Treatment Of Atypical Endometrial Hyperplasia Research Articles

EFFECTIVENESS OF HORMONAL TREATMENT IN PATIENTS WITH COMBINED ENDOMETRIAL PATHOLOGY AND BENIGN FORMATIONS OF MAMMARY GLANDS

Issues related to the treatment of HPE are still very relevant, which is due to the high frequency of relapses of this disease. Today, in the arsenal of modern medicine, there are various approaches to the treatment of HPE. However, the development of benign neoplasms of the mammary glands against the background of HPE limits the possibilities of conservative treatment. Hormonal therapy remains one of the most common methods of treating HPE.
 The purpose of the study: to optimize the treatment of patients with various types of hyperplastic processes of the endometrium in combination with benign diseases of the mammary glands.
 Materials and methods. A prospective study of 90 women aged 18 to 47 was conducted. The main group consisted of patients who were diagnosed with HPE and benign diseases of the mammary glands. The comparison group included patients who were diagnosed with HPE without accompanying pathology of the mammary glands. For the treatment of endometrial hyperplasia without atypia, medroxyprogesterone was used, for the treatment of atypical endometrial hyperplasia, medroxyprogesterone was used in combination with a gonadotropin-releasing hormone analog. For the treatment of patients with combined pathology, the commercial drug Danazol or medroxyprogesterone in combination with Koberlin was used.
 The results. The implementation of various treatment regimens for patients with HPE and benign breast neoplasms showed that the more effective treatment regimen was the one involving the use of Danazol. In this group of patients, the levels of estradiol and progesterone in the blood plasma normalized already after six months of using the drug.
 Conclusion. The study of the levels of estrogens, progestins and gonadotropic hormones showed that in the patients of the comparison group, the best treatment scheme is the combined use of medroxyprogesterone and gonadotropin-releasing hormone analogues compared to the monouse of only medroxyprogesterone. In patients with the combined pathology of HPE and mastopathy, the best treatment scheme is the use of Danazol.

Levonorgestrel-releasing intrauterine device plus metformin, or megestrol acetate plus metformin for fertility-sparing treatment of atypical endometrial hyperplasia and early endometrial carcinoma: a prospective, randomized, blind-endpoint design trial protocol

BackgroundEndometrial adenocarcinoma (EC) is the fifth most common cancer in women worldwide, standard treatment for EC includes hysterectomy, but it results in the loss of reproductive function. Thus, conservative treatment for these patients is strongly demanded, progestin therapy is widely accepted as the main fertility-sparing treatment for young women with endometrial hyperplasia with atypia (EHA) and well-differentiated endometrioid endometrial cancer. This trial will investigate the effectiveness of conservative treatment for obese women with early-stage EC.Method and designThis will be an open-label, 2-armed, randomized, phase-II single-center trial of LNG-IUD plus metformin or megestrol acetate (MA) plus metformin. A total of 88 participants will be randomly assigned into 2 treatment arms in a 1:1 ratio. Clinical, laboratory, ultrasound and radiology data, will be collected at baseline, and then at 3, 6, 9, 12, 18, and 24 months. EC biomarkers will be collected at baseline. The primary aim is to determine the efficacy of a levonorgestrel-releasing intrauterine device (LNG-IUD) plus metformin, or megestrol acetate (MA) plus metformin in achieving pathological complete response (pCR) at 12 months, as well as post-treatment pregnancy outcomes and recurrence rate. The secondary aims are to predict the response to an LNG-IUD plus metformin and MA plus metformin via clinical, blood, and tissue predictive biomarkers.ConclusionsProspective evidence for conservative treatment of EC is limited. New methods to achieve better CR rates with fewer side effects are needed. This trial will investigate the effectiveness of LNG-IUD plus metformin, and MA plus metformin, in obese women with early-stage EC, providing a non-surgical treatment option for these patients.Trial registration ChiCTR2200055624. The trial was registered at http://www.chictr.org.cn/listbycreater.aspx on January 15, 2022

Conservative Management of Atypical Endometrial Hyperplasia and Early Endometrial Cancer in Childbearing Age Women.

