Online ISSN 2623-2723, Print ISSN: 2338-0373 Jurnal Widya Medika Vol.

7 No 1 April 2021

EPIDEMIOLOGIC STUDY OF ENDOMETRIAL LESION CHARACTERISTICS BY

AGE IN PATHOLOGY DIAGNOSTIC CENTER IN SURABAYA 2015-2017

Sianty Dewi1, Imelda Theodora2, Bernadette Dian Novita3, Yulia Widyasari4, Ricardo
Gunadi4, Maria Amelia Suhardi4, Vincentius Diamantino Supit5

ABSTRACT
Background: The etiology of endometrial lesions varies from benign to malignant. Early
detection and management of malignancy give the best prognosis for the patient. While studies
in America and Europe report a 3-5% risk of malignancy in women below 50 years and a
significant increase up to 75-80% in postmenopausal, the availability of national
epidemiologic data is limited, therefore the study is held.Method: A descriptive- retrospective
study. Total sampling obtained from endometrial specimens in Pathology Diagnostic Center-
Prof JH Lunardhi, Sp.PA(K) from 2015 to 2017, while gestation-related, inadequate sample,
and incomplete report are excluded. Data analyzed by IBM SPSS 23.0 version. Result: Data
of 560 samples, 90% from curettage, 8% hysterectomy, and 2% hysteroscopy. The majority
belonged to the 40-49 age group (44.3%). Secretory phase endometrium is the most common
finding in the age group of 20-29 years (26.9%). Proliferative phase endometrium is the most
common finding. The highest incidence of endometrial hyperplasia occurred in the age group
of 40-49 years, for both typical and non-atypical. Endometrial malignancy was found mostly
in the 50-59 years (37.03%). Conclusion: The prevalence of endometrial lesions differed
according to age groups, with physiological changes, endometritis, polyps, and hyperplasia
were most common under 50 years old and the risk of malignancy increased 4.39 times (p.00)
beyond 50 years old.

Keyword: Endometrial Lesion, Hyperplasia, Age, Menopause, Malignancy

ABSTRAK
Latar Belakang: Etiologi lesi endometrium bervariasi dari kelainan jinak sampai keganasan.
Deteksi dan tata laksana dini pada keganasan memberikan prognosis terbaik. Penelitian di
Amerika dan Eropa melaporkan 3-5% resiko keganasan pada usia dibawah 50 tahun dan
meningkat signifikan sampai 75-80% paska menopause. Data epidemiologi nasional masih
terbatas sehingga penelitian ini perlu dilaksanakan. Metode: Studi deskriptif retrospektif.
Total sampel dari spesimen endometrium di Sentra Diagnostik Patologi Prof. JH Lunardhi,
SpPA(K) tahun 2015-2017 dengan kriteria eksklusi lesi terkait gestasi, sampel tidak adekuat

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Epidemiologic Study Of...... Dewi S, Theodora I, Novita BD, Widyasari Y, Gunadi R,
Suhardi MA, Supit VD

dan laporan tidak lengkap. Data dianalisa dengan IBM SPSS versi 23.0. Hasil: Data 560
sampel endometrium, 90% kuretase diikuti dengan histerektomi 8% dan histeroskopi 2%, yang
didominasi kelompok usia 40-49 tahun (44,3%). Endometrium fase sekresi merupakan temuan
yang terbanyak pada kelompok usia 20-29 tahun (26,9%). Endometrium fase proliferasi
merupakan temuan terbanyak pada kelompok usia 30-69 tahun dan usia 80-89 tahun. Pada
kelompok usia 70-79 tahun, temuan yang terbanyak adalah hiperplasia endometrium non-
atipikal (50%). Kejadian hiperplasia endometrium paling banyak terjadi pada kelompok usia
40-49 tahun, baik pada non-atipikal (55,3%) maupun atipikal (83,3%). Keganasan pada
endometrium paling banyak ditemukan pada kelompok usia 50-59 tahun (37,03%).
Kesimpulan: Prevalensi lesi endometrium berbeda sesuai kelompok umur, pada usia dibawah
50 tahun didapatkan endometritis, polip dan hiperplasia. Pada usia diatas 50 tahun risiko
keganasan meningkat 4,39 kali lipat ( p=0,00)

