Menopause

Construction of a nomogram prediction model for deep vein thrombosis in epithelial ovarian cancer

Objective: To develop and validate a nomogram prediction model for deep vein thrombosis (DVT) in epithelial ovarian cancer (EOC). Methods: Between May 2021 and May 2024, 429 EOC patients admitted to our hospital were retrospectively identified. The patients were randomly divided into a modeling group and a validation group. Based on whether DVT occurred, the modeling group was classified into a DVT group and a non-DVT group. The influencing factors associated with DVT in EOC were analyzed using multivariable logistic regression. R software was used to construct the nomogram model. The receiver operating characteristic (ROC) curve was used to evaluate the discrimination of the nomogram. Moreover, the decision curve analysis (DCA) was used to evaluate the clinical utility of the model. Results: Of 429 patients, 116 developed DVT, with an incidence rate of 27.04%. In the modeling group of 300 patients, 81 developed DVT, with an incidence rate of 27.00%. Multivariate logistic regression showed that age, BMI, hypertriglyceridemia, tumor staging, tumor grade, CA125 level, platelet count (PLT), and fibrinogen level (FIB) were independent risk factors for developing DVT in EOC ( P <0.05). The area under the ROC curve (AUC) for the modeling group was 0.893, and the AUC of the validation group was 0.973. The Hosmer-Lemeshow (H-L) test of the modeling group showed χ 2 =7.324 ( P= 0.722), and the H-L test of the validation group showed χ 2 =7.043 ( P= 0.711), suggesting good calibration. DCA curve showed that the threshold probability was between 0.08 and 0.97, the clinical value of the DVT nomogram model provided a net clinical benefit. Conclusion: Age, BMI, hypertriglyceridemia, tumor stage, tumor grade, CA125 level, platelet count (PLT), and fibrinogen level (FIB) are significant independent risk factors for EOC patients developing DVT. The nomogram constructed with these factors demonstrates good predictive performance and clinical utility in predicting the risk of DVT in EOC patients.

A prospective controlled study of sexual function and sexually related personal distress up to 12 months after premenopausal risk-reducing bilateral salpingo-oophorectomy

Abstract Objective: Premenopausal risk-reducing bilateral salpingo-oophorectomy (RRBSO) may impair sexual function, but the nature and degree of impairment and impact of estrogen therapy on sexual function and sexually related personal distress after RRBSO are uncertain. Methods: Prospective observational study of 73 premenopausal women at elevated risk of ovarian cancer planning RRBSO and 68 premenopausal controls at population risk of ovarian cancer. Participants completed the Female Sexual Function Index and the Female Sexual Distress Scale-Revised. Change from baseline in sexual function following RRBSO was compared with controls at 12 months according to estrogen therapy use. Results: Baseline sexual function domains did not differ between controls and those who underwent RRBSO and subsequently initiated (56.2%) or did not initiate (43.8%) estrogen therapy. At 12 months, sexual desire and satisfaction were unchanged in the RRBSO group compared with controls. After RRBSO, nonestrogen therapy users demonstrated significant impairment in sexual arousal (β-coefficient (95% confidence interval) −2.53 (−4.86 to −0.19), P < 0.03), lubrication (−3.40 (−5.84 to −0.96), P < 0.006), orgasm (−1.64 (−3.23 to −0.06), P < 0.04), and pain (−2.70 (−4.59 to 0.82), P < 0.005) compared with controls. Although sexually related personal distress may have been more likely after RRBSO, irrespective of estrogen therapy use, there was insufficient data to formally test this effect. Conclusions: The findings suggest premenopausal RRBSO adversely affects several aspects of sexual function which may be mitigated by the use of estrogen therapy. Further research is needed to understand the effects of RRBSO on sexual function and sexually related personal distress, and the potential for estrogen therapy to mitigate against any adverse effects.

Hysterectomy with or without ovarian conservation: similar associations with vascular health?

Barriers to hormone therapy following prophylactic bilateral salpingo-oophorectomy in BRCA1/2 mutation carriers

Abstract Objective This study aimed to identify barriers to hormone therapy (HT) use among women with BRCA1/2 mutations after prophylactic bilateral salpingo-oophorectomy (BSO). Methods A cross-sectional, electronic survey was conducted of BRCA1/2 mutation carriers at Women and Infants Hospital, Yale Medical Center, Hartford Healthcare, and Maine Medical Center. This study was a subanalysis of a subset of female BRCA1/2 mutation carriers who had undergone a prophylactic BSO. Data were analyzed using the Fisher's exact test or t test. Results We performed a subanalysis of 60 BRCA mutation carriers who underwent a prophylactic BSO. Only 24 women (40%) reported ever using HT. HT use was higher in women who underwent their prophylactic BSO at age younger than 45 years (51% vs. 25%, P = 0.06). Among all women who had a prophylactic BSO, the majority (73%) reported that a provider talked to them about using HT. Two thirds reported having seen contradictory information in the media about long-term consequences of HT. Seventy percent listed their provider as the primary influence in their decision to start HT. The most common reasons for not starting HT included it not being recommended by their physician (46%) and that it was not necessary (37%). Conclusions BRCA mutation carriers frequently undergo prophylactic BSO at young ages, and less than half report using HT. This study highlights barriers to HT use, such as patient fears and physician discouragement, and identifies potential areas to improve educational efforts.

Ultrasound-identified ovarian cysts: a guide to interpretation, management, and follow-up

Natural history and malignant potential of simple ovarian cysts in postmenopausal women: a systematic review and meta-analysis

Abstract Importance Postmenopausal ovarian masses are not uncommon, and the incidence of ovarian cancer rises sharply after menopause. Objective We conducted a systematic review and meta-analysis to investigate the natural history and malignant potential of postmenopausal simple ovarian cysts. Evidence Review PubMed, MEDLINE, EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), ClinicalTrials.gov, and ISRCTN (International Standard Randomized Controlled Trial Number Register) were searched from inception to January 31, 2022. Meta-analyses were conducted using R software. Findings Twelve cohort studies with 1,672 participants and 1,513 ovarian cysts were included. The rates of simple cysts remaining unchanged (38.90%; 95% CI, 19.79%-59.85%; P < 0.01) or disappearing (34.17%; 95% CI, 19.13%-50.93%; P < 0.01) were the highest during conservative observation. The surgery rate for the simple cyst was 19.04% (95% CI, 8.19%-32.92%; P < 0.01). The malignancy rate (including borderline tumors) was very low, approximately 1/10,000 (95% CI, 0% to 0.23%; P = 0.79). Conclusions Simple ovarian cysts in postmenopausal women were most likely to remain unchanged or disappear during follow-up. The malignancy rate was approximately 1 in 10,000. Personal preference is the most common reason for surgery.

What information do healthcare professionals need to inform premenopausal women about risk-reducing salpingo-oophorectomy?

Abstract Objective: The aim of this study was to identify the unmet information needs of healthcare professionals managing risk-reducing bilateral salpingo-oophorectomy (RRBSO) in premenopausal women. Methods: A cross-sectional survey of healthcare professionals managing high-risk women in Victoria, Australia. Questions included roles and responsibilities around RRBSO, perceived barriers to uptake of RRBSO, and unmet information needs. Results: One hundred eighteen healthcare professionals across 10 different disciplines and specialties were approached to participate, of whom 47 completed the survey. Most respondents were genetic counselors (47%) or nurses (19%) and all worked in the public health system. Almost all (81%) provided information about RRBSO, but there was considerable uncertainty about who was responsible for making decisions with high-risk women about RRBSO. Most (85%) were “quite a bit” or “extremely” confident about informing high-risk women about ovarian cancer risk reduction from RRBSO and the surgical procedure (47%), but only one-third were “quite a bit” or “extremely” confident about discussing (36%) or managing (31%) surgical menopause. Furthermore, surgical menopause was considered the main barrier (88%, “quite a bit” or “extremely”) to RRBSO. Most healthcare professionals (78%) wanted more information and resources about surgical menopause for high-risk women. Conclusions: There is uncertainty around the roles and responsibilities of healthcare professionals managing high-risk women around RRBSO. Surgical menopause is perceived as a major barrier to RRBSO and healthcare professionals lack confidence in managing this outcome. Video Summary: http://links.lww.com/MENO/A477.

Age cutoffs for cervical cancer screening: good medicine or ageism?

