Detection of endometrial cancer using tampon-based collection and methylated DNA markers.

OBJECTIVE: Alterations in DNA methylation are early events in endometrial cancer (EC) development and may have utility in EC detection via tampon-collected vaginal fluid. METHODS: For discovery, DNA from frozen EC, benign endometrium (BE), and benign cervicovaginal (BCV) tissues underwent reduced representation bisulfite sequencing (RRBS) to identify differentially methylated regions (DMRs). Candidate DMRs were selected based on receiver operating characteristic (ROC) discrimination, methylation level fold-change between cancers and controls, and absence of background CpG methylation. Methylated DNA marker (MDM) validation was performed using qMSP on DNA from independent EC and BE FFPE tissue sets. Women ≥45 years of age with abnormal uterine bleeding (AUB) or postmenopausal bleeding (PMB) or any age with biopsy-proven EC self-collected vaginal fluid using a tampon prior to clinically indicated endometrial sampling or hysterectomy. Vaginal fluid DNA was assayed by qMSP for EC-associated MDMs. Random forest modeling analysis was performed to generate predictive probability of underlying disease; results were 500-fold in-silico cross-validated. RESULTS: Thirty-three candidate MDMs met performance criteria in tissue. For the tampon pilot, 100 EC cases were frequency matched by menopausal status and tampon collection date to 92 BE controls. A 28-MDM panel highly discriminated between EC and BE (96% (95%CI 89-99%) specificity; 76% (66-84%) sensitivity (AUC 0.88). In PBS/EDTA tampon buffer, the panel yielded 96% (95% CI 87-99%) specificity and 82% (70-91%) sensitivity (AUC 0.91). CONCLUSION: Next generation methylome sequencing, stringent filtering criteria, and independent validation yielded excellent candidate MDMs for EC. EC-associated MDMs performed with promisingly high sensitivity and specificity in tampon-collected vaginal fluid; PBS-based tampon buffer with added EDTA improved sensitivity. Larger tampon-based EC MDM testing studies are warranted.

The relationship between muscle sympathetic nerve activity and systemic hemodynamics is altered in women with uterine fibroids.

Women with uterine fibroids (UF), benign tumors of the myometrium, have a higher prevalence of hypertension than women without UF. The cause for this relationship is unclear. Muscle sympathetic nerve activity (MSNA) is a regulator of arterial blood pressure, and it is possible that variations in MSNA predispose women with UF to develop hypertension. The purpose of this study was to assess baseline blood pressure and MSNA and the relationships between MSNA and systemic hemodynamics in women with and without UF. We measured blood pressure (brachial intra-arterial line), MSNA (microneurography), and systemic hemodynamics (total peripheral resistance and cardiac output) at rest in 14 healthy, normotensive, premenopausal women with UF (42 ± 2 years old) and 9 healthy, normotensive, premenopausal women without UF (41 ± 2 years old). Baseline blood pressure and MSNA did not differ between groups (p > 0.05 for both). In women with UF, there was a positive correlation between MSNA and total peripheral resistance (r = 0.75, p = 0.02), as well as a negative correlation between MSNA and cardiac output (r = -0.73, p = 0.03). In contrast, these relationships were not seen in women without UF (p > 0.05 for both relationships). These data suggest that autonomic interactions with systemic hemodynamics, and thus blood pressure regulation, are different in healthy women with UF compared to healthy women without UF.

A systematic review on the use of artificial intelligence in gynecologic imaging - Background, state of the art, and future directions.

OBJECTIVE: Machine learning, deep learning, and artificial intelligence (AI) are terms that have made their way into nearly all areas of medicine. In the case of medical imaging, these methods have become the state of the art in nearly all areas from image reconstruction to image processing and automated analysis. In contrast to other areas, such as brain and breast imaging, the impacts of AI have not been as strongly felt in gynecologic imaging. In this review article, we: (i) provide a background of clinically relevant AI concepts, (ii) describe methods and approaches in computer vision, and (iii) highlight prior work related to image classification tasks utilizing AI approaches in gynecologic imaging. DATA SOURCES: A comprehensive search of several databases from each database's inception to March 18th, 2021, English language, was conducted. The databases included Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, and Ovid Cochrane Database of Systematic Reviews and ClinicalTrials.gov. METHODS OF STUDY SELECTION: We performed an extensive literature review with 61 articles curated by three reviewers and subsequent sorting by specialists using specific inclusion and exclusion criteria. TABULATION, INTEGRATION, AND RESULTS: We summarize the literature grouped by each of the three most common gynecologic malignancies: endometrial, cervical, and ovarian. For each, a brief introduction encapsulating the AI methods, imaging modalities, and clinical parameters in the selected articles is presented. We conclude with a discussion of current developments, trends and limitations, and suggest directions for future study. CONCLUSION: This review article should prove useful for collaborative teams performing research studies targeted at the incorporation of radiological imaging and AI methods into gynecological clinical practice.

