Objective: To compare the effects and safety of dydrogesterone (DG) and medroxyprogesterone acetate (MPA) on the treatment in patients with endometrial hyperplasia without atypia (EH). Methods: This was a single-center, open-label, prospective non-inferior randomized controlled phase Ⅲ trial. From February 2019 to November 2021, patients with EH admitted to the Obstetrics and Gynecology Hospital of Fudan University were recruited. Enrolled patients were stratified according to the pathological types of simple hyperplasia (SH) or complex hyperplasia (CH), and were randomised to receive MPA or DG. Untill May 14, 2022, the median follow-up time after complete response (CR) was 9.3 months (1.1-17.2 months). The primary endpoint was the 6-month CR rate (6m-CR rate). The secondary endpoints included the 3-month CR rate (3m-CR rate), adverse events rate, recurrence rate, and pregnancy rate in one year after CR. Results: (1) A total of 292 patients with EH were enrolled in the study with the median age of 39 years (31-45 years). A total of 135 SH patients were randomly assigned to MPA group (n=67) and DG group (n=68), and 157 CH patients were randomly assigned to MPA group (n=79) and DG group (n=78). (2) Among 292 patients, 205 patients enrolled into the primary endpoint analysis, including 92 SH patients and 113 CH patients, with 100 patients in MPA group and 105 in DG group, respectively. The 6m-CR rate of MPA group and DG group were 90.0% (90/100) and 88.6% (93/105) respectively, and there were no statistical significance (χ²=0.11, P=0.741), with the rate difference (RD) was -1.4% (95%CI:-9.9%-7.0%). Stratified by the pathology types, the 6m-CR rate of SH patients was 93.5% (86/92), and MPA group and DG group were respectively 91.1% (41/45) and 95.7% (45/47); and the 6m-CR rate of CH patients was 85.8% (97/113), and MPA group and DG group were 89.1% (49/55) and 82.8% (48/58) respectively. The 6m-CR rates of the two treatments had no statistical significance either (all P>0.05). A total of 194 EH patients enrolled into the secondary endpoint analysis, including 88 SH patients and 106 CH patients, and 96 patients in MPA group and 98 in DG group, respectively. The 3m-CR rate of SH patients were 87.5% (77/88), while the 3m-CR rates of MPA group and DG group were 90.7% (39/43) and 84.4% (38/45), respectively; the 3m-CR rate of CH patients was 66.0% (70/106), and MPA group and DG group had the same 3m-CR rate of 66.0% (35/53). No statistical significance was found between the two treatments both in SH and CH patients (all P>0.05). (3) The incidence of adverse events between MPA group and DG group had no statistical significance (P>0.05). (4) A total of 93 SH patients achieved CR, and the cumulative recurrence rate in one year after CR were 5.9% and 0 in MPA group and DG group, respectively. While 112 CH patients achieved CR, and the cumulative recurrence rate in one year after CR were 8.8% and 6.5% in MPA group and DG group, respectively. There were no statistical significance between two treatment groups (all P>0.05). Among the 93 SH patients, 10 patients had family planning but no pregnancy happened during the follow-up period. Among the 112 CH patients, 21 were actively preparing for pregnancy, and the pregnancy rate and live-birth rate in one year after CR in MPA group were 7/9 and 2/7, while in DG group were respectively 4/12 and 2/4, and there were no statistical significance in pregnancy rate and live-birth rate between the two treatment groups (all P>0.05). Conclusions: Compared with MPA, DG is of good efficacy and safety in treating EH. DG is a favorable alternative treatment for EH patients.
