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FACTORS CONTRIBUTING TO THE DEVELOPMENT OF
ENDOMETRIAL HYPERPLASIA IN WOMEN OF ADVANCED
REPRODUCTIVE AGE
Dustova N.K.
Kurbonova G.R.
Bukhara State Medical Institute named after Abu Ali ibn Sino, Uzbekistan,
Bukhara, Gijduvanskiy st. 23,
Tel: +998 (65) 223-00-50 e-mail: info@bsmi.uz
https://doi.org/10.5281/zenodo.14500970
Resume.
The aim of the study is to determine the risk factors for the
development of hyperplastic complications in early reproductive age.
Materials and research methods.
To achieve the set goals and
objectives, a prospective study was organized, within the framework of which
the effectiveness of treatment in 120 women of reproductive age from 30 to 45
years was analyzed. Group 1 included 64 patients from 30 to 45 years with
uterine myoma and endometrial hyperplasia. Group 2 consisted of 56 patients
from 30 to 45 years with endometrial hyperplasia without uterine myoma.
Conclusion.
Despite the successes achieved in the study of the
etiopathogenesis, new methods of diagnostics and therapy of GPE, the problem
of treating patients with this pathology remains far from being solved. All this
dictates the need to optimize the tactics of managing patients with GPE in
primary care, which should be aimed not only at creating adequate
comprehensive approaches to predicting the development and recurrence of GE,
but also developing unified protocols for managing patients with this pathology.
Keywords:
hyperestrogenism, proliferation, apoptosis.
Relevance.
Endometrial hyperplasia (EH) is a benign pathological process
of the uterine mucosa, characterized by proliferation (growth) of glands and an
increase in the glandular-stromal ratio (ratio of glandular and stromal cells). The
main characteristic feature of the disease is the proliferation of the inner layer of
the uterus - the endometrium, leading to thickening and an increase in its
volume.
Hyperplastic processes of the endometrium still represent enormous
scientific, medical and social significance in terms of frequency of occurrence,
disorders of the reproductive system functions and lack of adequate treatment
methods [1,2,3]. Abnormal uterine bleeding, which is the most frequent clinical
manifestation of endometrial hyperplasia, is the most frequent reason for
visiting a gynecologist and is the second most common gynecological problem
associated with the referral of a woman for hospitalization [4,5]. The issues of
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treating patients with endometrial hyperplasia cover a wide range of
conservative and surgical methods. However, young women who want to
preserve their reproductive function (in the absence of cellular atypia) should
consider conservative therapy, among which hormonal therapy occupies a
leading place. In this regard, hormonal effects on hyperplastic endometrium
have not lost their clinical significance. Endometrial hyperplasia is known to be a
consequence of absolute or relative hyperestrogenism and progesterone
deficiency, which leads to excessive (uncontrolled) cell division and decreased
apoptosis [6,7].
The classical therapy for endometrial hyperplasia (EH) is the
administration of progestins to counteract the estrogenic effect. Progesterone
has an antiproliferative effect on the mitotic activity of endometrial cells.
Progestins reduce the number of estrogen receptors and accelerate their
catabolism by stimulating 17-beta-hydroxysteroid dehydrogenase and
sulfotransferase, and thus reduce the dominance of estrogens in the hormonal
background, leading to endometrial hyperplasia [8].
At present, based on the analysis of the work of gynecological hospitals, it is
important to develop the basis for determining the medical strategy for the
treatment of GE in relation to the choice of a conservative method of treating
women of reproductive age. In this direction, it seems promising to take into
account psychosomatic disorders, the frequency of which ranges from 30% to
57% of the total number of women seeking antenatal care [10,11]. Hyperplastic
processes in the endometrium are a large group of histological changes in the
glands and stroma of the endometrium, which are the basis for the formation of
neoplastic processes in the uterus. One of the most significant factors directly
associated with the risk of developing this pathology is the perimenopausal
period, when the frequency of hormone-dependent pathology increases.
Hyperplastic processes in the endometrium are one of the most common causes
of uterine bleeding and hospitalization. The question of the risk of developing
malignant transformation of GE remains open [1,2]. According to domestic and
foreign studies, the degree of risk of malignancy of various variants of GPE is
determined by the morphological state of the endometrium and depends, first of
all, on the severity of cellular atypia and, to a lesser extent, on age, the state of
the ovaries, concomitant endocrine diseases, and other factors [4]. It has been
proven that histopathological and molecular changes reflect the possible risk of
transition of GPE to EC.
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The complexity of the etiopathogenesis of GPE creates significant
difficulties in choosing treatment methods. This can explain the lack of uniform
recommendations for the choice of a drug, dose and optimal duration of its use,
which is often inadequate, and therefore, we have to deal with relapses of GPE
[5]. Recurrent uterine bleeding, oncological alertness in long-term proliferative
processes against the background of concomitant pathology, dictate the need to
use more active tactics for managing this contingent of patients [6]. Thus,
despite the successes achieved in the study of the etiopathogenesis, new
methods of diagnosis and therapy of GPE, the problem of treating patients with
this pathology remains far from being solved. All this dictates the need to
optimize the tactics of managing patients with GPE in primary care, which
should be aimed not only at creating adequate comprehensive approaches to
predicting the development and recurrence of GPE, but also developing uniform
protocols for managing patients with this pathology.
