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UDK 618.14
PREMENOPAUSAL ENDOMETRIAL DISORDERS:
HYPERPLASIA AS A PRECURSOR TO ONCOPATHOLOGY
Eshonova Kamola G`ayrat qizi
Republican Specialized Scientific and Practical Medical Center for
Maternal and Child Health
Toshkent, O‘zbekiston
Endometrial hyperplastic processes (EHP) rank among the most common
pathologies affecting women during the perimenopausal period. The aim of this
study is to emphasize the importance of early detection of endometrial hyperplasia
and the assessment of its oncogenic potential, utilizing modern classification
systems and diagnostic techniques. The research methodology includes a review of
scientific literature and clinical case analyses. The results demonstrate that timely
diagnosis and systematic follow-up significantly reduce the likelihood of malignant
transformation, lower the risk of cancer development, and contribute to the overall
improvement of patients’ health and quality of life.
Keywords: Endometrial hyperplasia, hyperplasia without atypia, atypical
hyperplasia, endometrial cancer, premenapause.
Endometrial hyperplasia (EH) is a pathological condition of the uterine
lining, characterized by morphological alterations within the endometrial tissue.
The primary feature of this process is an excessive proliferation of glandular
structures compared to the stroma, which significantly differs from the normal
proliferative endometrium. EH holds significant clinical importance due to its
potential to increase the risk of developing endometrial cancer over time [4].
Notably, hyperplastic changes in the endometrium are observed in 10–55% of
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women during the premenopausal period. The high recurrence rate and the
potential for malignant transformation make EH a pressing issue in modern
gynecology. Age-related hormonal changes complicate the assessment of general
health and oncological risks. Therefore, early and accurate diagnosis of EH plays
a crucial role in preventing reproductive system diseases and reducing the
likelihood of cancer, ultimately contributing to the preservation of women's health.
Research shows that the incidence of endometrial hyperplasia increases with age
and varies depending on the form of the disease, raising its prevalence from 10%
to 30%. Particularly, women aged 45 to 55 are most affected, and delayed diagnosis
often leads to the progression to chronic forms. Some specialists report that up to
50% of women in the late reproductive and perimenopausal stages experience rapid
development of endometrial hyperplasia, emphasizing the need for timely
diagnosis.
The primary aim of this study
is to explore the importance of predicting
the risk of endometrial precancer development in women during the premenopausal
period, based on the classification of endometrial hyperplastic processes.
Materials and Methods:
The search for scientific articles was conducted
using databases such as PubMed, SCOPUS, JSST (WHO), the International
Agency for Research on Cancer (IARC), and the Royal College of Obstetricians
and Gynaecologists (RCOG) in the United Kingdom. This approach ensured a
comprehensive and informative coverage of the research topic. The analysis
included scientific papers published between 2020 and 2025. The primary
keywords used during the search were: endometrial hyperplasia, endometrial
neoplasms, non-atypical hyperplasia, and atypical hyperplasia. A total of 76 articles
were initially identified; however, 31 articles were excluded due to reasons such as
duplication, insufficient quality of results and discussions, study design issues, or
failure to meet inclusion criteria.
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Results and Discussion:
From the perspective of modern medicine,
endometrial hyperplasia is considered a multifactorial (polyetiological) condition.
Its development and progression may be influenced by a variety of factors. Several
research findings suggest that one of the primary contributors to the formation of
endometrial hyperplastic processes is relative hyperestrogenism arising from
progesterone deficiency [10]. The imbalance caused by excessive estrogen
exposure and reduced progesterone levels may be linked to endogenous,
exogenous, or genetic factors. Such conditions are often observed in women with
neuroendocrine disorders, chronic anovulation, early onset of menstruation,
delayed menopause, and estrogen-secreting tumors [8]. Thus, in the premenopausal
period, the risk of developing endometrial hyperplasia is mainly associated with
the prolonged accumulation of estrogen effects in the div, which in turn depends
on the duration of hormonal imbalance. Importantly, not only the current estradiol
level but also the long-term presence of hormonal dysregulation plays a crucial role
in this process.
Therefore, maintaining hormonal balance and conducting regular
monitoring of the endometrium should be considered key preventive measures. In
most patients diagnosed with endometrial hyperplasia, various forms of uterine
bleeding are observed. During the premenopausal period, this pathology is
typically characterized by irregular, prolonged, and recurrent uterine bleeding,
differing from normal patterns. Additionally, some patients experience menstrual
cycle disturbances, the development of anemia due to excessive blood loss, and
general weakness. These symptoms are critically important for diagnosis, allowing
for early detection and timely intervention [10]. Often, the presence of these
symptoms prompts patients to seek medical attention promptly, thereby increasing
the likelihood of identifying endometrial cancer at an early stage. Early diagnosis
and appropriate treatment significantly improve the prognosis: for cases detected
at stage I, the five-year survival rate reaches 80–90%. Therefore, it is crucial for
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women to pay close attention to any abnormal uterine bleeding and seek medical
advice without delay to enable early diagnosis and effective treatment [8].