Female ; Humans ; Adult ; Medroxyprogesterone Acetate/adverse effects* ; Endometrial Hyperplasia/pathology* ; Dydrogesterone/adverse effects* ; Hyperplasia ; Prospective Studies

Objective: To investigate the impact of molecular classification and key oncogenes on the oncologic outcomes in patients with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) receiving fertility-preserving treatment. Methods: Patients with EC and AEH undergoing progestin-based fertility-preserving treatment and receiving molecular classification as well as key oncogenes test at Obstetrics and Gynecology Hospital, Fudan University from January 2021 to March 2023 were reviewed. Hysteroscopic lesion resection and endometrial biopsy were performed before initiating hormone therapy and every 3 months during the treatment to evaluate the efficacy. The risk factors which had impact on the treatment outcomes in EC and AEH patients were further analyzed. Results: Of the 171 patients analyzed, the median age was 32 years, including 86 patients with EC and 85 patients with AEH. The distribution of molecular classification was as follows: 157 cases (91.8%) were classified as having no specific molecular profile (NSMP); 9 cases (5.3%), mismatch repair deficient (MMR-d); 3 cases (1.8%), POLE-mutated; 2 cases (1.2%), p53 abnormal. No difference was found in the cumulative 40-week complete response (CR) rate between the patients having NSMP or MMR-d (61.6% vs 60.0%; P=0.593), while the patients having MMR-d had increased risk than those having NSMP to have recurrence after CR (50.0% vs 14.4%; P=0.005). Multi-variant analysis showed PTEN gene multi-loci mutation (HR=0.413, 95%CI: 0.259-0.658; P<0.001) and PIK3CA gene mutation (HR=0.499, 95%CI: 0.310-0.804; P=0.004) were associated with a lower cumulative 40-week CR rate, and progestin-insensitivity (HR=3.825, 95%CI: 1.570-9.317; P=0.003) and MMR-d (HR=9.014, 95%CI: 1.734-46.873; P=0.009) were independent risk factors of recurrence in EC and AEH patients. Conclusions: No difference in cumulative 40-week CR rate is found in the patients having NSMP or MMR-d who received progestin-based fertility-preserving treatment, where the use of hysteroscopy during the treatment might be the reason, while those having MMR-d have a higher risk of recurrence after CR. Oncogene mutation of PTEN or PIK3CA gene might be associated with a lower response to progestin treatment. The molecular profiles help predict the fertility-preserving treatment outcomes in EC and AEH patients.
Pregnancy ; Female ; Humans ; Adult ; Hyperplasia ; Progestins ; Fertility Preservation ; Endometrial Neoplasms/pathology* ; Endometrial Hyperplasia/surgery* ; Treatment Outcome ; Precancerous Conditions ; Fertility ; Class I Phosphatidylinositol 3-Kinases ; Retrospective Studies

Carcinoma, Squamous Cell/pathology* ; Endometrial Hyperplasia/pathology* ; Endometrial Neoplasms/pathology* ; Endometrium/pathology* ; Female ; Humans ; Hyperplasia/pathology*

OBJECTIVE: To analyze the efficacy and prognosis of fertility-sparing therapy of the patient with complex atypical hyperplasia (CAH) and endometrial cancer (EC). METHODS: Clinical data of 191 EC and CAH patients who received fertility-sparing therapy in Peking University People's Hospital between January 2009 and September 2021 were recruited retrospectively. Outcomes of remission, recurrence and pregnancy were analyzed. RESULTS: (1) Efficacy and efficacy-related factors: The complete response (CR) rate was 86.1% (161/187) for all the patients, and the CR rate of the CAH patients were higher than that of the EC patients (92.7% vs. 79.1%, P=0.007), the CR rate was significant higher in the CAH patients (OR=2.786, P=0.035). (2) The recurrence rate was 19.3% (31/161), and the recurrence rate of the EC patients were much higher than that of the CAH patients (26.4% vs. 13.5%, P=0.039). The median recurrence time was 22.5 (9.0, 50.0) months. (3) The high risk factors of recurrence were pathological type of EC (χ²=4.880, P=0.027), without the use of metfor-min (χ²=7.075, P=0.008), longer time to complete remission (>7 months) (χ²=6.204, P=0.013), and no pregnancy (χ²=6.765, P=0.009). (4) Results of pregnancy and related factors: Among the patients who achieved CR, 108 patients had fertility willing with the pregnancy rate of 41.7% (45/108), and the live birth rate was 34.3% (37/108). The live birth rate was lower in EC than that in the CAH patients (28.6% vs. 42.4%, P=0.045). The median time to achieve pregnancy was 10.50 (5.75, 33.25) months. The pregnancy rate was significant higher in the patients with pregnancy history (OR=9.468, P < 0.001) and in those who received assisted reproductive therapy (OR=7.809, P < 0.001). CONCLUSION Fertility-sparing therapy of CAH and EC patients is effective resulting in high disease remission and certain pregnancy. However, the high recurrence rate and low pregnancy rate are still key problems for EC and CAH patients, therefore close monitoring and follow-up are indicated.
