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Journal of Gynecologic Oncology Jul 2023To examine the effectiveness of progestin re-treatment for recurrent endometrial intraepithelial neoplasia (EIN), atypical endometrial hyperplasia (AH) and endometrial... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To examine the effectiveness of progestin re-treatment for recurrent endometrial intraepithelial neoplasia (EIN), atypical endometrial hyperplasia (AH) and endometrial cancer (EC) following initial fertility-sparing treatment.
METHODS
A comprehensive systematic review and meta-analysis were conducted by an Expert Panel of the Japan Society of Gynecologic Oncology Endometrial Cancer Committee. Multiple search engines, including PubMed/MEDLINE and the Cochrane Database, were searched in December 2021 using the keywords "Endometrial neoplasms," "Endometrial hyperplasia," "Endometrial intraepithelial neoplasia," "Fertility preservation," "Progestins," AND "Recurrence." Cases describing progestin re-treatment for recurrent EIN, AH and EC were compared with cases that underwent conventional hysterectomy. The primary outcomes were survival and disease recurrence, and the secondary outcome was pregnancy.
RESULTS
After screening 238 studies, 32 with results for recurrent treatment were identified. These studies included 365 patients (270 received progestin re-treatment and 95 underwent hysterectomy). Most progestin re-treatment involved medroxyprogesterone acetate or megestrol acetate (94.5%). Complete remission (CR) following progestin re-treatment was achieved in 219 (81.1%) cases, with 3-, 6- and 9-month cumulative CR rates of 22.8%, 51.7% and 82.6%, respectively. Progestin re-treatment was associated with higher risk of disease recurrence than conventional hysterectomy was (odds ratio [OR]=6.78; 95% confidence interval [CI]=1.99-23.10), and one patient (0.4%) died of disease. Fifty-one (14.0%) women became pregnant after recurrence, and progestin re-treatment demonstrated a possibility of pregnancy (OR=2.48; 95% CI=0.94-6.58).
CONCLUSION
This meta-analysis suggests that repeat progestin therapy is an effective option for women with recurrent EIN, AH and EC, who wish to retain their fertility.
Topics: Pregnancy; Female; Humans; Endometrial Hyperplasia; Progestins; Retrospective Studies; Neoplasm Recurrence, Local; Endometrial Neoplasms; Fertility Preservation; Treatment Outcome
PubMed: 36929578
DOI: 10.3802/jgo.2023.34.e49 -
Analytical Methods : Advancing Methods... Mar 2023Steroid hormones have been listed as priority pollutants in the environment, and their detection and pollution control deserve our extensive attention. In this study, a...
Steroid hormones have been listed as priority pollutants in the environment, and their detection and pollution control deserve our extensive attention. In this study, a modified silica gel adsorbent material was synthesized by benzoyl isothiocyanate reaction with hydroxyl groups on the silica gel surface. The modified silica gel was used as a solid phase extraction filler for the extraction of steroid hormones from water, which was further analyzed by the HPLC-MS/MS method. The FT-IR, TGA, XPS, and SEM analysis indicated that benzoyl isothiocyanate was successfully grafted on the surface of silica gel to form a bond with an isothioamide group and benzene ring as the tail chain. The modified silica gel synthesized at 40 °C showed excellent adsorption and recovery rates for three steroid hormones in water. Methanol at pH 9.0 was selected as the optimal eluent. The adsorption capacity of the modified silica gel for epiandrosterone, progesterone, and megestrol acetate was 6822 ng mg, 13 899 ng mg, and 14 301 ng mg, respectively. Under optimal conditions, the limit of detection (LOD) and limit of quantification (LOQ) for 3 steroid hormones by modified silica gel extraction with HPLC-MS/MS detection were 0.02-0.88 μg L and 0.06-2.22 μg L, respectively. The recovery rate of epiandrosterone, progesterone, and megestrol was between 53.7% and 82.9%, respectively. The modified silica gel has been successfully used to analyze steroid hormones in wastewater and surface water.
