(BMI) greater than or equal 25 kg/m² and

(BMI) greater than or equal 25 kg/m² and

PRACE ORYGINALNE
Sandra MROZIŃSKA1
Tomasz MILEWICZ2
Marta KIAŁKA2
Katarzyna GOSZTYŁA3
Małgorzata LURZYŃSKA4
Monika KABZIŃSKA-TUREK5
There is no difference in the plasma cortisol
level between women with body mass index
(BMI) greater than or equal 25 kg/m² and
polycystic ovary syndrome and the control
group without polycystic ovary syndrome and
BMI 25 kg/m²
Poziom kortyzolu we krwi nie różni się pomiędzy
kobietami ze wskaźnikiem masy ciała (BMI) większym
lub równym 25 kg/m² i zespołem policystycznych
jajników oraz kobietami z BMI większym lub równym
25 kg/m² bez zespołu policystycznych jajników
Katedra i Klinika Chorób Metabolicznych,
Uniwersytet Jagielloński Collegium Medicum,
Kraków
Kierownik:
Prof. dr hab. n. med. Maciej Małecki
1
Klinika Endokrynologii Ginekologicznej,
Katedra Ginekologii i Położnictwa, Uniwersytet
Jagielloński Collegium Medicum, Kraków
Kierownik:
Dr hab. n. med. Robert Jach
2
Oddział Neurologiczny Centrum Medyczne
w Łańcucie
Ordynator:
Lek. med. Trąd Marek
3
Klinika Pneumonologii Instytut Gruźlicy i
Chorób Płuc Oddział Terenowy im. Jana i Ireny
Rudników w Rabce-Zdrój
Kierownik:
Dr hab. n. med. Zbigniew Doniec, prof. nadzw.
4
Klinika Ginekologii i Onkologii, Katedra
Ginekologii i Położnictwa, Uniwersytet
Jagielloński Collegium Medicum, Kraków
Kierownik:
Prof. dr hab. n. med. Antoni Basta
5
Additional key words:
kortyzol
PCOS
otyłość
Dodatkowe słowa kluczowe:
cortisol
PCOS
obesity
Adres do korespondencji:
Sandra Mrozińska
Katedra i Klinika Chorób Metabolicznych
UJ CM
ul. Kopernika 15
31-501 Kraków,
e-mail: [email protected]
Przegląd Lekarski 2016 / 73 / 4
A 4-8% of women of reproductive
age suffer from the polycystic ovary
syndrome (PCOS). The clinical and/
or biochemical hyperandrogenemia
is found up to 75% of women with
PCOS. It is unclear whether the hyperandogenemia in PCOS is caused
directly by this disorder or by obesity.
The recent studies have shown that
the cortisol level in PCOS patients can
be elevated, decreased or comparable
to the control group. The aim of our
study was to assess the cortisol plasma level in women with body mass
index greater than or equal to 25 kg/
m², with and without PCOS. The study
population consisted of 17 overweight
women with PCOS and 44 overweight
women without PCOS. There were not
statistically significant differences in
the body mass (group 1: 88.9±17.0 kg,
vs. group 2: 84.4±15.2 kg; NS) nor the
body mass index between both groups
(group 1: 31.7±5.9 kg/m², vs. group 2:
30.6±5.4 kg/m²; NS). The groups did not
differ in TSH, FSH, estradiol, SHBG,
prolactin level at the baseline. There
was no statistically significant difference between both groups in the cortisol
levels at 5 a.m. and 7 a.m. Our study
suggests that there is no difference in
the morning and 7 p.m. cortisol level
between the women with and without
PCOS among the population of women
with body mass index greater than or
equal 25 kg/m².
Około 4-8% kobiet w wieku rozrodczym choruje na zespół policystycznych jajników (PCOS). Kliniczne i / lub
biochemiczne cechy hiperandrogenemii obserwuje się u 75% z nich. Nie jest
jednoznaczne, czy hiperandrogenizm
w PCOS jest spowodowany bezpośrednio przez to zaburzenie czy towarzyszącą często temu zespołowi otyłość.
