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Vol 1, No 3

July 2013 Patients with endometriotic cyst 119

Research Article

Serum Adiponectin Level is Lower in Patients with Endometriotic Cyst


Tingkat Adiponektin Serum Lebih Rendah pada Pasien dengan Kista Endometriosis

Fahdiansyah, Ruswana Anwar, Setyorini Irianti


Department of Obstetrics and Gynecology
Faculty of Medicine University of Padjadjaran/
Dr. Hasan Sadikin Hospital
Bandung

Abstract Abstrak

Objectives: To analyse the difference of serum adiponectin level Tujuan: Untuk menganalisis perbedaan tingkat adiponektin serum
between patients with endometriotic cyst and those with non-en- antara pasien dengan kista endometriosis dan mereka dengan kista
dometriotic cyst, and its difference between endometriosis stages. non-endometriosis, dan perbedaannya antara tahap endometriosis.
Methods: This is a cross-sectional comparative analytical study in- Metode: Penelitian ini merupakan studi analitik potong lintang kom-
volving 25 women with endometriotic cyst and 25 women with non- paratif yang melibatkan 25 wanita dengan kista endometriosis dan 25
endometriotic cyst, which had undergone laparoscopy or laparo- wanita dengan kista non-endometriosis, yang telah menjalani lapa-
tomy surgery. Blood samples were withdrawn and checked for se- roskopi atau operasi laparotomi. Sampel darah diambil dan diperiksa
rum adiponectin level in PRODIA laboratory in Jakarta. Serum kadar adiponektin serum di laboratorium PRODIA di Jakarta. Tingkat
adiponectin level of both groups were then measured and com- adiponektin serum dari kedua kelompok kemudian diukur dan diban-
pared. The study was conducted in Dr. Hasan Sadikin Hospital in dingkan. Penelitian dilakukan di Rumah Sakit Dr. Hasan Sadikin pada
September- December 2012. bulan September-Desember 2012.
Results: Shows no significant difference in subjects characteristic Hasil: Tidak terdapat perbedaan yang signifikan dalam karakteristik
which are age (p = 0.994) and BMI (p = 0.267). There is a significant subjek yaitu usia (p = 0,994) dan BMI (p = 0,267). Ada perbedaan yang
difference (p < 0.0001) between serum adiponectin level in en- signifikan (p<0,0001) antara kadar adiponektin serum pada kelom-
dometriosis group (mean = 3.91 1.976) with level of which in non- pok endometriosis (mean = 3,91 1,976) dengan kelompok non-
endometriosis group (mean = 8.59 1.977). There is no significant endometriosis (rata-rata = 8,59 1,977). Tidak ada perbedaan yang
difference (p = 0.384) of serum adiponectin level between stage III signifikan (p = 0,384) tingkat adiponektin serum antara stadium III
endometriosis (mean = 4.24 1.8168) and stage IV endometriosis endometriosis (mean = 4,24 1,8168) dan stadium IV endometriosis
(mean = 3.54 2.1531). (mean = 3,54 2,1531).
Conclusion: Serum adiponectin level in patients with endometriotic Kesimpulan: Tingkat adiponektin serum pada pasien dengan kista
cyst is significantly lower compared to level of which in patients with endometriosis secara signifikan lebih rendah dibandingkan dengan
non-endometriotic cyst. There is no significant difference of serum tingkat yang pada pasien dengan kista non-endometriosis. Tidak ada
adiponectin level between endometriosis stages. perbedaan yang signifikan tingkat serum adiponektin antara tahap
endometriosis.
[Indones J Obstet Gynecol 2013; 1-3: 119-23]
[Maj Obstet Ginekol Indones 2013; 1-3: 119-23]
Keywords: adiponectin, endometriotic cyst, non-endometriotic
cyst, endometriosis stage Kata kunci: adiponektin, kista endometriosis, kista non-endometrio-
sis, tahap endometriosis

Correspondence: Fahdiansyah. Department of Obstetrics and Gynecology. Faculty of Medicine University of Padjadjaran, Bandung.
Telephone: 022-70835010. Email: ukupf@yahoo.co.id

