Endometrial Cancer in Reproductive-Aged Females: Etiology and Pathogenesis.

Endometrial cancer is the most common gynecologic malignancy in developed countries, and the incidence is rising in premenopausal females. Type I EC is more common than Type II EC (80% vs. 20%) and is associated with a hyperestrogenic state. Estrogen unopposed by progesterone is considered to be the main driving factor in the pathogenesis of EC. Studies show that BMI > 30 kg/m2, prolonged duration of menses, nulliparity, presence of polycystic ovarian syndrome, and Lynch syndrome are the most common causes of EC in premenopausal women. Currently, there are no guidelines established to indicate premenopausal patients who should be screened. This review aims to synthesize current data on the etiology, risk factors, presentation, evaluation, and prognosis of endometrial cancer in this population.

Endometrial stripe thickness: a preoperative marker to identify patients with endometrial intraepithelial neoplasia who may benefit from sentinel lymph node mapping and biopsy.

OBJECTIVES: The goal of our study was to identify preoperative factors in patients with endometrial intraepithelial neoplasia that are associated with concurrent endometrial cancer to select patients who may benefit from sentinel lymph node (SLN) assessment at the time of hysterectomy. METHODS: Retrospective single institution cohort study of patients with a preoperative diagnosis of endometrial intraepithelial neoplasia who underwent hysterectomy with or without staging from January 2010 to July 2020. Modified Poisson regression was used to calculate risk ratios (RR) and 95% confidence intervals (CI). RESULTS: Of 378 patients with a preoperative diagnosis of endometrial intraepithelial neoplasia, 275 (73%) had endometrial intraepithelial neoplasia and 103 (27%) had invasive cancer on final pathology. Age (p=0.003), race (p=0.02), and hypertension (p=0.02) were significantly associated with concurrent endometrial cancer. The median preoperative endometrial stripe was significantly greater in the endometrial cancer group (14 mm (range 10-19)) than in the endometrial intraepithelial neoplasia group (11 mm (range 8-16); p=0.002). A preoperative endometrial stripe ≥20 mm was associated with double the risk of endometrial cancer on final pathology (crude RR 2.0, 95% CI 1.3 to 2.9) and preoperative endometrial stripe ≥15 mm was 2.5 times more likely to be associated with high risk Mayo criteria on final pathology (crude RR 2.5, 95% CI 1.2 to 5.2). Of those with concurrent endometrial cancer, 5% were stage IB, 29% had tumors >2 cm, and 1% had grade 3 histology. Only 3% of all patients underwent lymph node evaluation. CONCLUSIONS: In a large cohort of patients with a preoperative diagnosis of endometrial intraepithelial neoplasia, less than a third had invasive cancer and even fewer had pathologic features considered high risk for nodal metastasis, arguing against the use of routine SLN dissection in these patients. Endometrial stripe ≥15 mm may be a useful preoperative marker to identify patients at higher risk for concurrent endometrial cancer and may be an important criterion for use of selective SLN dissection in carefully selected patients with endometrial intraepithelial neoplasia.

A single-cell atlas of human and mouse white adipose tissue.

White adipose tissue, once regarded as morphologically and functionally bland, is now recognized to be dynamic, plastic and heterogenous, and is involved in a wide array of biological processes including energy homeostasis, glucose and lipid handling, blood pressure control and host defence1. High-fat feeding and other metabolic stressors cause marked changes in adipose morphology, physiology and cellular composition1, and alterations in adiposity are associated with insulin resistance, dyslipidemia and type 2 diabetes2. Here we provide detailed cellular atlases of human and mouse subcutaneous and visceral white fat at single-cell resolution across a range of body weight. We identify subpopulations of adipocytes, adipose stem and progenitor cells, vascular and immune cells and demonstrate commonalities and differences across species and dietary conditions. We link specific cell types to increased risk of metabolic disease and provide an initial blueprint for a comprehensive set of interactions between individual cell types in the adipose niche in leanness and obesity. These data comprise an extensive resource for the exploration of genes, traits and cell types in the function of white adipose tissue across species, depots and nutritional conditions.

