linked or associated with the ability to breastfeed?
Based on clinical observations and a former pilot
study,
15
we hypothesised that: (1) metformin in pregnancy
would not affect breastfeeding; (2) breast size increment
during pregnancy is important for successful breastfeeding;
(3) high maternal androgen levels would have a negative
impact on breastfeeding.
4,16
Study design
The present study is a follow-up of the ‘Metformin treat-
ment in pregnant PCOS women’ (PregMet) study, which
was a prospective, randomised, double-blind, multicentre
trial, comparing 2000 mg of metformin daily against pla-
cebo from the first trimester to delivery.
5
In short, the
inclusion criteria were: (1) PCOS diagnosed according to
the Rotterdam criteria;
17
(2) age 18–45 years; (3) gesta-
tional age between 5 and 12 weeks; and (4) a singleton via-
ble fetus shown on ultrasonography. The exclusion criteria
were: alanine aminotransferase (ALAT) > 90 iu/l; serum
creatinine concentration > 130 lmol/l; known alcohol
abuse; previously diagnosed diabetes mellitus or fasting
serum glucose > 7.0 mmol/l at the time point of inclusion;
treatment with oral glucocorticoids; or use of drugs known
to interfere with metformin.
Two hundred and seventy-four pregnancies (in 258
women) were randomly assigned to treatment with either
metformin or placebo (16 women participated twice). In
one patient a partial 21-hydroxylase deficiency had been
overlooked, but she was excluded after randomisation.
Randomisation, blinding and the measurements performed
are described in detail elsewhere.
5
All participants received
written and individual verbal counselling on diet and life-
style at inclusion. Thereafter treatment with 500 mg of
metformin (metformin hydrochloride, Metformin; Weifa
AS, Oslo, Norway) or identically coated placebo tablets was
initiated. The participants were instructed to take one tab-
let twice daily during the first week and two tablets twice
daily for the rest of the study period, i.e. until delivery.
Study medication was stopped upon delivery. To counter-
act a possible adverse effect of metformin on vitamin B lev-
els, patients were advised to take 0.8 mg of folic acid daily,
and one daily multivitamin tablet containing both vitamins
B
6
and B
12
.
Standardised interviewer-administered questionnaires
were used to obtain self-reported data on former medical
and gynaecologic/obstetric history, ethnicity, employment,
smoking habits, study medication and concomitant medi-
cation. Biometric variables, including height, weight, blood
pressure and heart rate, were recorded at inclusion and at
each pre-scheduled visit at gestational weeks 19, 24, 32 and
36. Fasting blood samples were directly analysed at each
study centre for plasma glucose. A 75-g oral glucose toler-
ance test (OGTT) was performed at inclusion, and at gesta-
tional weeks 19 and 32, according to the World Health
Organization (1998) recommendations.
18,19
Venous blood
samples were drawn from an antecubital vein between
08:00 and 11:00 hour, after an overnight fast. Blood pres-
sure and heart rate were measured while the patient was in
the sitting position after at least 10 minutes of comfortable
rest in a chair. The blood pressure was measured three
times, 2 minutes apart, with digital devices. The mean of
the second and third measurements was calculated. Body
weight was recorded with light clothes on and without
shoes. Gestational age was determined by mid-pregnancy
ultrasound examination, measuring bi-parietal diameter,
femur length and mean abdominal diameter of the fetus.
The follow-up study
The participants in the PregMet study gave their written
consent to be contacted after the end of the original study.
Out of the 274 pregnancies included in the PregMet study,
three patients had miscarriages, 12 dropped out, one was
excluded because of misdiagnosis and two babies died peri-
natally. Sixteen women participated twice. Only their first
participation was included in the follow-up study. Two
hundred and forty women were invited to participate in
the follow-up study. One year after delivery a questionnaire
and prepaid envelope was sent by mail. A reminder was
sent about 2–3 weeks later to the non-responders. At this
time point the participants were not aware of whether they
had been randomised to metformin or to placebo.