Dotychczasowe badania wykazały
zarówno podwyższony, obniżony jak
i porównywalny poziom kortyzolu u
pacjentek z PCOS względem grupy
kontrolnej. Celem naszej pracy była
ocena poziomu kortyzolu w osoczu
u kobiet z BMI większym lub równym
25 kg/m², z i bez PCOS. Badana populacja składa się z 17 kobiet z nadwagą
i PCOS oraz 44 kobiet z nadwagą i bez
PCOS. Nie wykazano statystycznie
znamiennych różnic w masie ciała
(grupa 1: 88,9±17,0 kg, w porównaniu
z grupą 2: 84,4±15,2 kg, p>0,05), ani
wskaźniku masy ciała pomiędzy obydwiema grupami (grupy 1: 31,7±5,9
kg/m2, vs. grupa 2: 30,6±5,4 kg/m2;
p>0,05). Obydwie grupy nie różniły się
poziomem TSH, FSH, estradiolu, SHBG
ani prolaktyny. Nie wykazano istotniej
statystycznie różnicy pomiędzy grupami w poziomie kortyzolu o godzinie
5:00 i 19:00. Nasze badania sugerują,
iż nie ma różnicy w poziomie kortyzolu
o godzinie 5 rano oraz 7 po południu
pomiędzy kobietami bez PCOS oraz z
PCOS, w populacji kobiet z BMI większym lub równym 25 kg/m².
Introduction
A 4-8% of women of reproductive age
suffer from the polycystic ovary syndrome
(PCOS) [1,2] and it is one of the most common endocrine disorders that causes infertility [3]. To diagnose the disease the patient
has to meet two of three criteria: oligoovulation or anovulation, clinical or biochemical
features of hyperandrogenism, the polycystic
ovary in the ultrasound [4]. The clinical and/
or biochemical hyperandrogenemia is found
up to 75% of women with PCOS [2,5]. The
207
main source of androgens in those patients
are polycystic ovaries [6]. Increased levels
of andrenal androgens, such as total testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEAS) are observed in the
blood samples of PCOS women [5-7]. Azziz
et al. suggest that excess levels of adrenal
androgens in PCOS women is not connected
with hypersensitivity to adrenocorticotropic
hormone (ACTH) stimulation [8]. The cortisol
level in a PCOS patient can be elevated, decreased or comparable to the control group
[9-12]. It is suggested that the elevated level
of cortisol may be explained by mechanism
of negative feedback [13]. The low level of
cortisol triggers the hypothalamic–pituitary–
adrenal axis. It is reported that there is not
strong connection between systematic cortisol level and obesity but it is reported that
the saliva cortisol level is correlated with
body mass index [14]. It is unclear whether
the hyperandogenemia in PCOS is caused
directly by this disorder or by obesity, that
is more statistically significantly frequent
in PCOS patients, as is present in 61% in
pooled women with PCOS [15]. Roelfsema et
al. demonstrated that cortisol production rate
in similarly increased in obese women with
PCOS and control obese women without this
disorder [16]. Vassiliadi et al. has shown that
the activity of 5α-reductase is higher in both,
obese and nonobese PCOS women [17].
The aim of our study was to assess the
cortisol plasma level in women with body
mass index greater than or equal 25 kg/m²
with and without PCOS.
Materials and methods
The study population consisted of 17
overweight women with PCOS and 44
overweight women without PCOS. The
overweight was defined as the body mass
index (BMI, weight in kilograms divided by
the square of height in meters) equal to or
greater than 25 kg/m². From all patients
the blood samples were taken during the
follicular phase, between the 5th – 8th day of
the menstrual cycle. The levels of thyreotropin (TSH), luteinizing hormone (LH), follicle
stimulating hormone (FSH), estradiol, sex
hormone-binding globulin (SHBG), prolactin, testosterone, dehydroepiandrosterone
sulfate (DHEAS), and cortisol level at 5 a.m.
and 7 p.m. were measured. The cortisol
level was assessed using electrochemiluminescence method (ECLIA). The patients
had also undergone a glucose tolerance test
(OGTT) and the insulin levels during the test
were obtained. To assess the differences
between groups the appropriate parametric
and non-parametric tests were used. The
significance level (alpha) at 0.05 was set for
all tests. The statistical analysis of obtained
data was performed one-way ANOVA using
STATISTICA 8.0 software.