Total hysterectomy and bilateral adnexectomy is the standard treatment for atypical endometrial hyperplasia and early-stage endometrial cancer. However, the recommended surgical treatment precludes future pregnancy when these conditions are diagnosed in women in their fertile age. In these patients, fertility-sparing treatment may be feasible if the desire for childbearing is consistent and specific conditions are present. This review summarizes the available evidence on fertility-sparing management for atypical endometrial hyperplasia and early-stage endometrial cancer. Historically, oral progestins have been the mainstay of conservative management for atypical endometrial hyperplasia and stage IA endometrioid endometrial cancer with no myometrial invasion, although there is no consensus on dosage and treatment length. Intrauterine progestin therapy has proved a valid alternative option when oral progestins are not tolerated. GnRH analogs, metformin, and hysteroscopic resection in combination with progestins appear to increase the overall efficacy of the treatment. After a complete response, conception is recommended; alternatively, maintenance therapy with strict follow-up has been proposed to decrease recurrence. The risk of disease progression is not negligible, and clinicians should not overlook the risk of hereditary forms of the disease in young patients, in particular, Lynch syndrome. Hysterectomy is performed once the desire for childbearing desire has been established. The conservative management of atypical endometrial hyperplasia and early-stage endometrial cancer is feasible, provided a strong desire for childbearing and permitting clinical–pathological conditions. However, patients must be aware of the need for a strict follow-up and the risk of progression with a possible consequent worsening of the prognosis. More homogenous and well-designed studies are necessary to standardize and identify the best treatment and follow-up protocols.

Metabolic syndrome is an independent risk factor for time to complete remission of fertility-sparing treatment in atypical endometrial hyperplasia and early endometrial carcinoma patients

ObjectiveFertility-sparing treatment of atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EC) patients has recently emerged important social health topic. This study is designed to explore the risk factors for time to complete remission (CR) of fertility-sparing treatment in woman with AEH and early EC.MethodsA retrospective study was designed with clinical data from 106 patients admitted between January 2012 to December 2019. Univariate and multivariate logistic analysis were used to explore independent risk factors for time to CR. These factors were employed in receiver operator characteristic (ROC) curve and the decision curve analysis (DCA) to evaluate predictive accuracy of time to CR. Stratified analysis and interactive analysis was also performed for more in-depth perspective.ResultsUnivariate analysis showed that fasting blood glucose levels (FBG, OR = 1.6, 95%CI: 0.6–2.5, P = 0.020), metabolic syndrome (MetS, OR = 3.0, 95%CI: 1.1–5.0, P = 0.003), and polycystic ovary syndrome (PCOS, OR = 2.0, 95%CI: 0.5–3.4, P = 0.009) were associated with time to CR. Among these factors, multivariate analysis confirmed MetS (OR = 3.1, 95%CI: 1.0–5.2, P = 0.005) was an independent risk factor. The area under the ROC curve (AUC) of MetS was higher than FBG and PCOS (AUC = 0.723 vs 0.612 and 0.692). The AUC of FBG combined with PCOS was 0.779, and it was improved to 0.840 when MetS was included (P < 0.05). Additionally, MetS played different roles in time to CR in various groups. Moreover, we found high-density lipoprotein (HDL) and MetS had an interactive effect for time to CR.ConclusionMetS is an independent risk factor for time to CR and should be taken seriously in fertility-sparing management of AEH and early EC patients.

Safety and efficacy of levonorgestrel-releasing intrauterine device in the treatment of atypical endometrial hyperplasia and early endometrial cancer.

To investigate the recurrence rate, live-birth rate, and treatment outcomes of levonorgestrel-releasing intrauterine device (LNG-IUD) for the management of atypical endometrial hyperplasia (AEH) or Grade-1 endometrial cancer (EC) in patients who desire fertility-sparing treatment and those seeking conservative treatment without fertility preservation. We prospectively enrolled nine patients from a single institution between April 2009 and September 2013 who were followed up for 60 months after LNG-IUD insertion. The median patient age was 35 (range: 29-39) years. The overall recurrence rate was 56% (5/9). The median interval between removal of the LNG-IUD and recurrence was 20.5 (range: 2-30) months. Three of the nine patients had Grade-1 EC, and six had AEH. The response rates to the LNG-IUD in patients with Grade-1 EC and AEH were 66% and 100%, respectively. Four patients (three with AEH, one with Grade-1 EC) experienced recurrence 6 months after MPA treatment and all 4 (100%) had complete response. Eight patients desired fertility preservation, of which 37% (3/8) conceived after receiving fertility treatment and 25% (2/8) had a live birth; the remaining three had previously received MPA for 6 months and had a recurrence; of these, 1 had a live birth. LNG-IUD is effective for the management of AEH and EC in young patients who desire fertility-sparing treatment, including those ineligible for MPA owing to the presence of comorbidities and those with recurrence after MPA treatment (6-month treatment), and patients seeking conservative treatment without fertility preservation.

