Metformin for endometrial hyperplasia.
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ABSTRACT:
SUBMITTER: Clement NS
PROVIDER: S-EPMC6485333 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC6779615 | biostudies-literature
Project description:ObjectiveProgestin based therapy is the preferred option for fertility-sparing treatment of reproductive-age women with preserved fertility in endometrial hyperplasia (EH) or early endometrial cancer (EEC). Our objective was to investigate whether metformin could enhance the efficacy of progestin-based therapies by meta-analysis.MethodsWe conducted a meta-analysis of randomized or non-randomized controlled trials by searching of PubMed, Embase, Web of science, and Cochrane database from inception to November 8, 2022. The results of enrolled studies were pooled using meta-analysis to estimate the effect of progestin plus metformin on remission, recurrence, pregnancy rate and live birth rate.ResultsIn the analysis of progestin administered systemically or locally, complete response (CR) was significantly higher in progestin plus metformin versus progestin alone in the EH group (pooled OR 2.08, 95% CI 1.29 to 3.34, P=0.003), in the EEC group (pooled OR 1.86, 95% CI 1.13 to 3.05, P=0.01), but not in EEC and EH group (pooled OR 1.46, 95% CI 0.97 to 2.21, P=0.07). In the analysis of progestin administered systemically, complete response was improved in progestin plus metformin versus progestin alone, in the EH group (pooled OR 2.47, 95% CI 1.45 to 4.21, P=0.0009), in the EEC group (pooled OR 2.09, 95% CI 1.18 to 3.71, P=0.01), and in the EEC and EH group (pooled OR 2.03, 95% CI 1.16 to 3.54, P=0.01). The relapse rates of patients with EEC and EH were not different (pooled OR 0.54, 95% CI 0.24 to 1.20, P=0.13). For obstetric outcomes, the addition of metformin improved pregnancy rate (pooled OR 1.55, 95% CI 0.99 to 2.42, P=0.05), but not live birth rate (pooled OR 0.95, 95% CI 0.45 to 2.01, P=0.89).ConclusionFor fertility-sparing management, compared to progestin alone, the outcomes of patients with endometrial hyperplasia and early endometrial cancer were more improved with progestin plus metformin because progestin plus metformin increases the rate of remission and pregnancy.
| S-EPMC10320576 | biostudies-literature
Project description: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.
| S-EPMC9636609 | biostudies-literature
Project description:BackgroundIn reproductive-aged women, the incidence of atypical endometrial hyperplasia (AEH) or endometrioid endometrial carcinoma (EEC) is rising globally. The study aimed to investigate the effectiveness of hysteroscopic curettage followed by megestrol acetate (MA) plus metformin as conservative treatment in AEH and early EEC.MethodsWe retrospectively studied AEH and stage IA, grade 1 EEC patients treated with hysteroscopic curettage followed by MA (160 mg/d) plus metformin (1500 mg/d) from January 2010 to December 2020 at Fudan University Shanghai Cancer Center. Treatment outcomes were assessed by complete response (CR) rate, recurrence rate, and pregnancy outcomes. Univariate and multivariate analyses were performed via the logistic regression model.ResultsThe study included 79 patients, 31 (39.2%) with AEH and 48 (60.8%) with EEC. The medians of age (years) and follow-up time (months) were 30 and 39.5, respectively. Seventy-six patients (96.2%) finally achieved CR. The median time to CR was 3.6 (3.0-20.6) months. The CR rate after 3 months, 6 months, and 1 year was 55 (69.6%), 67 (84.8%), and 72 (91.1%), respectively. Recurrence occurred in 26 (34.2%) patients. Treatment duration ⩾9 months was associated with a lower recurrence rate after CR (P = .012). Fourteen (93.3%) of the 15 recurrent patients who received progestin re-treatment achieved CR again. Finally, 29 patients delivered live births.ConclusionsHysteroscopy followed by MA plus metformin can achieve CR in short time and is overall safe. Consolidation treatment should be prolonged to decrease the recurrence rate, despite a shorter time to CR.