Time Trends in Unilateral and Bilateral Oophorectomy in a Geographically Defined American Population.

OBJECTIVE: To evaluate trends in the incidence of premenopausal unilateral and bilateral oophorectomy between 1950 and 2018. METHODS: The Rochester Epidemiology Project medical records-linkage system was used to identify all women aged 18-49 years who were residents of Olmsted County, Minnesota, and underwent unilateral or bilateral oophorectomy before spontaneous menopause between January 1, 1950, and December 31, 2018. Population denominators were derived from the U.S. Decennial Censuses for the years 1950-2010, and intercensal year population denominators were linearly interpolated. For 2011-2018, the annual population denominators were obtained from the U.S. Census projections. Where appropriate, overall incidence rates were age-adjusted to the total U.S. female population from the 2010 Census. RESULTS: There were 5,154 oophorectomies in Olmsted County across the 69-year period between 1950 and 2018, and 2.9% showed malignant disease on pathology. A total of 2,092 (40.6%) women underwent unilateral oophorectomy, and 3,062 (59.4%) women underwent bilateral oophorectomy. More than half (n=1,750, 57.2%) of the bilateral oophorectomies occurred between 1990 and 2009. Until 1975-1979, the incidence of unilateral oophorectomy was mostly higher than bilateral oophorectomy. From 1980-1984 until 2000-2004, the incidence of bilateral oophorectomy more than doubled and the incidence of unilateral oophorectomy declined. After 2005, both procedures declined and converged to a similar incidence in 2015-2018. The decline in premenopausal bilateral oophorectomy over the past 14 years (2005-2018) was most pronounced for women who underwent oophorectomy concurrently with hysterectomy or did not have any ovarian indication. CONCLUSION: The incidence rates of unilateral and bilateral oophorectomy have varied greatly across the 69-year period of this study. In the past 14 years, the incidence of premenopausal unilateral and bilateral oophorectomy has decreased. These trends reflect the effects of the initial 2005-2006 publications and the subsequent expanding body of evidence against the practice of oophorectomy for noncancer indications.

Uterine and Fibroid Imaging Analysis from the FIRSTT Study.

Background: Women with uterine fibroids often seek uterine-preserving treatments, rather than hysterectomy. Imaging-defined endpoints following nonsurgical treatments for fibroids are limited. Materials and Methods: Fibroid Interventions: Reducing Symptoms Today and Tomorrow (FIRSTT), a randomized controlled trial of uterine artery embolization (UAE) versus magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS), enrolled premenopausal women with symptomatic uterine fibroids. In this subanalysis, we report imaging results up to 36 months after UAE or MRgFUS. Magnetic resonance imaging (MRI) was performed at baseline for all women and during the 36 months after treatment if they did not meet other study endpoints. The main outcome of this subanalysis was fibroid volume reduction (defined both in terms of total fibroid load and volume of the largest fibroid), uterine volume reduction, and nonperfused volume. Results: During 2010-2014, 25 of the 37 women who were randomized and treated at Mayo Clinic had a 24-month follow-up MRI (11 UAE; 14 MRgFUS); among these women, 15 (7 UAE and 8 MRgFUS) had a 36-month follow-up MRI. Average age for the cohort was 44.1 (standard deviation, SD = 4.4) years. Nine patients had a second fibroid procedure by 36 months (seven in the MRgFUS arm and two in UAE arm). Median total fibroid load reduction was ∼50% in both treatment arms at both 24- and 36-month follow-up. Volume of the largest fibroid decreased more in the MRgFUS arm, whereas uterine volume decreased more in the UAE arm (neither reached statistical significance). At 24 months, median nonperfused volume was higher in the UAE arm (92%) than the MRgFUS arm (10%). Conclusions: Similar fibroid volume reduction was seen for the MRgFUS and UAE treatments in this comparative effectiveness study. Nonperfused volume 24 months after the procedure was higher in the UAE arm than in the MRgFUS arm. Clinical Trial Registration Number: NCT00995878, clinicaltrials.gov.