Topics: Silica Gel; Water; Tandem Mass Spectrometry; Progesterone; Spectroscopy, Fourier Transform Infrared; Androsterone; Steroids; Isothiocyanates
PubMed: 36807579
DOI: 10.1039/d2ay01852g -
Gynecological Endocrinology : the... Dec 2023To investigate safety and effectiveness of NOMAC-E2 and levonorgestrel-containing COCs (COC) in users over 40. (Observational Study)
Observational Study
OBJECTIVE
To investigate safety and effectiveness of NOMAC-E2 and levonorgestrel-containing COCs (COC) in users over 40.
METHODS
In this large, observational study, new users of NOMAC-E2 and COC were recruited in Europe, Australia, and Latin America and followed-up questionnaires. Incidence of venous thromboembolism (VTE) was expressed as incidence rate (IR; events/10 women-years [WY]). Unintended pregnancy was expressed by the Pearl Index (PI; contraceptive failures/100 WY). Mood and weight changes were defined as mean changes in mood score and percentage of body weight.
RESULTS
Overall, 7,762 NOMAC-E2 and 6,059 COC users over 40 were followed-up. NOMAC-E2 showed no increased VTE risk compared to COC; confirmed events: 5 NOMAC-E2 (IR 5.9; 95% CI, 1.9-13.7) vs 4 COC (IR 5.9; 95% CI, 1.6-15.1). Unintended pregnancy did not differ substantially between cohorts; confirmed events: 4 NOMAC-E2 (PI 0.05; 95% CI, 0.01-0.13) vs 5 COC (PI 0.08; 95% CI, 0.03-0.18). No differential effect on mood and weight was observed between cohorts.
CONCLUSIONS
NOMAC-E2 can be considered a valid alternative to COC in perimenopausal women.
Topics: Pregnancy; Female; Humans; Contraceptives, Oral, Combined; Ethinyl Estradiol; Estradiol; Venous Thromboembolism; Megestrol; Norpregnadienes
PubMed: 36690019
DOI: 10.1080/09513590.2023.2166032 -
Gynecological Endocrinology : the... Dec 2023To investigate unintended pregnancy and changes in mood, acne, and weight in NOMAC-E2 vs levonorgestrel-containing COC (COC) users under 25 years. In this large,... (Observational Study)
Observational Study
To investigate unintended pregnancy and changes in mood, acne, and weight in NOMAC-E2 vs levonorgestrel-containing COC (COC) users under 25 years. In this large, observational study, new users (first-ever users of an eligible COC or restarting with the same or a new eligible COC after a break of at least 2 months) of NOMAC-E2 and COC were recruited in 12 countries in Europe, Australia, and Latin America and followed up questionnaires for up to 2 years. Unintended pregnancy was expressed by the Pearl Index (PI; contraceptive failures/100 women-years). Crude (HR) and adjusted hazard ratios (HR) were calculated. Mood and acne changes were defined as change of score from baseline. Weight change was defined as percent change of body weight. Overall, 12,829 NOMAC-E2 users and 17,095 COC users under 25 were followed-up. The risk of unintended pregnancy was statistically significantly lower in the NOMAC-E2 cohort; confirmed events: 30 NOMAC-E2 (PI 0.24; 95% CI, 0.16-0.35) vs 94 COC (PI 0.51; 95% CI, 0.41-0.62). The HR for unintended pregnancy comparing NOMAC-E2 to COC was 0.47 (95% CI, 0.31-0.71) and the HR was 0.52 (95% CI, 0.34-0.78). No differential effect on acne, mood, and weight was observed between cohorts. NOMAC-E2 shows a significantly better contraceptive effectiveness in young women and has no differential effect on acne, mood, and weight compared to COC.
Topics: Pregnancy; Female; Humans; Contraceptives, Oral, Combined; Estradiol; Contraceptive Effectiveness; Megestrol; Levonorgestrel; Acne Vulgaris
PubMed: 36617423
DOI: 10.1080/09513590.2022.2162036 -
Journal of Gynecologic Oncology Jan 2023To evaluate the effect of levonorgestrel-releasing intrauterine system (LNG-IUS) plus oral megestrol acetate (MA) as fertility-preserving treatment in patients with... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of the effect of oral megestrol acetate with or without levonorgestrel-intrauterine system on fertility-preserving treatment in patients with early-stage endometrial cancer: a prospective, open-label, randomized controlled phase II trial (ClinicalTrials.gov NCT03241914).