The participants were asked about the length of exclusive
breastfeeding (in months) and at what point in time they
stopped breastfeeding. We asked about bra size before
pregnancy and bra size at the end of pregnancy. Bra sizes
were recorded in the following manner: A = 1; B = 2;
C = 3; D = 4; E = 5. Bra chest circumferences were
recorded as: 70, 75, 80, 85, 90, 95 or 100 cm. An increase
from 70 to 75 cm also results in an increase of one cup
size. If a woman had 80B in early pregnancy and 85C at
Vanky et al.
1404 ª 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology ª 2012 RCOG
delivery, this implies an increase of two bra cup sizes (from
B to C = 1 and from 80 to 85 = 1).
Data management
All data entry, data management and data analyses were
performed at the Institute of Laboratory Medicine, Chil-
dren’s and Women’s, Norwegian University of Science and
Technology. Questionnaires were sent out successively
1 year postpartum.
Statistical analysis
The data are analysed according to the intention-to-treat
principle using pasw statistics 18.0 for WINDOWS
(SPSS Inc., Chicago, USA). The differences between the
study groups were compared with two-tailed t-tests for
independent samples. Where normality could not be
assumed, the Mann–Whitney U-test was used. Fisher’s
exact test was used for the evaluation of discrete data. Val-
ues are reported as means (SDs) or absolute numbers. A
two-tailed P < 0.05 was considered significant. A v
2
test
was used to test differences between the groups. If the
smallest expected value in a cell was less than five, we used
Fisher’s exact test. Associations were investigated with
univariate and multivariate linear regression analyses.
Two-tailed tests were used throughout. No adjustments for
multiple testing were performed.
Results
One hundred and eighty-six women with PCOS out of 240
who participated in the PregMet study responded to the
questionnaire at 1 year postpartum. No differences were
found in baseline data between those who were randomised
to the metformin and the placebo groups during pregnancy
(Table 1).
Metformin effect on breastfeeding
There were no differences in the duration of exclusive
breastfeeding or the duration of partial breastfeeding
between mothers with PCOS treated with metformin and
those treated with placebo (Table 2).
Breast size and breastfeeding
There were no differences in breast size before pregnancy
or breast size increment during pregnancy between the
metformin and the placebo groups (Table 2). The increase
in breast size was unrelated to maternal body mass index
(BMI) or change in BMI (data not shown).
The duration of both exclusive and partial breastfeeding
correlated positively with breast size increment in preg-
nancy in both univariate and multivariate regression analy-
ses (Table 3). Furthermore, increased BMI was related to a
shorter duration of partial breastfeeding. When the infants
were 3 months old, 26 women had stopped breastfeeding.
No or inadequate milk production was given as the reason
in 24 cases. Maternal dehydroepiandrostenedione-sulphate
(DHEAS), testosterone and free testosterone index (FTI) in
late pregnancy had no impact on breast size increment or
duration of breastfeeding (Table 3).
Effect of breast size increment during pregnancy
When we dichotomised women into those who reported
an increase in bra size during pregnancy and those who
did not, women with no breast size increment had higher
blood pressure, were more obese, had higher fasting insu-
lin and triglyceride levels already at inclusion in the first
trimester of pregnancy, compared with those who experi-
enced breast size increment (Table 4). Also, at the end of
pregnancy, women with no breast size increment were
more obese, but had gained less weight during pregnancy.
Weight gain in pregnancy did not correlate with breast
size increment, when adjusted to baseline BMI. After
delivery, women with no breast size increment had a
shorter period of exclusive and partial breastfeeding
(Table 4).
Discussion
The most important findings of the present study are: (1)
that neither metformin nor androgens had any impact on
breast size increment in pregnancy or breastfeeding; and
(2) women with PCOS who do not have breast size incre-
ment during pregnancy seem to be more metabolically
deranged and breastfeed less than those with breast size
increment.
The frequency of breastfeeding is high in the Norwegian
population. It is a part of a targeted health policy, and is
encouraged and facilitated by authorities through maternity
out-patient clinics, paid maternity leave and information
campaigns. There is a general opinion supported by health
authorities that breastfeeding is beneficial both for the
mother and the baby, and that all women who can breast-
feed should do so. This is clearly reflected in the present
study by the high frequency and long duration of breast-
feeding.