Fertility-sparing treatment for endometrial cancer and atypical endometrial hyperplasia in patients with Lynch Syndrome: Molecular diagnosis after immunohistochemistry of MMR proteins.

IntroductionLynch Syndrome (LS) represents the hereditary condition that is most frequently associated with endometrial cancer (EC). The aim of this study is to assess the presence of Lynch Syndrome (LS) in young women with mismatch repair (MMR)-deficient atypical endometrial hyperplasia (AEH) and non-myoinvasive FIGO G1 endometrioid EC and its possible impact on the outcome of conservative treatment.MethodsSix MMR-deficient cases identified from a previous cohort of 69 conservatively treated patients were selected to be screened for germline mutations in MMR genes. In each patient, the outcomes of conservative treatment for AEH and EEC, including response, relapse, progression, and pregnancy, were assessed.ResultsFive out of 6 patients underwent genetic test for LS. Three out of these 5 patients showed a positive genetic test. Patient 1 showed the c.942 + 2 T>A heterozygous variant of MSH2 mutation; after 12 months of complete response, she had relapse and progression of disease. Patient 4 showed the c.2459-1G>C variant of MSH2 mutation; after complete response, she failed to achieve pregnancy; she had relapse after 24 months and underwent hysterectomy. Patient 6 showed the c.803 + 1 heterozygous variant of PMS2 mutation; she had relapse of disease after 18 months from the first complete response and then underwent hysterectomy.ConclusionsIn this series, 3 out of 6 women with MMR-deficiency had LS. None of the patients achieved pregnancy, and those who responded to treatment had subsequent relapse of disease. Patients undergoing fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer should perform MMR immunohistochemical analysis in order to screen LS.

Nodal Assessment in Endometrial Atypical Hyperplasia

Objective: Atypical endometrial hyperplasia (AH) is the neoplastic precursor more often associated with endometrial cancer (EC). Nowadays, 25–50% of patients subjected to hysterectomy for preoperative AH are diagnosed with EC at the final pathological analysis. Furthermore, there is no consensus on which preoperative AH patients would benefit from sentinel lymph node mapping. This study aimed to evaluate nodal assessment and preoperative cancer risk factors in preoperative AH patients undergoing nodal surgical staging. Methods: Patients undergoing surgical treatment for AH were retrospectively included in the analysis. Patients were divided into two groups (AH and EC groups) based on the final surgical pathology. The ESGO/ESTRO/ESP risk classification was used for EC cases. Design: This was a retrospective study. Results: Of the 207 AH patients treated, 152 cases met the inclusion criteria. Among preoperative AH patients with final EC diagnosis, 39 patients were in the low-risk group (25.7%), 8 in the intermediate-risk group (5.3%), 4 in high-intermediate (2.6%), and 3 patients were allocated in the high-risk group (2.0%). Fifty-four total patients underwent nodal surgical staging. Only one nodal micrometastasis (0.7%) was found at ultrastaging. Multivariate analysis showed abnormal uterine bleeding (AUB) (p = 0.01), hypertension (p < 0.01), and endometrial thickness ≥20 mm (p = 0.02) statistically more represented in patients with EC at final surgical analysis. EC risk was 2.9 (95% CI: 1.29–6.48) in AUB, 2.7 (95% CI: 1.06–6.92) in hypertension, and 3.1 (95% CI: 1.19–7.97) in endometrial thickness ≥20 mm cases. Limitations: The present study has limitations inherent in its retrospective nature. Conclusion: The overall risk of nodal metastases in preoperative AH patients was low. Conversely, 9.9% of the preoperative AH patients belonged to the intermediate or high-risk group for EC at the final histological examination. Preoperative cancer risk factors would identify AH patients for whom nodal staging could be suggested.