According to the WHO and the International Agency for Research on Cancer
(IARC), endometrial cancer is one of the leading causes of death among women
worldwide. Based on WHO reports, approximately a quarter of endometrial cancer
cases originate from previously benign changes in the endometrial lining. This
process generally develops slowly over an average period of 6-7 years. Therefore,
early detection of hyperplastic processes and dynamic monitoring play a crucial
role in reducing cancer risk [2]. The complexity of the mechanisms underlying the
development of endometrial hyperplasia and the potential severe complications of
this pathology highlight the need for early diagnosis, risk prediction of
complications, and the development of effective treatment strategies. The active
implementation of these strategies in clinical practice is essential for improving the
course of the disease and reducing the risk of cancer development [3]. Endometrial
cancer (EC) ranks fifth among the most common cancers in women. In recent years,
particularly in developed countries, the incidence of this disease has been
increasing. According to IARC data, in 2020, 417,367 new cases of endometrial
cancer were recorded globally, with 97,370 deaths related to the disease [9][11].
The classification of endometrial hyperplasia is primarily based on its
histological characteristics and oncogenic potential. From a histopathological
perspective, this process is characterized by an excessive proliferation of
endometrial glands relative to the normal proliferative endometrium, with a dense
arrangement of glands in relation to the stroma, yet without stromal invasion [12].
The primary diagnostic methods for detecting this condition include biopsy,
curettage of the uterine cavity, or histological evaluation of tissue samples obtained
through hysterectomy. These methods play a crucial role in detecting hyperplastic
processes and assessing their oncogenic risk.
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In 2014, the World Health Organization (WHO) proposed a new
classification of endometrial hyperplasia, dividing it into two main groups based
on the presence or absence of cellular atypia: atypical hyperplasia and non-atypical
hyperplasia. This approach allows for a clear assessment of the oncological risk of
the pathology and the selection of individual treatment methods for patients [3].
Currently, the new classification proposed by WHO in 2014 has been accepted by
the Royal College of Obstetricians and Gynaecologists (RCOG) and the British
Society of Gynaecological Endoscopy (BSGE). However, many scientific studies
and evidence-based data still use the WHO's 1994 nomenclature [13]. This has led
to the parallel use of two classification systems in scientific and clinical practice.
According to the new classification, endometrial hyperplasia is assessed based on
morphological features, considering the degree of changes in the glandular and
stromal components and the presence of nuclear atypia [10]. Hyperplasia is
therefore classified into two types: non-atypical hyperplasia and atypical
hyperplasia. Each group is further divided into two forms: simple hyperplasia,
where no significant changes in the glandular architecture are observed, and
complex hyperplasia, characterized by dense glandular arrangement, branching,
and budding. This classification serves as an essential diagnostic criterion in
clinical practice for assessing the risk of hyperplastic processes and managing them
effectively.
New clinical recommendations are developed based on the presence or
absence of nuclear atypia [5]. Nuclear atypia is characterized by the enlargement
of cell nuclei and the presence or absence of nucleoli within them. At the molecular
level, endometrial hyperplasia shares many common features with endometrioid
carcinoma. In patients with atypical hyperplasia, the risk of developing endometrial
carcinoma can reach up to 50% [11]. Therefore, the challenging issue is that
predicting the risk of endometrial carcinoma in patients with atypical hyperplasia
is difficult, and distinguishing hyperplasia from intraepithelial neoplasia
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histopathologically can be challenging. To confirm the diagnosis of endometrial
hyperplasia and differentiate it into atypical and non-atypical forms, histological
examination of endometrial tissue is required. Endometrial samples can be
collected in an outpatient or inpatient setting, depending on the patient. This
diagnostic approach ensures accurate disease analysis and helps in determining the
optimal treatment strategy.
