UNASSIGNED: COVID-19 vaccination has been related to menstrual irregularities; however, the effect on postmenopausal women is unknown. The aim of this study was to analyze the prevalence of postmenopausal bleeding (PMB) after COVID-19 vaccination.
UNASSIGNED: A retrospective study was conducted in the Department of Gynecology in Hospital del Mar. Consecutive postmenopausal women with data available and endometrial biopsy were included between February 2021 and January 2022. Patients were stratified between COVID-19 vaccinated and unvaccinated groups. PMB after 30 days from last vaccine dose was considered unrelated to vaccine. Endometrial pathology diagnoses were stratified into benign or malignant. Univariable and multivariable of regression analysis on variables potentially associated with PMB was performed.
UNASSIGNED: A total of 381 patients were included, 91 in the vaccinated group and 290 in the unvaccinated group. Prevalence of PMB in the vaccinated group was 75.8% compared to 59.0% in the unvaccinated group (p < 0.005). No increase in endometrial malignant pathology was observed among the vaccinated group (p = 0.189). Multivariable analysis that correlates factors associated with PMB suggests COVID-19 vaccine and malignant endometrial biopsy as independent risk variables.
UNASSIGNED: A higher prevalence of PMB was associated with COVID-19 vaccine. Endometrial histological results showed no association with COVID-19 vaccination, but endometrial biopsy should be performed for PMB.

Neuroendocrine tumors (NETs) are malignant neoplasms that can be associated with specific hormonal syndromes. We describe a novel syndrome of postmenopausal vaginal bleeding and ovarian estradiol overproduction due to ovarian NET localizations. An extensive workup was performed for 2 index patients with ovarian metastases of small bowel neuroendocrine tumors and symptoms of postmenopausal vaginal bleeding. Clinically significant ovarian estrogen production was demonstrated by a combination of ovarian vein sampling and normalization of circulating estrogen levels after oophorectomy. Immunohistochemical analyses revealed marked aromatase immunoactivity in the ovarian NET cells, while CYP17A1 and SF-1 were detected in the adjacent ovarian stromal cells but not the NET cells. Ex vivo and in vivo endocrine tests were unable to identify a paracrine mechanism of ovarian estradiol overproduction by NET cells. A retrospective search of electronic medical records revealed that 21% (14/66) of postmenopausal patients with an ovarian NET localization reported symptoms of vaginal blood loss. Together, these findings support the presence of a novel NET-associated hormonal syndrome.

Endometrial adenocarcinoma is a prevalent malignancy among postmenopausal women, often presenting with symptoms such as abnormal vaginal bleeding and pelvic pain. We present a case of a 60-year-old postmenopausal female who exhibited abnormal vaginal bleeding for three months, accompanied by pelvic pain and unintentional weight loss. Clinical evaluation, including physical examination, imaging studies, and histopathological examination, led to the diagnosis of well-differentiated endometrial adenocarcinoma. The patient underwent an abdominal hysterectomy with bilateral salpingo-oophorectomy, and histopathological analysis confirmed invasive tumor involvement in the lower uterine segment and cervix. The final pathological tumor, node, and metastasis (TNM) staging was reported as pT1b No Mx, FIGO (International Federation of Gynecology and Obstetrics) stage II. This case underscores the importance of considering endometrial adenocarcinoma in the differential diagnosis of postmenopausal bleeding and highlights the significance of timely diagnosis and multidisciplinary management for optimizing patient outcomes.