Clinicopathologic characteristics and risk factors for endometrial malignancy in postmenopausal women with endometrial thickening

Abstract Objective: To evaluate the clinicopathological characteristics and risk factors for endometrial malignancy in postmenopausal women with endometrial thickening. Methods: This was a retrospective study. Postmenopausal women with endometrial thickening (defined as the thickest endometrial portion in the sagittal uterine plane was greater than or equal to 5 mm) through transvaginal ultrasound in our outpatient department, and further referred to the gynecology department at Xuanwu Hospital for hysteroscopic diagnostic curettage assessment between January 2018 and March 2021 were included. According to the histopathological results, participants were divided into the benign group and malignant group. Univariate analysis was used to compare the differences in various factors, including demographics, clinical characteristics, medical complications, and ultrasound characteristics, between the two groups. Multiple logistic regression analysis was used to identify the factors that were independent contributors to the development of endometrial malignancy. Receiver operating characteristic analysis of endometrial thickness (ET) to predict endometrial malignancy was performed. Results: In total, 385 eligible cases were included in the analysis. The results suggested that older age (odds ratio [OR] 1.061, 95% confidence interval [CI] 1.008-1.116, P = 0.023), thicker ET (OR 5.032, 95% CI 2.453-10.322, P < 0.001), irregular menstruation in the past (OR 19.203, 95% CI 1.936-190.431, P = 0.012), postmenopausal bleeding (OR 12.341, 95% CI 4.440-34.302, P < 0.001), and polypoid mass-like lesions (OR 30.330, 95% CI 8.974-102.509, P < 0.001) were risk factors that were independently associated with the development of endometrial malignancy in postmenopausal women with increased ET. The optimal critical value of ET in predicting malignancy was 9.5 mm, and the sensitivity and specificity were 71.70% and 71.69%, respectively. Conclusions: For postmenopausal women with endometrial thickening, our results suggested that women who are older, have a thicker ET, had irregular menstruation in the past, have postmenopausal bleeding, and have polypoid mass-like lesions should seek medical attention as soon as possible and undergo further invasive examination. The use of 9.5 mm as the ET value to prompt investigations may be acceptable since it is unlikely to miss any atypical endometrial hyperplasia or endometrial cancer.

Comparative safety of conjugated estrogens/bazedoxifene versus estrogen/progestin combination hormone therapy among women in the United States: a multidatabase cohort study

Abstract Objective To assess the risk of select safety outcomes including endometrial cancer, endometrial hyperplasia, and breast cancer among women using conjugated estrogens/bazedoxifene (CE/BZA) as compared with estrogen/progestin combination hormone therapy (EP). Methods We conducted a new-user cohort study in five US healthcare claims databases representing more than 92 million women. We included CE/BZA or EP new users from May 1, 2014, to August 30, 2019. EP users were propensity score (PS) matched to users of CE/BZA. Incidence of endometrial cancer, endometrial hyperplasia, breast cancer, and eight additional cancer and cardiovascular outcomes were ascertained using claims-based algorithms. Rate ratios (RR) and differences pooled across databases were estimated using random-effects models. Results The study population included 10,596 CE/BZA and 33,818 PS-matched EP new users. Rates of endometrial cancer and endometrial hyperplasia were slightly higher among CE/BZA users (1.6 and 0.4 additional cases per 10,000 person-years), although precision was limited because of small numbers of cases (endometrial cancer: RR, 1.50 [95% confidence interval {CI}, 0.79-2.88]; endometrial hyperplasia: RR, 1.69 [95% CI, 0.51-5.61]). Breast cancer incidence was lower in CE/BZA users (9.1 fewer cases per 10,000 person-years; RR, 0.79; 95% CI, 0.58-1.05). Rates of other outcomes were slightly higher among CE/BZA users, but with confidence intervals compatible with a wider range of possible associations. Conclusions CE/BZA users might experience slightly higher rates of endometrial cancer and endometrial hyperplasia, and a lower rate of breast cancer, than EP users in the first years of use.

Cervical cancer screening in menopause: when is it safe to exit?

Abstract Importance and Objective Despite a decreasing incidence of cervical cancer in North America overall, disparities in screening and cervical cancer rates persist, especially in the postmenopausal age group. Methods We reviewed the literature regarding cervical cancer screening considerations for postmenopausal persons, with a focus on cervical cancer in postmenopausal persons, existing guidelines, screening methods, and gaps in care. Discussion and Conclusion Postmenopausal persons are an important population at risk because age 65 years in the United States and up to 70 years in some parts of Canada is a milestone for screening cessation if the criteria are met. Unfortunately, inadequate screening is common, with most women 65 years or older discontinuing (exiting) screening despite not meeting the criteria to do so. Screening cessation recommendations are nuanced, and if not all criteria are met, screening should be continued until they are. Cervical cancer screening should be stopped at the recommended age if adequate screening has occurred or at any age if life expectancy is limited or the patient has had a hysterectomy in the absence of high-grade preinvasive cervical lesions or cervical cancer. Human papillomavirus infection, which is causally linked to almost all cervical cancer cases, can persist or reactivate from a prior infection or can be newly acquired from sexual contact. With more persons aging with a cervix in place, the potential for cervical cancer has increased, and higher cancer rates may be observed if recommended screening is not adhered to. We propose an algorithm based on current cervical cancer screening guidelines to aid providers in identifying whether exit criteria have been met. Until adequate screening has been confirmed, cervical cancer screening should continue.

Use of exogenous hormones in those at increased risk for breast cancer: contraceptive and menopausal hormones in gene carriers and other high-risk patients

Abstract Importance and Objective Addressing the hormonal needs of individuals at increased risk of breast cancer (BC) can be a challenge. Observational, prospective, and case-control data support the safety of hormonal contraception in women, often with the added benefits of ovarian and endometrial cancer risk reduction. The majority of data on menopausal hormone therapy (HT) in the highest-risk patients comes from studies of patients with pathogenic variants in BRCA1 and BRCA2 who undergo early surgical menopause. The benefits of risk-reducing salpingo-oophorectomy are not minimized by HT, whereas its use mitigates accelerated osteoporosis and cardiovascular disease. In other patients at increased risk, such as with family history, studies have shown little risk with significant benefit. Methods We review evidence to help women's health practitioners aid patients in making choices. The paper is divided into four parts: 1, contraception in the very high-risk patient (ie, with a highly penetrant BC predisposition gene); 2, contraception in other patients at increased risk; 3, menopausal HT in the gene carrier; and 4, HT in other high-risk patients. Discussion and Conclusion Women at increased risk for BC both early and later in life should be offered reassurance around the use of premenopausal and postmenopausal hormone therapies. The absolute risks associated with these therapies are low, even in the very high-risk patient, and the benefits are often substantial. Shared decision making is key in presenting options, and knowledge of the data in this area is fundamental to these discussions.

Short-term impact of surgically induced menopause on cognitive function and wellbeing in women at high risk for ovarian cancer following risk-reducing bilateral salpingo-oophorectomy

Abstract Objective: Risk-reducing bilateral salpingo-oophorectomy (RRSO) is an effective strategy to prevent pelvic serous carcinoma for women at high risk of developing ovarian cancer; however, it results in premature menopause. Data is lacking to adequately counsel these women about potential effects of premature menopause on cognition and quality of life. Methods: A prospective study in premenopausal women at high risk of ovarian cancer to determine changes in cognition over time after RRSO and the impact of hormone therapy (HT) on cognition. Participants were surveyed before and after surgery using the Functional Assessment of Cancer Therapy-Cognitive questionnaire and questions regarding domains of wellbeing at 6, 12 and 18 months. Data was tested for changes across time using mixed model regression and logistic regression. Results: Fifty-seven women were included. Sixty-three percent of participants used HT. At 6 months postoperatively, perceived cognitive impairment declined by 5.5 points overall (4.4 in non-HT users and 6 in HT users), P = 0.003. The other domains of cognition assessed did not change significantly over time and the use of HT did not impact scores. Sleep disruption was common in this cohort and was not mitigated by HT. Self-reported depression improved after RRSO (P = 0.004). Conclusion: Women at high risk of ovarian cancer who choose RRSO may experience declines in cognition within the first 6 months of surgical menopause. HT may cause small declines in perceived cognitive impairment at 6 months after RRSO. Women can expect more sleep disruption after menopause, which is not mitigated by HT. Video Summary: http://links.lww.com/MENO/A697.

lncRNA HEIH accelerates cell proliferation and inhibits cell senescence by targeting miR-3619-5p/CTTNBP2 axis in ovarian cancer

Abstract Objective: Epithelial ovarian cancer is the most lethal malignancy in gynecology. Numerous studies have confirmed that long noncoding RNAs (lncRNAs) are abnormally expressed in ovarian cancer and are closely associated with the cell proliferation and senescence in cancers. However, the role and underlying molecular mechanism of long noncoding RNA high expression in hepatocellular carcinoma (HEIH) in ovarian cancer remain unknown. Methods: Experiments including Real-time quantitative polymerase chain reaction, RNA immunoprecipitation, luciferase reporter, Fluorescence in situ hybridization, western blot, colony formation assays, β-galactosidase senescence assay, cell apoptosis, proliferation, invasion, and migration assays were applied to investigate the role of HEIH in ovarian cancer. The data were expressed as the mean ± standard deviation. Student t test was used to compare the data between two groups. The one-way analysis of variance was applied to compare the data among multiple groups with Tukey post hoc test. All experiments were repeated three times. P < 0.05 was considered statistically significant. Results: Herein, HEIH expression was found to be up-regulated in ovarian cancer tissues (n = 25; twofold higher than normal tissues, P < 0.05) and cell lines (sixfold higher than normal ovarian epithelial cell line on average, P < 0.05), and high HEIH expression predicted poor prognosis (survival rate is about 25% after 40 mo; P < 0.05). Moreover, we found that HEIH accelerated proliferation, migration, and invasion, whereas inhibited cell senescence in ovarian cancer (P < 0.05). In mechanism, HEIH was confirmed to serve as a sponge for miR-3619-5p, and miR-3619-5p counteracted HEIH-mediated regulation of ovarian cancer (P < 0.05). Besides, cortactin-binding protein 2 (CTTNBP2) was found to be the downstream target of miR-3619-5p. Rescue assays validated that CTTNBP2 up-regulation significantly reversed the inhibitory effects of HEIH knockdown on ovarian cancer progression (P < 0.05). Furthermore, we found that HEIH facilitated tumor growth in vivo by regulating CTTNBP2 expression (P < 0.05). Conclusions: In conclusion, our research revealed that HEIH accelerated cell proliferation, migration and invasion, whereas inhibited cell senescence in ovarian cancer via targeting the miR-3619-5p/CTTNBP2 axis. These findings may be valuable for finding new therapeutic targets to improve ovarian cancer treatment.

