scholarly journals Analysis of the causes of unsuccessful hormonal treatment of non-atypical endometrial hyperplasia in premenopousal women

2020 ◽  
Vol 24 (4) ◽  
pp. 604-610
Author(s):  
O. Gromova ◽  
V. Potapov ◽  
D. Hasachih ◽  
O. Haponova ◽  
G. Kukina
Keyword(s):  
Endometrial Hyperplasia ◽  
Progesterone Receptors ◽  
Hormonal Treatment ◽  
Normal Endometrium ◽  
Endometrial Cells ◽  
Atypical Endometrial Hyperplasia ◽  
Treatment Type ◽  
Progestin Treatment ◽  
Glandular Cells ◽  
Micronized Progesterone

Annotation. Non-atypical endometrial hyperplasia (NEH), despite of benign morphology, may be insensitive to the hormonal treatment and has a tendency to recurrence and progression to atypia in some cases. The study purpose was the investigation of different type of progestins treatment results and comparison of progesterone receptors (PGR) and Е-cadherin expression in the sensitive NEH(+) and resistant NEH(–) to progestin treatment type of NEH. Prospective study of three groups of women with histologically confirmed NEH, who took different progestins during 6 months was done: І group – 96 women, who took micronized progesterone orally 200 mg per day continually, ІІ group – 161 women, who took dydrogesterone 20 mg per day continually, ІІІ group – 54 women, who were inserted LNG-IUD 52 mg. Control histopathological investigations of the endometrial samplings at 3 and 6 months were done. Expression of PGR and Е-cadherin by immunohistochemistry were investigated in the start samples of endometrium for all 63 NEH(–) women, 48 NEH(+) women and 20 control samples of normal proliferative and secretory endometrium. In the result of the study only nonsignificant and unreliable differences between different progestins efficacy were found. It was 75% normal endometrium samples till 6 months for micronized progesterone, 81.4% for dydrogesterone and 83.3% for LNG-IUD. Data analysis of PGR expression in the NEH(–) endometrium has shown significantly less week expression as for glandular cells (50.82±0.73), as for stromal cells (47.34±0.82) in comparison to the NEH(+) endometrial samples (glandular – 183.7±3.1; stroma 166.4±2.3; р<0.05) and normal proliferative (193.2±8.5 і 178.7±6.3 respectively; р<0.05) and secretory (140.2±4,4 і 116.6±3,1 respectively; р<0.05) endometrium. Е-cadherin expression in the glandular endometrial cells NEH(–) mostly was negative (86.4%) and 13.6% cells only demonstrated its week expression. NEH(+) women cells predominantly showed a positive reaction. It was often enough week (49.2%) and moderate (34.4%), but only in the 16.4% samples were negative. Thus, the use of progestogens for the treatment of NEH in women with low expression of PGR and negative expression of E-cadherin in the endometrium is inappropriate. Investigations of PGR та Е-cadherin expression in the endometrium of women with NEH before starting treatment may provide an opportunity to predict negative result in advance and chose alternative therapeutical approach.

scholarly journals PROSPECTIVE STUDY OF THE EFFECTIVENESS OF DIFFERENTIATED THERAPY OF ENDOMETRIUM HYPERPLASIA WITHOUT ATYPIA IN WOMEN IN REPRODUCTIVE AGE

2021 ◽  
pp. 406-412
Author(s):  
D. Khaskhachykh ◽  
V. Potapov ◽  
G. Kukina ◽  
I. Garagulya
Keyword(s):  
Prospective Study ◽  
Endometrial Hyperplasia ◽  
Progesterone Receptors ◽  
Abnormal Uterine Bleeding ◽  
Endometrial Tissue ◽  
Reproductive Age ◽  
Women Studies ◽  
Endometrial Cells ◽  
Positive Effects ◽  
Micronized Progesterone

The paper considers the issues of improving the effectiveness of treatment of endometrial hyperplasia without atypia in women of reproductive age with the use of progestins as a pathogenetic therapy and should be personalized (targeted) taking into account the receptor sensitivity of endometrial tissue to progestins. The positive effects of progestin use are mainly due to the expression of progesterone receptors in the endometrial tissue, which must be taken into account during hormone therapy. A prospective study was performed in 60 patients of reproductive age with abnormal uterine bleeding, who according to the results of histological examination of endometrial tissue was diagnosed with endometrial hyperplasia without atypia. All patients were treated with micronized progesterone at a dose of 400 mg / day continuously for 6 months. To determine the effect of the use of progestins was performed by studying the expression of receptors for estrogen (ER) and progesterone (PR) in histological blocks of the endometrium by immunohistochemistry. In all women there was a significant expression of EP in endometrial cells, which led to its proliferative activity against the background of reduced expression of progesterone receptors by 65%, which caused no effect of therapy in 25% of women. Studies have shown that when deciding on the appointment of micronized progesterone for the treatment of endometrial hyperplasia without atypia, it is recommended to study the expression of progesterone receptors in endometrial tissue to clarify the possibility of a pharmacological effect. Treatment of endometrial hyperplasia without atypia with progesterone drugs is not effective in low expression of progesterone receptors in endometrial tissue. Based on this, we can identify a group of women with progesterone-resistant hyperplasia who require other treatments.