Clinical implications of morular metaplasia in fertility-preserving treatment for atypical endometrial hyperplasia and early endometrial carcinoma patients

ObjectiveMorular metaplasia (MM) is a benign epithelial metaplasia that sometimes appears in atypical endometrial hyperplasia (AEH) and endometrioid endometrial carcinoma (EEC). However, the clinical implications of MM for fertility-preserving treatment in AEH and EEC patients are unclear. This study investigated the clinical features and impact of MM on the efficacy of fertility-preserving treatment.MethodsWe retrospectively studied 427 AEH and EEC patients who received fertility-preserving treatment. Clinical features, treatment efficacy, and onco-fertility results were compared between patients with and without MM.ResultsMM appeared in 147 of 427 (34.4%) patients. Among them, 49 (33.3%) had MM only before treatment (BEF group), 32 (21.8%) had sustained MM before and during treatment (SUS group), and 66 (44.9%) had MM only during treatment (DUR group). The BEF group had a higher 12-month CR rate (98.0% vs 85.7%, p = 0.017) and shorter therapeutic duration to achieve CR (4.0 vs 5.7 months, p = 0.013) than the non-MM group had. In comparison with the non-MM group, the SUS and DUR groups had a lower CR rate after 7 months of treatment (SUS vs non-MM, 37.5% vs 61.1%, p = 0.010; DUR vs non-MM 33.3% vs. 61.1%, p < 0.001), and a longer median therapeutic duration to achieve CR (SUS vs non-MM, 7.6 vs. 4.0 months, p = 0.037; DUR vs non-MM, 7.9 vs. 4.0 months, p < 0.001).ConclusionAppearance of MM only before treatment was positively correlated with outcome of fertility-preserving treatment, while sustained MM or appearance of MM only during treatment implied poorer outcome of fertility-preserving treatment in AEH and EEC patients.

Therapeutic options of endometrial hyperplasia management. Current recommendations and prospective directions of treatment

Endometrial hyperplasia (EH) is a pathological condition characterized by proliferation of the endometrial glands with an increase in the glands/stroma ratio compared to normal proliferative endometrium. EH is a precursor to the development of one of the most common gynecological malignancies – endometrial cancer. There are EH without atypia and with atypia.Total hysterectomy with bilateral salpingo-oophorectomy is the method of choice in the treatment of atypical EH. It is important to eliminate risk factors – overweight patients should lose weight by adjusting diet, increase physical activity. Recently, aromatase inhibitors have also proven to be an effective treatment option for EH with atypia. Oral progestogens and the levonorgestrel-releasing intrauterine device are methods of choice for conservative treatment of premenopausal and postmenopausal women with atypical EH.However, not all patients can use progestins for a long time due to possible side effects. Failure of progestin treatment may depend on various factors, such as the patient’s age, health status, other conditions, and the degree or type of hyperplasia. So it is important to look for new methods of EH management and adjuvant drugs that will potentiate the effectiveness of basic treatment, as well as opportunities to reduce the risks of progesterone receptor resistance and potentiation of progestins. Cridanimod is a new small molecule that has been shown in studies to increase the progesterone receptors expression in the endometrium. It has been suggested that in combination with progestin therapy it increases the progesterone receptors expression and thus improves the effectiveness of treatment. Research results allows to consider the possibility of using cridanimod in complex EH therapy, especially against the background of viral infection. Cridanimod reduces the risk of resistance to progestogen therapy in EH, provides the best result after conservative treatment and reduces the number of relapses.

Criteria for resumption of assisted reproductive technology intervention after fertility-sparing treatment of atypical endometrial hyperplasia and endometrial cancer