The accuracy of ascites cytology in diagnosis of advanced ovarian cancer in postmenopausal women prior to neoadjuvant chemotherapy; Methodological issues - Answer

The accuracy of ascites cytology in diagnosis of advanced ovarian cancer in postmenopausal women prior to neoadjuvant chemotherapy; Methodological issues

The accuracy of ascites cytology in diagnosis of advanced ovarian cancer in postmenopausal women prior to neoadjuvant chemotherapy

AbstractObjective:To evaluate the accuracy of ascites cytology in the diagnosis of epithelial ovarian cancer among postmenopausal women.Methods:Ascites samples of women older than 51 years sent for cytology evaluation at our institution between 2010 and 2015 were retrospectively compared to final histology. The sensitivity, specificity, negative, and positive predictive values were calculated. Immunohistochemistry stain results were collected to determine diagnostic profiles.Results:A total of 551 patients, 51 years and over had both cytology and diagnostic histology samples. Of those, 161 patients had pathology confirmed ovarian tumors, 155 of which were malignant. Of the 155 cases of ovarian cancer, 125 patients had malignant cells on cytology examination (true positive); in 30 cases, ascites was negative for malignancy (false negative). In six cases both ascites and final pathology were negative for malignancy (true negative). There were no cases of positive cytology and negative final pathology (ie, no false-positive cases). The sensitivity, specificity, positive, and negative predictive value for cytology diagnosis of ovarian cancer were 80.6%, 100%, 100%, and 16.7%, respectively. Immunohistochemistry was done on cell blocks in 79 cases of ovarian cancer, 75 (94.9%) had profiles diagnostic for ovarian origin.Conclusions:Ascites cytology for postmenopausal women older than 51 years with immunohistochemistry is highly accurate in diagnosis of ovarian cancer. Neoadjuvant chemotherapy can be safely prescribed based on paracentesis evaluations.Video Summary:http://links.lww.com/MENO/A570.

Delay in diagnosis and increasing incidence of vulvar cancer: a root cause analysis

Obesity increases endometrial cancer risk in Chinese women with postmenopausal bleeding

Abstract Objective: We examined the relationship between body mass index (BMI) at referral and subsequent diagnosis of endometrial cancer in a cohort of Chinese women presenting with postmenopausal bleeding, to determine whether BMI of 25 kg/m2 would serve to delineate women at increased risk of endometrial cancer. Methods: This cohort included 4,164 Chinese women referred for postmenopausal bleeding from 2002 to 2013. For all women, a medical history was taken, and physical examination, BMI measurement, transvaginal pelvic ultrasonography, and endometrial sampling were performed. Additional investigations were performed as indicated clinically. The presence of risk factors for endometrial cancer and histological diagnoses were compared among groups defined by the standard Asian BMI cut-off values. Results: Within the cohort, 868 (20.8%) were overweight (BMI 23-24.9 kg/m2) and 1,611 (38.7%) were obese (BMI ≥25 kg/m2), and 162 (3.9%) had endometrial cancer. The prevalence of endometrial cancer correlated with BMI category (P < 0.001). On multivariate analysis, BMI ≥25 kg/m2 was independently associated with 1.57 times risk of endometrial cancer (95% CI 1.13-2.20, P = 0.008) compared with BMI less than 25 kg/m2. Conclusion: When managing postmenopausal bleeding in Chinese women, the Asian BMI standard for obesity at 25 kg/m2 identified 51% of endometrial cancers in this group and denoted a 57% increased risk of endometrial cancer. Thus obesity could be used to triage women presenting with postmenopausal bleeding for prioritized investigations.

Menopausal hormone therapy for BRCA-mutation carriers: attitudes of Israeli healthcare providers before and after a brief educational intervention

Abstract Objective: BRCA-mutation carriers are offered risk-reducing bilateral salpingo-oophorectomy (RRBSO) at age 35 to 40 years, leading to major life-quality and health-related issues associated with early menopause. Hormone therapy (HT) may significantly alleviate menopausal symptoms without increasing breast or ovarian cancer risk in BRCA carriers. We investigated attitudes of Israeli healthcare providers to HT post-RRBSO in BRCA carriers, before and after a brief educational intervention. Methods: In this pre-post survey of gynecologic departments in Israel, healthcare providers were given questionnaires (based on scores of 1-4) assessing attitudes to prescribing HT in different clinical scenarios, before and after an educational intervention on current knowledge about HT in BRCA-mutation carriers. Higher scores indicated higher tendency to prescribe HT. Mean and median scores were calculated for each scenario, and the association between scores and various healthcare providers’ characteristics were assessed. The change in attitude pre versus postintervention was evaluated, and the Cohen's d effect size was calculated. Results: Of the 200 healthcare providers who were offered participation, 162 responded. Of them, 25.3% were obstetricians, 13.6% gynecologists, 5.55% gynecologic-oncologists, 8% medical oncologists, 38.9% obstetrics-gynecology residents, and 8.6% were nurses. Median age was 44 (interquartile range 36-58); 42.6% were males. Higher score correlated weakly with older age, but did not correlate with gender or personal HT/menopause experience. Significantly higher mean and median preintervention scores were obtained by gynecologists (3.2±0.96; 4 [2.25-4]) and gynecologic-oncologists (3.6 ± 0.78; 4 [3.6-4.0]) than by medical oncologists (2.6 ± 1.06; 2.13 [1.88-3.81]), obstetricians (2.7 ± 1.09; 2.25 [1.88-4.0]), residents (2.48 ± 0.99; 2 [1.69-3.56]) or nurses (2.2 ± 0.92; 2 [1.5-2.69]). Overall scores were higher postintervention (P < 0.001, effect size d = 0.901). The change in scores postintervention was most prominent among younger participants and nurses. Conclusions: In Israel, it is acceptable to offer HT post-RRBSO to healthy BRCA-mutation carriers. Younger healthcare workers and nurses tend to be more hesitant, yet they are more likely to adopt a pro-HT attitude after an educational intervention. Such intervention is likely to improve overall care for BRCA-mutation carriers.

Does preventive oophorectomy increase the risk of depression in BRCA mutation carriers?

Abstract Objective: BRCA mutation carriers are advised to undergo bilateral salpingo-oophorectomy to prevent ovarian cancer. The abrupt hormonal withdrawal associated with early surgical menopause has been shown to increase the risk of depression and anxiety among women in the general population. The impact in women with a BRCA1 or BRCA2 mutation is not known. Methods: We undertook a matched prospective study of BRCA mutation carriers to evaluate the impact of oophorectomy on self-reported initiation of antidepressant use. We identified women with no personal history of cancer or depression and prospectively evaluated the frequency of self-reported medication use after surgery. Each exposed participant (oophorectomy) was randomly matched to a control participant (no oophorectomy) according to year of birth (within 3 years), BRCA mutation type (BRCA1 or BRCA2), and country of residence (Canada, United States, Poland). A total of 506 matched sets were included. We estimated the odds ratio (OR) and 95% confidence intervals (CIs) of antidepressant use (ever/never) following preventive oophorectomy in the entire study population and stratified by age at oophorectomy and by use of hormone therapy. Results: Oophorectomy was not associated with more frequent antidepressant use among BRCA mutation carriers (OR = 0.46; 95% CI 0.22-0.96). We observed reductions in the odds of antidepressant medication use among women who underwent oophorectomy before the age of 50 years (OR = 0.33; 95% CI 0.14-0.78) and among those who initiated hormone therapy use after oophorectomy (OR = 0.35; 95% CI 0.14-0.90). Findings were similar when the analysis was based on self-reported depression (rather than antidepressant use). Conclusions: Although based on a small number of women, these findings suggest that oophorectomy does not increase psychological distress among women at an elevated risk of ovarian cancer.