New Variant Of Hormonal Treatment For Atypical Endometrial Hyperplasia And An Early Endometrial Cancer With Fertility Preservation

2019 ◽  
pp. 36-45
Author(s):  
Olga V. Novikova ◽  
Cholpon A. Avasova ◽  
Elena G. Novikova ◽  
Ksenia V. Krasnopolskaya ◽  
Yulia A. Lozovaya ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Fertility Preservation ◽  
Endometrial Hyperplasia ◽  
Hormonal Treatment ◽  
Atypical Endometrial Hyperplasia ◽  
New Variant

Liquid-Based Endometrial Cytology Using SurePath™ Is Not Inferior to Suction Endometrial Tissue Biopsy in Clinical Performance for Detecting Endometrial Cancer Including Atypical Endometrial Hyperplasia

2017 ◽  
Vol 61 (2) ◽  
pp. 133-139 ◽  
Author(s):  
Fumiko Yanaki ◽  
Yasuo Hirai ◽  
Azusa Hanada ◽  
Ken Ishitani ◽  
Hideo Matsui
Keyword(s):  
Endometrial Hyperplasia ◽  
Clinical Performance ◽  
Endometrial Tissue ◽  
Final Histology ◽  
Endometrial Cells ◽  
Atypical Endometrial Hyperplasia ◽  
Tissue Biopsy ◽  
Biopsy Specimens ◽  
Detection Tool ◽  
Endometrial Cytology

Objective: We evaluated the clinical performance of liquid-based endometrial cytology (SurePath™) for detecting endometrial malignancies by comparison with the performance of suction endometrial tissue biopsy. Study Design: From November 2011 to May 2013, we consecutively collected 1,118 liquid-based endometrial cytology specimens and 674 suction endometrial tissue biopsy specimens. Results: The rate of nonpositive final histology in nonpositive liquid-based endometrial cytology (98.2%) was higher than the rate of nonpositive final histology in nonpositive suction endometrial tissue biopsy (97.0%). None of the clinical performance values of liquid-based endometrial cytology for detecting the endometrial malignancies were statistically inferior to those of the suction endometrial tissue biopsy. When the positivity threshold was more than “atypical endometrial cells of undetermined significance,” the rate of positive liquid-based endometrial cytology from cases with a positive final histology (84.5%) was higher than the rate of positive suction endometrial tissue biopsy from cases with a positive final histology (69.8%). However, there were still no significant differences among all the performance values. Conclusions: Our liquid-based endometrial cytology would be more appropriate in various clinical situations as the initial detection tool for endometrial malignancies, rather than suction endometrial tissue biopsy. In addition, it could be used in screening for endometrial malignancies on a broader scale.

Risk of progression in complex and atypical endometrial hyperplasia: clinicopathologic analysis in cases with and without progestogen treatment

2004 ◽  
Vol 14 (2) ◽  
pp. 348-353 ◽  
Author(s):  
L.-C. Horn ◽  
U. Schnurrbusch ◽  
K. Bilek ◽  
B. Hentschel ◽  
J. Einenkel
Keyword(s):  
Vaginal Bleeding ◽  
Endometrial Hyperplasia ◽  
Hormonal Treatment ◽  
Atypical Hyperplasia ◽  
Endometrioid Adenocarcinoma ◽  
Endometrioid Carcinoma ◽  
Total Hysterectomy ◽  
Atypical Endometrial Hyperplasia ◽  
Risk Of Progression ◽  
Leading Symptom