Kata Kunci: Lesi Endometrium, Hiperplasia, Umur, Menopaus, Keganasan

1) Obstetrics and Gynecology Department, Faculty of Medicine of Widya Mandala Catholic University
Surabaya 2) Pathology Anatomy Department, Faculty of Medicine Widya Mandala Catholic University
Surabaya 3) Pharmacology and Therapy Department, Faculty of Medicine Widya Mandala Catholic University
Surabaya 4) Alumni of Faculty of Medicine Widya Mandala Catholic University Surabaya 5) Gotong Royong
Hospital Surabaya. Corresponding email: [email protected]

BACKGROUND Histopathology abnormalities vary

Endometrial lesions may occur among age groups of women. Endometrial
anytime in a woman’s life, which prompts lesion among young women is caused by
them to visit medical facilities with the hormone imbalance, while endometrial
chief complaint of vaginal bleeding. The hyperplasia and endometrial malignancy
etiology varies from benign changes caused occur among older women [3].
by hormone exposure, endometrial polyps, Data on the prevalence of
chronic endometritis, endometrial endometrial lesions based on age helps the
hyperplasia, and endometrial malignancy. physician in managing patient complaints
Endometrial hyperplasia is potentially and stakeholders in establishing policies for
progressed to endometrial malignancy screening in high-risk age groups. The
according to clinicopathology and epidemiological study regarding the
epidemiology past studies [1]. In 2018, the prevalence of endometrial lesions in
estimated prevalence of endometrial Indonesia is limited, therefore a thorough
cancers was 33.9/100.000 and becoming report is needed.
the second-largest cancer prevalence
worldwide after cervical cancer[2].

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Online ISSN 2623-2723, Print ISSN: 2338-0373 Jurnal Widya Medika Vol. 7 No 1 April 2021

METHODS Anatomical Pathology Clinic run by Prof.

This research was a descriptive, JH Lunardhi in Surabaya and analyzed
observational, and retrospective study. The using the IBM SPSS version 23.0 program.
population was women who had undergone The chart of epidemiology distribution is
pathology examinations of the shown in numbers and percentages.
endometrium from January 2015 to
RESULT
December 2017. The total sampling method 560 reports of the endometrial examination
includes endometrial examinations met the inclusion criteria, with 90% of
obtained from curettage, hysteroscopy, and specimens obtained by curettage, 2%
hysterectomy. The exclusion criteria were hysteroscopy, and 8% hysterectomy.
gestation-related lesions, inadequate Hysteroscopic classifications are presented
samples, and incomplete reports. The to demonstrate the use of technology in
research was carried out from October 1, patient management.
2020, to December 31, 2020, at the