The impact of tumor fragmentation in patients with stage I uterine leiomyosarcoma on patterns of recurrence and oncologic outcome.

OBJECTIVE: To evaluate the impact of tumor fragmentation on oncologic outcomes in patients with stage I uterine leiomyosarcoma (uLMS). METHODS: We identified all patients diagnosed with stage I uLMS presenting to our institution within three months of primary surgery, 1/2000-1/2019. Patients with recurrent disease were excluded. The non-morcellated group had total hysterectomy without documented specimen fragmentation; the morcellated group, total hysterectomy with documented specimen fragmentation. We defined fragmentation as manual fragmentation or morcellation (via power morcellator or otherwise) of the specimen in peritoneal cavity or vagina. Appropriate statistical analyses were performed. RESULTS: 152 patients met inclusion criteria. 107 (70%) underwent total hysterectomy (non-morcellated); 45 (30%) underwent morcellation. Median age at diagnosis for the entire cohort was 55 years (range 30-91). Median follow-up was 42.1 months (range 1.1-197.8). 40 (26.3%) patients had primary surgery at our institution, 112 (73.7%) at an outside hospital. In total 110 (72.3%) recurred: 72/107 (67.2%) non-morcellated; 38/44 (86.3%) morcellated. Median progression-free survival (PFS) for non-morcellated versus morcellated was 13.8 (95%CI 9.2-20.2) versus 7.3 months (95%CI 3-13.1), HR 1.5 (95%CI 1.02-2.24); P = 0.04. Median overall survival (OS) for non-morcellated versus morcellated was 82.1 (95%CI 52.4-122) versus 47.8 months (95%CI 28.5-129.6), HR 1.1 (95%CI 0.67-1.82); P = 0.7. Among patients with recurrence, 69.4% of non-morcellated recurred at hematogenous sites only, 18.1% recurred in peritoneum only; 28.9% of morcellated recurred at hematogenous sites, 63.2% in peritoneum. Race, lymphovascular invasion, postoperative chemotherapy, were independently associated with PFS. Mitotic index was independently associated with OS. CONCLUSIONS: Tumor fragmentation/morcellation was associated with significantly higher risk of recurrence and a nearly 4-fold increase in peritoneal recurrence. Prognostic biomarkers remain important in predicting oncologic outcomes, independent of fragmentation or treatment.

Adjuvant therapy for grade 3, deeply invasive endometrioid adenocarcinoma of the uterus.

BACKGROUND: Patients with grade 3, deeply invasive endometrioid adenocarcinoma are typically managed with primary surgery. The role and type of adjuvant therapy used is controversial. We sought to evaluate the role of adjuvant radiation and/or chemotherapy in women with deeply invasive grade 3 endometrioid tumors. METHODS: A multi-center retrospective chart review was performed at three large medical institutions in the United States. Patients with grade 3 endometrioid adenocarcinoma invading >50% of the myometrium were included. Medical records were queried to evaluate whether lymph node assessment was performed, the status of the lymph nodes, adjuvant treatment strategy used, and dates of death or recurrence. RESULTS: Between 1984 and 2013, 257 patients were identified with a median follow-up of 3.08 years. Most patients (84.7%) had evaluation of pelvic and/or para-aortic lymph nodes and 43% had positive lymph nodes. For node negative patients, there was no difference in overall survival (OS) between those who received adjuvant pelvic radiation +/- vaginal brachytherapy (n=52) vs brachytherapy alone (n=46) (5-year probabilities were 0.73 vs 0.70, P=0.729). Among patients with positive lymph nodes (n=92), the adjuvant treatment strategy utilized impacted OS, with women undergoing a combination of chemotherapy and external beam radiation having the best outcomes (P=0.003). CONCLUSIONS: Among women with grade 3, deeply invasive endometrioid adenocarcinoma, vaginal cuff brachytherapy alone resulted in similar survival when compared with pelvic radiation in node negative patients. The combination of chemotherapy with external beam radiation was associated with improved OS for women with positive nodes.