In most cases, the endometrioid adenocarcinoma of the endometrium is preceded by hyperplasia with different risk of progression into carcinoma. The original histologic slides from 560 consecutive cases with complex and atypical hyperplasia were re-examined to assess the interobserver-correlation. The hyperplasias were analyzed separately for their likelihood of progression to carcinoma in patients with and without progestogen hormonal therapy. In all cases, a fractional re-curreting was performed to establish the state of the disease.The leading symptom was vaginal bleeding in 65.5% of the cases in the postmenopausal period. Eighty-six percent of the patients presented with obesity (BMI > 30 kg/m2), 23% had had an exogeneous use of estrogens. Twenty-two cases were reclassified as simple hyperplasia and excluded from further analysis. The interobserver-correlation was 91% for complex, 92% for atypical hyperplasia, and 89% for endometrioid carcinoma, representing an overall correlation of 90%. Two percent of the cases with complex hyperplasia (8/390) progressed into carcinoma and 10.5% into atypical hyperplasia. Fifty-two percent of the atypical hyperplasias (58/112) progressed into carcinomas. In the case of progestogen treatment (n = 208; P < 0.0001) 61.5% showed remission confirmed by re-curetting, compared with 20.3% of the cases without hormonal treatment (n = 182; P < 0.0001).Endometrial hyperplasia without atypia is likely to respond to hormonal treatment. Especially in postmenopausal situation, atypical hyperplasia should be treated with total hysterectomy.

MODERN OUTLOOKS ON PREVALENCE OF ESR1 AND PRG POLYMORPHISM IN WOMEN OF REPRODUCTIVE AGE WITH ENDOMETRIAL HYPERPLASIA

2020 ◽  
pp. 112-120
Author(s):  
I.M. Ordiyants ◽  
A.A. Kuular ◽  
A.A. Yamurzina ◽  
T.A. Bazieva
Keyword(s):  
Endometrial Hyperplasia ◽  
Progesterone Receptors ◽  
Reproductive Age ◽  
Control Group ◽  
Women Of Reproductive Age ◽  
Atypical Endometrial Hyperplasia ◽  
Group 3 ◽  
The Subject ◽  
Polymerase Chain ◽  
Group 2

Prevalence of proliferative processes is very high nowadays. Moreover, such processes easily transform into malignant ones. However, pathogenesis of endometrial hyperplasia (EH) is not fully understood. Imbalance of estrogen and progesterone, as well as estrogen and progesterone receptors is the reason for hyperplastic process onset in hormone-dependent tissues. Currently, there are no markers that could serve as objective predictors for EH development. It is unclear, whether EH transforms into cancer or spontaneously improves. The purpose of the study is to determine prevalence of ESR1 and PRG polymorphism in women of reproductive age with endometrial hyperplasia. Materials and Methods. Trial subjects (n=143) were divided into three groups: Group 1 consisted of 53 patients with glandular and glandular-cystic EH without atypia; Group 2 contained 34 patients with atypical EH; Group 3 was the control group. Polymerase chain reaction of DNA synthesis was used to conduct molecular and genetic loci study. Statistical analysis of the data obtained was performed with SAS JMP 11 and Statistica 10. Results. Mutant CC-allele of PvuII ESR1 polymorphism was found in every fourth woman with glandular endometrial hyperplasia and in every third patient with atypical endometrial hyperplasia. Prevalence of GG genotype of XbaI ESR1 polymorphism did not have any statistically significant differences in comparison with the control group. Mutant TT-allele of Val660Leu PRG polymorphism in glandular endometrial hyperplasia was 1.8 times more common in experimental groups than in the control one. Homozygous AA-genotype of 331G/A PRG polymorphism was not identified in women with endometrial hyperplasia. Conclusion. In endometrial hyperplasia, prevalence of mutant CC-allele of PvuII C/T ESR1 polymorphism leads to a decrease in ERa sensitivity, whereas prevalence of mutant TT-allele of Val660Leu PRG polymorphism leads to impaired sensitivity and a decrease in the biosynthesis rate of progesterone receptors. EH etiology and pathogenesis in women of reproductive age still remains the subject for future scientific research. Keywords: estrogen receptors, progesterone receptors, glandular endometrial hyperplasia, atypical endometrial hyperplasia. Актуальность проблемы пролиферативных процессов связана с высокой частотой распространения и высоким риском их трансформации в злокачественный процесс. В настоящее время до конца не изучен патогенез гиперплазии эндометрия (ГЭ). Причиной формирования гиперпластического процесса в гормонально-зависимых тканях может быть дисбаланс эстрогенов и прогестерона, а также эстрогеновых и прогестероновых рецепторов. В настоящее время отсутствуют маркеры, которые могли бы служить объективными предикторами развития ГЭ в направлении трансформации в рак или, наоборот, спонтанной ее регрессии. Цель исследования. Определить частоту встречаемости полиморфизмов генов ESR1 и PRG у пациенток репродуктивного возраста с различными вариантами гиперплазии эндометрия. Материалы и методы. Все обследованные женщины (143 чел.) были поделены на три группы: I группу составили 53 пациентки с железистой и железисто-кистозной ГЭ без атипии; II группу – 34 пациентки с атипической гиперплазией эндометрия; III группа стала контрольной. Молекулярно-генетическое исследование локусов проведено методом полимеразной цепной реакции синтеза ДНК. Статистический анализ полученных данных выполнен в программах SAS JMP 11 и Statistica 10. Результаты. Мутантный аллель СС полиморфизма PvuII гена ESR1 обнаружен у каждой четвертой женщины с железистой гиперплазией эндометрия и у каждой третей пациентки с атипической гиперплазией эндометрия. Частота встречаемости генотипа GG полиморфизма XbaI гена ESR1 в сравнении с группой контроля не имела статистически значимых различий. Мутантный аллель ТТ полиморфизма Val660Leu гена PRG при железистой гиперплазии эндометрия встречался в 1,8 раза чаще, чем в группе контроля. Гомозиготный генотип АА полиморфизма 331G/A гена PRG у женщин с гиперплазией эндометрия выявлен не был. Выводы. При гиперплазии эндометрия преобладание мутантного аллеля CC полиморфизма PvuII C/T гена ESR1 приводит к снижению чувствительности ERa, а преобладание мутантного аллеля TT полиморфизма Val660Leu гена PRG – к нарушению чувствительности и снижению скорости биосинтеза прогестероновых рецепторов. Предметом исследований по-прежнему остается концепция этиологии и патогенеза ГЭ у женщин репродуктивного возраста, что требует дальнейшего научного поиска. Ключевые слова: эстрогеновые рецепторы, прогестероновые рецепторы, железистая гиперплазия эндометрия, атипическая гиперплазия эндометрия.