Exploring factors that impact uptake of risk-reducing bilateral salpingo-oophorectomy (RRBSO) in high-risk women

Abstract Objective: Only risk-reducing bilateral salpingo-oophorectomy (RRBSO) has been shown to reduce ovarian cancer deaths in high-risk women. Uptake of RRBSO is, however, suboptimal and reasons are not well defined. More information is needed about the barriers to RRBSO and patient needs for information and care. Methods: Cross-sectional study including the Perception of Cancer Risk Scale, factors affecting decision-making about RRBSO, and unmet information needs were measured using a purpose-designed questionnaire. Results: Of the 193 high-risk women aged 30 to 50 approached, 60 (31%) agreed to participate. Respondents were either considering or had recently undergone premenopausal RRBSO. Most (49/60) had no personal history of cancer; 11/60 had previous breast cancer. Overall, responses did not differ between pre- and post-RRBSO participants. The main barriers to RRBSO were surgical menopause and loss of fertility. Other concerns included the impact on sexual function and bone health. Reduction in ovarian cancer risk and prolonged life expectancy were the main drivers for RRBSO. Participants understood that RRBSO reduced cancer risk, although most substantially overestimated their personal ovarian cancer risk. High-risk women wanted more information about how to manage the short- and long-term consequences of surgical menopause. Conclusions: Concerns about surgical menopause and loss of fertility are barriers to RRBSO for high-risk women despite understanding the benefits of reduced cancer risk. There is an unmet need for more information about effectively managing the noncancer consequences of RRBSO in premenopausal women. Video Summary: http://links.lww.com/MENO/A478.

Factors affecting surgical decision-making in carriers of BRCA1/2 pathogenic variants undergoing risk-reducing surgery at a dedicated hereditary ovarian cancer clinic

Abstract Objective: Women with germline BRCA1/2 pathogenic variants have a significantly elevated lifetime risk of ovarian and fallopian tube cancer. Bilateral salpingo-oophorectomy (RRSO) is associated with a 90% reduction in the development of tubal and ovarian cancer. At our tertiary hospital, we have a dedicated clinic where women predisposed to hereditary ovarian/tubal cancer receive counseling on reproduction, risk reduction, surgical prophylaxis, and menopausal aftercare. The objective of this study was to evaluate the choices that Canadian women with BRCA1/2 pathogenic variants make regarding ovarian cancer risk reduction within this highly specialized multidisciplinary clinic. Methods: This retrospective chart review included all women with confirmed BRCA1/2 mutations referred to the Familial Ovarian Cancer Clinic at Women's College Hospital, Toronto, Canada over a 45-month time period. Patient demographics, preoperative consultation notes and investigations, intraoperative findings, and pathology were recorded. Results: A total of 191 women were included in our cohort; 140 (73.3%) underwent risk-reducing surgery and 51 (26.7%) deferred or declined surgery. In women who underwent surgical prevention (median age 45 [30-72] y), 123 (87.9%) underwent RRSO and 17 (12.1%) chose a risk-reducing bilateral salpingectomy with deferred oophorectomy. Of the women undergoing RRSO, 11 (8.9%) women chose concurrent hysterectomy. Prevalent themes affecting decision-making included fears around premature surgical menopause, family planning, and concerns around development of endometrial cancer related to tamoxifen. Conclusion: Women with BRCA1/2 pathogenic variants face challenging decisions regarding risk reduction and care providers must be knowledgeable and supportive in helping women make informed and individualized choices about their care. Video Summary: http://links.lww.com/MENO/A857.

The challenging screen detection of ovarian cancer in BRCA mutation carriers adhering to a 6-month follow-up program: results from a 6-years surveillance

Abstract Objective: Approximately 25% of ovarian cancer (OC) cases are related to an inherited predisposition. Genetic mutations for the oncosuppressor genes BRCA1 and 2 have the best-known linkage to a higher incidence of OC and breast cancer, in approximately 70% to 80% of hereditary OC cases. To provide the first comprehensive clinical description of screen-detected (SD) OCs during a 6-years surveillance of a cohort of young BRCA carriers and carriers who refuse risk-reducing salpingo-oophorectomy. Methods: A prospective cohort study in a university hospital describing 191 women with BRCA1 and 2 mutations adhering continuously to our surveillance between 2015 and 2020, including a 6-monthly evaluation of cancer antigen 125 (CA 125) with concomitant transvaginal ultrasound (TVUS) performed by a dedicated specialist. Main outcomes were tumor's laterality, CA 125 at diagnosis, TVUS and computed tomography (CT) findings. Results: Risk-reducing salpingo-oophorectomy was performed in 58/191 (30.4%) of mutation carriers during the study period (one OC case identified). Nine SD-OCs and no interval OCs were found in the remaining 133 women. OCs (FIGO stage I or II: 88.9%) occur mainly in BRCA 1 (77.8%), being bilateral in 85.7% BRCA 1 and unilateral in 100% BRCA 2. No lesions involved only the tubes: left ovaries/tubes were more frequently involved. We have described three new possible scenarios regarding imaging: 1) Evident cases (33.3%, TVUS and CT obvious for OC, CA 125 sensitivity: 100%), 2) Possible cases (55.6%, TVUS and CT are in general accordance, documenting new TVUS signs: increased solid pattern of the ovary with peripheral cortical small cysts, hypoechoic circular mass near the ovary, intraparenchymal small hyperechoic foci), and 3) Hidden cases (11.1%, the smallest lesion but the highest stage (IIIA2), with CA 125 44.2 U/mL and concomitant endometrial hyperplasia). Conclusions: Different diagnostic tools must integrate to ensure early diagnosis of OC in BRCA mutation carriers adhering to a follow-up program.

The effect of hormone therapy on breast density following risk-reducing salpingo-oophorectomy in women with an increased risk for breast and ovarian cancer

Abstract Objective: To compare the effect of tibolone to conjugated estrogens with medroxyprogesterone-acetate (CEE + MPA) on breast density, as a predictor for breast cancer risk, in women with a high risk of breast and ovarian cancer. Methods: Women aged 30-50 (N = 114) who had undergone risk-reducing salpingo-oophorectomy (RRSO) were randomized to tibolone or CEE + MPA. Results: Breast density decreased 46% after RRSO in untreated women, 39% after treatment with tibolone, and 17% after treatment with CEE + MPA; the decrease in breast density after CEE + MPA was significantly different compared with that of untreated women (P = 0.017). Conclusions: A decline in breast density is seen after premenopausal RRSO despite the use of both CEE + MPA or tibolone, although lower breast density is seen after tibolone use.

Maintaining cognitive function in surgically menopausal women: the importance of estrogen

The clinical performance of different cervical cancer screening strategies in premenopausal and postmenopausal women

Objectives: This study evaluates the clinical performance of high-risk human papillomavirus (HR-HPV) testing, liquid-based cytology (LBC), and HR-HPV and LBC co-testing for detecting cervical intraepithelial neoplasia (CIN) in premenopausal and postmenopausal women. Methods: A total of 6,085 premenopausal and 4,766 postmenopausal women were recruited for cervical cancer screening using LBC and HR-HPV testing. Following screening, colposcopy and biopsy for pathology were performed according to established protocols. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) for detecting CIN2/3 or worse (CIN2/3+). Results: The sensitivity of LBC for detecting CIN2+ was 73.4% (95% CI=60.7%-83.3%) in premenopausal women and 58.8% (95% CI=44.2%-72.1%) in postmenopausal women. In contrast, significantly higher sensitivities were observed for HR-HPV testing and HR-HPV and LBC co-testing, both of which showed sensitivities of 96.9% (95% CI=88.2%-99.5%) in premenopausal women and 98.0% (95% CI=88.2%-99.9%) in postmenopausal women. While HR-HPV and LBC co-testing demonstrated superior specificity compared with HR-HPV testing alone [95.8% (95% CI=95.2%-96.3%) vs. 86.3% (95% CI=85.4%-87.1%) in premenopausal women; 93.7% (95% CI=92.9%-94.3%) vs. 80.6% (95% CI=79.5%-81.7%) in postmenopausal women], it also exhibited the highest PPV for CIN2+ prediction [19.6% (95% CI=15.4%-24.4%) in premenopausal women; 14.5% (95% CI=10.9%-18.6%) in postmenopausal women] compared with LBC or HR-HPV testing alone. Conclusions: HR-HPV and LBC co-testing demonstrates comparable high clinical accuracy for detecting CIN2+ in both premenopausal and postmenopausal women, with a preference for its use in postmenopausal screening.

Quality of life and associated factors in climacteric women surviving gynecological cancer: an observational study

Objective: To identify factors associated with climacteric symptoms and quality of life in women with and without a history of gynecological cancer. Methods: A cross-sectional study was conducted from November 2022 to May 2024 in a tertiary hospital’s menopause clinic in Campinas, Brazil. Women aged 30 years or above with climacteric symptoms were included, excluding those undergoing treatment for these symptoms or with debilitating conditions. Climacteric symptoms were assessed using the Menopause Rating Scale (MRS), and quality of life by the Women’s Health Questionnaire (WHQ). Statistical analyses included descriptive tests, χ 2 , Mann-Whitney, and Poisson regression ( P <0.05). Results: A total of 184 women (mean age 49.6±9.5 y) were included, of whom 54.3% had a history of cancer (29.3% breast, 14.1% cervical, 7.6% ovarian, 2.7% endometrial, 0.5% vulvar). The mean age at menopause was 44.2±6.7 years; 58.5% had treatment-induced menopause. Median MRS and WHQ scores were 27 and 0.58, respectively. No association was found between a history of cancer and overall symptom severity or reduced quality of life. In multivariate analysis, worse quality of life was independently associated with higher severity of somatovegetative symptoms (PR: 2.10; 95% CI: 1.16-3.79) and psychological symptoms (PR: 1.90; 95% CI: 1.07-3.36). Conclusion: A history of gynecological cancer was not associated with increased climacteric symptoms or poorer quality of life. Menopausal symptoms, especially vasomotor and psychological domains, were the main factors related to lower quality of life.