Figure 1. Distribution of Procedures Figure 2. Distribution of procedures done

Done to Obtained Endometrial Tissue. based on age group

Figure 3. Distribution of age underwent sampling procedures

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Epidemiologic Study Of...... Dewi S, Theodora I, Novita BD, Widyasari Y, Gunadi R,
Suhardi MA, Supit VD
Table 1. Result of Biopsy Based on Age
Age Group
Total
20-29 30-39 40-49 50-59 60-69 70-79 80-89
Irregular Shedding 1 (3,8%) 10 (6,0%) 16 (6,4%) 4 (4,4%) 0 (0%) 0 (0%) 0 (0%) 31 (5,5%)
Endometrial polyp 6 (23,1%) 34 (20,2%) 27 (10,8%) 10 (11,1%) 1 (5,0%) 0 (0%) 0(0%) 78(13,9%)
Long Standing Progesterone Effect 2 (7,7%) 7 (4,2%) 4(1,6%) 0(0%) 0(0%) 0(0%) 0 (0%) 13(2,3%)
Undifferentiated Carcinoma 0 (0%) 1 (0,6%) 0 (0%) 1 (1,1%) 0 (0%) 0(0%) 0 (0%) 2 (0,4%)
Atrophic Endometrium 0 (0%) 0 (0%) 0 (0%) 2 (2,2%) 1 (5%) 0 (0%) 0 (0%) 3 (0,5%)
Atrophic Endometrium with Cystic Changes 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (5%) 0 (0%) 0 (0%) 1 (0,2%)
Proliferative Phase Endometrium 6(23,1%) 45(26,8%) 65(26,1%) 37(41,1%) 9 (45%) 2 (33,3%) 2(66,7%) 166 (29,5%)
Secretory Phase Endometrium 7 (26,9%) 31 (18,5%) 41(16,5%) 4 (4,4%) 0(0%) 0(0%) 0(0%) 83 (14,7%)
Nonatypical Hyperplasia 1 (3,8%) 27 (16,1%) 68 (27,3%) 21 (23,3%) 3 (15%) 3 (50%) 0(0%) 123 (21,8%)
Atypical Hyperplasia 1 (3,8%) 0 (0%) 10 (4%) 1 (1,1%) 0 (0%) 0 (0%) 0 (0%) 12 (2,1%)
Chronic Endometritis 1 (3,8%) 7 (4,2%) 11 (4,4%) 1 (1,1%) 1 (5%) 1 (16,7%) 1 (33,3%) 23 (4,1%)
Grade 1 Endometrioid Carcinoma 0 (0%) 2 (1,2%) 0 (0%) 2 (2,2%) 0 (0%) 0 (0%) 0 (0%) 4 (0,7%)
Grade 2 Endometrioid Carcinoma 1 (3,8%) 0 (0%) 4 (1,6%) 2 (2,2%) 3 (15%) 0 (0%) 0 (0%) 10 (1,8%)
Grade 3 Endometrioid Carcinoma 0 (0% 1 (0,6%) 0 (0,0%) 1 (1,1%) 0 (0%) 0 (0%) 0 (0%) 2 (0,4%)
High grade endometrial Adenocarcinoma 0 (0%) 0 (0%) 0 (0%) 1 (1,1%) 0 (0%) 0 (0%) 0 (0%) 1 (0,2%)
Moderately differentiated adenocarcinoma 0 (0%) 1 (0,6%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (0,2%)
Papillary Adenocarcinoma 0 (0%) 0 (0%) 0 (0%) 1 (1,1%) 0 (0%) 0 (0%) 0 (0%) 1 (0,2%)
Endometrial Stromal Sarcoma DD Malignant Mixed
0 (0%) 0 (0%) 0 (0%) 1 (1,1%) 0 (0%) 0 (0%) 0 (0%) 1 (0,2%)
Müllerian Tumor
Endometrial Stromal Tumor 0 (0%) 1 (0,6%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (0,2%)
Endometrioid Adenocarcinoma with squamous
0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (5%) 0 (0%) 0 (0%) 1 (0,2%)
metaplasia
Endometrioid Adenocarcinoma, Well differentiated 0 (0%) 0 (0%) 0 (0%) 1 (1,1%) 0 (0%) 0 (0%) 0 (0%) 1 (0,2%)
Nonkeratinizing Squamous Cell Carcinoma, intermediate
0 (0%) 1 (0,6%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (0,2%)
cell type
Polypoid Adenocarcinoma, well differentiated 0 (0%) 0 (0%) 1 (0,4%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (0,2%)
20
Total 26 (100%) 168 (100%) 248 (100%) 90 (100%) 6 (100%) 3 (100%) 560 (100%)
(100%)

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RESULT 40-49 age group (n=16/31;51.6%).