OBJECTIVE
To evaluate the effect of levonorgestrel-releasing intrauterine system (LNG-IUS) plus oral megestrol acetate (MA) as fertility-preserving treatment in patients with early-stage endometrial cancer (EEC).
METHODS
In this single-center, phase II study with open-label, randomized and controlled design, young patients (18-45 years) diagnosed with primary EEC were screened, who strongly required fertility-preserving treatment. Patients were randomly assigned (1:1) into MA group (160 mg oral daily) or MA (160 mg oral daily) plus LNG-IUS group. Pathologic evaluation on endometrium retrieved by hysteroscopy was performed every 3 months. The primary endpoint was complete response (CR) rate within 16 weeks of treatment. The secondary endpoints were CR rate within 32 weeks of treatment, adverse events, recurrent and pregnancy rate.
RESULTS
Between July 2017 and June 2020, 63 patients were enrolled and randomly assigned. Totally 56 patients (26 in MA group; 28 in MA + LNG-IUS group) were included into primary-endpoint analyses. The median follow-up was 31.6 months (range, 3.1-94.0). No significant difference in 16-week CR rate were found between MA and MA + LNG-IUS groups (19.2% vs. 25.0%, p=0.610; odds ratio=1.40; 95% confidence interval=0.38-5.12), while the 32-week CR rates were also similar (57.1% and 61.5%, p=0.743), accordingly. More women in MA + LNG-IUS group experienced vaginal hemorrhage (46.4% vs. 16.1%; p=0.012) compared with MA group. No intergroup difference was found regarding recurrence or pregnancy rate.
CONCLUSION
Compared with MA alone, the addition of LNG-IUS may not improve the early CR rate for EEC, and may produce more adverse events instead.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03241914.
Topics: Humans; Female; Levonorgestrel; Megestrol Acetate; Prospective Studies; Endometrium; Endometrial Neoplasms
PubMed: 36562136
DOI: 10.3802/jgo.2023.34.e32 -
Experimental and Therapeutic Medicine Jan 2023Cachexia, a complex disorder that results in depletion of adipose tissue and skeletal muscle, is driven by anorexia, metabolic abnormalities and inflammation. There are...
Cachexia, a complex disorder that results in depletion of adipose tissue and skeletal muscle, is driven by anorexia, metabolic abnormalities and inflammation. There are limited therapeutic options for this syndrome. Previous evidence has demonstrated that increasing adipose tissue may improve quality of life and survival outcomes in cachexia. Cisplatin, as a chemotherapy drug, also causes cachexia during antitumor therapy due to its adverse effects. To establish a rat model of cachexia, the animals were intraperitoneally treated with cisplatin at doses of 1, 2 and 3 mg/kg, and the rats that responded to cisplatin at the optimal dose were used to test the effect of nomegestrol acetate (NOMAc). Rats that were assessed to be sensitive to cisplatin were randomly grouped and intragastrically administered vehicle, 5 or 10 mg/kg megestrol acetate (MA) or 2.5, 5 or 10 mg/kg NOMAc. The body weights and food consumption of the rats were assessed. Serum IL-6 and TNF-α levels were assessed using ELISA. The protein expression levels of adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), peroxisome proliferator activated receptor γ (PPARγ), fatty acid synthase (FASN) and sterol regulatory element-binding protein-1 (SREBP-1) from inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT) were evaluated using western blotting. The optimal way to establish a chemotherapy-induced rat model of cachexia demonstrated in the present study was to intraperitoneally administer the rats with 2 mg/kg cisplatin for 3 consecutive days. NOMAc (2.5, 5 mg/kg) and MA (10 mg/kg) were able to significantly ameliorate the loss of body weight in the cisplatin-induced cachectic rats. NOMAc significantly reduced the serum levels of TNF-α at 10 mg/kg. Morphologically, iWAT atrophy, with a remarkable reduction in adipocyte volume, was observed in the cisplatin-induced cachectic rats, but the effects were reversed by administering 5, 10 mg/kg NOMAc or 10 mg/kg MA. Furthermore, 2.5 mg/kg NOMAc markedly reduced the protein expression levels of the lipolysis genes HSL and ATGL, and 5 mg/kg NOMAc markedly enhanced the protein expression levels of adipogenesis genes, including FASN, SREBP-1 and PPARγ in iWAT but not in eWAT. NOMAc was demonstrated to improve cachexia at lower doses compared with MA. Overall, NOMAc is likely to be a promising candidate drug for ameliorating cancer cachexia induced by cisplatin.