UNASSIGNED: The objective of this study was to verify the clinical predictive performance of methylated cysteine dioxygenase type 1 (CDO1m) and CUGBP Elav-like family member 4 (CELF4m) in endometrial cancer (EC) women with postmenopausal bleeding (PMB).
UNASSIGNED: A single-center, prospective, and case-control study was conducted in the Gansu Provincial Maternity and Child-care Hospital with 138 female postmenopausal patients enrolled in 2022. All patients underwent body mass index (BMI) detection, transvaginal ultrasonography (TVUS) detection, carbohydrate antigen 125 detection, and the cervical exfoliated cell CDO1/CELF4 gene methylation detection to analyze the sensitivity, specificity, and accuracy of different screening tests statistically with the biopsy and/or dilation and curettage (D&C) pathological diagnosis under hysteroscopy as the gold standard.
UNASSIGNED: There was no significant difference in age between the EC group and the non-EC group, P = 0.492. Using quantitative polymerase chain reaction (qPCR) technology, we validated the CDO1 and CELF4 methylation detection with 87.5% sensitivity and 95.9% specificity as a useful strategy for the triage of women with PMB for the detection of EC. In addition, 100% of type II EC (n = 6) were positively detected by the CDO1 or CELF4 methylation test.
UNASSIGNED: The CDO1 and CELF4 methylation test with high specificity as an auxiliary diagnostic tool or alternative method provides physicians with a reference to distinguish between benign and malignant tumors in women with postmenopausal bleeding, to justify the necessity of using invasive methods to confirm diagnosis.

Unscheduled bleeding on hormone replacement therapy (HRT) can affect up to 40% of users. In parallel with the increase in HRT prescribing in the UK, there has been an associated increase in referrals to the urgent suspicion of cancer pathway for unscheduled bleeding. On behalf of the British Menopause Society (BMS) an expert review panel was established, including primary and secondary care clinicians with expertise in the management of menopause, with representatives from key related organisations, including the Royal College of Obstetricians & Gynaecologists, the British Gynaecological Cancer Society, British Society for Gynaecological Endoscopy, Royal College of General Practitioners and Faculty of Sexual and Reproductive Health, and service development partners from NHS England and GIRFT (Getting it Right First Time). For each topic, a focused literature review was completed to develop evidence led recommendations, where available, which were ratified by consensus review within the panel and by guideline groups.

OBJECTIVE: To evaluate the feasibility of further reducing the incidence of occult endometrial cancer in women undergoing hysterectomy for benign gynecological indications.
METHODS: Patients who underwent hysterectomies for presumed benign gynecologic conditions at Peking Union Medical College Hospital were retrospectively identified. Patients with occult endometrial cancer, which was defined as endometrial cancer diagnosed on postoperative histopathology with no preoperative confirmed malignancy, were selected.
RESULTS: 24/7558 (0.32%; 95% CI 0.20-0.47%) patients undergoing hysterectomy for benign indications had occult endometrial cancer. Asymptomatic patients with normal endometrial imaging all tended to have favorable pathology. Heavy menstrual bleeding was the most overlooked AUB pattern in the premenopausal group. In the postmenopausal group, all the patients with serous adenocarcinoma or G3 endometrioid adenocarcinoma histology/stage T1b disease/LVSI space invasion had a history of persistent or recurrent PMB ≥ 6 months and/or an intracavitary lesion > 20 mm in diameter. 3/4 of the samples of the postmenopausal patients did not have adequate endometrium for evaluation.
CONCLUSIONS: To further reduce the incidence of occult endometrial cancer, physicians should focus on the patient\'s bleeding pattern and actively implement endometrial sampling whenever indicated. Transvaginal ultrasonography is a valuable preoperative evaluation. Hysteroscopy with directed biopsy is the preferred procedure in postmenopausal patients.