Estrogen and progesterone receptors and cyclooxygenase-2 expression in endometrial cancer, endometrial hyperplasia, and normal endometrium

2005 ◽  
Vol 97 (2) ◽  
pp. 483-488 ◽  
Author(s):  
Francisco J. Orejuela ◽  
Lois M. Ramondetta ◽  
Judith Smith ◽  
Jubilee Brown ◽  
Luciano B. Lemos ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Endometrial Hyperplasia ◽  
Progesterone Receptors ◽  
Cyclooxygenase 2 ◽  
Estrogen And Progesterone Receptors ◽  
Normal Endometrium

scholarly journals The PTENP1 Pseudogene, Unlike the PTEN Gene, Is Methylated in Normal Endometrium, As Well As in Endometrial Hyperplasias and Carcinomas in Middle-Aged and Elderly Females

Acta Naturae ◽  
2018 ◽  
Vol 10 (1) ◽  
pp. 43-50 ◽  
Author(s):  
T. F. Kovalenko ◽  
K. V. Morozova ◽  
L. A. Ozolinya ◽  
I. A. Lapina ◽  
L. I. Patrushev
Keyword(s):  
Endometrial Hyperplasia ◽  
Venous Blood ◽  
Mrna Translation ◽  
The Body ◽  
Pten Gene ◽  
Middle Aged ◽  
Normal Endometrium ◽  
Tissue Samples ◽  
Endometrial Cells ◽  
Age Related

The tumor suppressor PTEN controls multiple cellular functions, including cell cycle, apoptosis, senescence, transcription, and mRNA translation of numerous genes. In tumor cells, PTEN is frequently inactivated by genetic mutations and epimutations. The aim of this study was to investigate the methylation patterns of the PTEN gene and its pseudogene PTENP1 as potential genetic markers of endometrial hyperplasia (EH) and endometrial carcinoma (EC). Methylation of the 5-terminal regions of the PTEN and PTENP1 sequences was studied using methyl-sensitive PCR of genomic DNA isolated from 57 cancer, 43 endometrial hyperplasia, and normal tissue samples of 24 females aged 17-34 years and 19 females aged 45-65 years, as well as 20 peripheral venous blood samples of EC patients. None of the analyzed DNA samples carried a methylated PTEN gene. On the contrary, the PTENP1 pseudogene was methylated in all analyzed tissues, except for the peripheral blood. Comparison of PTENP1 methylation rates revealed no differences between the EC and EH groups (0.80 p 0.50). In all these groups, the methylation level was high (71-77% in patients vs. 58% in controls). Differences in PTENP1 methylation rates between normal endometrium in young (4%) and middle-aged and elderly (58%) females were significant (p 0.001). These findings suggest that PTENP1 pseudogene methylation may reflect age-related changes in the body and is not directly related to the endometrium pathology under study. It is assumed that, depending on the influence of a methylated PTENP1 pseudogene on PTEN gene expression, the pseudogene methylation may protect against the development of EC and/or serve as a marker of a precancerous condition of endometrial cells.

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