The aim of the study
was the definition of risk factors for the development of
hyperplastic complications in early reproductive age.
Materials and research methods.
To achieve the set goals and objectives, a
prospective study was organized, within the framework of which the
effectiveness of treatment in 120 women of reproductive age from 30 to 45
years was analyzed.
Group 1
included 64 patients aged 30 to 45 years with uterine myoma and
endometrial hyperplasia. In patients of this group, despite the presence of
uterine myoma, the development of endometrial hyperplasia is not directly
related to the presence of myoma.
Group 2
consisted of 56 patients aged 30 to 45 years with endometrial
hyperplasia without uterine myoma. In these patients, the absence of myoma
allowed us to evaluate hyperplastic processes in the endometrium without the
influence of this factor.
Control group
included 20 healthy women aged 30 to 45 years, in whom
ultrasound examination did not reveal hyperplastic processes or organic
changes in the endometrium, such as uterine myoma, polyps or adenomyosis.
These women served as a control group for comparison with patients in the first
two groups in order to identify characteristic changes associated with
endometrial pathology (Table 1).
The study was conducted at the Tashkent City Hospital No. 4 in the gynecology
department from 2021 to 2023. Before starting the treatment course, all
participants were carefully assessed for clinical manifestations of the disease,
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and their hormonal status was analyzed. In particular, the levels of hormones
such as estradiol, progesterone, lutropin (LH), follitropin (FSH) and prolactin in
the blood serum were measured.
The following inclusion criteria were taken into account when hospitalizing
women to participate in the study:
Absence of oncological diseases according to the initial examination
results.
The absence of endocrine pathology, including diabetes mellitus, hypo-
and hyperthyroidism, obesity, which allows us to exclude the influence of these
conditions on the hormonal background and treatment results.
Age from 30 to 45 years, corresponding to the late reproductive period.
The absence of acute inflammatory processes in the pelvic organs
ensures the absence of external inflammatory effects on the results of the study.
Informed voluntary consent to participate in the study and to undergo all
necessary medical and diagnostic procedures, guaranteeing the legal and ethical
correctness of the study.
These criteria ensure the reliability and objectivity of the data obtained,
eliminating possible distortion of the results.
Table 1.
Distribution of patients by age (n=120)
Age
30-35
years
old
36-40
years
old
41-45
years
old
Total
Group 1
16 (25%)
22 (34.4%)
26 (40.6%)
64
(100%)
Group 2
11 (19.6%)
20 (35.7%)
25 (44.7%)
56
(100%)
Control
group
6 (30%)
8 (40%)
6 (30%)
20
(100%)
In Group 1, there were 16 patients (25%) in the 30-35 age range, 22 patients
(34.4%) in the 36-40 age range, and 26 patients (40.6%) in the 41-45 age range.
In Group 2, there were 11 patients (19.6%) in the 30-35 age category, 20
patients (35.7%) in the 36-40 age category, and 25 patients (44.7%) in the 41-
45 age category. In the control group, there were 6 patients (30%) in the 30-35
age range, 8 patients (40%) in the 36-40 age range, and 6 patients (30%) in the
41-45 age range.
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The majority of patients in both groups lived in urban areas: 65.6% in group 1
and 67.9% in group 2. Rural residence was less common, accounting for 34.4%
in group 1 and 32.1% in group 2.
In both groups, the largest percentage is made up of working women: 50.0% in
Group 1 and 50.0% in Group 2. Housewives make up 31.3% in Group 1 and
32.1% in Group 2. Female students are a minority, making up 18.8% in Group 1
and 17.9% in Group 2.
Table 2 shows the main reasons for hospitalization of patients included in the
study.
Table 2.
Main indications for hospitalization of patients included in the study (n=120)
Indications for hospitalization
1
group
(n=64)
%
Group
2
(n=56)
%
r
Uterine bleeding
50
78.1 42
75.0 >0.05
Endometrial changes according
to ultrasound data
14
21.9 14
25.0 >0.05
In the main group, consisting of 64 patients, uterine bleeding was observed in 50
women (78.1%), and endometrial changes according to ultrasound data were
observed in 14 patients (21.9%). In the comparison group, which included 56
patients, uterine bleeding was recorded in 42 women (75.0%), and endometrial
changes were observed in 14 patients (25.0%). The differences between the
groups were not statistically significant (p> 0.05).
According to the study data, patients in Group 1, which included women with
uterine myoma, more often complained of heavy (62.5%) and prolonged
(50.0%) menstruation, which was also often irregular (46.9%). A significant
number of women in this group had a combination of two or more complaints,
indicating more pronounced clinical manifestations of the disease. The duration
of clinical symptoms in patients in Group 1 ranged from 1 to 6 years, which is
logical, given the presence of uterine myoma, which is often accompanied by
such symptoms.