Transvaginal ultrasound (TVUS) is of significant importance in diagnosing
conditions in perimenopausal women, primarily in detecting myomas, endometrial
polyps, pregnancy, and other causes of abnormal uterine bleeding. It also helps in
assessing the endometrial thickness, identifying hyperplastic processes, and
predicting oncological risks. The thickness of the endometrium changes
physiologically depending on the phase of the menstrual cycle, and it can reach up
to 18 mm during the secretory phase [5]. Therefore, when deviations from the
normal range are observed, especially when the endometrial thickness exceeds 5
mm in postmenopausal women, further investigations are necessary to exclude
malignancy. To establish an accurate diagnosis, detect pathological processes, and
confirm the type of hyperplasia, endometrial sampling and histological
examination are recommended. There are several methods for obtaining an
endometrial sample, with the simplest being an endometrial biopsy performed in
an outpatient setting using a plastic cannula (Pipelle). This method has a long
history of safety and effectiveness and is widely used due to its minimally invasive
nature. The biopsy procedure involves inserting the Pipelle cannula into the uterine
cavity through the cervix and collecting tissue samples using a special vacuum
technique. This procedure is well-accepted by patients, causes minimal pain, and
can often be performed without anesthesia or with minimal local anesthetics.
Hysteroscopic-guided sampling is another recommended method for
obtaining endometrial tissue. Studies indicate that this approach is particularly
beneficial in diagnosing endometrial polyps, endometrial cancer, and hyperplasia.
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It not only enables precise visual monitoring of the biopsy process but also
improves the quality of tissue samples, minimizes the risk of incorrect results, and
reduces the need for repeat biopsies in cases of uncertainty. A biopsy obtained
through hysteroscopy is considered more accurate compared to traditional
methods, as it allows direct visualization of the affected area, enabling the
collection of several samples from suspicious sites when necessary. This is
especially important in the presence of focal hyperplasia or polypoid pathologies.
In addition, hysteroscopy can be used for therapeutic purposes, allowing for the
removal of small polyps or localized hyperplastic changes, which further adds to
its clinical value.
Thus, hysteroscopy demonstrates high sensitivity and specificity in
identifying endometrial pathologies, playing a crucial role in accurate diagnosis
and selecting an individualized approach for patient management.
Endometrial hyperplasia can progress to endometrial cancer, with its
development rate depending on the degree of architectural changes in the tissue and
the presence or absence of nuclear atypia [6][8]. These factors play a crucial role
in assessing the risk of cancer development and determining whether more
intensive monitoring or treatment is necessary [9]. Untreated or inadequately
treated endometrial hyperplasia can lead to severe complications, including the
development of endometrial cancer, which is the most dangerous consequence.
Abnormal proliferation of endometrial cells, especially in cases of complex or
atypical hyperplasia, increases the risk of malignant changes. Furthermore,
insufficient treatment of hyperplasia can lead to worsening abnormal uterine
bleeding, prompting the patient to seek repeated medical attention [5]. The
recurrence of complaints from the patient may indicate the progression of the
disease, which can lead to the transition of hyperplasia to atypical forms,
significantly raising the risk of nuclear atypia and potentially accelerating the
development of endometrial cancer in the future.
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Conclusion:
Endometrial hyperplasia, especially in its simple or atypical
forms, is a significant factor that increases the risk of developing endometrial
cancer. The main factors influencing the progression of the disease are the degree
of changes in tissue architecture and the presence of nuclear atypia. Inadequate
treatment may lead to the worsening of the disease, an increased risk of malignant
transformation, and the exacerbation of severe symptoms, such as abnormal uterine
bleeding. Timely diagnosis and appropriate therapy are crucial for preventing
complications and reducing the risk of malignant changes.
Literature:
1.
American Cancer Society. (2021). Endometrial Cancer: Risks and
Prevention. Retrieved from https://www.cancer.org.
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Green, A., & Thompson, L. (2017). Endometrial Hyperplasia and Its
Precursor Lesions: Clinical Implications for Diagnosis and Treatment.
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IARC. (2020). Global Cancer Statistics: Endometrial Cancer Overview.
International Agency for Research on Cancer, Lyon.
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Jones, R., & Brown, M. (2019). Molecular Mechanisms in Endometrial
Hyperplasia: The Role of Hormonal Imbalance. European Journal of
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National Cancer Institute (NCI). (2021). Endometrial Cancer: Risk Factors
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Royal College of Obstetricians and Gynecologists (RCOG). (2014).
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Smith, J., & Jones, P. (2020). Endometrial Hyperplasia and Its Role in
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Eshonova Kamola G`ayrat qizi +998(93)397-37-93 kamola.eshonova@mail.ru
Respublika ixtisoslashtirilgan ona va bola salomatligi ilmiy-amaliy tibbiyot
markazining
1-bosqich tayanch doktoranti (PhD)
Eshonova Kamola G`ayrat qizi +998(93)397-37-93 kamola.eshonova@mail.ru
1st-year doctoral student (PhD) at the Republican Specialized Scientific-
Practical Medical Center for Maternal and Child Health
Эшонова Камола Гайрат кизи +998(93)397-37-93 kamola.eshonova@mail.ru
Докторант 1-го года (PhD) Республиканского специализированного научно-
практического медицинского центра здоровья матери и ребенка