Multicenter study comparing oncologic outcomes after lymph node assessment via a sentinel lymph node algorithm versus comprehensive pelvic and paraaortic lymphadenectomy in patients with serous and clear cell endometrial carcinoma.

OBJECTIVES: To compare survival after nodal assessment using a sentinel lymph node (SLN) algorithm versus comprehensive pelvic and paraaortic lymphadenectomy (LND) in serous or clear cell endometrial carcinoma, and to compare survival in node-negative cases. METHODS: Three-year recurrence-free survival (RFS) and overall survival were compared between one institution that used comprehensive LND to the renal veins and a second institution that used an SLN algorithm with ultra-staging with inverse-probability of treatment weighting (IPTW) derived from propensity scores to adjust for covariate imbalance between cohorts. RESULTS: 214 patients were identified (118 SLN cohort, 96 LND cohort). Adjuvant therapy differed between the cohorts; 84% and 40% in the SLN and LND cohorts, respectively, received chemotherapy ± radiation therapy. The IPTW-adjusted 3-year RFS rates were 69% and 80%, respectively. The IPTW-adjusted 3-year OS rates were 88% and 77%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of surgical approach (SLN vs LND) with progression and death was 1.46 (95% CI: 0.70-3.04) and 0.44 (95% CI: 0.19-1.02), respectively. In the 168 node-negative cases, the IPTW-adjusted 3-year RFS rates were 73% and 91%, respectively. The IPTW-adjusted 3-year OS rates were 88% and 86%, respectively. In this subgroup, IPTW-adjusted HR for the association of surgical approach (SLN vs LND) with progression and death was 3.12 (95% CI: 1.02-9.57) and 0.69 (95% CI: 0.24-1.95), respectively. CONCLUSION: OS was not compromised with the SLN algorithm. SLN may be associated with a decreased RFS but similar OS in node-negative cases despite the majority receiving chemotherapy. This may be due to differences in surveillance.

Role of lymphadenectomy in endometrial cancer with nonbulky lymph node metastasis: Comparison of comprehensive surgical staging and sentinel lymph node algorithm.

OBJECTIVES: To compare survival and progression outcomes between 2 nodal assessment approaches in patients with nonbulky stage IIIC endometrial cancer (EC). METHODS: Patients with stage IIIC EC treated at 2 institutions were retrospectively identified. At 1 institution, a historical series (2004-2008) was treated with systematic pelvic and para-aortic lymphadenectomy (LND cohort). At the other institution, more contemporary patients (2006-2013) were treated using a sentinel lymph node algorithm (SLN cohort). Outcomes (hazard ratios [HRs]) within the first 5 years after surgery were compared between cohorts using Cox models adjusted for type of adjuvant therapy. RESULTS: The study included 104 patients (48 LND, 56 SLN). The use of chemoradiotherapy was similar in the 2 cohorts (46% LND vs 50% SLN), but the use of chemotherapy alone (19% vs 36%) or radiotherapy alone (15% vs 2%) differed. Although there was evidence of higher risk of cause-specific death (HR, 2.10; 95% CI, 0.79-5.58; P = 0.14) and lower risk of para-aortic progression (HR, 0.27; 95% CI, 0.05-1.42; P = 0.12) for the LND group, the associations did not meet statistical significance. The risk of progression was not significantly different between the groups (HR, 1.27; 95% CI, 0.60-2.67; P =0 .53). In parsimonious multivariable models, high-risk tumor characteristics and nonendometrioid type were independently associated with lower cause-specific survival and progression-free survival. CONCLUSIONS: In EC patients with nonbulky positive lymph nodes, use of the SLN algorithm with limited nodal dissection does not compromise survival compared with LND. Aggressive pathologic features of the primary tumor are the strongest determinants of prognosis.