Endometrial Hyperplasia/pathology* ; Endometrial Neoplasms/drug therapy* ; Female ; Fertility Preservation/methods* ; Humans ; Hyperplasia ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To evaluate the effectiveness of oral contraceptive pill (OCP) as therapy for endometrial hyperplasia (EH) without atypia in reproductive-aged women compared with oral progestin. METHODS: A retrospective cohort study was carried out in our reproductive center. Consecutive patients diagnosed with infertility and non-atypical EH identified through electronic database who met inclusion criteria (n=309). Patients were assigned to two treatment groups: OCP (n=216) and oral progestin (n=93); clinical and reproductive outcomes were recorded. RESULTS: Reversal of EH to normal endometrium, clinical pregnancy, live birth and miscarriage rate. Women in OCP group were younger, had higher prevalence of Polycystic Ovary Syndrome and other uterine pathology and longer duration of infertility than women in progestin group. Reversal of EH was observed in 93.52% women on OCP and in 86.02% women on progestin (p=0.032; adjusted odds ratio [aOR]= 2.35; 95% confidence interval [CI]=1.06-5.21) after the initial course of treatment for 2 to 6 months. Cyclic OCP (n=184) resulted in better response to treatment compared to continuous OCP (n=32) (95.11% vs. 84.38%; p=0.039; aOR =3.60; 95% CI =1.12-11.55). Clinical pregnancy rate in OCP group was marginally higher than progestin group (87/208, 41.83% vs. 27/90, 30.00%; p=0.054). Miscarriage (25.29% vs. 29.63%; p=0.654) and live birth rate (31.25% vs. 21.11%; p=0.074) were comparable between the groups. CONCLUSION: For the first time we demonstrate that OCP is an effective therapy for non-atypical EH and is associated with higher remission rate compared with oral progestin. Reproductive outcomes are reassuring and comparable between the two groups.
Abortion, Spontaneous ; Cohort Studies ; Contraceptives, Oral, Combined ; Drug Therapy ; Endometrial Hyperplasia ; Endometrium ; Female ; Humans ; Infertility ; Live Birth ; Odds Ratio ; Pathology ; Polycystic Ovary Syndrome ; Pregnancy ; Pregnancy Rate ; Prevalence ; Progestins ; Reproductive History ; Retrospective Studies

OBJECTIVE: To assess the clinical usefulness and diagnostic accuracy of ultrasonographic measurement of endometrial thickness (ET) in women with endometrial hyperplasia or cancer (EH+). METHODS: This retrospective cohort study included 29,995 consecutive women who underwent transvaginal ultrasonography (TVS) for an incidental finding of a thickened endometrium at the health screening and promotion center at Asan Medical Center between 2006 and 2010. Among 959 patients with endometrial abnormalities, 92 patients were included in this study. A total of 867 patients were excluded: 416 were lost to follow-up; 263 did not undergo endometrial biopsy; 155 had endometrial polyps; 17 had submucosal myomas; and 16 had insufficient tissue samples. Endometrial histology was the reference standard for calculating accuracy. RESULTS: Of the 92 patients, 78 (84.8%) had normal pathology, while 14 (15.2%) had endometrial pathology (EH+), including 5 patients (35.7%) with simple hyperplasia without atypia, 3 (21.4%) with complex hyperplasia, and 6 (42.9%) with endometrial carcinoma, all stage Ia. The area under the receiver-operating characteristic curve was 0.75 (95% confidence interval [CI], 0.593–0.906). The cut-off value for ET was 8 mm, indicating that TVS ET had a fair accuracy in diagnosing carcinoma, had a sensitivity of 100% (95% CI, 62.9–100.0%) and a specificity of 24.3% (95% CI, 15.2–36.3%). CONCLUSION: TVS is useful for detecting EH+, with a cut-off value for ET of 8 mm having a high sensitivity for detecting endometrial pathologies and the ability to identify women highly unlikely to have EH+, thereby avoiding more invasive endometrial biopsy.