The prevalence of endometrial Endometrial polyps were found mostly in
lesions is listed in Table 1. Based on this the 30-39 age group (n=34/78;43.6%).
table, the endometrial secretion phase was Chronic endometritis was also found
the most common finding in the 20-29 year mostly in the 40-49 age group
age group (26.9%). Proliferation phase (11/23;47.8%), and endometrial lesions
endometrium was the most common caused by prolonged progesterone exposure
finding found in the age group 30-39 years were commonly found in the 30-39 age
(26.8%), 50-59 years (41.1%), 60-69 years group (n=7/13;53.8%). In the 50-59 age
(45%). and aged 80-89 years (66.7%). In group, most findings were endometrial
the 40-49 years and 70-79 years age group, atrophy (n=2/3;66.7%) while in the 60-69
the most common finding is non-atypical age group, most of the findings were
endometrial hyperplasia (27,3% and 50% endometrial atrophy cystic changes
respectively). (n=1/1;100%).
The result of endometrial irregular
shredding was most commonly found in the

Table 2. Age group domination for endometrial lesion

Percentage of most common
Endometrial lesion Age group
age group in a finding *

Long-standing progesterone effect 30-39 y.o 53.8% (7/13)

Endometrial polyp 30-39 y.o 43.6% (34/78)

Irregular shedding 40-49 y.o 51.6% (16/31)

Chronic Endometritis 40-49 y.o 47.8% (11/23)

83.3% (10/12) – Atypical**

Non-atypical and typical endometrial hyperplasia 40-49 y.o
55.3% (68/123) – Typical***

Endometrial atrophy 50-59 y.o 66.7% (2/3)

Endometrial malignancy 50-59 y.o 37.0% (10/27)

 For example:7 out of 13 cases of long-standing progesterone effects were found in 30-39 y.o
** 10 out of 12 cases of atypical hyperplasia found in 40-49 y.o
*** 68 out of 123 cases of typical hyperplasia found in 40-49 y.o

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Epidemiologic Study Of...... Dewi S, Theodora I, Novita BD, Widyasari Y, Gunadi R,
Suhardi MA, Supit VD

Figure 4. Prevalence of Benign and Malignant Lesions across Age Group

Figure 5. Endometrial Malignancy Distribution

Endometrial malignancy were commonly cell carcinoma (n=1/27;3.7%), and
found in 50-59 y.o (n=10/27;37.03%). endometrial stromal sarcoma tumor with
Malignancies found in this research Mixed Mullerian Tumor as its differential
dominated by endometrioid diagnosis (n=1/27;3.7%). Endometrioid
adenocarcinoma (n = 23/27; 85.1%) carcinoma was mostly found in grade II
followed by undifferentiated carcinoma (n=10/16;62.5%).
(n=2/27;7.4%), non-keratinizing squamous

Tabel 3. Rissygk of Malignancy

Findings Odds
Total P-Value
Malignant Benign Ratio

Count 13 428 441

< 50 years old
% within Risiko 2.9% 97.1% 100.0% 4.39 0.000*
Risk
Count 14 105 119
≥ 50 years old
% within Risiko 11.8% 88.2% 100.0%
Count 27 533 560
Total
% within Risiko 4.8% 95.2% 100.0%

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Women at 50 years old and above have a their peers. This finding was statistically
4.39 times higher risk of malignancy than significant p = 0.000.

Figure 6. The trend of cases found from 2015-2017

Prevalence of malignancy was the fifth decade as much as 35.9% [5]. This
unchanged in 3 years, while the benign difference might happen due to
lesion increased rate by 20% annually from multifactorial influences such as genetics,
145 cases in 2015, 176 cases in 2016, and ethnics or environmental such as diet,
212 cases in 2017. nutrition, and activities.[6].
This study reported proliferation
DISCUSSION
phase of the endometrium was 29.5%and
Irregular shedding of endometrium
secretory 14.7% with the age range of the
occurs due to regression failure of the
endometrium in the proliferation phase
corpus luteum lead to prolonging
varying at the age of 20-89, while the
progesterone exposure. Irregular
endometrium in the secretion phase was
endometrial shedding was found across
ages, mostly in the 40-49 year age group (n mostly found in the 20-29 year age group.