| S-EPMC9297462 | biostudies-literature
Project description:Using mouse models of endometrial tumorigenesis based on two of the most common molecular alterations found in primary human UEC we sought to characterize the transition from CAH to carcinoma to identify clinically useful biomarkers. In order to identify novel candidate genes associated with invasion, global gene expression profiles were compared from uteri with extensive CAH and carcinoma. Keywords: Gene expression profiling
2008-11-20 | GSE10866 | GEO
Project description:Using mouse models of endometrial tumorigenesis based on two of the most common molecular alterations found in primary human UEC we sought to characterize the transition from CAH to carcinoma to identify clinically useful biomarkers. In order to identify novel candidate genes associated with invasion, global gene expression profiles were compared from uteri with extensive CAH and carcinoma. Keywords: Gene expression profiling RNA was extracted from uterine segments with either CAH or invasive carcinoma from Pten+/-;Mlh1-/- , Pten+/-;Mlh1+/+ and Wild type female mice. The RNA was hybridized to Affymetrix mouse 430A chip in order to determine changes in global gene expression patterns
2008-11-19 | E-GEOD-10866 | biostudies-arrayexpress
Project description:ObjectiveAlthough a fraction of endometrial hyperplasia cases have concurrent endometrial carcinoma, patient characteristics associated with concurrent malignancy are not well described. The aim of our study was to identify predictive clinico-pathologic factors for concurrent endometrial carcinoma among patients with endometrial hyperplasia.MethodsA case-control study was conducted to compare endometrial hyperplasia in both preoperative endometrial biopsy and hysterectomy specimens (n=168) and endometrial carcinoma in hysterectomy specimen but endometrial hyperplasia in preoperative endometrial biopsy (n=43). Clinico-pathologic factors were examined to identify independent risk factors of concurrent endometrial carcinoma in a multivariate logistic regression model.ResultsThe most common histologic subtype in preoperative endometrial biopsy was complex hyperplasia with atypia [CAH] (n=129) followed by complex hyperplasia without atypia (n=58) and simple hyperplasia with or without atypia (n=24). The majority of endometrial carcinomas were grade 1 (86.0%) and stage I (83.7%). In multivariate analysis, age 40-59 (odds ratio [OR] 3.07, p=0.021), age≥60 (OR 6.65, p=0.005), BMI≥35kg/m(2) (OR 2.32, p=0.029), diabetes mellitus (OR 2.51, p=0.019), and CAH (OR 9.01, p=0.042) were independent predictors of concurrent endometrial carcinoma. The risk of concurrent endometrial carcinoma rose dramatically with increasing number of risk factors identified in multivariate model (none 0%, 1 risk factor 7.0%, 2 risk factors 17.6%, 3 risk factors 35.8%, and 4 risk factors 45.5%, p<0.001). Hormonal treatment was associated with decreased risk of concurrent endometrial cancer in those with ≥3 risk factors.ConclusionsOlder age, obesity, diabetes mellitus, and CAH are predictive of concurrent endometrial carcinoma in endometrial hyperplasia patients.
| S-EPMC7521604 | biostudies-literature
Project description:Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH.
| S-EPMC4695458 | biostudies-literature
Project description: Not available
| S-EPMC8200645 | biostudies-literature
Project description:Phosphatase and tensin homolog (PTEN) is a protein that acts as a tumor suppressor by dephosphorylating the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. Loss of PTEN function has been implicated in the pathogenesis of a number of different tumors, particularly endometrial carcinoma (ECa). ECa is the most common neoplasia of the female genital tract. Our study evaluates an association between the morphological appearance of endometrial hyperplasia and endometrial carcinoma and the degree of PTEN alterations. A total of 45 endometrial biopsies from Slovak women were included in present study. Formalin-fixed and paraffin-embedded tissue samples with simple hyperplasia (3), complex hyperplasia (5), atypical complex hyperplasia (7), endometrioid carcinomas G1 (20) and G3 (5), and serous carcinoma (5) were evaluated for the presence of mutations in coding regions of PTEN gene, the most frequently mutated tumor suppressor gene in endometrial carcinoma. 75% of the detected mutations were clustered in exons 5 and 8. Out of the 39 mutations detected in 24 cases, 20 were frameshifts and 19 were nonsense, missense, or silent mutations. Some specimens harboured more than one mutation. The results of current study on Slovak women were compared to a previous study performed on Polish population. The two sets of results were similar.
| S-EPMC4465682 | biostudies-literature