Tao brush endometrial cytology is a sensitive diagnostic tool for cancer and hyperplasia among women presenting to clinic with abnormal uterine bleeding.

BACKGROUND: Abnormal uterine bleeding requires the investigation of the endometrium. Histology is typically used but there remains room for the improvement and use of cytology. METHODS: Women presenting for clinically indicated office endometrial biopsy were prospectively enrolled. Tao endometrial brushing and office endometrial biopsy were performed, and surgical procedure if clinically indicated. Tao brush cytology specimens were blindly reviewed by up to three pathologists, consensus obtained, and scored as: benign, atypical (favor benign), suspicious, positive for malignancy, or non-diagnostic. Cytology and histology were compared to surgical pathology to determine sensitivity, specificity, positive, and negative predictive values to detect AH (atypical hyperplasia) or EC (endometrial cancer). RESULTS: Clinical indications of 197 enrolled patients included postmenopausal bleeding (90, 45.7%), abnormal uterine bleeding (94, 47.7%), and abnormal endometrium on ultrasound without bleeding (13, 6.6%). Of the 197 patients, 185 (93.9%) had cytology score consensus and a total of 196 (99.5%) had consensus regarding cytology positivity. Surgical pathology diagnoses (N = 85) were 13 (15.3%) FIGO grade 1 or 2 EC, 3 (3.5%) AH, and 69 (81.2%) benign endometrium. Sensitivity and specificity to detect EC or AH were 93.7% and 100%, respectively, via endometrial biopsy; 87.5% and 63.8%, respectively, via endometrial cytology when scores of malignancy, suspicious, or atypical were considered positive. CONCLUSIONS: In a high-risk population, Tao brush endometrial cytology showed high sensitivity to detect AH and EC comparable to biopsy histology when considering scores of malignancy, suspicious, atypical, and non-diagnostic. Revisiting the potential value of endometrial cytology in the contemporary era of endometrial diagnostic workup is warranted.

Quantifying procedural pain associated with office gynecologic tract sampling methods.

OBJECTIVE: Emerging technologies may enable detection of endometrial cancer with methods that are less invasive than standard biopsy methods. This study compares patient pain scores among 3 office gynecologic tract sampling methods and explores their potential determinants. METHODS: A prospective study including 3 sampling methods (tampon, Tao brush (TB), endometrial biopsy (EB)) was conducted between December 2015 and August 2017 and included women ≥45 years of age presenting with abnormal uterine bleeding, postmenopausal bleeding, or thickened endometrial stripe. Patients rated pain after each sampling procedure using a 100-point visual analog scale (VAS). RESULTS: Of 428 enrolled, 190 (44.39%) patients underwent all 3 sampling methods and reported a VAS score for each. Nearly half were postmenopausal (n = 93, 48.9%); the majority were parous (172, 90.5%) of which 87.8% had at least one vaginal delivery. Among the 190 patients, the median (IQR) pain score was significantly lower for sampling via tampon (0 [0,2]) compared to TB (28 [12, 52]) or EB (32 [15, 60]) (both p < 0.001, Wilcoxon signed rank test). Among women who underwent tampon sampling, age and pain scores showed a weak positive correlation (Spearman rank correlation, r = 0.14; p = 0.006); EB sampling was associated with a weak inverse correlation between parity and pain scores (r = -0.14; p = 0.016). CONCLUSION: Gynecologic tract sampling using a tampon had significantly lower pain than both EB and TB. Pain with tampon sampling was positively correlated with age and pain with EB sampling was inversely correlated with parity. Pain scores for TB and EB were not significantly related to age, menopausal status, or BMI.

Abdominal Ice after Laparoscopic Hysterectomy: A Randomized Controlled Trial.