Multicenter study comparing oncologic outcomes between two nodal assessment methods in patients with deeply invasive endometrioid endometrial carcinoma: A sentinel lymph node algorithm versus a comprehensive pelvic and paraaortic lymphadenectomy.

OBJECTIVES: To compare oncologic outcomes in the staging of deeply invasive endometrioid endometrial carcinoma (EEC) using a sentinel lymph node algorithm (SLN) versus pelvic and paraaortic lymphadenectomy to the renal veins (LND); to compare outcomes in node-negative cases. METHODS: At two institutions, patients with deeply invasive (≥50% myometrial invasion) EEC were identified. One institution used LND (2004-2008), the other SLN (2005-2013). FIGO stage IV cases were excluded. Clinical characteristics and follow-up data were recorded. RESULTS: 176 patients were identified (LND, 94; SLN, 82). SLN patients were younger (p = 0.003) and had more LVSI (p < 0.001). 9.8% in the SLN and 29.8% in the LND cohorts, respectively, received no adjuvant therapy (p < 0.001). There was no association between type of assessment and recurrence; adjusted hazard ratio (aHR; LND vs. SLN) 0.87 (95%CI 0.40, 1.89) PFS. After controlling for age and adjuvant therapy, there was no association between assessment method and OS (aHR 2.54; 95%CI 0.81, 7.91). The node-negative cohort demonstrated no association between survival and assessment method: aHR 0.69 (95%CI 0.23, 2.03) PFS, 0.81 (95%CI 0.16, 4.22) OS. In the node-negative cohort, neither adjuvant EBRT+/-IVRT (HR 1.63; 95%CI 0.18, 14.97) nor adjuvant chemotherapy+/-EBRT+/-IVRT (HR 0.49; 95%CI 0.11, 2.22) were associated with OS, compared to no adjuvant therapy or IVRT-only. CONCLUSION: Use of an SLN algorithm in deeply invasive EEC does not impair oncologic outcomes. Survival is excellent in node-negative cases, irrespective of assessment method. Adjuvant chemotherapy in node-negative patients does not appear to impact outcome.

Molecular analysis of high-grade serous ovarian carcinoma with and without associated serous tubal intra-epithelial carcinoma.

Many high-grade serous carcinomas (HGSCs) of the pelvis are thought to originate in the distal portion of the fallopian tube. Serous tubal intra-epithelial carcinoma (STIC) lesions are the putative precursor to HGSC and identifiable in ~ 50% of advanced stage cases. To better understand the molecular etiology of HGSCs, we report a multi-center integrated genomic analysis of advanced stage tumors with and without STIC lesions and normal tissues. The most significant focal DNA SCNAs were shared between cases with and without STIC lesions. The RNA sequence and the miRNA data did not identify any clear separation between cases with and without STIC lesions. HGSCs had molecular profiles more similar to normal fallopian tube epithelium than ovarian surface epithelium or peritoneum. The data suggest that the molecular features of HGSCs with and without associated STIC lesions are mostly shared, indicating a common biologic origin, likely to be the distal fallopian tube among all cases.High-grade serous carcinomas (HGSCs) are associated with precursor lesions (STICs) in the fallopian epithelium in only half of the cases. Here the authors report the molecular analysis of HGSCs with and without associated STICs and show similar profiles supporting a common origin for all HGSCs.

Comparison of a sentinel lymph node mapping algorithm and comprehensive lymphadenectomy in the detection of stage IIIC endometrial carcinoma at higher risk for nodal disease.