INTRODUCTION
dometriosis also affect the physical, mental, and so-
Endometriosis is a benign gynecological illness, cial health.1
which recently is being concerned by experts. In
Incidence of endometriosis is not exactly known,
both developed and developing countries, many
as endometriosis is often left misdiagnosed or un-
studies have been conducted about endometriosis.
diagnosed. A study conducted in Mayo clinic few
However, until now, its etiology and pathogenesis
years ago found endometriosis in about 50% of
have not been clearly understood. Endometriosis
women who had undergone surgery in pelvic area,
is defined as endometrium-like tissue found out-
without mentioning the indications of the proce-
side uterus, especially in ovaries and pelvic cavity,
dures.1,2
which causes a chronic inflammatory reaction. En-
dometriosis is found in about 10% of women in Many theories are proposed about pathogenesis
reproductive age. Beside affect the womans repro- of endometriosis. Recently it is believed that regur-
ductive health, the clinical manifestations of en- gitation of menstrual blood is the most common
Indones J
120 Fahdiansyah et al Obstet Gynecol
etiology of endometriosis, as the tubouterine mus- properly managed because they were undiagnosed.
cle in endometriosis is weakened, which allows en- While on the other hand, the illness develops fur-
dometrial cells to spread into peritoneal cavity. En- ther, causing chronic pelvic pain, organ distortion,
dometriosis is an estrogen-dependent illness, and infertility.2,3,9
where estrogen plays an important part in en-
Understanding this situation, a question is for-
dometriosis development. This can be seen in the
mulated about the role of adiponectin in patho-
way that endometriosis does not occur before
genesis of endometriotic cyst. This is expected to
menarche and very rarely does in women with
open our insight wider about factors involved in
anovulatory women. Even though endometriosis
pathogenesis of endometriosis.
could occur in postmenopausal women, this is as-
sociated with the high level of estrogen due to obe- Based on the pathogenesis concepts developing
sity or estrogen therapy.1,3 nowadays, we are interested in learning about the
Non-endometriotic cyst mentioned in this study role of adiponectin in endometriotic cyst develop-
is the ovarian cyst beside endometriosis, it is a sac ment, by analyzing serum adiponectin level mo-
containing fluid or semisolid material which grows lecular-defected endometriosis patients. Studies
within the ovary. Etiology of the non-endometriotic conducted in some centres found decline of serum
cyst is disruption of hormone production in hypo- adiponectin level. However, none of them had sta-
thalamus, hypophysis, or ovaries. Excessive secre- ted that the declined serum adiponectin level has
tion of estrogen follows these kind of cysts. Based a role in endometriosis pathogenesis or in predict-
on the formation process, the cysts are divided into ing endometriosis recurrence.
non-neoplastic cyst and neoplastic cyst.4 From the description above, the topic of this
Adiponectin is an adipocyte-specific protein study can be defined:
(adipocytokine) circulating in blood, found in high Endometriosis is an illness of which etiopathogene-
level. Beside anti-diabetic effect, adiponectin also sis is not yet understood. Endometriosis is believed
has pleiotropic effects, such as anti-inflammatory, to be estrogen-dependent, where estrogen has an
anti-angiogenic, and anti-atherosclerotic.5-7 important part in the development of endometrio-
sis. The increase of estrogen level enhances the ac-
Adiponectin has been proven to be expressed by tivity of endometriosis. This increase of estrogen is
endometrial tissue also, in much lower level than caused by declined synthesis of the protein which
its circulating level, and the level are insignificantly binds estrogen (SHBG) by liver. This liver disorder
different along menstrual cycle. Adiponectin recep- is caused by insulin resistance by low uptake of
tors, AdipoR1 and AdipoR2, are also found in en- glucose in circulation. These processes are prece-
dometrial tissue in varied expression along the ded by low adiponectin level. Non-endometriotic
menstrual cycle, being highest in the middle of se- cyst originated not from endometrial tissue. The in-
cretion phase.7,8 crease of estrogen does not affect its development,
therefore neither does adiponectin. The level of
Takemura, et al. in 2005 reported that serum
adiponectin is believed to explain the development
adiponectin level in women with endometriosis is
and etiopathogenesis of endometriosis. Thus, ana-
significantly lower than level of which in women
lyzing adiponectin level in patients with endo-
without endometriosis. It is not known whether
metriotic cyst and comparing it with the level of
that was the cause or effect of endometriosis.8
which in patients with non-endometriotic cyst is
Until now, no data shows the association be- expected to prove the role of adiponectin in patho-
tween adiponectin level and endometriosis inci- genesis of endometriotic cyst. Whether there was
dence in Indonesia. Based on the description men- difference of adiponectin level between patients
tioned above, a question is formulated; whether or with endo-metriotic cyst and non-endometriotic
not adiponectin level differs in Indonesian women cyst would be reported in this study.
with and without endometriotic cyst.
Most of our people reject to undergo diagnostic METHOD
laparoscopy, the gold standard diagnostic examina-
tion. Surgery, even the minor ones, are still consid- This is a cross-sectional comparative analytical
ered terrifying, painful, risky, and costs a lot, so that study involving 50 patients presented to gyneco-
many cases of endometriosis are ignored or not logy polyclinic and fertility-endocrinology-repro-
Vol 1, No 3
July 2013 Patients with endometriotic cyst 121
duction polyclinic of Dr. Hasan Sadikin Hospital, Smirnov test. While the BMI, which are not-nor-
Bandung in September-December 2012. There mally-distributed numerical data, are compared
were 25 subjects for each endometriotic cyst and with unpaired t-test. Statistical analysis with con-
non-endometriotic cyst group. Patients would un- fidence level of 95% results in p value of > 0.05,
dergo laparotomy or laparoscopy surgery, and means that the age and BMI of both groups are
blood sample would be taken. Serum adiponectin considered similar. The homogeneity of the sub-
level of the samples was compared between the jects allows them to be analyzed further.
endometriotic cyst group with the non-endometri-
otic cyst, and between the endometriosis stages by Table 2. Comparison of Serum Adiponectin Level in Pa-
American Society of Reproductive Medicine (r- tients with Endometriotic Cyst and non-Endometriotic Cyst.
ASRM).
Serum Group
For categorical data, the statistical analysis per- Adiponectin Endometriotic Non-endometriotic
Significance
Level
formed was chi-square test for 2x2 table and Kol- Cyst (n=25) Cyst (n=25)