Androgens such as testosterone inhibit lactation, and in
the era before dopamine agonists, testosterone alone, or in
combination with estrogens, was used to inhibit lacta-
tion.
20,21
In our pilot study we found that the pre-andro-
gen DHEAS showed a weak negative correlation with
breastfeeding in women who have PCOS.
4
In a random
sample of women, mid-pregnancy androgen levels corre-
lated negatively with breastfeeding.
16
Therefore, we hypoth-
esised that elevated levels of androgens interferes with
lactation. In the present study mean androgen levels were
high in the first trimester in women with PCOS, suggesting
Metformin and breastfeeding in PCOS pregnancy
ª 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology ª 2012 RCOG 1405
that metabolic derangement is already present at this stage.
Although we found no negative impact of DHEAS or FTI
on breastfeeding, obesity, higher blood pressure, high
serum triglycerides and high fasting insulin levels correlated
negatively with breastfeeding, suggesting an association
with metabolic function.
There is an old notion among nursing counsellors that
mothers without ‘milk pain’ or a certain degree of breast
Table 2. Breast size and breast feeding in women with PCOS according to treatment allocation
n Metformin n Placebo P
Pre-pregnancy bra cup size (no.) 97 3.1 ± 1.2 86 3.0 ± 1.3 0.93
Pre-pregnancy bra chest circumference (cm) 97 83.0 ± 7.7 86 81.5 ± 7.1 0.15
Late pregnancy bra cup size (no.) 96 3.7 ± 1.2 85 3.7 ± 1.3 0.87
Late pregnancy bra chest circumference (cm) 97 84.8 ± 7.1 86 83.8 ± 7.2 0.38
Change in bra cup size (no.) 97 0.7 ± 0.7 86 0.7 ± 0.7 0.80
Change in chest circumference (no.) 97 0.3 ± 0.6 86 0.5 ± 0.7 0.16
Total bra cup change in pregnancy (no.) 97 1.1 ± 1.0 87 1.2 ± 1.1 0.77
Exclusive breast feeding (months) 98 4.5 ± 2.8 88 3.9 ± 2.9 0.08
*
Any breast feeding (months) 98 8.8 ± 3.9 88 8.5 ± 4.0 0.59
*
Bra cup sizes: A = 1; B = 2; C = 3; D = 4; E = 5.
Bra chest circumferences: 70, 75, 80, 85, 90, 95 and 100 cm (an increase from 70 to 75 cm results in an increase of one cup size).
If a woman had a bra size of 80B in early pregnancy and 85C at delivery, this would indicate an increase of two sizes in the total bra cup size.
*Mann–Whitney U-test.
Table 1. Maternal characteristics in the first trimester (baseline data) and at the end of pregnancy according to treatment allocation in pregnancy
n Metformin n Placebo P
First trimester
Age (years) 98 29.7 ± 4.4 88 29.1 ± 4.3 0.38
BMI (kg/m
2
) 98 29.3 ± 7.1 88 27.4 ± 6.0 0.11***
Systolic blood pressure (mmHg) 98 119 ± 12 88 116 ± 11 0.90***
Diastolic blood pressure (mmHg) 98 72 ± 9 88 71 ± 9 0.37***
Fasting glucose (mmol/l) 98 4.6 ± 0.5 88 4.6 ± 0.6 0.68
2-hour glucose (mmol/l) 97 5.7 ± 1.6 87 5.7 ± 1.6 0.98
Insulin (pmol/l) 96 109 ± 79 85 101 ± 80 0.53
Testosterone (nmol/l) 96 4.3 ± 1.9 85 4.2 ± 2.0 0.91
DHEAS (lmol/l) 96 4.8 ± 2.1 85 4.7 ± 2.1 0.74
FTI 96 0.24 ± 0.11 86 0.23 ± 0.14 0.40
Smoking no. (%) 98 9 (10) 88 3 (3) 0.14*
Single/married or cohabiting 95 5/90 87 0/87 0.06 *
Education (£ 12 years/>12 years) 95 29/66 86 32/54 0.34
End of pregnancy
BMI (kg/m
2
) 93 32.5 ± 7.0 78 31.3 ± 5.5 0.19***
BMI gain in pregnancy (kg/m
2
) 93 3.0 ± 2.8 78 3.8 ± 1.7 0.25***
Systolic blood pressure (mmHg)** 97 121 ± 13 88 117 ± 12 0.04***
Diastolic blood pressure (mmHg)** 98 76 ± 9 88 74 ± 10 0.54***
Fasting glucose (mmol/l)** 88 4.4 ± 0.7 70 4.4 ± 0.5 0.96
Fasting insulin (pmol/l)** 97 139 ± 77 88 157 ± 109 0.19
Testosterone (nmol/l)** 97 5.3 ± 2.5 88 6.2 ± 5.3 0.15
DHEAS (lmol/l)** 97 3.3 ± 1.6 94 2.7 ± 1.2 0.007
FTI** 96 0.15 ± 0.09 88 0.17 ± 0.14 0.40
Smoking no. (%)** 98 5 (5) 86 2 (2) 0.45
*Fischer’s exact test.