STUDY OBJECTIVE: To assess the impact of abdominal ice packs on opioid use and pain control after laparoscopic hysterectomy DESIGN: Randomized controlled trial. SETTING: Academic tertiary care medical center. PATIENTS: Total of 142 adult women undergoing laparoscopic (either conventional or robotic) hysterectomy were randomized to control (n = 69) or intervention (n = 73). Exclusion criteria included preoperative opioid use, planned intensive care unit admission or same-day discharge, an incision ≥4 cm, and regional anesthesia use. INTERVENTIONS: Subjects in the intervention group had a large ice pack placed directly on the lower abdomen before leaving the operating room. The ice pack was maintained continuously for 12 hours postoperation, as desired thereafter until discharge, and continued use encouraged after discharge for up to 48 hours. MEASUREMENTS AND MAIN RESULTS: Total opioids administered postoperatively, while inpatient and after dismissal, were assessed in morphine milligram equivalents. Postoperative pain, as well as analgesia acceptability and side effects, were assessed using validated measures: Brief Pain Inventory and Overall Benefit of Analgesia Score. Median morphine milligram equivalent was lower in the intervention group than the controls from inpatient stay on the floor to completion of opioid use as an outpatient (22.5 vs 26.2) but was not statistically significant (p = .79). There was no significant difference between the groups in Brief Pain Inventory assessment of postoperative pain severity (p = .80) or pain interference (p = .36) or Overall Benefit of Analgesia Score total score (p = .88). Most patients in the intervention group were very satisfied with ice pack use (n = 51, 79.7%) and very likely to recommend it to friends or family (n = 54, 83.1%). There were no adverse events related to ice pack use. CONCLUSION: There was no significant difference in postoperative opioid use or pain assessment with ice pack use after laparoscopic hysterectomy. However, most of the subjects expressed high satisfaction specific to ice pack use and would recommend its use to others, suggesting potential desirability as adjunct therapy in postoperative pain control.

Comparison of Clinical Performance Between Two Generations of Magnetic Resonance-guided Focused Ultrasound Systems in Treatments of Uterine Leiomyomas.

OBJECTIVES: The aim of this study was to evaluate the impact of technology improvements on the outcomes of magnetic resonance-guided focused ultrasound (MRgFUS) treatments of symptomatic uterine leiomyomas (uterine fibroids). The study compared ablation volumes and incidence of adverse events in patient groups treated with two generations of MRgFUS systems from a single vendor. METHODS: The present study describes the results of a retrospective comparative study of two groups of women with symptomatic uterine leiomyomas who were clinically treated with MRgFUS at a single institution. Group 1 (n = 130) was treated using the first-generation system between March 2005 and December 2009. Group 2 (n = 71) was treated using the second-generation between December 2013 and September 2019. RESULTS: The second-generation MRgFUS system resulted in significantly improved nonperfused volume ratios in both dark and bright T2 fibroid categories compared with the first-generation system (dark - 80% versus46 %, p = 0.00002 and bright - 46% versus 32%, p = 0.001). There have been no recorded hospital admissions, no skins burns, and no reported major adverse events since the introduction of this second-generation ExAblate 2100 system with advanced safety and treatment planning features. CONCLUSION: This study has demonstrated that improvements to current MRgFUS technology resulted in significantly increased efficacy and patient safety of clinical treatments of patients with symptomatic uterine leiomyomas.

NAMS 2019 Pre-Meeting Symposium, September 2019, Chicago Illinois: The Perimenopause.

The North American Menopause Society held the 2019 Pre-Meeting Symposium on September 25, 2019, in Chicago, Illinois, to review the current state of the science related to the physiology of the perimenopause and to address management of the most prevalent and pressing clinical issues. The perimenopause, as defined by the Stages of Reproductive Aging Workshop + 10, encompasses the menopause transition as well as the first year following menopause, the final menstrual period. This phase in the continuum of women's reproductive lives had been one of the least well understood. Fortunately, contributions from a number of prospective, longitudinal, decades-long studies have provided a better understanding of the perimenopause, whereas posing important new questions related to symptom interaction and linkages between symptoms and long-term health. There is now added clarity to distinguish the effects of reproductive hormonal changes from aging. The variation in symptoms, including vasomotor symptoms, among women over time including differences in experiences by ethnicity and race, provides paradigm shifts in clinical perspective. Refinements in understanding the character, timing, and potential predictive markers for menstrual cycles during the transition have emerged. From the perspective of myriad clinical management challenges, significant progress in recommendations for evaluation and therapeutic approaches has been achieved. Finally, recognizing the menopause transition as an opportunity to initiate positive lifestyle changes to enhance future health was emphasized.