Oncofertility and female fertility preservation: a clinical update

Certain cancer and medical treatments can be harmful to fertility by depleting the egg supply. The risk to fertility is dependent on the patient’s age, ovarian reserve before treatment, specific medication, or treatment and dosage. For women at risk of developing ovarian insufficiency because of gonadotoxic treatment, fertility preservation options include embryo, oocyte, and ovarian-tissue cryopreservation. Surgical procedures that can protect fertility for patients facing pelvic radiation therapy include ovarian transposition and uterine transposition. This Practice Pearl will focus on fertility preservation options for women facing medical treatment, a core component of oncofertility.

Effects of menopausal hormone therapy on the risk of ovarian cancer: Health Insurance Database in South Korea–based cohort study

Abstract Objective This study aimed to evaluate the risk of ovarian cancer associated with hormone therapy regimens using a Korean population–based study. Methods This retrospective cohort study used national health checkup and insurance data from January 1, 2002, to December 31, 2019, provided by Korea's National Health Insurance Service. Women older than 40 years who recorded “menopause” in the questionnaire from 2002 to 2011 were included in this study. Menopausal hormone therapy (MHT) preparations were classified into tibolone, combined estrogen plus progestin by the manufacturer, combined estrogen plus progestin by physician, estrogen, and topical estrogen groups. The number of participants recorded as menopausal during the national health examination between 2002 and 2011 was 2,506,271. The MHT and non-MHT groups consisted of 373,271 and 1,382,653 patients, respectively. The hazard ratios (HR) of ovarian cancer according to MHT type, age at inclusion, body mass index, region, socioeconomic status, Charlson comorbidity index, age at menarche, age at menopause, parity, smoking, alcohol consumption, physical exercise, and period from menopause to inclusion were evaluated. Results The risk of ovarian cancer was reduced in the tibolone group (HR, 0.84; 95% confidence interval, 0.75-0.93; P = 0.003) and in patients in rural areas (HR, 0.90; 95% confidence interval, 0.845-0.98; P = 0.013). The risk of ovarian cancer was not related to the other MHT treatments. Conclusion Tibolone was associated with a lower risk of ovarian cancer. No other MHT was associated with ovarian cancer.

Satisfaction with prophylactic risk-reducing salpingo-oophorectomy in BRCA mutation carriers is very high and little dependent on the participants’ characteristics at surgery: a prospective study

Abstract Objective: BRCA carriers are recommended to undergo prophylactic risk-reducing salpingo-oophorectomy (RRSO). Possible adverse health impacts of RRSO, particularly when done before natural menopause, can reduce the long-term satisfaction with this risk-reducing strategy. The aim of this study was to prospectively evaluate the level of satisfaction of women undergoing RRSO, also in relation to some specific characteristics at RRSO. Methods: A prospective cohort study was performed in the Modena Family Cancer Clinic of the University Hospital of Modena (Italy). All BRCA1/2 confirmed mutation carriers who decided to undergo RRSO were recruited between 2016 and 2019. Results: Fifty-five women (29 BRCA1 and 26 BRCA2) (mean age: 50.4 ± 7.7 years [range 35-79]) were included with a mean follow-up after RRSO of 660.9 days (1.8 years) (range 35-1,688 days) (median: 549 days). No intraepithelial (Serous Tubal Intraepithelial Carcinoma)/invasive cancers were found (0%) at RRSO. No vasomotor symptoms at 1 month after surgery were reported by 11/22 (50%) premenopausal women at RRSO. All women (100%) with new “RRSO-caused” vasomotor symptoms with no previous breast cancer initiated postmenopausal hormone therapy. At the final follow-up the satisfaction rate (0-100 visual analog scale points) of the participants was 96.4 ± 8.6 points (range 62-100). To the question “Would you undergo RRSO again if it was proposed today? (0-100 visual analog scale points)” the answer was 99.4 ± 3.2 points (range 79-100). These scores were in general very high and did not change in the different groups according to pre/postmenopausal status at RRSO, cancer survivors versus healthy women at RRSO, BRCA status, hormone therapy users/nonusers after RRSO, “RRSO-caused” symptoms versus not RRSO-caused (P > 0.05). Conclusions: Findings from this prospective study suggest that satisfaction with RRSO is very high and little dependent on the participants’ characteristics at surgery. Women at high risk for ovarian cancer are very satisfied with their choice of risk-reduction strategy. Video Summary: http://links.lww.com/MENO/A712.

Estrogen therapy in patients with gynecologic cancer: a survey of gynecologists and oncologists in the United States

Objective: Endometrial cancer (EC) and epithelial ovarian cancer (EOC) affect women of all ages, and the incidence of endometrial cancer in premenopausal women is rising. Menopause can be detrimental to longevity and quality of life, but evidence suggests estrogen therapy (ET) is safe in these patients. The purpose of this study was to evaluate the practice patterns of gynecologists and gynecologic oncologists (GYO) in the United States in regards to prescription of ET to gynecologic cancer patients. It was hypothesized that ET is underused in this population. Methods: In 2024, a web-based survey was administered through email or postcard mailer to members of the Society of Gynecologic Oncology and the American College of Obstetricians and Gynecologists. Participants were asked demographic questions and whether they provide ET for patients with a history of EC, EOC, and cervical cancer. Results: A total of 293 participants answered questions about at least one type of cancer. When asked if willing to provide ET, 63.82% (187/293) selected “yes” for EC, 65.19% (176/270) for EOC, and 96.8% (274/283) for cervical cancer. Due to lack of heterogeneity, cervical cancer was omitted from analysis. Gynecologic oncology providers were more likely than OBGYNs to prescribe ET for EC ( P = 0.0006) and EOC patients ( P = 0.0009). Those in practice for 10 or more years ( P = 0.022), or who identified as male ( P = 0.019), were more likely to prescribe ET to EC patients. Of those who do not prescribe ET, the most common reasons were belief that hormones are contraindicated, better options exist, and risk outweighs benefits. These options were selected more frequently by OBGYNs than GYOs. Conclusion: Many gynecologists, and some gynecologic oncologists, are uncomfortable prescribing hormone therapy to patients with a history of endometrial or epithelial ovarian cancer, despite evidence suggesting its safety. This indicates a need for clinician education to ensure patients are counseled appropriately about options for treating menopausal symptoms.

Indication for diagnostic oophorectomy without radiographic evidence: two cases of postmenopausal androgen-secreting ovarian hyperplasia

Objectives: Hyperandrogenism, while one of the most common endocrine disorders in women, is relatively uncommon in the postmenopausal population. When present, it may be indicative of an underlying rare androgen-secreting ovarian tumor. Here, we report 2 cases: a 63-year-old woman with 2 years of male-pattern baldness and hirsutism and a 71-year-old female with 2 years of progression to complete scalp alopecia, hirsutism, and libido changes. Methods: Upon endocrine evaluation, testosterone concentrations were markedly elevated for both patients. In the first case, there was no radiologic evidence of ovarian mass on ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI). In the second case, transvaginal ultrasound (TVUS) detected an ovarian lesion, which guided further radiologic workup; however, positron emission tomography (PET) and MRI were unremarkable. Results: In case 1, surgical pathology upon total hysterectomy with bilateral salpingo-oophorectomy revealed bilateral Leydig cell hyperplasia. For case 2, surgical intervention revealed a right ovarian steroid cell tumor with contralateral stromal and hilus cell hyperplasia. Conclusion: In both patients, testosterone levels normalized immediately following total hysterectomy with bilateral salpingo-oophorectomy. In conjunction, these 2 cases highlight the importance of having a high clinical suspicion for steroid cell tumors or hyperplasia in postmenopausal women presenting with features of hyperandrogenism and elevated testosterone levels despite unrevealing radiographic findings.

Association between hormone therapy and glioma risk in US women: a cancer screening trial

Abstract Objective Gliomas are the most common primary brain tumors in adults, and the role of hormone therapy (HT) in their development remains controversial. This study with a cohort design aimed to investigate the association between HT use and glioma risk using the data from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Methods We analyzed data from 75,335 women, aged 50-78, who were enrolled between 1993 and 2001. The median follow-up period was 11.82 years. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationship between HT use and glioma risk, adjusting for various potential confounders. Results Over the follow-up period, 101 participants were diagnosed with glioma. After adjusting for relevant variables, there was no significant association between HT use and glioma risk (HR, 1.16; 95% CI, 0.75-1.81). Similarly, no significant associations were found when considering HT status or duration of use. However, in subgroup analysis by education, marital status, body mass index, oral contraceptive, hysterectomy, ovariectomy, ever been pregnant, age at menarche, and age at menopause, we found that a significant positive association was only observed in the group with at least college graduate (HR, 3.00; 95% CI, 1.02-8.84). The interaction effect for education was not significant ( P = 0.056) Conclusions Our findings suggest no overall link between HT use and glioma risk. Further research is needed to confirm these results.