<h3>Objectives:</h3> The purpose of this study was to identify criteria for safe resumption of assisted reproductive technologies (ART) in women diagnosed with atypical endometrial hyperplasia (AH) or endometrial cancer (EC) during infertility evaluation and managed with a fertility-sparing approach. <h3>Methods:</h3> A retrospective review was performed of women diagnosed with AH or EC during infertility workup at a multi-site academic tertiary care center between 1/1/2009 and 12/1/2018. The primary outcome was the number of benign endometrial samplings required by clinicians prior to resumption of ART. Secondary outcomes included recurrence rates, type and duration of treatment, and sampling modalities. Descriptive statistics were calculated. <h3>Results:</h3> In this pragmatic sample, 22 women were treated for AH (55%) and EC (45%). Two failed medical management and proceeded with hysterectomy and five were lost to follow-up or deferred fertility. Fifteen women (68%) achieved pathologic response and were cleared to resume ART. Mean age of this subset was 34.8 (±4.0) years with mean BMI 33.9 (±10.6) kg/m². Oncologic diagnosis was AH in 87% and EC in 13%. Uterine factor (60%) and ovulatory dysfunction (47%) were the two most common infertility diagnoses. Initial treatments included oral progestins (73%), levonorgestrel intrauterine devices (13%), or a combination of these two modalities (13%). Of these fifteen women, eleven (73%) were cleared for ART after one benign endometrial sampling ("one-sample") and four (27%) were cleared after two consecutive benign endometrial samplings performed three to four months apart ("two-sample"). In the one-sample group, D&C was used for sampling in 73% and EMB in 27%. The benign sampling that cleared the patient for ART was the first sampling performed during treatment in 64%. In the two-sample group, all samplings were performed using EMB. The average treatment duration was 6.3 vs 10.9 months in the one- vs two-sample subsets. One woman from each group underwent hysterectomy despite clearance. Four of the remaining ten women in the one-sample group (40%) experienced recurrence, compared to zero in the two-sample group. All recurrences were managed with resumption of progesterone-based treatment. One woman (25%) was cleared after one subsequent benign sampling and three (75%) after two. <h3>Conclusions:</h3> Most gynecologic oncologists cleared patients to proceed with ART after a single endometrial sampling demonstrated pathologic response following progesterone-based treatment for AH/EC. Short interval recurrence was common, but with potential for salvage response. Future work should utilize prospective analyses to evaluate for differences in recurrence rates based on various clearance criteria.

Fertility-Sparing Treatment for Atypical Endometrial Hyperplasia and Endometrial Cancer: A Cochrane Systematic Review Protocol.

Endometrial cancer is the fifth most common cancer in women and atypical endometrial hyperplasia is a precancerous lesion. Obesity is an important risk factor for endometrioid endometrial adenocarcinoma and endometrial hyperplasia. Progesterone is recommended as first-line treatment in endometrial cancer or atypical endometrial hyperplasia in women who wish to preserve fertility, but optimal treatment schedules have not been defined. Metformin or bariatric surgery may also be useful in these women. The effectiveness and safety of fertility-preserving treatments being used for women with atypical endometrial hyperplasia and stageIA grade1 endometrial cancer is unclear. Therefore, the systematic review aims to determine this point. We will search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, trial registers, conference proceedings, abstracts, cooperative trial groups and reference lists. We will include randomised controlled trials (RCTs) that compare fertility-preserving therapy including orally administered progesterone versus a levonorgestrel-releasing intrauterine system (IUS), metformin, other pharmacological interventions or bariatric surgery, and any of these interventions with womb-removing surgery. Quasi-randomised trials, non-randomised trials and cohort studies will be included. Two review authors will independently assess study eligibility and risk of bias and extract data. The primary outcomes are complete pathologic response and live birth rate. Secondary outcomes include overall survival, progression-free survival, pregnancy rate, need for hysterectomy, adverse events, psychological symptoms and quality of life. This review aims to clarify the effectiveness and risks of fertility-preserving treatments, including complete pathologic response rate, live birth rates, need for surgical treatment, adverse events, psychological symptoms and quality of life. The broad scope of the review includes the use of progesterone, metformin to reverse insulin resistance, and bariatric surgery or operative hysteroscopy. The results may help to determine the optimal fertility-sparing treatment in endometrial cancer and atypical endometrial hyperplasia. Prospero 2019 number CRD42019145991.

Trends and characteristics of fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer in Japan: A survey by the gynecologic oncology committee of Japan Society of Obstetrics and Gynecology

Objective: Fertility-sparing treatment is an option for young patients with atypical endometrial hyperplasia (AEH) and endometrial cancer. However, its clinical features and current trends in treatment are relatively unknown in Japan. In this study, we aimed to collect and analyze nationwide data on fertility-sparing treatment for AEH and endometrial cancer patients in Japan. The objective of this study was to examine pathological complete remission (CR) rates and trends in fertility-sparing treatment for young AEH and endometrial cancer patients in Japan.

Clinical Predictive Factors of Response to Treatment in Patients Undergoing Conservative Management of Atypical Endometrial Hyperplasia and Early Endometrial Cancer.

