Hyperplastic processes of the endometrium

Hyperplastic processes of the endometrium (GPE) - pathological diffuse or focal proliferation (thickening) of the glandular and stromal component of the uterine mucosa with a predominant lesion of glandular structures.

[1], [2], [3], [4], [5], [6], [7]

Epidemiology

Hyperplastic processes of the endometrium are possible at any age, but their frequency significantly increases by the perimenopause period. Hyperplastic processes of the endometrium, according to most scientists, are referred to as precursors of the endometrial cancer itself. Simple endometrial hyperplasia without atypia passes into cancer in 1% of cases, polypoid form without atypia - 3 times more often. Simple atypical endometrial hyperplasia without treatment progresses to cancer in 8% of patients, complicated atypical hyperplasia - in 29% of patients.

The most common type of hyperplastic endometrial process is polyps, occurring in gynecological patients with a frequency of up to 25%. More often, polyps of the endometrium are detected in pre- and postmenopausal women. Endometrial polyps are malignant in 2-3% of observations.

[8], [9], [10], [11], [12], [13],

Causes of the hyperplastic endometrial processes

Most often, the endometrial hyperplastic processes are diagnosed in women with an increased concentration of estrogens of any genesis. The elevated estrogen content of women taking hormone replacement therapy (HRT) increases the risk of developing endometrial hyperplasia. Tamoxifen is considered effective in treating patients with breast cancer, but its use increases the risk of hyperplastic endometrial processes.

[14], [15], [16], [17], [18]

Symptoms of the hyperplastic endometrial processes

The main clinical manifestations of hyperplastic processes of the endometrium are uterine bleeding, more often acyclic in the form of metrorrhagia, less often of menorrhagia. Sometimes endometrial polyps are asymptomatic, especially in postmenopausal women.

Since the pathogenetic basis of hyperplastic processes of the endometrium is anovulation, the leading symptom in patients of reproductive age is infertility, as a rule, primary.

[19], [20], [21], [22]

Forms

There are three main types of hyperplastic endometrial processes: endometrial hyperplasia, endometrial polyps and atypical hyperplasia (adenomatosis).

In 1994, the WHO adopted a classification of endometrial hyperplasia based on the recommendations of leading gynecologists and pathomorphologists, including hyperplasia without cellular atypia and hyperplasia with cellular atypia (atypical endometrial hyperplasia or adenomatosis). In each group, simple and complex (complex) hyperplasia is distinguished, depending on the severity of proliferative processes in the endometrium.

Polyp of the endometrium is a benign tumor-like formation, originating from the basal layer of the endometrium. Pathognomonic anatomical sign of the endometrial polyp is its base "leg". Depending on the histological structure, glandular (functional or basal type), glandular fibrotic, fibrotic and adenomatous polyps of the endometrium are distinguished. Adenomatous polyps are characterized by intensive proliferation of glands and their epithelium with a relatively high mitotic activity. Adenomatous polyps are referred to as precancerous conditions. Glandular polyps are most typical for the reproductive period, glandular fibrotic - for pre- and perimenopause, fibrous-ferruginous and fibrotic - for postmenopause.

In the reproductive and premenopausal period of a woman's life, endometrial polyps as a histologically independent form can be determined both against the background of endometrial hyperplasia and in the normal mucosa of various phases of the menstrual cycle.

Polyps of the endometrium in postmenopause, as a rule, are single and can occur against the background of an atrophic mucosa. In the postmenopausal period, endometrial polyps sometimes reach large sizes and extend beyond the cervix, thereby imitating the polyp of the cervical canal.

The concept of "relapse" of the endometrial polyp is unacceptable if earlier hysteroscopic control was not applied when removing the endometrial polyp, since the removal of pathologically altered tissue is possible with scraping of the uterine mucosa without hysteroscopy.

From the morphological positions to the precancer, the endometrium includes hyperplasia with atypia (atypical hyperplasia) and adenomatous polyps.

[23], [24], [25]

Diagnostics of the hyperplastic endometrial processes

In addition to conventional methods of examination, an important point is the detection of concomitant diseases and evaluation of the liver, cardiovascular system (SSS), gastrointestinal tract (GIT), as it is important when choosing a method of treatment, especially the purpose of hormone therapy.

The main methods of diagnosing hyperplastic endometrial processes at the present stage include cytological examination of aspirates from the uterine cavity, transvaginal ultrasound, hydro sonography and hysteroscopy. However, the diagnosis can be finally verified only after a histological examination of the endometrium obtained with separate diagnostic curettage of the uterine mucosa.