Public awareness and provider counseling regarding postmenopausal bleeding as a symptom of endometrial cancer

Abstract Objectives Our study aims to understand public knowledge of postmenopausal bleeding as an endometrial cancer symptom and how past provider counseling on postmenopausal bleeding affects knowledge and care-seeking behaviors related to postmenopausal bleeding. Methods This was a cross-sectional survey study of people assigned female at birth. Study participants were recruited at a university research facility located at the Minnesota State Fair in September 2021. Participants answered questions about demographics, endometrial cancer knowledge, whether they had received counseling about postmenopausal bleeding, and whether and when they would present for care after experiencing postmenopausal bleeding. Results Six hundred forty-eight surveys were completed and included in analyses. Sixty-three percent of participants identified postmenopausal bleeding as a symptom of endometrial cancer. Those who correctly selected this symptom were more likely to be born in the United States, have a college education or higher, and have private insurance. Of the 145 postmenopausal participants, 46.5% reported that their provider counseled them on postmenopausal bleeding. Fifty-nine percent of the postmenopausal participants reported that they would tell their provider if they had postmenopausal bleeding after only one episode. Conclusions There is a need for increased recognition of postmenopausal bleeding and provider counseling on postmenopausal bleeding, and educational interventions should focus on public and provider awareness of endometrial cancer risks and symptoms.

Spontaneous pyometra in postmenopausal women and gynecologic cancer—a preliminary study based on experience of a tertiary medical center

Objective: Pyometra is a rare but serious condition, particularly in postmenopausal women. While commonly linked to postpartum or post-surgical complications, spontaneous pyometra may also be associated with underlying gynecologic malignancies. We aim to examine the association between postmenopausal spontaneous pyometra (PMSP) and gynecologic cancers. Methods: A retrospective review of consecutive women admitted with pyometra between 2007 and 2023, at a university-affiliated tertiary medical center. Demographic and clinical data were reviewed. Women with pyometra and gynecologic cancer were compared with those without. Results: Of 231 admissions for pyometra, 47 women with PMSP were identified. The cohort was divided into a benign group (n=35, 74.4%) and malignancy group (n=12, 25.6%). Endometrial carcinoma (n=8, 67%) was the predominant malignancy, followed by cervical cancer (n=4, 33%). Although age, age at menopause, and parity showed no significant statistical differences between the groups, a higher body mass index was significantly associated with endometrial malignancy ( P = 0.014). Postmenopausal bleeding as an accompanying symptom to pyometra was also more common in the malignancy group ( P =0.001). The prevalence of PMSP was 1.1% for endometrial cancer and 2.2% for cervical cancer. Conclusions: PMSP is significantly associated with gynecologic malignancies, particularly endometrial and cervical cancers. Notably, women with endometrial malignancy had a higher BMI and were more likely to present with accompanying postmenopausal bleeding. These findings suggest that in postmenopausal women presenting with spontaneous pyometra, clinicians should maintain a high index of suspicion for malignancy. Early identification and appropriate management are crucial to improving patient outcomes.

Socioeconomic marginalization is associated with delayed medical consultation among endometrial cancer patients presenting with postmenopausal bleeding

Abstract Objective The key presenting symptom of endometrial cancer is abnormal uterine bleeding, most commonly postmenopausal bleeding (PMB), which facilitates early-stage diagnosis. This study aimed to investigate factors influencing delayed medical consultation for PMB, and particularly its association with social determinants. Methods This is a retrospective study that included endometrial cancer patients receiving care in a gynecologic oncology department of a tertiary medical center who presented with PMB. Demographic and oncologic data was collected from the electronic medical charts. Israeli bureau of statistics data was used to assess community socioeconomic index, based on address. Women seeking consultation more than 1 month after experiencing PMB were compared to those seeking earlier care. Results Two hundred ninety-five women were included in the study. One hundred seventy-three sought care after less than 1 month of PMB (early presenters) and 122 sought care after more prolonged PMB (late presenters). Late presenters were more likely to be socioeconomically marginalized (odds ratio [OR], 1.8; P = 0.018), higher body mass index (OR, 1.040; P = 0.022), and greater parity (OR, 1.170; P = 0.032). Socioeconomic marginalized patients experienced a 7-day longer delay from diagnosis to surgery compared to their privileged counterparts (59 vs 52 d, P = 0.022). Conclusions Among women with endometrial cancer, longer duration of PMB before first seeking medical consultation is associated with socioeconomic marginalization. This highlights the need for targeted interventions to minimize delays in diagnosis and treatment initiation among patients from marginalized communities.

Efficacy, tolerability, and endometrial safety of ospemifene compared with current therapies for the treatment of vulvovaginal atrophy: a systematic literature review and network meta-analysis

Abstract Importance Ospemifene is a novel selective estrogen receptor modulator developed for the treatment of moderate to severe postmenopausal vulvovaginal atrophy (VVA). Objective The aim of the study is to perform a systematic literature review (SLR) and network meta-analysis (NMA) to assess the efficacy and safety of ospemifene compared with other therapies used in the treatment of VVA in North America and Europe. Evidence Review Electronic database searches were conducted in November 2021 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized or nonrandomized controlled trials targeting postmenopausal women with moderate to severe dyspareunia and/or vaginal dryness and involving ospemifene or at least one VVA local treatment were considered. Efficacy data included changes from baseline in superficial and parabasal cells, vaginal pH, and the most bothersome symptom of vaginal dryness or dyspareunia, as required for regulatory approval. Endometrial outcomes were endometrial thickness and histologic classifications, including endometrial polyp, hyperplasia, and cancer. For efficacy and safety outcomes, a Bayesian NMA was performed. Endometrial outcomes were compared in descriptive analyses. Findings A total of 44 controlled trials met the eligibility criteria (N = 12,637 participants). Network meta-analysis results showed that ospemifene was not statistically different from other active therapies in most efficacy and safety results. For all treatments, including ospemifene, the posttreatment endometrial thickness values (up to 52 wk of treatment) were under the recognized clinical threshold value of 4 mm for significant risk of endometrial pathology. Specifically, for women treated with ospemifene, endometrial thickness ranged between 2.1 and 2.3 mm at baseline and 2.5 and 3.2 mm after treatment. No cases of endometrial carcinoma or hyperplasia were observed in ospemifene trials, nor polyps with atypical hyperplasia or cancer after up to 52 weeks of treatment. Conclusions and Relevance Ospemifene is an efficacious, well-tolerated, and safe therapeutic option for postmenopausal women with moderate to severe symptoms of VVA. Efficacy and safety outcomes with ospemifene are similar to other VVA therapies in North America and Europe.

Triage method for endometrial biopsy in postmenopausal women: a multicenter retrospective cohort study

Abstract Objective To identify the optimal triage procedure for endometrial biopsies in postmenopausal women. Methods The clinical information of 470 postmenopausal women with endometrial biopsy results and postmenopausal bleeding (PMB) and/or transvaginal ultrasonography (TVU) abnormalities were collected at the gynecology departments of four general hospitals from March 2021 to March 2022. In the validation cohort, 112 women with TVU abnormalities who underwent endometrial biopsy at Xiangya hospital between May 2022 and May 2023 were enrolled. The endpoint was the final diagnosis based on hysteroscopy reports and biopsy pathology results. The sensitivity, specificity, positive predictive value, and negative predictive value were compared among the three triage methods. A nomogram prediction model was developed and validated. Results Referring women with TVU abnormalities for endometrial biopsy identified 100% malignant/premalignant lesions despite low specificity (19.7%). Among women with measurable endometrial thickness (ET), we suggest that the ET cutoff value for biopsy referral should be ≥4 mm. The PMB (odds ratio [OR], 3.241; 95% confidence interval [CI], 1.073-9.789), diabetes (OR, 10.915; 95% CI, 3.389-35.156), and endometrial thickness (OR, 1.277; 95% CI, 1.156-1.409) were independent predictive factors for endometrial (pre)malignancy. A nomogram prediction model was constructed (area under curve [AUC] = 0.802, 95% CI: 0.715 to 0.889). The ideal cutoff point was 22.5, with a sensitivity of 100.0% and a specificity of 15.7%. The external validation achieved an AUC of 0.798 (95% CI, 0.685-0.911). Conclusions It was possible to refer all postmenopausal women with TVU abnormity (ET ≥ 4 mm or other abnormal findings) for endometrial biopsy. Among women with TVU abnormalities, a nomogram was constructed, and a score greater than 22.5 suggested the need for referral for endometrial biopsy, while a score less than 22.5 suggested that regular follow-up was required, further improving the triage procedure.