mogorov Smirnov test for 2x3 table. For numerical Mean 3.91 8.59 p<0.0001**
data, such as level of adiponectin, Shapiro-Wilk SD 1.976 1.977
normality test was performed before the statistical
Note: ** unpaired t-test, p<0.05 (significant)
analysis. Then both groups of subjects were com-
pared with unpaired t-test for normally-distributed
data and Mann-Whitney test for data which were Table 2 shows that mean serum adiponectin
not normally-distributed. P value < 0.05 reflects level in patients with endometriotic cyst is lower
significant result. than those with non-endometriotic cyst. The non-
endometriotic cysts of the subjects were mucinous
Statistical analysis was performed with SPSS
cyst (n=8), mature teratoma (n=7), hemorrhagic
version 17.0 for Windows, with confidential level
luteal cyst (n=6), and follicle cyst (n=4). Statistical
of 95% for p value < 0.05.
analysis with confidence level of 95% results in p
value of < 0.05 or significant result. This shows a
RESULT significant difference of serum adiponectin level in
both groups, where serum adiponectin level in pa-
The result of this study would be reported as char- tients with endometriotic cyst is significantly lower
acteristics of subjects, serum adiponectin level, and
than those with non-endometriotic cyst.
the difference of serum adiponectin level in pa-
tients with endometriotic cyst compared to non-
endometriotic cyst. Characteristic of the subjects is Table 3. Comparison of Serum Adiponectin Level in Pa-
shown in Table 1. tients with Stage III and Stage IV Endometriotic Cyst.

Serum Group
Signi-
Adiponectin ficance
Table 1. Comparison of Characteristic of Subjects in Both Level
Stage III Endome- Stage IV Endome-
triosis (n=13) triosis (n=12)
Groups.
Rerata 4.24 3.54 p = 0.384**
Group
SD 1.81 2.15
Characteristic Endometriotic Non-Endome- Significance
Cyst triotic Cyst **
n=25 (%) n=25 (%) Note: unpaired t-test, p>0.05 (not significant)

Age (years old) p = 0.994*


< 20 1 (33.3%) 2 (66.6%) Table 3 shows that mean serum adiponectin
20 - 35 19 (47.5%) 21 (52.5%)
> 35 5 (71.2%) 2 (28.6%)
level in patients with stage III endometriosis is
higher than those of stage IV endometriosis. Statis-
BMI Mean SD 23.48 1.90481 24.20 2.56843 p = 0.267** tical analysis with confidence level of 95% results
Note: * Kolmogorov-Smirnov test, p > 0.05 (not significant), in p value of > 0.05, fails to prove any significant
** unpaired t-test, p > 0.05 (not significant)
difference of serum adiponectin level between both
groups. The serum adiponectin level in the group
As shown in Table 1, 50 subjects are differenti- with stage III endometriosis is higher, but not sig-
ated by age and BMI. The age of the subjects as nificantly, than the level of which in the group with
categorical data, are compared with Kolmogorov- stage IV endometriosis.
Indones J
122 Fahdiansyah et al Obstet Gynecol