Purpose: Predictive markers of response to conservative treatment of atypical endometrial hyperplasia (AEH) or early endometrial cancer (EEC) are still lacking. We aimed to assess clinical predictive factors of response to conservative treatment of AEH and EEC. Methods: All patients with AEH or EEC conservatively treated from January 2007 to June 2018 were retrospectively assessed. The associations between 23 clinical factors and outcomes of response to treatment were assessed with standard univariate analyses and multivariate logistic regression (significant p-value <0.05). The primary outcome was the association of each clinical factor with treatment failure (i.e., no regression or relapse of the disease). Secondary outcomes were the associations of each clinical factor with: (1) no regression, (2) relapse, or (3) pregnancy after treatment. Results: Forty-three women, 37 (86%) with AEH and 6 (14%) with EEC were included. At univariate analyses, treatment failure was associated with longer menstrual cycle (p = 0.002), infrequent menstrual bleeding (p = 0.04), and a diagnosis of EEC instead of AEH (p = 0.008). Among the secondary outcomes, no regression was associated with infrequent menstrual bleeding (p = 0.04), and a diagnosis of EEC instead of AEH (p < 0.001), while relapse was associated with longer menstrual cycles (p = 0.007). At multivariate analyses, odds ratio for treatment failure was 4.54 (95% confidence interval [CI], 0.24-84.4) for a diagnosis of EEC instead of AEH (p = 0.3), and 2.10 (95% CI, 1.03-4.29) for longer menstrual cycles (p = 0.042), while infrequent menstrual bleeding perfectly predicted treatment failure. Conclusions: Longer menstrual cycles and infrequent menstrual bleeding appear as independent predictive factors for conservative treatment failure in AEH and EEC. Further and larger studies are necessary to confirm these findings.

Medroxyprogesterone acetate plus metformin for fertility-sparing treatment of atypical endometrial hyperplasia and endometrial carcinoma: trial protocol for a prospective, randomised, open, blinded-endpoint design, dose-response trial (FELICIA trial)

IntroductionProgestin therapy is the only fertility-sparing treatment option for patients with atypical endometrial hyperplasia (AEH) and endometrial cancer (EC). However, the results of three meta-analyses revealed a high remission rate,...

Комбинированное применение агонистов гонадотропин-рилизинг-гормона и внутриматочной левоноргестрел-рилизинг-системы в лечении атипической гиперплазии эндометрия у женщин репродуктивного возраста

Комбинированное применение агонистов гонадотропин-рилизинг-гормона и внутриматочной левоноргестрел-рилизинг-системы в лечении атипической гиперплазии эндометрия у женщин репродуктивного возраста

Fertility-Sparing Treatment in Young Women with Atypical Endometrial Hyperplasia and Low-Grade Endometrial Cancer: A Tertiary Center Experience.

Objectives:To evaluate the oncologic and reproductive outcomes of patients with atypical endometrial hyperplasia and low grade stage 1 endometrial cancer who received medical treatment.Methods:We carried out a retrospective study on all patients aged 20-42 years with complex, atypical endometrial hyperplasia, and low-grade stage 1 endometrial cancer, who wished to preserve fertility and were treated at the Royal Hospital. We held this study between January 2006 and December 2016. The patients received oral megestrol acetate with or without a levonorgestrel intrauterine system. We assessed their response to progestin treatment in terms of treatment duration, time to response, pregnancy, time of surgery, and oncological outcome. We performed the statistical analysis using the SPSS 20.0 software.Results:Twenty patients met the inclusion criteria, and among them 90% had complete remission. Among these 90%, 55% had complete remission within six months of treatment. The recurrence rate was recorded in 11 patients (55%) and it was more frequent in obese patients with body mass index (BMI) ≥30 (p=0.001), who had complete response in > 6 months of hormonal treatment. About 15% of the patients required hysterectomy, and 12 (60%) patients conceived after full treatment.Conclusions:Fertility-sparing treatment of atypical endometrial hyperplasia and grade 1 stage 1 endometrial cancer in reproductive-age women is feasible. However, obese patients (BMI ≥ 30) had a higher recurrence rate.

Guideline No. 390-Classification and Management of Endometrial Hyperplasia.