Use of menopausal hormone therapy beyond age 65 years and its effects on women's health outcomes by types, routes, and doses

Abstract Objectives The study aims to assess the use of menopausal hormone therapy beyond age 65 years and its health implications by types of estrogen/progestogen, routes of administration, and dose strengths. Methods Using prescription drug and encounter records of 10 million senior Medicare women from 2007-2020 and Cox regression analyses adjusted for time-varying characteristics of the women, we examined the effects of different preparations of menopausal hormone therapy on all-cause mortality, five cancers, six cardiovascular diseases, and dementia. Results Compared with never use or discontinuation of menopausal hormone therapy after age 65 years, the use of estrogen monotherapy beyond age 65 years was associated with significant risk reductions in mortality (19% or adjusted hazards ratio, 0.81; 95% CI, 0.79-0.82), breast cancer (16%), lung cancer (13%), colorectal cancer (12%), congestive heart failure (CHF) (5%), venous thromboembolism (3%), atrial fibrillation (4%), acute myocardial infarction (11%), and dementia (2%). For the use of estrogen and progestogen combo-therapy, both E+ progestin and E+ progesterone were associated with increased risk of breast cancer by 10%-19%, but such risk can be mitigated using low dose of transdermal or vaginal E+ progestin. Moreover, E+ progestin exhibited significant risk reductions in endometrial cancer (45% or adjusted hazards ratio, 0.55; 95% CI, 0.50-0.60), ovarian cancer (21%), ischemic heart disease (5%), CHF (5%), and venous thromboembolism (5%), whereas E+ progesterone exhibited risk reduction only in CHF (4%). Conclusions Among senior Medicare women, the implications of menopausal hormone therapy use beyond age 65 years vary by types, routes, and strengths. In general, risk reductions appear to be greater with low rather than medium or high doses, vaginal or transdermal rather than oral preparations, and with E2 rather than conjugated estrogen.

Endometrial microbiota from endometrial cancer and paired pericancer tissues in postmenopausal women: differences and clinical relevance

Abstract Objective The incidence of postmenopausal endometrial cancer (EC) is rising, and the uterine microbiota has recently been suggested to be an etiology of EC. However, the differences in microbiota profiles in paired EC and the adjacent non-EC endometrium, and the functional microbiota of clinical relevance remain largely unknown. Therefore, we examined the differences in microbiota profiles between EC and non-EC endometrium and investigated their clinical relevance to EC. Methods Twenty-eight EC-affected postmenopausal women undergoing hysterectomy were enrolled. Endometrial microbiome from paired EC and adjacent non-EC tissue samples were detected using 16S rRNA sequencing, and the data were analyzed using R language software. Results The α diversity and evenness of the endometrial bacterial community significantly increased in EC tissues than those in pericancer tissues (P < 0.05 for all variables). Lactobacillus and Gardnerella were the main bacterial genera present in both EC and adjacent non–EC-invading endometrium, whereas Prevotella, Atopobium, Anaerococcus, Dialister, Porphyromonas, and Peptoniphilus were more commonly enriched in the EC endometrium (corrected P < 0.05 for all variables). Finally, the abundance of some observed endometrial bacteria was associated with clinical aspects, particularly the vaginal pH, vaginal Lactobacillus abundance, and EC clinical stage. Conclusions Paired EC and adjacent non-EC endometrium harbor different endometrial microbiota, and the functional bacteria residing in the endometrium are clinically relevant but require further investigation.

Cytological characteristics of premalignant cervical epithelial lesions in postmenopausal women based on endocrine indices and parakeratosis

Abstract Objective To identify useful cytological findings for detecting premalignant lesions in postmenopausal women, cervicovaginal smear samples were analyzed and compared between women with or without premalignant lesions based on endocrine indices and presence of parakeratosis (PK). Methods The cervicovaginal smear samples of postmenopausal women with premalignant lesions (n = 94) and those who were without (n = 344), who were diagnosed between 2012 and 2014 were retrieved and analyzed. Women cytologically diagnosed with malignancy or those with suspicion of malignancy were excluded from this study. Cytological endocrine indices, such as the maturation index (MI) and eosinophilic index (EI) and the prevalence of PK were compared between the groups and analyzed using the 2 × 2 χ2 test. The association of endocrine indices combined with the presence of PK and histological findings was also evaluated. Results Postmenopausal women with premalignant lesions had higher endocrine indices (EI of ≥11%; 65% vs. 43%, P < 0.01, f = 0.18) and a higher prevalence of PK positivity (PK ≥ 1; 46% vs. 7%, P < 0.01, f = 0.44) than those without lesions. Further analysis indicated that the combination of high EI and the presence of PK in postmenopausal women with cytological premalignant cases was highly associated with histological squamous intraepithelial lesions (SIL) (86% in women with premalignant lesions vs. 53% in those without; P = 0.01, f = 0.34). Conclusion Our research demonstrated that high EI and PK positivity were correlated with SIL in postmenopausal women. These cytological findings could provide potential diagnostic clues for detecting dysplasia.

Factors associated with use of hormone therapy after preventive oophorectomy in BRCA mutation carriers

Abstract Objective: Bilateral salpingo-oophorectomy (oophorectomy) is recommended to women with a germline BRCA1 or BRCA2 mutation before natural menopause to prevent ovarian and fallopian tube cancer. The adverse effects of early surgical menopause are well established. Although many of the side effects can be ameliorated by the use of hormone therapy (HT); use of HT in this group of predominantly young patients remains suboptimal. The goal of this study was to identify the frequency of HT use, as well as predictors of HT uptake in BRCA mutation carriers who underwent preventive oophorectomy before natural menopause. Methods: Eligible participants were identified from a longitudinal study of BRCA mutation carriers. We included premenopausal women with no personal history of cancer who underwent oophorectomy before age 50 and who had a minimum of 2 years of follow-up. Detailed information on HT use and other important variables was collected by a research questionnaire every 2 years. Descriptive statistics were used to evaluate the use of HT in various subgroups. Results: A total of 793 women with a BRCA1 or BRCA2 mutation were included in this analysis. The mean age at oophorectomy was 42 years (range 28-49). Sixty-one percent of the women reported using HT after oophorectomy. Factors associated with HT use included young age at surgery, a high level of education and preventive mastectomy. Conclusions: The uptake of HT after oophorectomy in women with a BRCA1 or BRCA2 mutation varies by age, education, and surgical history. Clinician and patient awareness may lead to better utilization of HT in women who undergo oophorectomy at an early age to help mitigate the adverse effects associated with surgical menopause.

Executive function after risk-reducing salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers: does current mood and early life adversity matter?

Abstract Objective: Despite the fact that negative mood and executive dysfunction are common after risk-reducing salpingo-oophorectomy (RRSO), occurring in up to a third of women, little is known about risk factors predicting these negative outcomes. Adverse childhood experiences (ACE) predict poorer health in adulthood and may be a risk factor for negative outcomes after RRSO. Given the complex relationship between early life stress, affective disorders, and cognitive dysfunction, we hypothesized that ACE would be associated with poorer executive function and that mood symptoms would partially mediate this relationship. Methods: Women who had undergone RRSO were included in the study (N = 552; age 30-73 y). We measured executive function (continuous performance task, letter n-back task, and Brown Attention Deficit Disorder Scale Score), exposure to early life stress (ACE questionnaire), and mood symptoms (Hospital Anxiety and Depression Scale). Generalized estimating equations were used to evaluate the association between ACE and executive dysfunction and the role of mood symptoms as a mediator in this relationship. Results: ACE was associated with greater severity of subjective executive dysfunction (adjusted mean difference [aMD] = 7.1, P = 0.0005) and worse performance on both cognitive tasks (continuous performance task: aMD = –0.1, P = 0.03; n-back: aMD = –0.17, P = 0.007). Mood symptoms partially mediated ACE associations with sustained attention (21.3% mediated; 95% CI: 9.3%-100%) and subjective report of executive dysfunction (62.8% mediated; 95% CI: 42.3%-100%). Conclusions: The relationship between childhood adversity and executive dysfunction is partially mediated by mood symptoms. These data indicate that assessing history of childhood adversity and current anxiety and depression symptoms may play a role in treating women who report cognitive complaints after RRSO. Video Summary: http://links.lww.com/MENO/A571.

Postmenopausal giant ovarian tumor: a rare case report and literature review

Abstract Objective A giant ovarian tumor weighing 62 kg and containing 51 L cyst fluid is rare among postmenopausal women, and an early diagnosis contributes to a good prognosis. Methods We report a case of a 62-kg giant ovarian tumor, the largest ovarian tumor ever reported in China. A 64-year-old woman with a giant pelvic abdominal mass underwent surgery. Because of the occurrence of serious perioperative and postoperative complications, we then conducted a literature review to investigate possible risk factors for severe complications. Results During the operation, 51 L of intratumoral fluid was drained, and a giant ovarian tumor of approximately 62 kg was removed. The pathological examination showed that the tumor was a mucinous borderline one. The patient had perioperative hypotension and postoperative respiratory failure. After a comprehensive literature review, we found that the occurrence of serious complications may not be related to tumor volume and weight but age and the amount of fluid in the tumor. Conclusions The high incidence of severe complications should be carefully considered when huge ovarian tumors or tumors containing a large amount of tumor fluid in postmenopausal women are removed.