BACKGROUND: Recurrent postmenopausal bleeding (PMB) occurs in 6%-25% of postmenopausal women who have experienced a previous episode of PMB. The question of whether recurrent PMB leads to a higher risk of endometrial cancer (EC) in comparison to a single episode of PMB is, however, controversial. Furthermore, little is known about predictive factors for recurrent PMB.
METHODS: A multicenter prospective cohort study was conducted over a 5-year period in four hospitals in the Netherlands. Women with PMB undergoing endometrial sampling and aged 40 years and older were included. Occurrence of recurrent PMB was retrospectively determined. Primary outcomes included (1) the incidence of recurrent PMB and (2) differences in pathological findings between patients with a single episode vs recurrent PMB. Secondary outcomes included (1) the association between diagnosis of benign polyps at first PMB and pathological findings at recurrent PMB and (2) factors predictive for recurrent PMB.
RESULTS: A total of 437 women with PMB were included, of whom 360 were at risk of recurrent PMB. With a median follow-up of 61 months (IQR (Interquartile range) 44-73), 26.4% experienced recurrent PMB. Patients with recurrent PMB were more often diagnosed with benign polyps (34.7% vs. 25.1%, p-value 0.015) and less frequently with a malignancy (5.3% vs. 17.8%, p-value 0.015), compared to patients with a single episode of PMB. Benign polyps at initial PMB were not associated with a (pre)malignancy at recurrence (OR 4.16, 95% CI 0.75-23.03). Predictive factors for recurrent PMB included use of hormone replacement therapy (HRT) (OR 3.32, 95% CI 1.64-6.72), and benign polyps at initial PMB (OR 1.80, 95% CI 1.07-3.04).
CONCLUSIONS: Recurrent PMB is common in women with a previous episode of PMB. Compared to patients with a single episode of PMB, patients with recurrent PMB and benign histological outcomes at accurate workup during their first episode were less often diagnosed with malignancies and more frequently with benign polyps. Benign polyps at first PMB are predictive for recurrent PMB, but not for a higher risk of (pre)malignancy.

Background Postmenopausal bleeding (PMB) is defined as blood loss from the genital tract occurring 12 months or more after an individual\'s last menstrual period. It is important for women to recognize abnormal symptoms during menopause, with PMB being one of the most critical. PMB is a common clinical presentation and can be indicative of endometrial carcinoma. A thorough clinical assessment and endometrial histopathology can ensure early diagnosis and treatment of malignancy in high-risk patients. Materials and Methods This study included 120 women with PMB. Their clinical and histopathological characteristics were studied, and correlations between the characteristics were investigated. Patients were evaluated according to their age, parity, duration of menopause, and socioeconomic status. Various comorbidities such as diabetes mellitus, hypertension, and obesity were noted. Results The patients ranged in age from 45 to 80 years, with a mean age of 54.97 ± 5.86 years. Fifty-nine (49.16%) of the patients presented with PMB within 3 years of menopause. PMB was seen most commonly in patients with parity 3, accounting for 37 (30.83%) of the cases. Endometrial thickness was increased in 100 (83.33%) cases. The most common causes of PMB were simple hyperplasia without atypia (SHWOA) in 36 (36%) patients and atrophic endometrium in 14 (14%) patients. Twelve (10%) of the patients had endometrial carcinoma. Benign causes of PMB were present in 91 (75.3%) cases, whereas 29 (24.1%) had a malignant cause. Weakly positive, but significant correlations (P < 0.05) were seen between the development of malignancy and increasing age (Pearson correlation coefficient, r = 0.263) parity (r = 0.244), and body mass index (r = 0.272). Conclusions PMB is considered abnormal. Benign causes are more common, but malignant causes are possible. In the current study, endometrial carcinoma was the most common malignant cause of PMB. Endometrial carcinoma incidence increased with greater endometrial thickness and more years since menopause. Histopathological examination remains the criterion standard for the correct diagnosis. Initiatives are recommended for increasing awareness about PMB to support prompt medical attention for a better prognosis.