OBJECTIVE: To determine if a sentinel lymph node (SLN) mapping algorithm will detect metastatic nodal disease in patients with intermediate-/high-risk endometrial carcinoma. METHODS: Patients were identified and surgically staged at two collaborating institutions. The historical cohort (2004-2008) at one institution included patients undergoing complete pelvic and paraaortic lymphadenectomy to the renal veins (LND cohort). At the second institution an SLN mapping algorithm, including pathologic ultra-staging, was performed (2006-2013) (SLN cohort). Intermediate-risk was defined as endometrioid histology (any grade), ≥50% myometrial invasion; high-risk as serous or clear cell histology (any myometrial invasion). Patients with gross peritoneal disease were excluded. Isolated tumor cells, micro-metastases, and macro-metastases were considered node-positive. RESULTS: We identified 210 patients in the LND cohort, 202 in the SLN cohort. Nodal assessment was performed for most patients. In the intermediate-risk group, stage IIIC disease was diagnosed in 30/107 (28.0%) (LND), 29/82 (35.4%) (SLN) (P=0.28). In the high-risk group, stage IIIC disease was diagnosed in 20/103 (19.4%) (LND), 26 (21.7%) (SLN) (P=0.68). Paraaortic lymph node (LN) assessment was performed significantly more often in intermediate-/high-risk groups in the LND cohort (P<0.001). In the intermediate-risk group, paraaortic LN metastases were detected in 20/96 (20.8%) (LND) vs. 3/28 (10.7%) (SLN) (P=0.23). In the high-risk group, paraaortic LN metastases were detected in 13/82 (15.9%) (LND) and 10/56 (17.9%) (SLN) (%, P=0.76). CONCLUSIONS: SLN mapping algorithm provides similar detection rates of stage IIIC endometrial cancer. The SLN algorithm does not compromise overall detection compared to standard LND.

Impact of Robotic Platforms on Surgical Approach and Costs in the Management of Morbidly Obese Patients with Newly Diagnosed Uterine Cancer.

BACKGROUND: Minimally invasive surgery (MIS) is associated with decreased complication rates, length of hospital stay, and cost compared with laparotomy. Robotic-assisted surgery-a method of laparoscopy-addresses many of the limitations of standard laparoscopic instrumentation, thus leading to increased rates of MIS. We sought to assess the impact of robotics on the rates and costs of surgical approaches in morbidly obese patients with uterine cancer. METHODS: Patients who underwent primary surgery at our institution for uterine cancer from 1993 to 2012 with a BMI ≥40 mg/m(2) were identified. Surgical approaches were categorized as laparotomy (planned or converted), laparoscopic, robotic, or vaginal. We identified two time periods based on the evolving use of MIS at our institution: laparoscopic (1993-2007) and robotic (2008-2012). Direct costs were analyzed for cases performed from 2009 to 2012. RESULTS: We identified 426 eligible cases; 299 performed via laparotomy, 125 via MIS, and 2 via a vaginal approach. The rates of MIS for the laparoscopic and robotic time periods were 6 % and 57 %, respectively. The rate of MIS was 78 % in this morbidly obese cohort in 2012; 69 % were completed robotically. The median length of hospital stay was 5 days (range 2-37) for laparotomy cases and 1 day (range 0-7) for MIS cases (P < 0.001). The complication rate was 36 and 15 %, respectively (P < 0.001). The rate of wound-related complications was 27 and 6 %, respectively (P < 0.001). Laparotomy was associated with the highest cost. CONCLUSIONS: The robotic platform provides significant health and cost benefits by increasing MIS rates in this patient population.

Invasion Patterns of Metastatic Extrauterine High-grade Serous Carcinoma With BRCA Germline Mutation and Correlation With Clinical Outcomes.