When gynecologic surgery is needed, are women's ovarian function being preserved as often as it should be?

Age-associated trends of vulvar cancer in the US

Abstract Objective: Medical societies have over the years moved away from recommending routine pelvic examinations in older, asymptomatic women above age 65. Consequently, vulvar examination is a largely neglected component of the physical examination, unless sent to a specialist for gynecological evaluation. In recognition of these recommendations, we analyzed US trends in vulvar cancer incidence, age, and stage at diagnosis, survival, and association with human papillomavirus (HPV). Methods: Cases of vulvar and cervical cancer from 1992 to 2014 were extracted from the National Cancer Institute's Surveillance, Epidemiology, and End Results and Centers for Disease Control's data on age at diagnosis, stage of disease, and HPV-association were analyzed and compared. Incidence and mortality rates were extracted and calculated. Results: From 1992-2014, there was a 14.3% increase in vulvar cancer rates. The absolute average incidence rate was 2.25, with HPV still being seen in vulvar carcinomas in women 65 years and above. Cervical cancer mortality rates declined by 34.2%, while vulvar cancer death rates were unchanged. We show increased intervals for cervical cancer screening is associated with later stage vulvar cancer detection. The proportion of vulvar cancer cases diagnosed in women age <50 steadily decreased, from 42.05% of cases in 1992-1996 to 19.75% of total cases in 2012-2015. Meanwhile, vulvar cancer cases diagnosed in women > 65 yo increased from 36.62% of cases in 1992-1996 to 49.82% of cases in 2012-2015. Conclusion: The incidence of vulvar cancer increases with age, with the median age of diagnosis 67 years, with HPV (+) tumors occurring into 70's and 80's. Though medical societies do not routinely recommend an external genital examination in women 65 years and above, we show this is a missed opportunity to improve cancer outcomes in some older females. Video Summary: http://links.lww.com/MENO/A678.

Gray matter volume in women with the BRCA mutation with and without ovarian removal: evidence for increased risk of late-life Alzheimer's disease or dementia

Abstract Objective Ovarian removal prior to spontaneous/natural menopause (SM) is associated with increased risk of late life dementias including Alzheimer's disease. This increased risk may be related to the sudden and early loss of endogenous estradiol. Women with breast cancer gene mutations (BRCAm) are counseled to undergo oophorectomy prior to SM to significantly reduce their risk of developing breast, ovarian, and cervical cancers. There is limited evidence of the neurological effects of ovarian removal prior to the age of SM showing women without the BRCAm had cortical thinning in medial temporal lobe structures. A second study in women with BRCAm and bilateral salpingo-oophorectomy (BSO) noted changes in cognition. Methods The present, cross-sectional study examined whole-brain differences in gray matter (GM) volume using high-resolution, quantitative magnetic resonance imaging in women with BRCAm and intact ovaries (BRCA-preBSO [study cohort with BRCA mutation prior to oophorectomy]; n = 9) and after surgery with (BSO + estradiol-based therapy [ERT]; n = 10) and without (BSO; n = 10) postsurgical estradiol hormone therapy compared with age-matched women (age-matched controls; n = 10) with their ovaries. Results The BRCA-preBSO and BSO groups showed significantly lower GM volume in the left medial temporal and frontal lobe structures. BSO + ERT exhibited few areas of lower GM volume compared with age-matched controls. Novel to this study, we also observed that all three BRCAm groups exhibited significantly higher GM volume compared with age-matched controls, suggesting continued plasticity. Conclusions The present study provides evidence, through lower GM volume, to support both the possibility that the BRCAm, alone, and early life BSO may play a role in increasing the risk for late-life dementia. At least for BRCAm with BSO, postsurgical ERT seems to ameliorate GM losses.

Analysis of factors related to endometrial cancer in postmenopausal women with endometrial thickening

Abstract Objective To investigate the factors related to endometrial cancer (EC) in postmenopausal women with endometrial thickening and the value of endometrial thickness (ET) in predicting EC. Methods A retrospective study of 385 referrals to our department for hysteroscopic diagnostic curettage assessment was carried out. Univariate analysis and multiple logistic regression analysis were used to identify the independent contributors to the development of EC. The ability of ET to predict EC was evaluated by receiver operating characteristic curve analysis. Results The follow-up period from the identification of endometrial thickening to pathological confirmation of EC was from 2 weeks to 3 months. In the postmenopausal bleeding (PMB) group, a total of 47 participants’ specimens were pathologically malignant. Older age and polypoid mass-like lesions (P < 0.001) were independent factors associated with EC. The optimal critical value of ET in predicting EC was 9.5 mm, with a sensitivity and specificity of 70.21% and 70.67%, respectively. In the non-PMB group, six participants had evidence of malignant pathology, and only polypoid mass-like lesions were an independent factor associated with EC (P < 0.001). Conclusions For postmenopausal women with increased ET and PMB, older age, thicker ET, and polypoid mass-like lesions on transvaginal ultrasound were independent associated factors for EC. An ET greater than 9.5 mm is a threshold for predicting EC. For postmenopausal women with increased ET without PMB, the incidence of endometrial malignancy is low. If the woman has polypoid mass-like lesions on transvaginal ultrasound, she should receive further attention.

Decision-making surrounding ovarian cancer risk-reducing surgery: perspectives from a diverse population

Objective: Individuals with BRCA1/2 pathogenic variants (PV) are recommended risk-reducing salpingo-oophorectomy between 35 and 45 years of age to prevent ovarian cancer. Trials evaluating the oncologic safety of risk-reducing salpingectomy are ongoing. One’s decision on the type and timing of surgery has implications for fertility, quality of life, and long-term health. Published literature on patient preferences has focused on White women from North America and Europe; thus, findings are not necessarily generalizable to patients from other backgrounds. To address this gap, we sought to assess decision-making around ovarian cancer risk-reducing surgery among a racially and ethnically diverse population with BRCA1/2 PVs. Methods: Between February 2023 and November 2023, patients with BRCA1/2 PVs were invited to participate in a one-time, semi-structured, one-on-one interview. Interviews were recorded, transcribed, and analyzed using an inductive approach by two independent coders. Results: Among 15 participants, the median age was 41 years (range 24-64). Ten participants identified as Hispanic, Black, or Asian. Two identified as gender queer. Six had a history of breast cancer. Ten had undergone risk-reducing surgery for ovarian cancer (seven salpingo-oophorectomy and three salpingectomy). Concerns about surgical menopause were a primary consideration for all participants. Other influencing factors included fertility, oncologic safety, history of breast cancer, sexual function, sense of control, gender identity, and mental health. Conclusion: This study identified themes that influenced decision-making among BRCA1/2 PV carriers considering or having undergone risk-reducing gynecologic surgery in a racially and ethnically diverse population. These insights can help clinicians better support patients undergoing this process, with the objective of providing patient-centered, culturally sensitive care.

Clinicopathological features of endometrial lesions in asymptomatic postmenopausal women with thickened endometrium

Abstract Objective To analyze the clinical and pathological features of asymptomatic postmenopausal women with an incidentally detected increase in endometrial thickness (ET) by transvaginal ultrasound examination and discuss the cutoff value of ET for the timely discovery of endometrial malignancy. Methods This was a retrospective study of postmenopausal women with asymptomatic thickened endometrium (greater than or equal to 5 mm) screened by transvaginal ultrasound who were referred to the gynecology department at Xuanwu Hospital between January 2018 and March 2021. Data on participant demographics, clinical characteristics, and histopathology outcomes were collected. We stratified the participants into the benign group and malignant group according to pathology results and assessed differences between the two groups. A receiver operating characteristic curve was used to identify the cutoff value of ET for predicting endometrial malignancy in postmenopausal women with asymptomatic thickened endometrium. Results A total of 163 eligible cases were included in the analysis. The results showed that only ET was significantly different between the two groups. The median ET was significantly higher in the malignant group than in the benign group (1.20 vs 0.80, P = 0.023). The optimal cutoff value of ET was 10 mmwith the maximum AUC (0.881, 95% CI 0.810-0.952, P = 0.024), and the sensitivity and specificity for the diagnosis of endometrial malignancy were 100%and 80%, respectively. Among the 47 women with ET ≥ 10mm, the prevalence of endometrial malignancy was 6.3%, which was significantly higher than that among women with ET < 10mm (P = 0.023). Conclusion For postmenopausal women with asymptomatic endometrial thickening, the prevalence of endometrial malignancy is significantly higher when ET is ≥ 10 mm. If ET is ≥ 10mm, further histopathological testing should be recommended to exclude endometrial malignancy. Further large-sample and prospective studies are needed to determine the predictive value of ET.

The challenges of screening large populations: transvaginal ultrasound and endometrial screening for endometrial cancer

Is obesity predictive of endometrial cancer for women with postmenopausal bleeding?