Biopsy ; Chungcheongnam-do ; Cohort Studies ; Diagnosis ; Endometrial Hyperplasia ; Endometrial Neoplasms ; Endometrium ; Female ; Humans ; Hyperplasia ; Incidental Findings ; Lost to Follow-Up ; Mass Screening ; Myoma ; Pathology ; Polyps ; Retrospective Studies ; Sensitivity and Specificity ; Ultrasonography

OBJECTIVE: This study is to compare the baseline characteristics and symptoms between groups with leiomyoma only (group M; myoma group), adenomyosis only (group A; adenomyosis group), and leiomyoma and adenomyosis together (group B; group for both disease). METHODS: Selected patients were who received total abdominal hysterectomy, laparoscopy-assisted vaginal hysterectomy, or total laparoscopic hysterectomy from January 2014 to December 2015, and whose pathology result showed leiomyoma (n=74), adenomyosis (n=27), or both (n=63). Baseline characteristics and symptoms were reviewed from the medical records. Researched characteristics included patients' age, degeneration of leiomyoma, endometrial hyperplasia, endometriosis, weight of the removed uterus, menopause before the surgery, method of the surgery, necessity for blood transfusion before and after the surgery, difference of hemoglobin level before and after the surgery, and number of gravida, para, and abortion. RESULTS: Eleven symptoms were checked. Thirty-eight point four percent of total subject had uterine leiomyoma and adenomyosis at the same time. Number of abortion was higher in the group B. The group B showed a tendency of presenting more menorrhagia, dysfunctional uterine bleeding, acute lower abdominal pain, and urinary frequency. Symptoms related to mass effect seem to be relative to uterine leiomyoma, and symptoms related to menorrhagia seems to be relative to adenomyosis. The group M showed suddenly growing mass symptoms, and was more likely to have massive hemorrhage during the surgery. It is hard to differentiate coexistence of uterine leiomyoma and adenomyosis from each disease. CONCLUSION: Coexistence of two disease exhibits mixed symptoms of each disease, but shows different tendency.
Abdominal Pain ; Adenomyosis ; Blood Transfusion ; Endometrial Hyperplasia ; Endometriosis ; Female ; Hemorrhage ; Humans ; Hysterectomy ; Hysterectomy, Vaginal ; Leiomyoma ; Medical Records ; Menopause ; Menorrhagia ; Methods ; Metrorrhagia ; Myoma ; Pathology ; Retrospective Studies ; Uterus

OBJECTIVES: To uncover gynecologic conditions with similar transvaginal sonographic findings of thick uterine endometrium with honeycomb appearance in pre-and postmenopausal women.METHODS: We retrospectively reviewed cases of patients with endometrial tissue biopsy from January 2010 to December 2016. We also collected office flexible hysteroscopic findings and surgical pathologic results. We analyzed data from 393 patients with confirmed endometrial pathology. Among these patients, 69 had transvaginal ultrasonographic images with thick uterine endometrium and honeycomb or “Swiss cheese” appearance.RESULTS: We found gynecologic conditions such as submucosal leiomyoma with degeneration, endometrial polyp, pseudocystic endometrial change associated with tamoxifen use, progesterone associated endometrial change, pyometra, retained placenta, and uterine synechiae manifested with similar thick endometrium with “Swiss cheese” appearance in transvaginal sonographic images. The most common diagnosis in postmenopausal women was atrophic endometritis, followed by endometrial cancer and endometrial polyps. The most common diagnosis in premenopausal women was abnormal uterine bleeding without pathologic conditions.CONCLUSIONS: Sonographic findings of thick uterine endometrium with “Swiss cheese” appearance need to be considered together with a thorough review of the patient's history and chief complaint before making a tentative diagnosis due to the various conditions sharing the feature.