Risk assessment of endometrial cancer and endometrial intraepithelial neoplasia in women with abnormal bleeding and implications for clinical management algorithms.

BACKGROUND: Most endometrial cancer cases are preceded by abnormal uterine bleeding, offering a potential opportunity for early detection and cure of endometrial cancer. Although clinical guidelines exist for diagnostic workup of abnormal uterine bleeding, consensus is lacking regarding optimal management for women with abnormal bleeding to diagnose endometrial cancer. OBJECTIVE: We report the baseline data from a prospective clinical cohort study of women referred for endometrial evaluation at the Mayo Clinic, designed to evaluate risk stratification in women at increased risk for endometrial cancer. Here, we introduce a risk-based approach to evaluate diagnostic tests and clinical management algorithms in a population of women with abnormal bleeding undergoing endometrial evaluation at the Mayo Clinic. STUDY DESIGN: A total of 1163 women aged ≥45 years were enrolled from February 2013 to May 2019. We evaluated baseline absolute risks and 95% confidence intervals of endometrial cancer and endometrial intraepithelial neoplasia according to clinical algorithms for diagnostic workup of women with postmenopausal bleeding (assessment of initial vs recurrent bleeding episode and endometrial thickness measured through transvaginal ultrasound). We also evaluated risks among women with postmenopausal bleeding according to baseline age (<60 vs 60+ years) as an alternative example. For this approach, biopsy would be conducted for all women aged 60+ years and those aged <60 years with an endometrial thickness of >4 mm. We assessed the clinical efficiency of each strategy by estimating the percentage of women who would be referred for endometrial biopsy, the percentage of cases detected and missed, and the ratio of biopsies per case detected. RESULTS: Among the 593 women with postmenopausal bleeding, 18 (3.0%) had endometrial intraepithelial neoplasia, and 47 (7.9%) had endometrial cancer, and among the 570 premenopausal women with abnormal bleeding, 8 (1.4%) had endometrial intraepithelial neoplasia, and 7 (1.2%) had endometrial cancer. Maximum risk was noted in women aged 60+ years (17.7%; 13.0%-22.3%), followed by those with recurrent bleeding (14.7%; 11.0%-18.3%). Among women with an initial bleeding episode for whom transvaginal ultrasound was recommended, endometrial thickness did not provide meaningful risk stratification: risks of endometrial cancer and endometrial intraepithelial neoplasia were nearly identical in women with an endometrial thickness of >4 mm (5.8%; 1.3%-10.3%) and ≤4 mm (3.6%; 0.9%-8.6%). In contrast, among those aged <60 years with an endometrial thickness of >4 mm, the risk of endometrial cancer and endometrial intraepithelial neoplasia was 8.4% (4.3%-12.5%), and in those with an endometrial thickness of ≤4 mm, the risk was 0% (0.0%-3.0%; P=.01). The most efficient strategy was to perform biopsy in all women aged 60+ years and among those aged <60 years with an endometrial thickness of >4 mm, with the lowest percentage referred to biopsy while still detecting all cases. CONCLUSION: Existing clinical recommendations for endometrial cancer detection in women with abnormal bleeding are not consistent with the underlying risk. Endometrial cancer risk factors such as age can provide important risk stratification compared with the assessment of recurrent bleeding. Future research will include a formal assessment of clinical and epidemiologic risk prediction models in our study population as well as validation of our findings in other populations.

Comparative effectiveness of hysterectomy versus myomectomy on one-year health-related quality of life in women with uterine fibroids.