Cytological examination of aspirates from the uterine cavity is recommended as a screening of the pathology of the endometrium and determining its state in dynamics against hormonal therapy. This method allows to determine the severity of proliferative changes, but does not give a clear idea of its pathomorphological structure.

Transvaginal ultrasound scanning is a valuable method of diagnosing endometrial hyperplastic processes in connection with high informativeness, non-invasiveness, harmlessness for the patient. Ultrasound can evaluate not only the state of the endometrium, but also the myometrium, identify adenomyosis, myoma of the uterus. Also, ultrasound should be performed to determine the size of the ovaries and evaluate their functions.

Diagnosis of endometrial hyperplasia in ultrasound is based on the detection of increased in the anteroposterior size of the median maternal echo (M-echo) with increased acoustic density. In menstruating women, the M-echo thickness should be assessed in accordance with the phase of the menstrual cycle. It is best to conduct a study immediately after menstruation, when a thin M-echo corresponds to the complete rejection of the functional layer of the endometrium, and an increase in the anteroposterior size of the M-echo all over, or locally, is regarded as a pathology. To distinguish glandular hyperplasia of an endometrium from atypical at US it is not possible.

If the postmenopause period does not exceed 5 years, the thickness of the M-echo up to 5 mm is considered the norm, with a postmenopause of more than 5 years, the M-echo thickness should not exceed 4 mm (for a homogeneous structure). The accuracy of the diagnosis of ultrasound in hyperplastic processes of the endometrium is 60-70%.

Hydro sonography can significantly improve the results of diagnostics. The ultrasonic picture of the endometrial polyps shows ovoid, less often rounded inclusions in the structure of the M-echo and the uterine cavity of increased echolocation. Diagnostic difficulties arise in glandular polyps of the endometrium, which have a leaf-shaped or flattened configuration in the shape of the uterine cavity and are not capable of leading to thickening of the M-echo. According to the acoustic conductivity, they are close to the surrounding endometrium. Registration of color echoes during Doppler study in the inclusion structure makes it possible to differentiate polyps with intrauterine synechia, and in menstruating patients with blood clots, but blood flow in color duplex mapping in polyps is not always determined. Informativeness of transvaginal ultrasound with polyps of endometrium is 80-90%. Contrasting the uterine cavity with hydrosonography can improve the diagnostic capabilities of ultrasound. Transvaginal hydrosonography and endometrial biopsy allow 98% to diagnose GGE.

The informative value of hysteroscopy in the diagnosis of endometrial hyperplastic processes is 63-97% (depends on the type of hyperplastic endometrium processes). Hysteroscopy is necessary both before scraping the uterine mucosa to clarify the nature of the pathology and its localization, and after it in order to control the thoroughness of tissue removal. Hysteroscopy allows you to visually assess the condition of the walls of the uterus, identify adenomyosis, submucous uterine fibroids and other forms of pathology. Atypical endometrial hyperplasia does not have characteristic endoscopic criteria, the hysteroscopic pattern resembles the usual glandular-cystic hyperplasia. In severe atypical hyperplasia, glandular polypoid growths of faint yellowish or grayish color can be identified.

Histological examination of scrapings of the mucous membrane of the uterus is the final method for diagnosing hyperplastic endometrial processes.

[26], [27]

Treatment of the hyperplastic endometrial processes

Therapy in women of different ages consists of stopping bleeding, restoring menstrual function in the reproductive period or reaching menopause at an older age, and preventing the recurrence of the hyperplastic process.

Treatment of endometrial hyperplastic processes in patients of reproductive age

The traditional method of treating hyperplastic processes of the endometrium is hormonal therapy.

Relapses of the hyperplastic process of the endometrium indicate insufficient therapy or hormonal active processes in the ovaries, which requires the specification of their condition, including visual diagnostic methods (ultrasound, laparoscopy, ovarian biopsy). The absence of morphological changes in the ovaries allows to continue hormonal therapy with higher doses of drugs. It is necessary to exclude the infectious factor as a possible cause of the disease and inefficiency of hormone therapy.

With ineffectiveness of hormone therapy, recurrence of endometrial hyperplasia without atypia is appropriate ablation (resection) of the endometrium. Ablation of the endometrium can be carried out by various methods: using mono- and bipolar coagulators, a laser, cylinders. Necessary conditions for the ablation: the woman's unwillingness to have children in the future, age over 35, the desire to save the uterus, the size of the uterus is not more than 10 weeks gestation. Myoma of the uterus is not considered a contraindication to ablation of the endometrium; if none of the nodes is more than 4-5 cm, adenomyosis worsens the results of the operation.

