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Minerva Medica Feb 2021Primary surgery is effective in low-risk endometrial cancer (EC). However, in young women, this approach compromises fertility. Therefore, fertility-sparing management... (Review)
Review
INTRODUCTION
Primary surgery is effective in low-risk endometrial cancer (EC). However, in young women, this approach compromises fertility. Therefore, fertility-sparing management in the case of atypical endometrial hyperplasia, or grade 1 EC limited to the endometrium can be considered.
EVIDENCE ACQUISITION
We performed a literature review to identify studies involving women with EC or atypical hyperplasia who underwent fertility-sparing management. We conducted multiple bibliographic databases research from their inception to May 2020.
EVIDENCE SYNTHESIS
Oral therapy with medroxyprogesterone acetate and megestrol acetate is recommended based on extensive experience, although without consensus on dosages and treatment length. The pooled complete response rate, recurrence rate, and pregnancy rate of EC were 76.3%, 30.7% and 52.1%, respectively. Endometrial hyperplasia was associated with better outcomes. LNG-IUSs appears an alternative treatment, particularly in patients who do not tolerate oral therapy. In a randomized controlled trial, megestrol acetate plus metformin guaranteed an earlier complete response rate than megestrol acetate alone for endometrial hyperplasia. Hysteroscopic resection followed by progestogens is associated with a higher complete response rate, live birth rate, and lower recurrence rate than oral progestogens alone. Pooled complete response, recurrence, and live birth rates were 98.1%, 4.8% and 52.6%.
CONCLUSIONS
Fertility preservation appears feasible in young patients with grade 1 EC limited to the endometrium or atypical endometrial hyperplasia. Progestins are the mainstay of such management. The addition of Metformin and hysteroscopic resection seems to provide some improvements. However, fertility preservation is not the standard approach for staging and treatment, potentially worsening oncologic outcomes.
Topics: Administration, Oral; Drug Carriers; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Fertility Preservation; Humans; Hysteroscopy; Levonorgestrel; Metformin; Progestins
PubMed: 33205638
DOI: 10.23736/S0026-4806.20.07072-X -
Journal of Obstetrics and Gynaecology :... Jul 2022Endometrial cancer is the most common malignancy of the female genital tract. Approximately 25% of cases occur in premenopausal women, and up to 5% of cases occur in... (Review)
Review
Endometrial cancer is the most common malignancy of the female genital tract. Approximately 25% of cases occur in premenopausal women, and up to 5% of cases occur in women who are younger than 40 years old. The survival rate in these cases is 99%; therefore, uterine-sparing management could be considered under strict criteria selection and the strong desire of the woman to preserve uterus and fertility. Diagnosis should be performed after a hysteroscopic biopsy instead of dilatation and curettage. The highest remission rate was achieved after combining a hysteroscopic resection with hormonal therapy compared to single hormonal treatment. The most common regiments are the following progestins: megestrol acetate (MA) and medroxyprogesterone acetate (MPA) taken orally with a daily dosage of 160 mg-320 mg for MA and 250 mg-600 mg for MP. Evaluations at three and six months could be performed by office endometrial biopsy and/or hysteroscopic directed biopsy especially in the presence of levonorgestrel intrauterine system, and in cases of remission, either a pregnancy attempt or maintenance therapy should be considered. After childbearing, hysterectomy with bilateral salpingo-oophorectomy is recommended, whereas ovarian preservation could be considered depending on the patient's age and whether they fulfil the strict criteria selection.
Topics: Adult; Antineoplastic Agents, Hormonal; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Fertility Preservation; Humans; Hysteroscopy; Levonorgestrel; Pregnancy; Uterus
PubMed: 34989284
DOI: 10.1080/01443615.2021.2006164 -
The Cochrane Database of Systematic... Sep 2022Chronic loss of appetite in cystic fibrosis concerns both individuals and families. Appetite stimulants have been used to help cystic fibrosis patients with chronic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic loss of appetite in cystic fibrosis concerns both individuals and families. Appetite stimulants have been used to help cystic fibrosis patients with chronic anorexia attain optimal body mass index (BMI) and nutritional status. However, these may have adverse effects on clinical status. This is an updated version of the original review.
OBJECTIVES
To systematically search for and evaluate the evidence on the beneficial effects of appetite stimulants in the management of cystic fibrosis-related anorexia and synthesise reports of any side effects.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register and online trials registries; handsearched reference lists; and contacted local and international experts to identify relevant trials. Last search of the Cystic Fibrosis Trials Register: 23 May 2022. Last search of online trial registries: 10 May 2022.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials of appetite stimulants compared to placebo, control, no treatment or different appetite stimulants, or to the same appetite stimulants at different doses or regimens for at least one month in adults and children with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Review authors independently extracted data and assessed risk of bias of the included trials. We used the GRADE approach to assess the certainty of the evidence and performed meta-analyses.