OBJECTIVE: To compare long-term health-related quality of life (HRQOL) 1 year after hysterectomy or myomectomy for treatment of uterine fibroids (UFs) and to determine whether route of procedure, race, or age affected improvements in HRQOL. DESIGN: Prospective cohort study. SETTING: Eight clinical sites throughout the United States. PATIENT(S): A total of 1,113 premenopausal women with UFs who underwent hysterectomy or myomectomy as part of Comparing Options for Management: Patient-Centered Results for Uterine Fibroids. INTERVENTION(S): None. MAIN OUTCOME MEASURE (S): Self-reported HRQOL measures including Uterine Fibroid Symptom Quality of Life, the European QOL 5 Dimension Health Questionnaire, and the visual analog scale at baseline and 1-year after hysterectomy or myomectomy. RESULT (S): Hysterectomy patients were older with a longer history of symptomatic UF compared with myomectomy patients. There were no differences in baseline HRQOL. After adjustment for baseline differences between groups, compared with myomectomy, patients' HRQOL (95% confidence interval [CI], 5.4, 17.2) and symptom severity (95% CI, -16.3, -8.8) were significantly improved with hysterectomy. When stratified across race/ethnicity and age, hysterectomy had higher HRQOL scores compared with myomectomy. There was little difference in HRQOL (95% CI, 0.1 [-9.5, 9.6]) or symptom severity (95% CI, -3.4 [-10, 3.2]) between abdominal hysterectomy and abdominal myomectomy. CONCLUSION (S): HRQOL improved in all women 1 year after hysterectomy or myomectomy. Hysterectomy patients reported higher HRQOL summary scores compared with myomectomy patients. When stratified by route, minimally invasive hysterectomy had better HRQOL scores than minimally invasive myomectomy. There was little difference in scores with abdominal approaches.

Improving patient access through office hysteroscopy clinic redesign.

BACKGROUND AND OBJECTIVE: Patients with abnormal uterine bleeding (AUB) often require hysteroscopy as part of the diagnostic workup. The purpose of this study was to improve efficiency by shortening the time to patient appointment for office hysteroscopy. INTERVENTIONS: Preintervention, nurse practitioners (NPs) and gynecologists saw patients with abnormal uterine bleeding (AUB) separately. This created inefficiency for the patients, frequently requiring second visits for hysteroscopy. A new hysteroscopy clinic was designed to increase practice efficiency. A collaborative team model was created including consecutive visits with NPs and gynecologists. Each patient with AUB was first evaluated by an NP, followed immediately by a shorter visit with a gynecologist for office hysteroscopy as indicated. NPs managed other diagnostic evaluation and bleeding treatment if hysteroscopy was not warranted. Collaborative clinic staffing consisted of two NPs seeing patients with AUB paired with one gynecologist for procedural support. MEASUREMENTS AND RESULTS: Electronic records of 393 patients scheduled for AUB visits from January to June 2015 were evaluated for preintervention data. Postintervention, 647 patient records were reviewed from January to June of 2016. During the preintervention period, 30% of patients had a hysteroscopy appointment scheduled within 0-13 days from the initial visit for AUB. Postintervention, the wait time for appointments decreased, with 63% of patients scheduled within 0-13 days. Clinic redesign also resulted in an increase of 57.5% in appointment slots. No-show rates and appointment fill rates were not adversely affected. CONCLUSIONS: A collaborative team-based care model using NPs and gynecologists improved efficiency and access to office hysteroscopy services.

Short-term quality of life after myomectomy for uterine fibroids from the COMPARE-UF Fibroid Registry.