**Last measured or registered in pregnancy: i.e. for those who passed gestational week 36 it was gestational week 36, for those who gave birth
after gestational week 24 but before gestational week 36 it was the last visit before birth.
***Mann–Whitney U-test.
Vanky et al.
1406 ª 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology ª 2012 RCOG
tension have difficulties in breastfeeding. We are, however,
not aware of any studies that have explored the correlation
between breast size increment and breastfeeding. We evalu-
ated breast size increment simply by asking about increases
in bra size during pregnancy. An increase in bra size corre-
lates positively with the duration of exclusive and partial
breastfeeding. When adjusting for variables known to cor-
relate with or influence breastfeeding in a multivariate
regression model, we find that breast size increment still
correlates positively with both exclusive and partial breast-
feeding. This has not been reported before, and confirms
clinical observations. The reason given for not breastfeeding
at 3 months postpartum was shortage of milk in 86% of
cases, not lack of motivation.
Interestingly, in comparing women with PCOS who expe-
rience breast size increment or not during pregnancy, we
find metabolic differences between the groups. Those with
no breast size increment have higher blood pressure, and
higher fasting insulin and triglyceride levels in early preg-
nancy. They are more obese in both early and late pregnancy.
Both the exclusive and the partial breastfeeding periods are
shorter compared with those with breast size increment.
Some, but not all, epidemiological studies indicate that
breast milk protects the offspring from obesity and
diabetes.
22–24
Our results might be open for a different
understanding or interpretation. Underlying metabolic and/
or endocrine factor(s) may be a common trait that both
promote breast size increment and facilitate the ability to
breastfeed. As mothers with no breast size increment,
resulting in no or just a short period of breastfeeding, are
more obese and have higher insulin levels, their offspring
may be more prone to develop obesity and diabetes, inde-
pendent of breast milk. A recent retrospective study reports
on more android obesity, more insulin resistance, and
higher blood pressure and cholesterol levels 16–20 years
after the last pregnancy in women who had a shorter dura-
tion of breastfeeding.
25
The authors conclude that brief
breastfeeding induces weight retention and fat mass accu-
mulation, resulting in increased risk of cardiometabolic dis-
orders in later life. These findings support ours, although
we interpret them differently: women who are not able to
breastfeed are metabolically inferior compared with those
who breastfeed easily.
The weakness of the study is the self-reported bra size.