Characteristic histopathologic features have been described in high-grade serous carcinoma associated with BRCA abnormalities (HGSC-BRCA), which are known to have relatively favorable clinical outcomes. The aim of this study was to evaluate the clinical significance of invasion patterns in metastatic HGSC-BRCA cases. Of the 37 cases of advanced-stage HGSC with known BRCA1 or BRCA2 germline mutation retrieved from our institutional files, 23 patients had a germline mutation of BRCA1 and 14 had a BRCA2 mutation. The pattern of invasion at metastatic sites was recorded and classified as a pushing pattern (either predominantly or exclusively), an exclusively micropapillary infiltrative pattern, or an infiltrative pattern composed of papillae, micropapillae, glands, and nests (mixed infiltrative pattern). Histologic evaluation of metastases was performed without knowledge of genotype or clinical outcome. Clinical data were abstracted from medical records. Median age was 56 years (range, 31 to 73 y). All patients presented at stage IIIC or IV and underwent complete surgical staging followed by chemotherapy. All 37 HGSC-BRCA cases showed either pushing pattern metastases (30; 81%) or infiltrative micropapillary metastases (7; 19%). No HGSC-BRCA case exhibited metastases composed solely of mixed infiltrative patterns. Among the 7 infiltrative micropapillary cases, 6 had a BRCA1 germline mutation versus 1 with a BRCA2 mutation. The median time of follow-up was 26 months (range, 13 to 49 mo). All 7 patients with infiltrative micropapillary metastases either experienced recurrence or died of disease (5 recurrences and 2 deaths), which was significantly worse than what was seen in patients with predominantly pushing pattern metastases, of whom 16 of 30 (53%) experienced recurrence (n=14) or died of disease (n=2) (P=0.03). In conclusion, the recognition of different invasion patterns of metastatic extrauterine HGSC-BRCA has prognostic implications. The infiltrative micropapillary pattern is associated with poor outcomes and is more frequently seen in BRCA1-associated HGSC than in BRCA2 cases.

The role of adjuvant therapy in uterine leiomyosarcoma.

Uterine leiomyosarcoma (uLMS) is a rare mesenchymal tumor of the gynecologic tract. Although diagnosed in only 1-3% of patients with uterine cancer, uLMS accounts for the majority of uterine cancer-related deaths. The standard of care for patients with uLMS includes total hysterectomy and bilateral salpingo-oophorectomy (BSO). There are no standard recommendations regarding adjuvant or palliative therapy. Many cytotoxic and targeted agents have been studied in clinical trials in an effort to identify an effective therapy that may alter the natural history of this disease. Unfortunately, as of now, there are no adjuvant therapy regimens that improve overall survival in this patient population. There is, therefore, an unmet need to identify a novel therapy that will improve the survival of women diagnosed with this aggressive disease. Here we summarize the existing literature on adjuvant therapy in uLMS, specifically highlighting advances made in the last 5 years.

Low-Volume Lymph Node Metastasis Discovered During Sentinel Lymph Node Mapping for Endometrial Carcinoma.

PURPOSE: The aim of this study was to characterize treatment patterns and oncologic outcomes in patients with low-volume lymph node metastasis (isolated tumor cells [ITCs] and micrometastasis [MM]) discovered during sentinel lymph node (SLN) mapping for endometrial carcinoma. METHODS: We identified endometrial cancer cases treated surgically from September 2005 to April 2013 in which SLN mapping was performed. MM was defined as tumor within a lymph node measuring >0.2 mm but <2.0 mm, and ITCs were those measuring ≤0.2 mm. RESULTS: Overall, 844 patients, with a median age of 61 years (range 30-90), met the inclusion criteria. Histology was as follows: endometrioid, 724 (85.8 %) patients; serous, 104 (12.3 %) patients; and clear cell, 16 (1.9 %) patients. The median number of lymph nodes resected was six (range 0-60), and the median number of SLNs was two (range 0-15). Overall, 753 (89.2 %) patients were node-negative, 23 (2.7 %) had ITCs only, 21 (2.5 %) had MM only, and 47 (5.6 %) had macrometastasis. Adjuvant chemotherapy was administered to 106 (14 %) of 753 node-negative patients, 19 (83 %) of 23 patients with ITCs, 17 (81 %) of 21 patients with MM, and 42 (89 %) of 47 with macrometastasis. Median follow-up was 26 months (range 0-108). Three-year recurrence-free survival was as follows: node-negative patients, 90 % (±1.5); ITCs only, 86 % (±9.4); MM only, 86 % (±9.7); and macrometastasis, 71 % (±7.2) [p < 0.001]. CONCLUSIONS: Patients with ITCs and MM frequently received adjuvant chemotherapy and had improved oncologic outcomes in comparison to those with macrometastasis to the lymph nodes. Further prospective study is needed to determine optimal post-resection management in patients with ITCs or MM alone.