Biopsy ; Diagnosis ; Endometrial Neoplasms ; Endometritis ; Endometrium ; Female ; Gynatresia ; Humans ; Hyperplasia ; Leiomyoma ; Menopause ; Pathology ; Placenta, Retained ; Polyps ; Progesterone ; Pyometra ; Retrospective Studies ; Tamoxifen ; Ultrasonography ; Uterine Hemorrhage

Opinions on ovariohysterectomy (OHE) of bitches vary depending on region and country. In this descriptive, prospective cross-sectional study, uterine tracts and ovaries exhibiting gross pathologic findings (n = 76) were collected post-surgery from a reference population of 3,600 bitches (2.11% incidence) that underwent elective OHE during September to November 2013 and evaluated by histopathology examination. Data were evaluated by using descriptive statistics and chi-squared tests. Bitches were of crossbred background with average age 5 years (range 0.6–8.0 years) and most were nulliparous (69.7%) with no anamnesis of reproductive diseases (81.6%). Frequencies of proestrus, estrus, and diestrus were 42.1%, 6.6%, and 19.7%, respectively. The presence of mammary gland masses (5.3%) significantly correlated with histopathologic findings in ovaries and age of the bitch (p < 0.05). Predominant uterine histopathologies included cystic endometrial hyperplasia, periglandular fibrosis, lymphoplasmocytary endometritis, and adenomyosis (19.7%, 14.5%, 4.0%, and 2.6%, respectively). In ovaries, hyperplasia of rete ovarii, follicular cysts, oophoritis, adenoma of the rete ovarii, cysts of superficial structures, and granulosa cell tumors (10.5%, 10.5%, 7.9%, 4.0%, 2.6%, and 2.6%, respectively) were observed. The results reveal the presence of subclinical pathologies in healthy bitches, suggesting that OHE at an early age is beneficial for prevention of reproductive pathologies.
Adenoma ; Adenomyosis ; Animals ; Cross-Sectional Studies* ; Diestrus ; Dogs* ; Endometrial Hyperplasia ; Endometritis ; Estrus ; Female ; Fibrosis ; Follicular Cyst ; Granulosa Cell Tumor ; Hyperplasia ; Mammary Glands, Human ; Oophoritis ; Ovary* ; Pathology ; Proestrus ; Prospective Studies ; Uterus*

OBJECTIVE: To describe the endometrial pathologic lesions in premenopausal breast cancer patients with a history of tamoxifen (TMX) use. METHODS: We retrospectively reviewed the medical records of 120 premenopausal breast cancer patients with a history of TMX use that had undergone a gynecological examination. RESULTS: Among 120 patients, 44.2% (n=53) were asymptomatic with an endometrial thickness ≥5 mm, as assessed by transvaginal ultrasonography. Of the patients that reported abnormal uterine bleeding, 5% (n=6) had an endometrial thickness <5 mm and 20% (n=24) had an endometrial thickness ≥5 mm by transvaginal ultrasonography. The final group of patients were asymptomatic, but showed an abnormal endometrial lesion, such as an endometrial polyp, by transvaginal ultrasonography (30.8%, n=37). Of the 56 benign lesions that were histologically reviewed, 50 (41.7%) were endometrial polyps, 3 (2.5%) were submucosal myomas, 2 (1.7%) were endometrial hyperplasias, and 1 (0.8%) was chronic endometritis. There were 64 (53.3%) other non-pathologic conditions, including secreting, proliferative, and atrophic endometrium, or in some cases, there was insufficient material for diagnosis. In our data, only one case was reported as a complex hyperplasia without atypia arising from an endometrial polyp, and one patient was diagnosed with endometrioid adenocarcinoma. CONCLUSION: For premenopausal breast cancer patients with a history of TMX use, the majority of the patients were asymptomatic, and endometrial polyps were the most common endometrial pathology observed. Therefore, we believe that endometrial assessment before starting TMX treatment, and regular endometrial screening throughout TMX treatment, are reasonable suggestions for premenopausal breast cancer patients.
Breast Neoplasms* ; Breast* ; Carcinoma, Endometrioid ; Diagnosis ; Endometrial Hyperplasia ; Endometritis ; Endometrium ; Female ; Gynecological Examination ; Humans ; Hyperplasia ; Hysteroscopy ; Mass Screening ; Medical Records ; Myoma ; Pathology ; Polyps* ; Retrospective Studies ; Tamoxifen* ; Ultrasonography ; Uterine Hemorrhage