BACKGROUND: Uterine fibroids may decrease quality of life in a significant proportion of affected women. Myomectomy offers a uterine-sparing treatment option for patients with uterine fibroids that can be performed abdominally, laparoscopically (with or without robotic assistance), and hysteroscopically. Quality of life information using validated measures for different myomectomy routes, especially hysteroscopic myomectomy, is limited. OBJECTIVE: To compare women's perception of their short-term health-related quality of life measures and reported time to return to usual activities and return to work for different routes of myomectomy. MATERIALS AND METHODS: Comparing Options for Management: Patient-centered Results for Uterine Fibroids (COMPARE-UF) is a prospective nationwide fibroid registry that enrolled premenopausal women seeking treatment for uterine fibroids at 8 clinical sites. For this analysis, we included women undergoing hysteroscopic, abdominal, or laparoscopic myomectomy who completed the postprocedure questionnaire scheduled between 6 and 12 weeks after surgery. Health-related quality of life outcomes, such as pain, anxiety, and return to usual activitie, were assessed for each route. The hysteroscopic myomectomy group had large differences in demographics, fibroid number, and uterine size compared to the other groups; thus, a direct comparison of quality of life measures was performed only for abdominal and laparoscopic approaches after propensity weighting. Propensity weighting was done using 24 variables that included demographics, quality of life baseline measures, and fibroid and uterine measurements. RESULTS: A total of 1206 women from 8 COMPARE-UF sites underwent myomectomy (338 hysteroscopic, 519 laparoscopic, and 349 abdominal). All women had substantial improvement in short-term health-related quality of life and symptom severity scores, which was not different among groups. Average symptom severity scores decreased about 30 points in each group. Return to usual activities averaged 0 days (interquartile range, 0-14 days) for hysteroscopic myomectomy, 21 days (interquartile range, 14-28 days) for laparoscopic myomectomy, and 28 days (interquartile range, 14-35 days) for abdominal myomectomy. After propensity adjustment, quality of life outcomes in the laparoscopic and abdominal myomectomy groups were similar except for more anxiety in the laparoscopic myomectomy group and slightly more pain in the abdominal myomectomy group. After propensity weighting, return to usual activities favored laparoscopic compared to abdominal procedures; median time was the same at 21 days, but the highest quartile of women in the abdominal group needed an additional week of recovery (interquartile range,14.0-28.0 for laparoscopic versus 14.0-35.0 for abdominal, P < .01). Time to return to work was also longer in the abdominal arm (median, 22 days; interquartile range, 14-40 days, versus median, 42; interquartile range, 27-56). CONCLUSION: Women who underwent myomectomy had substantial improvement in health-related quality of life, regardless of route of myomectomy. After propensity weighting, abdominal myomectomy was associated with a nearly 2-week longer time to return to work than laparoscopic myomectomy.

Long-term risk of de novo mental health conditions after hysterectomy with ovarian conservation: a cohort study.

OBJECTIVE: The aim of this research was to study the long-term risk of de novo mental health conditions in women who underwent hysterectomy with bilateral ovarian conservation compared with age-matched referent women. METHODS: Using the Rochester Epidemiology Project records-linkage system, we identified a historical cohort of 2,094 women who underwent hysterectomy with ovarian conservation for benign indications at age ≥18 years and with an index date between 1980 and 2002 in Olmsted County, Minnesota. Each woman was age-matched (±1 y) to a referent woman residing in the same county who had not undergone hysterectomy or any oophorectomy before the index date. These two cohorts were followed historically to identify de novo mental health conditions. We estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) using Cox proportional hazards models adjusted for 20 preexisting chronic conditions and other potential confounders. We also calculated absolute risk increases (ARIs) and reductions (ARRs) at 30 years of follow-up. RESULTS: Over a median follow-up of 21.9 years, women who underwent hysterectomy at any age experienced increased risks of de novo depression (adjusted HR 1.26; 95% CI, 1.12-1.41; ARI 6.6%) and anxiety (adjusted HR 1.22; 95% CI, 1.08-1.38; ARI 4.7%). The association for depression increased significantly with younger age at hysterectomy, but did not vary significantly by indication. Interactions were not significant for anxiety. CONCLUSIONS: Hysterectomy, even with ovarian conservation, is associated with an increased long-term risk of de novo depression and anxiety, especially when performed in women who are younger. : Video Summary:http://links.lww.com/MENO/A465.

A prospective clinical cohort study of women at increased risk for endometrial cancer.

OBJECTIVE: To evaluate endometrial cancer (EC) risk assessment and early detection strategies in high-risk populations, we designed a large, prospective cohort study of women undergoing endometrial evaluation to assess risk factors and collect novel biospecimens for future testing of emerging EC biomarkers. Here we report on the baseline findings of this study. METHODS: Women aged ≥45 years were enrolled at the Mayo Clinic from February 2013-June 2018. Risk factors included age, body mass index (BMI), smoking, oral contraceptive and hormone therapy use, and parity. We collected vaginal tampons, endometrial biopsies, and Tao brush samples. We estimated mutually-adjusted odds ratios (OR) and 95% confidence intervals (CI) using multinomial logistic regression; outcomes included EC, atypical hyperplasia, hyperplasia without atypia, disordered proliferative endometrium, and polyps, versus normal endometrium. RESULTS: Subjects included 1205 women with a mean age of 55 years; 55% were postmenopausal, and 90% had abnormal uterine bleeding. The prevalence of EC was 4.1% (n = 49), predominantly diagnosed in postmenopausal women (85.7%). Tampons and Tao brushings were obtained from 99% and 68% of women, respectively. Age (OR 1.14, 95% CI 1.1-1.2) and BMI (OR 1.39, 95% CI 1.1-1.7) were positively associated with EC; atypical hyperplasia (OR 1.07, 95% CI 1.0-1.1; OR 2.00, 95% CI 1.5-2.6, respectively), and polyps (OR 1.06, 95% CI 1.0-1.1; OR 1.17, 95% CI 1.0-1.3, respectively); hormone therapy use and smoking were inversely associated with EC (OR 0.42, 95%, 0.2-0.9; OR 0.43, 95% CI, 0.2-0.9, respectively). Parity and past oral contraception use were not associated with EC. CONCLUSIONS: Well-established EC risk factors may have less discriminatory accuracy in high-risk populations. Future analyses will integrate risk factor assessment with biomarker testing for EC detection.