Menopause education: needs assessment of American obstetrics and gynecology residents.

OBJECTIVE: This study aims to understand the current teaching of menopause medicine in American obstetrics and gynecology residency programs. METHODS: A Web-based survey was e-mailed to all American obstetrics and gynecology residency directors, with a request that they forward it to their residents. RESULTS: Of 258 residency program directors contacted, 79 (30.6%) confirmed forwarding the survey. In all, 1,799 people received the survey, with 510 completions, for a response rate of 28.3%. Most residents reported that they had limited knowledge and needed to learn more about these aspects of menopause medicine: pathophysiology of menopause symptoms (67.1%), hormone therapy (68.1%), nonhormone therapy (79.0%), bone health (66.1%), cardiovascular disease (71.7%), and metabolic syndrome (69.5%). Among fourth-year residents who will be entering clinical practice soon, a large proportion also reported a need to learn more in these areas: pathophysiology of menopause symptoms (45.9%), hormone therapy (54.2%), nonhormone therapy (69.4%), bone health (54.2%), cardiovascular disease (64.3%), and metabolic syndrome (63.8%). When asked to rate the most preferred modalities for learning about menopause, the top choice was supervised clinics (53.2%), followed by case presentations (22.2%), formal lectures (21.3%), small groups (14.7%), Web-based learning (7.8%), and independent reading (5.2%). Only 20.8% of residents reported that their program had a formal menopause medicine learning curriculum, and 16.3% had a defined menopause clinic as part of their residency. CONCLUSIONS: It seems that some American residency programs do not fulfill the educational goals of their residents in menopause medicine. A curriculum would be beneficial for increasing knowledge and clinical experience on menopause issues.

Hormone replacement therapy in gynecologic cancer survivors: why not?

PURPOSE: As a result of treatment, many women with gynecologic malignancies will go through menopause and display climacteric symptoms at an earlier age than occurs naturally. Iatrogenic menopause may adversely affect quality of life and health outcomes in young female cancer survivors. Hormone replacement therapy (HRT) has often been withheld from women with gynecologic cancer because of concern that it might increase the risk of relapse or the development of new primary cancers. The purpose of this review was to examine the published literature on menopause management in gynecologic cancer survivors and highlight the risks and benefits of conventional and alternative HRT in this population. METHODS: A comprehensive literature search of English language studies on menopause management in gynecologic cancer survivors and women with a hereditary predisposition to a gynecologic malignancy was performed in MEDLINE databases through December 2010. RESULTS: Both our review and a 2008 Cochrane review of randomized trials on the effects of long-term HRT demonstrate that for menopausal women in their 40s or 50s with and without gynecologic cancer, the absolute risks of estrogen-only HRT are low. Several prospective observational studies and randomized trials on HRT use in women with a genetic predisposition for or development of a gynecologic malignancy suggest benefits in quality of life with no proven adverse oncologic effects as a result of short-term HRT use. CONCLUSION: In select women, it is reasonable to discuss and offer conventional HRT for the amelioration of menopausal symptoms and to improve quality of life. HRT does not appear to increase the risk of gynecologic cancer recurrences; however, this conclusion was largely based on observational data and smaller prospective studies.