У дисертації встановлена роль стероїдних рецепторів у патогенезі аденоміозу за наявності супутньої патології ендометрія в постменопаузі. Матеріал дослідження – видалені матки з придатками від 117 пацієнток 49–76 років. Проведено гістологічне, імуногістохімічне дослідження з первинними антитілами до естрогенових, прогестеронових і андрогенових рецепторів із статистичним аналізом.
У жінок з аденоміозом дифузний фіброматоз діагностовано більш ніж у 25 % і міому матки – більш ніж у 20,0 % випадків.
Підтверджена гормональна залежність аденоміозу і ключова роль естрогенових і прогестеронових гормонів у його існуванні.
Вогнища аденоміозу розглядалися як автономне джерело продукції естрогенових і прогестеронових гормонів. Яєчники безпосередньо впливають на синтез прогестеронів і опосередковано – естрогену. Аденоміоз стимулює наявність позитивної естрогенової і меншою мірою прогестеронової експресії в еутопічному ендометрії і не впливає на рівень андрогенових рецепторів.
The thesis deals with the role of steroid receptors in the pathogenesis of adenomyosis in the presence of the concomitant postmenopausal endometrium pathology. The work is based on the results of a comprehensive study of removed uteruses with appendages of 87 postmenopausal women with adenomyosis with the concomitant pathology and without pathological changes, and 30 women with age-related changes, but without adenomyosis. The cases were divided into 4 groups depending on the presence of adenomyosis and background pathology (endometrial carcinoma of the endometrium and endometrial hyperplasia): 1) 27 women with adenomyosis and endometrial hyperplasia; 2) 30 women with adenomyosis and endometrial carcinoma of the endometrium; 3) 30 women with adenomyosis and age-related changes in the endometrium; 4) 30 women with age-related changes without adenomyosis (a comparison group). The following examination methods are used in the work: histological, immunohistochemical, statistical.
Diffuse fibromatosis was diagnosed in more than 25 % and uterine myoma in more than 20.0 % of the postmenopausal women with adenomyosis. The highest risk of concomitant myometrium pathology in women with adenomyosis and endometrial hyperplasia (uterine myoma is diagnosed in every second patient with adenomyosis and endometrial hyperplasia).
The prevalence of estrogen receptors (ER) expression in the eutopic endometrium in the presence of adenomyosis and hyperplastic processes was compared with the comparison group (p<0.01). A higher level of ER expression is typical for the endometrial epithelium with endometrial hyperplasia (7.33±0.31) and endometriall carcinoma of the endometrium (6.20±0.71) than for the endometrium with atrophic changes in the presence of adenomyosis (4.43±0.77). It is proved that the higher the level of differentiation of endometrial carcinoma cells, the higher the ER activity, both in endometrium with endometrial carcinoma of the endometrium and in the adenomyosis foci. A higher ER activity of the eutopic endometrium corresponds to higher ER expression in adenomyosis foci, which is confirmed by the presence of a direct of both medium and high and very high stable correlation between ER expression in eu- and ectopic endometrium by endometrial carcinoma of the endometrium (r 0.73). A similar tendency is found in the eutopic endometrium of other groups of women examined. A direct correlation was established, both moderate unstable at minimum r values and very high stable at maximum r values, between the expression rates of the components eu- and ectopic endometrium. Postmenopausal production of estrogens by ovarian cells significantly decreases regardless of the presence of adenomyosis or hyperplastic processes in the endometrium.
The activity of progesterone receptors (PR) in the eutopic endometrium decreases from a simple non-atypical to a complex atypical endometrial hyperplasia, and in patients with adenomyosis and endometrioid carcinoma of the endometrium – as the degree of endometrioid carcinoma cells differentiation decreases. The PR receptor activity differed in eutopic endometrium depending on the presence of adenomyosis. Patients with atrophy and adenomyosis had higher PR expression score in the eutopic endometrium than a comparison group women.
The preservation of the expression of the PR focuses of postmenopausal adenomyosis both by epithelial and stromal cells regardless of a concomitant pathology was proved. All of three groups of women with adenomyosis, positive immunohistochemical reactions with progesterone markers in glandular endometriosis cells were detected both in glandular (with endometrial hyperplasia average score – 4.67±0.53; with endometrial carcinoma of the endometrium – 5.30±0.81; with endometrium atrophy – 1.37±0,60), and in the stromal component (with endometrial hyperplasia average total score – 3.80±0.60; with endometrial carcinoma of the endometrium – 5.17±0.85; with endometrial atrophy – 2.27±0.48), which proves the hormonal dependence of adenomyosis foci and the key role of these hormones in adenomyosis incidence in the postmenopausal women.
Most groups of women with adenomyosis have direct correlation between PR expression and ectopic endometrium components (r 0.66). Therefore, adenomyosis foci are an autonomic structure, have a certain progesterone potential and exert a regulatory effect on the eutopic endometrium as PR stimulation, while maintaining their independence from feedback affect of the eutopic endometrium.
Progesterone synthetic ovarian function decreased in the ovarian tissue of the postmenopausal women, which was proved by the minimal and low rates of PR activity. When comparing the score of ER and PR expression of the eu- and ectopic endometrium, no differences were found between the indices (p>0.05). An exception is the women of the group with adenomyosis and endometrial hyperplasia, where the total PR expression in the eutopic endometrium cells dominated over the ectopic one (in glands: 7.15±0.29 vs. 7.15±0.29; in the stroma: 7.3±0.36 vs. 6.26±0.62) (p<0.01).
Minimal indices, and sometimes a complete absence of androgen receptors (AR) receptor expression in eu- and ectopic endometrium in the presence of adenomyosis were obtained. The absence of androgenic potential of adenomyosis foci and their influence on the AR level in the eutopic endometrium are shown.
The positive ovarian AR expression preserves in postmenopausal patients, which plays a leading role in the pathogenesis of adenomyosis as a possible source of further estrogen synthesis.
So, adenomyosis foci were regarded as an autonomous sources of estrogen and progesterone hormone production. The ovaries have a direct effect on the progesterone synthesis and indirectly on the estrogen synthesis. Endometrioid foci, in its turn, stimulate the presence of positive estrogen and less progesterone expression in the eutopic endometrium.
В диссертации установлена роль стероидных рецепторов в патогенезе аденомиоза при наличии сопутствующей патологии эндометрия в постменопаузе. Материал исследования – удаленные матки с придатками от 117 пациенток 49–76 лет. Проведено гистологическое, иммуногистохимическое исследование с первичными антителами к эстрогеновым, прогестероновым и андрогеновым рецепторам со статистическим анализом.
У женщин с аденомиозом диффузный фиброматоз диагностирован более чем у 25 % и миома матки – более чем в 20,0 % случаев.
Подтверждена гормональная зависимость аденомиоза и ключевая роль эстрогеновых и прогестероновых гормонов в его существовании.
Очаги аденомиоза рассматривались как автономный источник продукции эстрогеновых и прогестероновых гормонов. Яичники непосредственно влияют на синтез прогестеронов и опосредованно – эстрогенов. Аденомиоз стимулирует наличие положительной эстрогеновой и в меньшей степени прогестероновой экспрессии в еутопическом эндометрии и не влияет на уровень андрогеновых рецепторов.