Results
The data of 61 women was taken into
analysis. The first group contained 17
overweight women with PCOS (group1),
the second one 44 overweight women without PCOS (group 2). The mean age in the
group 1 was 25.2±3.8 years, in the control
31.0±8.0 years; p<000.1 (Tab. I). There
was no statistical significant difference in
208
the body mass (group 1: 88.9±17.0 kg, vs.
group 2: 84.4±15.2 kg; p >0.05) nor body
mass index between both groups (group 1:
31.7±5.9 kg/m2, vs. group 2: 30.6±5.4 kg/
m2; p>0.05). The groups did not differ in
TSH, FSH, estradiol, SHBG, prolactin level
at the baseline. The LH level was increased
in PCOS group in comparison to the control
group (9.1±5.6 IU/l vs. 6.0±3.6 IU/l ). There
was no statistically significant difference
between both groups in the cortisol levels at
5 a.m. and 7 a.m. (Tab. III). The testosterone
and DHEAS levels were higher in group of
overweight women with PCOS (p<0.001).
The glucose fasting level was lower in the
control group (5.1±0.8 mmol/l vs. 4.7±0.4
mmol/l; p<0.005). The insulin fasting was
18.7±14.64 in PCOS group vs. 19.5±17.2
in the control group (p>0.05).
Discussion
The study did not reveal a significant difference in cortisol level at 5 a.m. and 7 p.m.
in overweight PCOS cohort compared to
overweight women without PCOS. The true
is that one of the limitations of our study is
small population. The Roelfsema et al. have
also shown that diurnal cortisol production,
assessed by 24-h blood sampling at 20-min
intervals, was comparable between group
of obese women with PCOS and control
obese women [17]. The analyzed groups
in our study differ in age, the control group
was significant older. Chalew et al. have
demonstrated that in obese people the cortisol level increase with the age, the same
phenomenon was not observed in nonobese
group [23]. This could also interfere our
results. There was no difference in the BMI
between groups in our study (31.7±5.9 kg/
m2, vs. group 2: 30.6±5.4 kg/m2; p >0.05),
but it should be noticed that in the PCOS
group there were three women with morbid
obesity which is 17,65% of this group. In
the control group there were 3 women with
morbid obesity (including one women with
Table I
The clinical characteristics of overweight PCOS women (group 1) and overweight controls (group 2).
Charakterystyka kliniczna pacjentek z nadwagą i PCOS (grupa1) oraz pacjentek z nadwagą z grupy kontrolnej (grupa 2).
Overweighed women
with PCOS, n=17
Overweighed women,
n=44
Age (years)
mean value ± standard deviation [SD]
range
25.2±3.8
(17-32)
31.0±8.0
(16-49)
Body mass(kg)
mean value ±SD
range
88.9±17.0
(71-125)
Parameter
BMI
mean value ±SD
range
TSH (uIU/ml)
mean value ±SD
range
p
<0.001
84.4±15.2
(61-130)
NS
31.7±5.9
(25.5-43.3)
Including three women
with morbid obesity
30.6±5.4
(25.1-50.8)
Including three women with
morbid obesity
NS
2.0±0.9
(1.1-4.0)
1.9±0.8
(0.5-3.9)
NS
Table II
The hormonal characteristics of overweight PCOS women (group 1) and overweight controls (group 2).
Wartości poziomów hormonów u pacjentek z nadwagą i zespołem PCOS (grupa 1) oraz pacjentek z nadwagą z grupy
kontrolnej (grupa 2).
