68
INFLUENTIAL RISK FACTORS IN THE DEVELOPMENT OF ENDOMETRIAL
HYPERPLASIA DURING THE LATE REPRODUCTIVE PERIOD
Dustova N.K.
Kurbonova G.R.
Kodirova Z.K
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.15770981
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
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
69
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.
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.
70
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, 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.
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.
71
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 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
72
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 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
73
- 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)
%
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,
74
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).
References:
Используемая литература:
Foydalanilgan adabiyotlar:
1.
Gromova A.L. Relationship between recurrent hyperplastic processes of the
endometrium and genetic determinants Arg72Pro of the p53 gene and (ss) of the l-myc gene
// Novgorod State University Bulletin. 2016. No. 1 (92).
2.
Demakova N.A. Molecular genetic characteristics of patients with endometrial
hyperplasia and polyps // Scientific results of biomedical research. 2018. No. 2.
3.
Lapina I.A., Dobrokhotova Yu.E., Ozolinya L.A., Chirvon T.G., Taranov V.V. An integrated
approach to the management of patients with endometrial hyperplasia and metabolic
syndrome // Gynecology. 2021. No. 1.
4.
Nazirova Z.M. Modern possibilities of diagnostics of proliferative processes of the
endometrium // Economy and society. 2020. No. 4 (71).
5.
Orazov M.R., Mikhaleva L.M., Mullina I.A. Prediction of recurrent endometrial
hyperplasia // Difficult patient. 2021. No. 7.
6.
Orazov M.R., Mikhaleva L.M., Mullina I.A., Leffad L.M. Pathogenesis of recurrent
endometrial hyperplasia without atypia // Difficult patient. 2021. No. 6.
7.
Ponomarenko I.V., Demakova N.A., Altukhova O.B. Molecular mechanisms of
development of hyperplastic processes of the endometrium // Actual problems of medicine.
2016. No. 19 (240).
8.
Saduakasova Sh. M., Argynbaev E. K., Shadenova E. E., Khaldarbekova E. N. Clinical
effectiveness of hormonal therapy for endometrial hyperplasia // Bulletin of KazNMU. 2017.
No. 1.
9.
Sogikyan A.S., Idrisov Sh.T., Samsonova I.P. Efficiency of endometrial thermal ablation
using the Thermachoice system in the treatment of metrorrhagia and endometrial
hyperplastic processes (recurrent endometrial polyps) in peri- and menopause // Research'n
Practical Medicine Journal. 2016. No. Special issue.
10.
Tikhomirov A.L. Rationale for the use of combined oral contraceptives for the
prevention of recurrence of typical endometrial hyperplasia // Gynecology. 2018. No. 4.
11.
Tkachenko L.V., Sviridova N.I., Isaeva L.V. Prevention of recurrence of endometrial
hyperplasia in perimenopause // Bulletin of VolSMU. 2017. No. 4 (64).
12.
Filippova R.D., Neustroeva T.N., Pavlova-Afanasyeva M.P. Modern methods of treatment
of hyperplastic processes of the endometrium (new technology) // Research'n Practical
Medicine Journal. 2016. No. Special issue.
13.
Chekhoeva A. N., Gabaraev G. M., Baroeva M. D. Clinical and diagnostic aspects and
75
treatment tactics of endometrial hyperplastic processes from a modern perspective
(literature review) // Bulletin of new medical technologies. Electronic publication. 2019. No.
4.
14.
Shakirova E.A., Artymuk N.V. Risk factors for treatment failure and recurrent course of
endometrial hyperplastic processes in women of reproductive age with obesity //
Fundamental and Clinical Medicine. 2016. No. 1.
15.
Shakirova E.A., Zotova O.A. The state of metabolic processes in women of reproductive
age with obesity and hyperplastic processes of the endometrium // Fundamental and clinical
medicine. 2016. No. 2.
16.
Al-Kaabi M, Noel K, Al-Rubai AJ. Evaluation of immunohistochemical expression of stem
cell markers (NANOG and CD133) in normal, hyperplastic, and malignant endometrium. J Med
Life. 2022 Jan;15(1):117-123. doi: 10.25122/jml-2021-0206.
17.
Begum J, Samal R. A Clinicopathological Evaluation of Postmenopausal Bleeding and Its
Correlation with Risk Factors for Developing Endometrial Hyperplasia and Cancer: A
Hospital-Based Prospective Study. J Midlife Health. 2019 Oct-Dec;10(4):179-183. doi:
10.4103/jmh.JMH_136_18.
18.
Behrouzi R, Barr CE, Crosbie EJ. HE4 as a Biomarker for Endometrial Cancer. Cancers
(Basel). 2021 Sep 23;13(19):4764. doi: 10.3390/cancers13194764.
19.
Catena U, Della Corte L, Raffone A, Travaglino A, Lucci Cordisco E, Teodorico E, Masciullo
V, Bifulco G, Di Spiezio Sardo A, Scambia G, Fanfani F. Fertility-sparing treatment for
endometrial cancer and atypical endometrial hyperplasia in patients with Lynch Syndrome:
Molecular diagnosis after immunohistochemistry of MMR proteins. Front Med (Lausanne).
2022 Aug 25;9:948509. doi: 10.3389/fmed.2022.948509.
20.
Chae-Kim J, Garg G, Gavrilova-Jordan L, Blake LE, Kim TT, Wu Q, Hayslip CC. Outcomes of
women treated with progestin and metformin for atypical endometrial hyperplasia and early
endometrial cancer: a systematic review and meta-analysis. Int J Gynecol Cancer. 2021
Dec;31(12):1499-1505. doi: 10.1136/ijgc-2021-002699.
21.
Chen J, Cao D, Yang J, Yu M, Zhou H, Cheng N, Wang J, Zhang Y, Peng P, Shen K. Fertility-
Sparing Treatment for Endometrial Cancer or Atypical Endometrial Hyperplasia Patients With
Obesity. Front Oncol. 2022 Feb 18;12:812346. doi: 10.3389/fonc.2022.812346.
22.
Chen J, Cheng Y, Fu W, Peng X, Sun X, Chen H, Chen X, Yu M. PPOS Protocol Effectively
Improves the IVF Outcome Without Increasing the Recurrence Rate in Early Endometrioid
Endometrial Cancer and Atypical Endometrial Hyperplasia Patients After Fertility Preserving
Treatment . Front Med (Lausanne). 2021 Jul 27;8:581927. doi: 10.3389/fmed.2021.581927.