Not all women wear the correct sized bra, and there might
be some differences in size between different brands. There
is a possibility that women who actually increased in breast
size during pregnancy did not shift for a larger bra size. All
Table 3. The duration of breastfeeding in univariate and multivariate regression analyses
Univariate Multivariate
B 95% CI PB 95% CI P
Exclusively breast feeding (months)
Maternal age (years) )0.02 ()0.12; 0.07) 0.66 0.01 ()0.10; 0.12) 0.91
Maternal BMI (kg/m
2
)* )0.07 ()0.14; 0.01) 0.03 )0.03 ()0.10; 0.04) 0.42
Education (£ 12 years = 1; >12 years = 2) 0.54 ()0.40; 1.35) 0.29 0.26 ()0.73; 1.26) 0.60
FTI* )2.89 ()6.43; 0.65) 0.11 )2.68 ()6.34; 0.99) 0.15
DHEAS (lmol/l)* 0.03 ()0.26; 0.31) 0.86 0.13 ()0.17; 0.44) 0.39
Total change in bra cup size in pregnancy (no.) 0.77 (0.38; 1.15) <0.001 0.73 (0.28; 1.18) 0.002
Smoking (no = 1; yes = 2)* 0.39 ()1.78; )2.56) 0.72 )0.25 ()2.79; 2.29) 0.85
Fetal birthweight (g) 0.00 ()0.00; 0.00) 0.53 0.00 ()0.00; 0.00) 0.48
Fetal gestational age (days) )0.00 ()0.03; 0.03) 0.99 0.02 ()0.03; 0.07) 0.43
Randomisation (metformin = 1; placebo = 2) )0.61 ()1.43; 0.121) 0.15 )0.53 ()1.41; 0.35) 0.24
Any breastfeeding (months)
Maternal age (years) )0.06 ()0.19; 0.07) 0.34 )0.04 ()0.18; 0.11) 0.60
Maternal BMI (kg/m
2
) )0.19 ()0.28; )0.11) <0.001 )0.14 () 0.23; )0.04) 0.007
Education (£ 12 years = 1; >12 years = 2) 1.72 (0.52; 2.91) 0.005 1.14 ()0.17; 2.45) 0.09
FTI* )3.85 ()8.72; 1.02) 0.12 )3.17 ()7.99; 1.65) 0.20
DHEAS (lmol/l)* )0.07 ()0.46; 0.33) 0.72 0.17 ()0.23; 0.58) 0.40
Total change in bra cup size in pregnancy (no.) 0.90 (0.35; 1.43) 0.001 0.87 (0.17; 1.46) 0.005
Smoking (no = 1; yes = 2)* 1.14 ()1.82; 4.82) 0.45 )1.17 ()4.51; 2.17) 0.49
Fetal birthweight (g) 0.00 ()0.00; 0.00) 0.34 )0.00 ()0.00; 0.00) 0.24
Fetal gestational age (days) 0.01 ()0.04; 0.05) 0.82 0.00 ()0.07; 0.07) 0.93
Randomisation (metformin = 1; placebo = 2) )0.31 ()1.45; 0.82) 0.59 )0.18 ()1.34; 0.99) 0.77
*Last measured or registered in pregnancy: i.e. for those who passed gestational week 36 it was gestational week 36, and for those who gave
birth after gestational week 24 but before gestational week 36 it was the last visit before birth.
Metformin and breastfeeding in PCOS pregnancy
ª 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology ª 2012 RCOG 1407
in all bra size is a crude measurement, but it is three-
dimensional and we believe that women in general do
remember the size of their bra, as they have to ask or look
for it when shopping. If they don’t remember the size, they
can check the tag on the bra.
The fact that women who reported no increase in bra
size did not represent a random group is reflected by our
findings that they were more obese, and had higher blood
pressure, serum triglycerides and fasting insulin levels.
Finding this difference with a crude measurement indicates
that the significance would probably be more pronounced
using a more accurate tool.
In conclusion, metformin and androgens had no impact
on breastfeeding. Pregnant women with PCOS with no
breast size increment seem to be more metabolically dis-
turbed, and are less able to breastfeed.
Disclosure of interests
The authors have nothing to disclose.