Mental health conditions diagnosed before bilateral oophorectomy: a population-based case-control study.

OBJECTIVE: We studied eight mental health conditions diagnosed before bilateral oophorectomy performed for nonmalignant indications. METHODS: We identified 1,653 premenopausal women who underwent bilateral oophorectomy for a nonmalignant indication in Olmsted County, Minnesota, during a 20-year period (1988-2007). Each woman was matched by age (±1 year) to one population-based control who had not undergone bilateral oophorectomy before the index date (age range: 21-49 years). Both cases and controls were identified using the records-linkage system of the Rochester Epidemiology Project (REP http://www.rochesterproject.org). For eight mental health conditions, we calculated odds ratios (ORs) and their 95% confidence intervals (95% CIs) adjusted for race, education, and income using conditional logistic regression. RESULTS: Pre-existing mood disorders, anxiety disorders, and somatoform disorders were associated with increased risk of bilateral oophorectomy in overall analyses. These associations were also significant in women ≤45 years of age at index date. Personality disorders were associated with increased risk only in overall analyses and adjustment disorders only in women 46 to 49 years of age. Some of the associations were significantly different across strata by age at index date and by indication. There was also a linear trend of increasing adjusted ORs from 1.55 (95% CI 1.31-1.83) for one mental health condition to 2.19 (95% CI 1.40-3.41) for three or more conditions (trend P < 0.001). CONCLUSIONS: We identified several mental health conditions that were associated with bilateral oophorectomy for nonmalignant indications. Awareness of these associations may guide women and physicians in future decision-making and limit unindicated bilateral oophorectomies. VIDEO SUMMARY:: http://links.lww.com/MENO/A458.

Tubal Ligation and Age at Natural Menopause.

OBJECTIVE: To determine the effect of tubal ligation on age at natural menopause, as a marker of long-term ovarian function. METHODS: Three preexisting population-based cohorts were included in this cross-sectional study. Data from each cohort was analyzed separately. The cohorts were restricted to women who never smoked and had reached natural menopause, without prior hysterectomy or oophorectomy. The following variables were collected: race, age at menarche, age at menopause, history of hysterectomy or oophorectomy, gravidity and parity, tobacco use, and ever use of hormonal contraception. The type of tubal ligation and age at tubal ligation were manually abstracted in cohort 1. For cohorts 2 and 3, history of tubal ligation was obtained from an institutional form, completed by patient report. The primary outcome, age at natural menopause, was compared between the two groups (those with and without a history of tubal ligation). RESULTS: Inclusion criteria was met by 555 women from cohort 1, 1,816 women from cohort 2, and 1,534 women from cohort 3. Baseline characteristics did not differ between cohorts. The percentage with tubal ligation was the same in all cohorts: 26.0%, 25.5%, and 25.0%, respectively. Women with a tubal ligation were more likely to have had at least one pregnancy and to have used hormonal contraception compared with women without a tubal ligation. There was no significant difference in age at natural menopause in women who underwent tubal ligation (50.1, 49.9, 50.0 years, respectively) compared with those who did not (50.7, 49.6, 50.0 years, respectively). The type of tubal ligation (cohort 1 only) had no effect on age at menopause. CONCLUSIONS: Tubal ligation did not affect age at natural menopause in the three large cohorts included in this study.