= 16/31; 51.6%). The results are similar to Proliferative endometrium can be caused
by contraceptive use and medications for
research conducted at the Kandou Manado
abnormal uterine bleeding before curettage.
General Hospital which stated that most
Another study in Nigeria also found that the
irregular shedding cases were at 41-50
proliferation phase endometrium also
years old (33.87%) [4]. Also, research in
dominates (21.7%) and secretion phase
Nigeria states that irregular shedding was
endometrium (12.4%) [3]. Research in Italy
found most frequently in the fourth decade
as 43.3% [3]. However, another study states on women aged 30-40 years stated that the
endometrium does not age, but only
that the age of irregular shedding occurs in

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Epidemiologic Study Of...... Dewi S, Theodora I, Novita BD, Widyasari Y, Gunadi R,
Suhardi MA, Supit VD

changes when there is hormonal in which endometrial polyps were found to

administration or the menstrual cycle [7]. be the largest in the perimenopausal age
The most commonly used low-dose group. The low number of cases in the
oral contraceptive is progesterone, which younger age group may be due to the
inhibits proliferative changes in the spontaneous regression mechanism of
endometrium's normal cycle [8]. In this polyps, which are characteristic of changes
study, it was found that endometrial lesions in the endometrial cycle in women of
due to the effects of prolonged progesterone reproductive age.
were mostly found in the 30-39 year age
The number of endometrial polyps
group (n = 7/13; 53.8%). This might be
cases continued to decline, starting in the
related to the age of women who use
perimenopausal age group. Other studies
contraception, especially hormonal
have listed an increase in the prevalence of
contraceptives that contain progesterone
endometrial polyps with age due to
such as birth control pills, injection
prolonged exposure to estrogen and
contraceptives, or IUD with progesterone.
progesterone, which affects the
Prolonged progesterone exposure can also
proliferation and differentiation of the
be caused by abnormal uterine bleeding
endometrium [9]. The results of another
treatment.
study in Denmark also stated that the
In this study, it was found that the
prevalence of endometrial polyps would
prevalence of endometrial polyps was
continue to increase with age [10].
13.9%. The results of this study were higher
The prevalence of endometrial
than other studies in Nigeria, which only
atrophy was found to be 0.5% and was
included 3.1% [3]. This difference could be
found mostly in the 50-59 years age group.
due to differences in racial and ethnic
The prevalence of endometrial atrophy
characteristics in each population. In
accompanied by cystic changes is only
previous studies, it was found that
found in the 60-69 years age group. Our
menopause, the elderly (> 60 years),
study was consistent with previous studies
obesity, and diabetes mellitus are clinical
stating that atrophy in the endometrium was
parameters that can increase the risk of
found mostly in post-menopausal women.
developing benign and malignant
This is due to the loss of endometrial
endometrial polyps. The highest number of
stimulation by estrogen either externally or
cases of endometrial polyps in this study
internally after menopause, which causes
was found in the 30-39 year age group. This
the endometrial walls to become thin and
result is inconsistent with previous studies

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eventually atrophy [11]. Endometrial walls intermittent anovulation, there will be an