UNASSIGNED: Developing a non-invasive and reliable triage test for endometrial malignant lesions is an important goal, as it could help to reduce the number of invasive diagnostic procedures required and improve patient survival. We aimed to estimate the diagnostic value of DNA methylation levels in cervical cytological samples of endometrial cancer (EC) and endometrial atypical hyperplasia (AH).
UNASSIGNED: A total of 607 women who had indications for endometrial biopsy in the Department of Obstetrics and Gynecology of Cangzhou Central Hospital from October 2022 to April 2023 were enrolled in this study. The cervical exfoliated cells were collected for gene methylation before endometrial biopsy. Clinical information, tumor biomarkers, and endometrial thickness (ET) of transvaginal ultrasonography (TVS) were also collected. With endometrial histopathology as the gold standard, multivariate unconditional logistic regression was applied to analyze the risk factors of endometrial malignant lesions. The role of cysteine dioxygenase type 1 (CDO1) and CUGBP Elav-like family member 4 (CELF4) gene methylation as a triage strategy biomarker in endometrial malignant lesions was specifically explored.
UNASSIGNED: Multivariate logistic regression analysis showed that premenopausal ET ≥ 11 mm or postmenopausal ET ≥ 5 mm, CDO1 ΔCt ≤ 8.4, or CELF4 ΔCt ≤ 8.8 were the risk factors for AH and EC, with odds ratios (ORs) (95%CI) of 5.03 (1.83-13.82) and 6.92 (1.10-43.44), respectively (p-values < 0.05). The sensitivity and specificity of CDO1/CELF4 dual-gene methylation assay for AH and EC reached 84.9% (95%CI: 75.3%-94.5%) and 86.6% (95%CI: 83.8%-89.5%), respectively. ET combined with DNA methylation detection further improved the specificity to (94.9%, 95%CI: 93.1%-96.8%).
UNASSIGNED: The accuracy of cervical cytology DNA methylation is superior to that of other clinical indicators in the non-invasive examination of endometrial malignant lesions. DNA methylation combined with TVS can further improve the specificity and is a promising biomarker triage strategy in women with suspected endometrial lesions.

There is a growing literature base regarding menstrual changes following COVID-19 vaccination among premenopausal people. However, relatively little is known about uterine bleeding in postmenopausal people following COVID-19 vaccination.
This study aimed to examine trends in incident postmenopausal bleeding diagnoses over time before and after COVID-19 vaccine introduction, and to describe cases of new-onset postmenopausal bleeding after COVID-19 vaccination.
For postmenopausal bleeding incidence calculations, monthly population-level cohorts consisted of female Kaiser Permanente Northwest members aged ≥45 years. Those diagnosed with incident postmenopausal bleeding in the electronic medical record were included in monthly numerators. Members with preexisting postmenopausal bleeding or abnormal uterine bleeding, or who were at increased risk of bleeding due to other health conditions, were excluded from monthly calculations. We used segmented regression analysis to estimate changes in the incidence of postmenopausal bleeding diagnoses from 2018 through 2021 in Kaiser Permanente Northwest members meeting the inclusion criteria, stratified by COVID-19 vaccination status in 2021. In addition, we identified all members with ≥1 COVID-19 vaccination between December 14, 2020 and August 14, 2021, who had an incident postmenopausal bleeding diagnosis within 60 days of vaccination. COVID-19 vaccination, diagnostic procedures, and presumed bleeding etiology were assessed through chart review and described. A temporal scan statistic was run on all cases without clear bleeding etiology.
In a population of 75,530 to 82,693 individuals per month, there was no statistically significant difference in the rate of incident postmenopausal bleeding diagnoses before and after COVID-19 vaccine introduction (P=.59). A total of 104 individuals had incident postmenopausal bleeding diagnosed within 60 days following COVID-19 vaccination; 76% of cases (79/104) were confirmed as postvaccination postmenopausal bleeding after chart review. Median time from vaccination to bleeding onset was 21 days (range: 2-54 days). Among the 56 postmenopausal bleeding cases with a provider-attributed etiology, the common causes of bleeding were uterine or cervical lesions (50% [28/56]), hormone replacement therapy (13% [7/56]), and proliferative endometrium (13% [7/56]). Among the 23 cases without a clear etiology, there was no statistically significant clustering of postmenopausal bleeding onset following vaccination.
Within this integrated health system, introduction of COVID-19 vaccines was not associated with an increase in incident postmenopausal bleeding diagnoses. Diagnosis of postmenopausal bleeding in the 60 days following receipt of a COVID-19 vaccination was rare.