Parameter
Overweighed women
with PCOS, n=17
Overweighed women,
n=44
LH (IU/l)
mean value ±SD
range
9.1±5.6
(2.4-23.7)
6.0±3.6
(1.0-14.8)
p <0.05
FSH (IU/l)
mean value ±SD
range
5.2±1.6
(1.6-7.2)
5.1±2.0
(1.0-9.0)
NS
Estradiol (ng/l)
mean value ±SD
range
74.3±41.7
(26.2-183.7)
82.1±90.7
(7.8-608.0)
NS
SHBG (nmol/l)
mean value ±SD
range
50.2±24.5
(13-77)
42.5±30.0
(11-88.0)
NS
Prolactin (ug/l)
mean value ±SD
range
14.3±7.2
(2.4-31.5)
13.9±8.5
(2.0-28.0)
NS
Testosterone (nmol/l)
mean value ±SD
range
4.0±1.1
(3.1-7.7)
1.6±0,6
(0.3-2.7)
<0.001
DHEAS (ug/dl)
mean value ±SD
range
515.2±187.
(148-838.1)
266.0±107.0
(116.1-474)
<0.001
p
S. Mrozińska i wsp.
Table III
Mean plasma morning and evening cortisol levels in overweight PCOS women (group 1) and overweight
controls (group 2).
Średni poziom kortyzolu rano oraz popołudniu u pacjentek z nadwagą i PCOS (grupa 1) oraz u pacjentek z nadwagą
z grupy kontrolnej (grupa 2).
Overweight women
with PCOS, n=17
Overweight women, n=44
P
Cortisol 7 a.m. (mmol/l)
mean value ±SD
range
18.6±6.6
(8.2-29.1)
18.2±7.9
(2.3-37.2)
NS
Cortisol 5 p.m. (mmol/l)
mean value ±SD
range
7.8±4.1
(3.2-16.0)
7.9±5.2
(2.3-37.2)
NS
Parameter
BMI 50 kg/m²) which is 6,81% of the group.
Obesity as well as PCOS presence could
affect cortisol levels. Praveen et al. revealed
in their study that body weight was correlated negatively with morning plasma cortisol
and ACTH levels [18]. Travison et al observed lower plasma cortisol levels in obese
subjects than in lean controls [19]. Shabir et
al. showed that serum cortisol levels were
higher in lean PCOS women compared to
controls and overweight PCOS women.
Morning plasma cortisol level was lower
among obese women with PCOS and was
correlated negatively with BMI in PCOS women [20]. Prelević et al. revealed that mean
24-h cortisol concentrations were similar in
PCOS and controls as well in the obese
and nonobese PCOS patients. However,
the 24-h blood cortisol profile pattern was
different in women with PCOS as compared
to the controls. Lower cortisol levels were
observed during the night in PCOS women
compared to the controls. Moreover, these
changes were most marked in the nonobese
women with PCOS than either the controls
or obese PCOS subjects [10]. In our earlier
study, PCOS lean women showed the increased plasma cortisol level with impacted
diurnal secretion rate. Mean evening plasma
cortisol level was higher in PCOS patients
whereas there was no difference in mean
morning plasma cortisol level between groups [12]. It is possible that due to different
methodology in estimating the cortisol levels
[21] both in obese people [22] and women
with PCOS [8,23], it is still under discussion
what influence on cortisol level obesity and
PCOS play. A further study assessing the
cortisol levels and diurnal cortisol secretion
patterns should be done in the population of
women with and without PCOS, taking into
account body weight, body mass index and
body surface. The study suggest that both
elevated or reduced plasma cortisol level
in PCOS woman should be diagnosed and
Przegląd Lekarski 2016 / 73 / 4
all causes of this condition should be taken
into account because it is not one of the
characteristic features of the PCOS.
Conclusion
It appears that there is no difference in
our study in the morning and 7 p.m. cortisol
level between the women with and without
PCOS among the population of women with
body mass index greater than or equal 25
kg/m². A further investigation on this matter
should be done.
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