DISCUSSION with endometriosis. Adiponectin is recognized to


suppress the activity of macrophage. Besides, the
The characteristic of the subjects compared in this circulating level of adiponectin is associated with
study are the age and BMI, as these variables were proinflammatory condition related to endometrio-
anticipated to be confounding factors in this study, sis. Adiponectin also induces the phosphorylation
while the characteristic of subjects ought to be ho- of AMPK and suppresses secretion of IL-6, IL-8, and
mogeny so the study results would be valid. The MCP-1 induced by IL-1 in the endometrial cell cul-
statistical analysis of the characteristics results in ture, so that adiponectin is expected to is involved
p value of 0.994 for the age and 0.267 for the BMI, in physiology and pathology of endometrium. The
which means there is no significant difference of declined expression of adiponectin receptors in en-
characteristic between the group with endometrio- dometriosis might have a role in the pathophysio-
tic cyst and those with non-endometriotic cyst. logy of endometriosis.8
A study conducted by Kadowaki T. results in ne- This study result shows that mean level of
gative correlation between adiponectin with body adiponectin in subjects with stage III endometri-
weight, body fat mass, and insulin level. Loss of osis is higher than those of stage IV endometriosis.
body weight in obese individuals leads to increase Statistical analysis performed with unpaired t-test
of adiponectin level in plasma. On the other hand, with confidence level of 95% results in p value of
the low level of plasma adiponectinis found in con- 0.384 (p > 0.05). Thus, there is no significant dif-
ditions related to insulin resistance, such as cardio- ference of adiponectin level in patients with stage
vascular diseases.10 III and stage IV endometriosis, even though the
This study shows lower level of adiponectin in level of which in stage III endometriosis is higher
patients with endometriotic cyst compared to than those of stage IV endometriosis.
those with non-endometriotic cyst, with p value of This result is inconsistent with former study by
<0.0001 (p<0.05) which means that the difference Takemura, in which the adiponectin level in peri-
is significant. This result is consistent with the re- toneal fluid of women with endometriosis is signi-
port by Takemura. In which serum adiponectin ficantly lower than those who did not have en-
level in women with endometriotic cyst is signifi- dometriosis. This might be caused by the slow
cantly lower than women without endometriosis.8 turnover of adiponectin, relatively long half time of
Estrogen is recognized to stimulate the develop- adiponectin, and the relatively higher level of adi-
ment of endometriosis. The insulin resistance in- ponectin in the circulation.7,8
duced by low level of adiponectin is probably re-
To increase the sensitivity of adiponectin level
lated with the low level of SHBG. In conditions of
measurement in endometriosis, measurement of
insulin resistance, high level of insulin is found in
HMW level can be performed, as HMW molecular
circulation. This blocks SHBG production in the
structure is has been recognized having bioactivity,
liver, causing a potentiation effect to estrogen.
unlike MMW and LMW structure which are still un-
Adiponectin also inhibit angiogenesis, both in vitro
known. This also had been proven by Liu in sub-
and in vivo. This explains how the low level of
jects with metabolic syndrome, where HMW level
adiponectin did not inhibit angiogenesis, so en-
is positively correlated with metabolic syndrome,
dometriosis can occur.
while MMW (hexamer) and LMW (trimer) adipo-
Low circulating level of adiponectin is associated nectin does not and only correlates with the ideal
with increase of plasma insulin. The circulating in- body weight, consecutively.11
sulin level is inversely proportional with the level
of insulin-like growth factor-binding protein 1 This study is consistent with former study sta-
ting that adiponectin level in serum of women with
(IGFBP-1) bound to insulin-like growth factor 1
endometriotic cyst is significantly lower than those
(IGF-1), also reduces its biological effect. The low
without endometriosis.8
level of adiponectin enhances IGF-1 effect in stimu-
lating the development of endometriosis. Perito- This study is limited in some ways that some pre-
neal inflammation is involved in the pathogenesis existing conditions such as hypertension or cardio-
of endometriosis. Various cytokines are found in- vascular diseases, age, and obesity, might be influ-
creased in serum and peritoneal fluid of women ence the result as confounding factors.
Vol 1, No 3
July 2013 Patients with endometriotic cyst 123

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