PubMed: 36561625
DOI: 10.3892/etm.2022.11723 -
Annals of Translational Medicine Oct 2022A reasonable and effective control of chemotherapy-induced nausea and vomiting (CINV) plays an important role in the comprehensive treatment of cancer. Megestrol belongs...
Megestrol acetate dispersible tablets with a 5-HT3 receptor antagonist and dexamethasone 5-HT3 receptor antagonist plus dexamethasone, can better control chemotherapy-induced nausea and vomiting: a randomized controlled study.
BACKGROUND
A reasonable and effective control of chemotherapy-induced nausea and vomiting (CINV) plays an important role in the comprehensive treatment of cancer. Megestrol belongs to the 17α-hydroxyprogesterone derivative and is a highly effective synthetic progesterone. Recorded in the instructions may improve appetite and cachexia in patients with advanced tumors. In recent years, clinical practice and small sample studies have shown that megestrol combined with chemotherapy can improve CINV. This randomized controlled trial aimed to evaluate the clinical efficacy and safety of megestrol acetate combined with a 5-Hydroxytryptamine (5-HT3) receptor antagonist and dexamethasone in patients with CINV.
METHODS
Patients with malignant tumors who were treated with cisplatin-containing chemotherapy in our hospital from September 2018 to December 2019 were enrolled. A total of 120 patients were selected and randomly assigned to receive either megestrol acetate dispersible tablets with a 5-HT3 receptor antagonist and dexamethasone (megestrol group) or a 5-HT3 receptor antagonist plus dexamethasone (control group). Megestrol acetate dispersible tablets: 160 mg orally every morning from the day of chemotherapy until it lasts for ten days. Abstract IV of the quality-of-life scale for cancer patients in China was used to assess the quality of life (QOL) of the participants. All adverse reactions during chemotherapy were assessed according to the CTCAE 4.03 evaluation standard issued by the National Cancer Institute and divided into five grades according to severity.
RESULTS
For the control of nausea, the rates of complete prevention were significantly higher in the megestrol group than in the control patients during the delayed [53.3% (31/60) 30.0% (18/60), P=0.012] and overall [40.0% (24/60) 15.0% (9/60), P=0.002] observation periods. Moreover, the megestrol combination treatment group also achieved markedly higher rates of complete remission of vomiting than the control group during the delayed observation period [76.7% (46/60) 51.7% (31/60), P=0.001], achieving an overall higher proportion of remission during the study period [68.3% (41/60) 46.6% (28/60), P=0.0016].
CONCLUSIONS
The triple antiemetic protocol using megestrol acetate with a 5-HT3 receptor antagonist plus dexamethasone can improve CINV symptoms caused by highly emetogenic chemotherapy (HEC) with cisplatin, with an excellent control effect and few adverse reactions, especially for delayed CINV.
TRIAL REGISTRATION
Chinese Clinical Trial Registry ChiCTR1800017953.
PubMed: 36388808
DOI: 10.21037/atm-22-4809 -
Reproductive Health Nov 2022Endometrial adenocarcinoma (EC) is the fifth most common cancer in women worldwide, standard treatment for EC includes hysterectomy, but it results in the loss of...
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.
BACKGROUND
Endometrial 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 DESIGN
This 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.
CONCLUSIONS
Prospective 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.
Topics: Female; Humans; Pregnancy; Endometrial Hyperplasia; Endometrial Neoplasms; Intrauterine Devices, Medicated; Levonorgestrel; Megestrol Acetate; Metformin; Obesity; Prospective Studies; Randomized Controlled Trials as Topic; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36333773
DOI: 10.1186/s12978-022-01513-8 -
BJOG : An International Journal of... Jan 2023Fifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for decades, but there is limited evidence on response prediction with biomarkers and toxicity.