that experience atrophy will cause minor absence of progesterone to counteract
injury to occur and are the most common estrogen effects so that glandular
cause of postmenopausal bleeding [12]. proliferation continues [15]. However, the
The prevalence of chronic age at which endometrial hyperplasia
endometritis in this study was found to be occurs in Indonesia are younger if
4.1% and was mostly found in the 40-49 compared to the 2009 prevalence study in
year age group. Our study was consistent the United States with 63,688 samples who
with a previous study in India, which stated found that non-atypical endometrial
that chronic endometritis was found mostly hyperplasia was most prevalent at the age
in perimenopausal age [13]. Transvaginal of 50-54, and atypic endometrial
infection, intrauterine devices (IUD), hyperplasia occurred mostly at the age of
submucosal leiomyoma, and endometrial 60-64 [16]. Apart from the risk factors for
polyps are the most common causes of endometrial hyperplasia, the younger
chronic irritation of the endometrium, occurrence of endometrial hyperplasia in
leading to chronic inflammatory reactions this study might be explained because of
in the endometrium [11]. Chronic sample size at the age of 40-49 is three
endometritis is mostly found in women of times larger at the age of 50-59.
perimenopausal age, probably due to Most endometrial malignancies
menstrual cycle irregularities during occurred at the age of 50-59, with the
perimenopause. The endometrial number of cases as much as 4.7% of all
proliferation phase has been associated samples in this study. Previous studies on
with the incidence of plasma cell the prevalence of gynecological cancer in
endometritis. The longer the duration of the Indonesia in 2009 showed that the
proliferation phase during perimenopause prevalence of endometrial cancer was
increases the risk of developing mostly at the age of 45-54 years [17].
endometritis [14]. Another prevalence study of endometrial
The incidence of endometrial cancer at Dokter Sutomo Hospital with a
hyperplasia prevalence was highest in the sample of 95 people showed that
40-49 years age group, those with and endometrial cancer occurred mostly in the
without atypia. This result was following age of 51-60 years [18]. The population of
the theory that endometrial hyperplasia patients with endometrial cancer in
occurs mostly in the perimenopausal age Indonesia is younger than patients in the
due to intermittent anovulation. With United States. The number of endometrial

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Epidemiologic Study Of...... Dewi S, Theodora I, Novita BD, Widyasari Y, Gunadi R,
Suhardi MA, Supit VD

cancer prevalence in the United States is this gene mutation is unknown in

highest in the 55-64 years age group Indonesia.
(median 63 years) [19]. There are several
LIMITATION
probable reasons to explain this There were some limitations in this
phenomenon. The first possibility is that the study. The insufficient sample size of
sample size in our study and the past women aged 60 years and over may affect
prevalence study in Indonesia was still the prevalence rate of endometrial disease,
smaller than the sample size in the United particularly endometrial cancer. However,
States study. The second possibility is the the sample size in this study was relatively
existence of special risk factors that are superior compared to other studies in
owned by the population in Indonesia. The Surabaya. It is hoped that, with this large
most common type of malignancy in the sample, the numbers obtained can be more
endometrium is endometrioid carcinoma. representative of the actual situation.
In theory, endometrioid carcinoma For further research, studies with
accounted for 83% of cases of endometrial larger sample sizes, more even age
malignancies [20]. However, our study distribution, and detail clinical and
found that endometrioid carcinoma only epidemiological profiles are needed.
made 37.03% of all malignancies were Research is also necessary to investigate
present in this study. This may be due to the the prevalence of gene mutations or other
small sample of endometrial malignancy. factors which cause the younger occurrence
The risk factors for endometrial of endometrial hyperplasia and cancer in
hyperplasia and endometrial cancer are Indonesia.
chronic estrogen exposure and a relative
CONCLUSION
progesterone deficiency. This can occur
There were differences in the
due to increasing age, genetics, early
etiology of endometrial lesions based on
menarche, late menopause, obesity,
age groups. At a younger age, causes of
diabetes mellitus, PCOS, estrogen-
endometrial lesions include inflammatory
producing tumors, and
lesions, hormonal influences, polyps, and
immunosuppression. [21], [22]. Several
hyperplasia. The risk of endometrial
genetic mutations cause endometrial
malignancy increased 4.39 times at the age
malignancies, including PTEN Tumor
above 50 years significantly (p = 0.00). The
Suppressor Gene, PIK3CA, KRAS,
type of malignancy in the endometrium was
ARID1A, and TP53 [23]. The prevalence of
dominated by endometrioid

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adenocarcinoma The trend in the 10.35790/ecl.4.2.2016.14395.

prevalence of malignancy did not increase 5. Jairajpuri Z, Rana S, Jetley S.
in 3 years (2015 - 2017) while cases of Atypical uterine bleeding-
benign lesions increased by 20% per year. histopathological audit of
endometrium a study of 638 cases.
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Online ISSN 2623-2723, Print ISSN: 2338-0373 Jurnal Widya Medika Vol. 7 No 1 April 2021

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