In group 2, which included women without uterine myoma, menstrual cycle
disorders such as menorrhagia were observed in 23.2% of cases, and
metrorrhagia in 51.8% of cases, while menstruation remained irregular in
21.4% of patients. The duration of the disease in women from group 2 ranged
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from 2 months to 1 year. A combination of two or more complaints was
observed in 25.0% of women in group 2, indicating less pronounced, but still
significant clinical manifestations (Table 3).
Table 3
Main complaints of the examined patients (n=120)
Complaints
Main
group
(n=64)
%
Comparison
group
(n=56)
%
r
Heavy menstruation
40
62.5
29
51.8
>0.05
Long periods
32
50.0
13
23.2
<0.05
Irregularity
of
menstruation
30
46.9
12
21.4
<0.05
General
weakness,
increased fatigue
12
18.8
10
17.9
>0.05
Acyclic bleeding
6
9.4
5
8.9
>0.05
Bloody discharge after
and/or
before
menstruation
3
4.7
4
7.1
>0.05
No complaints were filed
9
14.1
12
21.4
>0.05
Thus, it should be noted that patients in group 1 with uterine myoma had earlier
and more pronounced clinical symptoms of the disease compared to group 2.
During the analysis of the family history of the study participants, it was found
that in close relatives of women from the second group, where uterine fibroids
were not observed, 47.1% of cases were benign tumors and tumor-like diseases
of the reproductive organs, including their combinations. In the first group,
where the participants suffered from uterine fibroids, such diseases were much
less common - only in 22.8% of cases (p<0.0001).
Regarding malignant diseases of the reproductive organs, they were registered
in 8.7% of cases among relatives of women from the second group, while among
relatives of the first group this figure was 7.6%, and no statistically significant
differences were observed (p>0.05).
These results indicate that women in the first group, where uterine fibroids
were more common, had a lower risk of developing malignant neoplasms, in
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contrast to the second group, where fibroids were absent, but family history
showed an increased risk of both benign and malignant diseases (Table 4).
Table 4.
Hereditary burden of the examined women (n=120)
Hereditary factors
Group 1
(n=64)
%
Group
2
(n=56)
%
Benign diseases of the reproductive system (isolated or in combination):
- Uterine fibroids
30
46.9
13
23.2
- Endometrial hyperplasia
12
18.8
10
17.9
- Adenomyosis
9
14.1
5
8.9
- Dyshormonal pathology of the
mammary glands
11
17.2
8
14.3
Malignant diseases of the reproductive system:
- Endometrial cancer
4
6.3
4
7.1
- Cervical cancer
2
3.1
1
1.8
- Ovarian cancer
1
1.6
1
1.8
- Breast cancer
2
3.1
2
3.6
- Others
2
3.1
2
3.6
Table 4 shows the distribution of hereditary burden among the examined
women in group 1 (with uterine myoma) and group 2 (without uterine myoma).
In group 1, benign diseases such as uterine myoma (46.9%) and endometrial
hyperplasia (18.8%) were more common, which is logical for this category of
patients. In group 2, where there was no myoma, benign pathologies were also
noted, but with a lower frequency. Malignant diseases such as endometrial
cancer and breast cancer were observed in both groups with comparable
frequency.
Table 5.
Structure of the main extragenital diseases in the examined women (n=120)
Extragenital diseases
Group
1
(n=64)
%
Group
2
(n=56)
%
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Diseases of the gastrointestinal
tract and hepatobiliary complex
43
67.2
19
33.9
Cardiovascular diseases
35
54.7
20
35.7
Obesity I-II degree
32
50.0
17
30.4
Chronic inflammatory diseases of
the upper respiratory tract
15
23.4
9
16.1
Urinary tract infections
13
20.3
10
17.9
Functional disorders of the
nervous system
11
17.2
12
21.4
Dyshormonal
pathology
of
mammary glands
15
23.4
12
21.4
The analysis showed that childhood infectious and inflammatory diseases such
as chickenpox, scarlet fever, measles and rubella were common among
participants in both study groups. The results showed no statistically significant
effect of these childhood diseases on the development of endometrial
hyperplastic processes in women in Group 1 with uterine myoma and Group 2
without myoma (p>0.05).
The presence of extragenital diseases in women was also studied. In the first
group, 80.9% of women had two or more extragenital diseases, which was
higher than 77.4% in the second group. Among the most common diseases in
women in the first group, gastrointestinal tract and hepatobiliary system
diseases were identified: chronic gastritis in 26.6% of patients, cholecystitis in
18.9%, peptic ulcer in 7.4%, and spastic enterocolitis in 15.8%. In the second
group, these diseases were less common, occurring in 33.7% of participants,
with chronic gastritis in 19.7%, spastic colitis in 4.7%, and cholecystitis in
14.2%.
Cardiovascular diseases were also observed more frequently in women with
uterine fibroids in the first group (54.5%) compared to the second group
(35.7%), with conditions such as vegetative-vascular dystonia, hypertension,
coronary heart disease, angina pectoris and varicose veins of the lower
extremities, and the differences were statistically significant (p<0.001).
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