Contribution to authorship
EV made substantial contributions to the conception and
design of the study, to the analysis and interpretation of
data, and to writing the article, and gave final approval of
the version to be published. JN contributed to the design
of the study, collected and analysed data, and revised and
gave final approval of the data to be published. HL con-
tributed to the design of the study, collected and analysed
data, and revised and gave final approval of the data to be
published. AH-H contributed to the design of the study,
collected and analysed data, and revised and gave final
approval of the data to be published. MM analysed
and interpreted the data, drafted the article and revised it
Table 4. Patient characteristics according to breast size increment in pregnancy
n No increase in bra size n Increase in bra size P
In the first trimester of pregnancy
Age (years) 59 30.1 ± 4.0 125 29.1 ± 4.5 0.07**
BMI (kg/m
2
) 59 30.6 ± 6.8 125 27.2 ± 6.2 0.001**
Systolic blood pressure (mmHg) 59 121 ± 11 125 116 ± 12 0.004**
Diastolic blood pressure (mmHg) 59 74 ± 10 125 71 ± 8 0.10**
Fasting glucose (mmol/l) 59 4.6 ± 0.5 125 4.6 ± 0.5 0.67
2-hour glucose (mmol/l) 59 5.8 ± 1.7 124 5.5 ± 1.5 0.24
Fasting insulin (pmol/l) 59 133 ± 119 120 92 ± 44 0.01
Total cholesterol (mmol/l) 59 4.65 ± 0.89 124 4.64 ± 0.96 0.94
HDL cholesterol (mmol/l) 59 1.61 ± 0.38 125 1.63 ± 0.37 0.79
Triglycerides (mmol/l) 59 1.36 ± 0.78 125 1.13 ± 0.54 0.05
Testosterone (nmol/l) 59 4.3 ± 2.3 120 4.3 ± 1.7 0.90
FTI 59 0.24 ± 0.15 120 0.23 ± 0.12 0.72
Smoking no. (%) 59 4 (6) 131 9 (7) 1.0***
At the end of pregnancy*
BMI (kg/m
2
) 56 33.9 ± 6.0 114 31.2 ± 7.3 0.001**
BMI gain in pregnancy (kg/m
2
) 56 2.8 ± 1.8 114 4.0 ± 4.3 0.003**
Systolic blood pressure (mmHg) 58 120 ± 12 125 118 ± 14 0.16**
Diastolic blood pressure (mmHg) 58 77 ± 10 125 75 ± 10 0.13**
Fasting glucose (mmol/l) 52 4.4 ± 0.4 105 4.4 ± 0.7 0.97
Fasting insulin (pmol/l) 59 152 ± 75 131 146 ± 102 0.65
Total cholesterol (mmol/l) 58 6.70 ± 1.20 125 6.70 ± 1.30 0.99
HDL cholesterol (mmol/l) 58 1.89 ± 0.44 125 1.81 ± 0.40 0.25
Triglycerides (mmol/l) 56 2.93 ± 1.20 125 2.79 ± 1.03 0.47
Testosterone (nmol/l) 58 5.9 ± 5.2 125 5.6 ± 3.5 0.71
FTI 58 0.16 ± 0.15 125 0.16 ± 0.10 0.82
Smoking no. (%) 59 1 (2) 123 6 (5) 0.44***
Postpartum
Exclusive breastfeeding (months) 59 3.4 ± 2.9 125 4.7 ± 2.7 0.006**
Any breastfeeding (months) 59 7.3 ± 4.5 125 9.3 ± 3.4 0.006**
Smoking no. (%) 59 5 (8) 123 15 (12) 0.61***
*Last measured in pregnancy, i.e. most often at gestational week 36. For those who gave birth before 36 weeks of gestation, it is measured at
the last visit before delivery.
**Mann–Whitney U-test.
***Fischer’s exact test.
Vanky et al.
1408 ª 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology ª 2012 RCOG
critically for important intellectual content, and gave final
approval of the version to be published. SMC made sub-
stantial contributions to the conception and design of the
study, to the analysis and interpretation of the data, and
approved the version to be published.
Details of ethics approval
The Committee for Medical Research Ethics of Health
Region IV, Norway, and The Norwegian Medicines Agency
approved the study (no. 145-04; 23 September 2004). Writ-
ten informed consent was obtained from each patient
before inclusion, and the declaration of Helsinki was fol-
lowed throughout the study. The study was conducted
according to principles of ‘Good Clinical Practice’, and the
trial is registered at ClinicalTrials.gov as NCT00159536.
Funding
The Liaison Committee between the Central Norway
Regional Health Authority and the Norwegian University
of Science and Technology (NTNU) funded the study.
Weifa AS (Oslo, Norway) supplied the study drug free of
charge, but had no role in the collection, analysis or inter-
pretation of the data, the writing of the article or any influ-
ence on the decision to submit it.
j
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ª 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology ª 2012 RCOG 1409
  • Article · Jan 2013 · European Journal of Endocrinology
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