The aim of this guideline is to aid primary care physicians and gynaecologists in the initial evaluation of women with suspected endometrial hyperplasia, to recommend the use of the 2014 World Health Organization classification for endometrial hyperplasia by all health care providers, and to guide the optimal treatment of women diagnosed with endometrial hyperplasia. Physicians, including gynaecologists, obstetricians, family physicians, general surgeons, emergency medicine specialists; nurses, including registered nurses and nurse practitioners; medical trainees, including medical students, residents, and fellows; and all other health care providers. Adult women (18 years and older) presenting with suspected or confirmed endometrial hyperplasia. The discussion relates to the medical therapy as well as surgical treatment options for women with and without atypical endometrial hyperplasia. For this guideline, relevant studies were searched in PubMed, Cochrane Wiley, and the Cochrane Systematic Reviews using the following terms, either alone or in combination, with the search limited to English language materials, human subjects, and published since 2000: (endometrial hyperplasia, endometrial intraepithelial neoplasia, endometrial sampling, endometrial curettage, diagnosis) AND (treatment, progestin therapy, surgery, LNG-IUS, aromatase inhibitors, metformin ), AND (obesity). The search was performed in April 2018. Relevant evidence was selected for inclusion in the following order: meta-analyses, systematic reviews, guidelines, randomized controlled trials, prospective cohort studies, observational studies, non-systematic reviews, case series, and reports. Additional significant articles were identified through cross-referencing the identified reviews. The total number of studies identified was 2152, and 82 studies were included in this review. The content and recommendations were drafted and agreed upon by the authors. The Executive and Board of the Society of Gynecologic Oncology of Canada reviewed the content and submitted comments for consideration, and the Board of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology framework. The interpretation of strong and weak recommendations was also included. The Summary of Findings is available upon request. It is expected that this guideline will benefit women with endometrial hyperplasia. This should guide patient informed consent before both medical and surgical management of this condition. Evidence will be reviewed 5 years after publication to decide whether all or part of the guideline should be updated. However, if important new evidence is published prior to the 5-year cycle, the review process may be accelerated for a more rapid update of some recommendations. RECOMMENDATIONS.

New Variant Of Hormonal Treatment For Atypical Endometrial Hyperplasia And An Early Endometrial Cancer With Fertility Preservation

New Variant Of Hormonal Treatment For Atypical Endometrial Hyperplasia And An Early Endometrial Cancer With Fertility Preservation

Long-term outcomes of progestin plus metformin as a fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer patients.

ObjectiveThe present study investigated long-term outcomes of medroxyprogesterone acetate (MPA) plus metformin therapy in terms of control of atypical endometrial hyperplasia (AEH) and endometrial cancer (EC), and post-treatment conception.MethodsWe retrospectively analyzed 63 patients (42 with EC; 21 with AEH) who underwent fertility-sparing management using MPA plus metformin. MPA (400 mg/day) and metformin (750–2,250 mg/day) were administered to achieve complete response (CR). Metformin was administered until conception, even after MPA discontinuation.ResultsOf the total patients, 48 (76%) had a body mass index (BMI) ≥25 kg/m2 and 43 (68%) showed insulin resistance. Sixty-one patients (97%) achieved CR within 18 months. CR rates at 6, 8–9, and 12 months were 60%, 84%, and 90%, respectively. During a median follow-up period of 57 months (range, 13–115 months), relapse occurred in 8 of 61 patients (13.1%) who had achieved CR. Relapse-free survival (RFS) in all patients at 5 years was 84.8%. Upon univariate analysis, patients with BMI ≥25 kg/m2 had significantly better prognoses than did those with BMI <25 kg/m2 (odds ratio=0.19; 95% confidence interval=0.05–0.66; p=0.009). Overall pregnancy and live birth rates per patient were 61% (19/31) and 45% (14/31), respectively.ConclusionsMPA plus metformin is efficacious in terms of RFS and post treatment conception. Moreover, metformin may be more efficacious for patients with BMI ≥25 kg/m2.

Does surgical treatment of atypical endometrial hyperplasia require referral to a gynecologic oncologist?

Patients with atypical endometrial hyperplasia in the United States are commonly referred to a gynecologic oncologist, given a moderate risk of concurrent carcinoma. However, selective referral of patients to nononcologic gynecologic surgeons for surgical treatment of atypical endometrial hyperplasia may offer increased access to care without compromising clinical outcomes. Nononcologic surgeons who consider providing surgical treatment for atypical endometrial hyperplasia must be able to offer minimally invasive surgery when appropriate and have sufficient surgical volume to deliver optimal clinical outcomes. Patients considering referral to a nononcologic surgeon must be thoroughly counseled regarding the risk of occult malignancy, the possibility of a second surgery for lymph node evaluation and/or oophorectomy, and the risk of morbidity that may accompany a second surgery. Available data suggest that approximately 2-6% of patients will have postoperative risk factors meriting consideration of a second surgery. Patients who are high-risk surgical candidates or who may desire nonsurgical or fertility-sparing treatment should universally be referred for consultation with a gynecologic oncologist.