The repeated occurrence of atypical endometrial hyperplasia in patients of reproductive age is an indication for in-depth examination and exclusion of the polycystic ovary syndrome.

Treatment in pre- and perimenopause

The first stage of treatment includes hysteroscopy with separate diagnostic curettage of the mucous membrane of the uterus. The choice of further therapy depends on the morphological structure of the endometrium, concomitant gynecological and extragenital pathology. The choice of hormonal preparation, the scheme and duration of treatment are also determined by the need to maintain a rhythmic menstrual-like reaction (under 50 years of age) or persistent termination of menstruation.

With recurrent endometrial hyperplasia without atypia, the impossibility of hormone therapy due to concomitant extragenital pathology, a hysteroscopic operation is indicated - ablation of the endometrium. Relapses of hyperplastic processes of the endometrium, as well as a combination of this pathology with uterine myoma and / or adenomyosis in patients in pre- and perimenopause are indications for surgical intervention (hysterectomy).

Treatment in postmenopausal women

Separate diagnostic curettage with hysteroscopy has been shown to patients with suspected pathology of the endometrium, revealed during screening. With the newly diagnosed endometrial hyperplasia in postmenopausal women, hormonal therapy is advisable.

With atypical hyperplasia of the endometrium in postmenopause, it is necessary to immediately solve the issue of a radical operation - pangysterectomy. With pronounced extragenital pathology and an increased risk of surgical treatment, long-term treatment is indicated as indicated in Table. 3 hormonal preparations.

On the background of hormone therapy, it is advisable to recommend hepatoprotectors, anticoagulants, antiaggregants in usual doses.

Recurrence of endometrial hyperplasia in postmenopausal women is an indication for surgical intervention: hysteroscopic ablation of the endometrium or extirpation of the uterus with appendages. Supposable supravaginal amputation of the uterus with appendages (in the absence of pathology of the cervix).

The main method of treatment of patients with endometrial polyps in postmenopause is targeted polypectomy. Radical removal of the endometrial polyp (with the basal layer at the location of the polyp) is possible only with the use of hysteroscopic equipment. For polypectomy, you can use both mechanical endoscopic instruments, and electrosurgical technology, as well as a laser. Electrosurgical excision of the polyp with hysteroscopy is recommended for fibrotic and parietal polyps of the endometrium, as well as for recurrent polyps of the endometrium.

After the removal of glandular and glandular fibrous polyps of the endometrium, hormone therapy is advisable. The type of hormonal therapy and the duration of its conduct depend on the morphological structure of the polyp, concomitant pathology.

Hormonal therapy for endometrial polyps in postmenopausal women

A drug	The glandular fibrous, fibrous polyps	Glandular polyps
Norethisterone	5 mg / day for 6 months	10 mg / day for 6 months
Hydroxyprogesterone caproate	250 mg once a week for 6 months	250 mg twice a week for 6 months
Medroxyprogesterone	10-20 mg / day for 6 months	20-30 mg / day for 6 months

Further management

Patients with hyperplastic endometrial processes should be on dispensary observation for at least 2 years after stopping hormonal therapy, with atypical hyperplasia (if hormonal therapy was performed), the period of dispensary follow-up should be at least 5 years. Mandatory ultrasound of pelvic organs and cytological examination of aspirates every 6 months. The sensitivity of endometrial biopsy with Pipelle is 99% for the definition of endometrial cancer and 75% for endometrial hyperplasia in postmenopausal women. In the detection of pathology, according to ultrasound and cytology, hysteroscopy and separate diagnostic curettage of the mucous uterus with histological examination of scrapings are indicated. Recurrence of hyperplastic processes of the endometrium serves as a basis for reviewing the tactics of reference. If the patient has received hormone therapy in full, the question of ablation (in the absence of pathology in the ovaries) or hysterectomy should be raised.

Difficulties in managing patients are patients who have been treated with ablation or resection of the endometrium, after which synechia can appear in the uterine cavity. Ultrasound for these patients should be carried out by a specialist who knows the interpretation of echographic signs of synechia. However, the presence of bloody discharge in these patients serves as an indication for hysteroscopy and separate diagnostic curettage of the uterine mucosa in the conditions of a specialized gynecological institution.

Forecast

With a properly differentiated approach to managing patients with hyperplastic endometrial processes, the effectiveness of treatment ranges from 80% (with hormonal therapy) and up to 90-100% (with endometrial ablation) in postmenopausal patients.

[28], [29], [30], [31], [32]