OBJECTIVES
To review the response and toxicity of progestin therapy and stratify response to progesterone receptor (PR) expression and tumour grade.
SEARCH STRATEGY
We used the search terms 'Endometrial cancer', 'Progestins', 'Disease progression', 'Recurrence' and related terms in Pubmed, Embase and Cochrane databases.
SELECTION CRITERIA
Studies on patients with advanced stage or recurrent EC treated with progestin monotherapy were included. Studies on adjuvant therapy, with fewer than ten cases and with sarcoma histology were excluded.
DATA COLLECTION AND ANALYSIS
Evaluation for bias was performed with the Revised Cochrane RoB2 tool for randomised studies and the ROBINS-I tool for non-randomised studies. A random effects meta-analysis was performed with the overall response rate (ORR), clinical benefit rate and toxicity as primary outcome measures.
MAIN RESULTS
Twenty-six studies (1639 patients) were included. The ORR of progestin therapy was 30% (95% CI 25-36), the clinical benefit rate was 52% (95% CI 42-61). In PR-positive EC, the ORR was 55%, compared with 12% in PR-negative disease (risk difference 43%, 95% CI 15-71). Severe toxicity occurred in 6.5%.
CONCLUSIONS
Progestin therapy is a viable treatment option in patients with advanced stage and recurrent EC with low toxicity and high ORR in PR-positive disease. The role of PR expression in relation to progression-free survival and overall survival is unclear.
Topics: Female; Humans; Progestins; Neoplasm Recurrence, Local; Endometrial Neoplasms
PubMed: 36264251
DOI: 10.1111/1471-0528.17331 -
International Journal of Biological... Dec 2022Obesity, fatty liver, type 2 diabetes, and Non-alcoholic fatty liver disease (NAFLD) are all metabolic diseases caused by excess food consumption. Existing drug...
Baicalein modulates mitochondrial function by upregulating mitochondrial uncoupling protein-1 (UCP1) expression in brown adipocytes, cytotoxicity, and computational studies.
BACKGROUND
Obesity, fatty liver, type 2 diabetes, and Non-alcoholic fatty liver disease (NAFLD) are all metabolic diseases caused by excess food consumption. Existing drug molecules had negative side effects and caused other diseases to develop (Orlistat causes angioedema, and menstrual irregularities; megestrol acetate causes hypertension, and insomnia). By enhancing lipid consumption and increasing nonshivering thermogenesis, targeting mitochondrial uncoupling protein-1 (UCP1) expression in adipocytes could be an auspicious treatment strategy against obesity or metabolic disorders associated with obesity.
METHODS
We used previously produced UCP1-A-GFP reporter cell lines in this investigation to find new pharmacological compounds against obesity or metabolic syndrome, which we then tested in cellular analysis, cytotoxicity, mitochondrial function, mitochondrial DNA quantification, mitochondrial ATP production, and in-silico models.
RESULTS
Baicalein was discovered to play a critical role in obesity prevention via altering mitochondrial function. Baicalein lowers ATP generation while increasing considerable UCP1 gene expression in brown adipocytes. As a result, cellular thermogenesis is boosted. The HEK293T cell line is harmless by baicalein. The investigation by the in-silico study revealed drug-protein interaction and UCP1 binding. Thus, our research clarifies baicalein's therapeutic role in metabolic and obesity-related illnesses via modulating mitochondrial activity (Supplementary Fig. 2).
CONCLUSIONS
Further studies are required in both murine and human models to understand the full mechanism of action by mitochondrial modulation. Drug development investigation also requires to development of a precise formulation.
Topics: Humans; Mice; Animals; Adipocytes, Brown; Uncoupling Protein 1; Adipose Tissue, Brown; Diabetes Mellitus, Type 2; HEK293 Cells; Mitochondria; Obesity; Adenosine Triphosphate; Mitochondrial Proteins
PubMed: 36252624
DOI: 10.1016/j.ijbiomac.2022.09.285