MAIN RESULTS
We included four trials (70 participants) comparing appetite stimulants (cyproheptadine hydrochloride and megestrol acetate) to placebo; the numbers of adults or children within each trial were not always reported. We assessed the certainty of evidence as low due to the small number of participants, incomplete or selective outcome reporting, and unclear risk of selection bias. Regarding our primary outcomes, a meta-analysis of two trials (42 participants) showed that appetite stimulants may produce a larger increase in weight (kg) at three months (mean difference (MD) 1.25 kg, 95% confidence interval (Cl) 0.45 to 2.05), and one trial (17 participants) showed a similar result at six months (MD 3.80 kg, 95% CI 1.27 to 6.33) (both low-certainty evidence). Results also showed that weight z score may increase with appetite stimulants compared to placebo at three months (MD 0.61, 95% CI 0.29 to 0.93; 3 studies; 40 participants; P < 0.001) and at six months (MD 0.74, 95% CI 0.26 to 1.22; 1 trial; 17 participants). There was no evidence of a difference in effect between cyproheptadine hydrochloride and megestrol acetate for either outcome. Only one trial (25 participants) reported analysable data for body composition (BMI), with results favouring cyproheptadine hydrochloride compared to placebo; a further trial (16 participants) narratively agreed with this result. All four trials reported on lung function at durations ranging from two to nine months. Considering analysable data, two trials (42 participants) found that appetite stimulants may make little or no difference in forced expiratory volume at one second (FEV) % predicted at three months, and one trial (17 participants) found similar results at six months. Two further three-month trials narratively agreed with these results. Limited information was reported for secondary outcomes. Two trials (23 participants) reported results showing that appetite stimulants may increase appetite compared to placebo at three months (odds ratio 45.25, 95% CI 3.57 to 573.33; low-certainty evidence). Only one study reported on quality of life, finding that cyproheptadine reduced fatigue in two participants compared with none with placebo. One study (25 participants) found no difference in energy intake between appetite stimulant or placebo at three months. Insufficient reporting of adverse effects prevented a full determination of their impact. Two studies (33 participants) narratively reported similar requirements for additional antibiotics between appetite stimulants and placebo at three months. AUTHORS' CONCLUSIONS: At six months in adults and children, appetite stimulants improved only two of the outcomes of this review: weight (or weight z score) and subjectively reported appetite. Insufficient reporting of side effects prevented a full determination of their impact. Whilst the data may suggest the potential use of appetite stimulants in treating anorexia in adults and children with cystic fibrosis, this is based upon low-certainty evidence from a small number of trials, therefore firm conclusions cannot be drawn. Clinicians need to be aware of the potential adverse effects of appetite stimulants and actively monitor any individuals prescribed these medications accordingly. Research is required to determine meaningful surrogate measures for appetite and to define what constitutes quality weight gain. Future trials of appetite stimulants should use a validated measure of symptoms including a disease-specific instrument for measuring poor appetite. This review highlights the need for multicentred, adequately powered, and well-designed trials to evaluate agents to safely increase appetite in people with cystic fibrosis and to establish the optimal mode of treatment.
Topics: Adult; Anorexia; Anti-Bacterial Agents; Appetite Stimulants; Child; Cyproheptadine; Cystic Fibrosis; Humans; Megestrol Acetate; Quality of Life
PubMed: 36149378
DOI: 10.1002/14651858.CD008190.pub3 -
Pharmaceuticals (Basel, Switzerland) Feb 2022Cisplatin is a well-known chemotherapeutic agent used to treat various types of cancers; however, it can also induce anorexia, which results in reduced food intake, loss... (Review)
Review
Cisplatin is a well-known chemotherapeutic agent used to treat various types of cancers; however, it can also induce anorexia, which results in reduced food intake, loss of body weight, and lower quality of life. Although drugs such as megestrol acetate and cyproheptadine are used to decrease this severe feeding disorder, they can also induce side effects, such as diarrhea and somnolence, which limit their widespread use. Various types of herbal medicines have long been used to prevent and treat numerous gastrointestinal tract diseases; however, to date, no study has been conducted to analyze and summarize their effects on cisplatin-induced anorexia. In this paper, we analyze 12 animal studies that used either a single herbal medicine extract or mixtures thereof to decrease cisplatin-induced anorexia. Among the herbal medicines, Ginseng Radix was the most used, as it was included in seven studies, whereas both Glycyrrhizae Radix et Rhizoma and Angelicae Gigantis Radix were used in four studies. As for the mechanisms of action, the roles of serotonin and its receptors, cytokines, white blood cells, ghrelin, and leptin were investigated. Based on these results, we suggest that herbal medicines could be considered a useful treatment method for cisplatin-induced anorexia.
PubMed: 35215322
DOI: 10.3390/ph15020208 -
International Urology and Nephrology Sep 2019Malnutrition, inflammation and poor quality of life are prevalent among elderly haemodialysis patients. Megestrol acetate (MA) is a synthetic progestin that is widely... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Malnutrition, inflammation and poor quality of life are prevalent among elderly haemodialysis patients. Megestrol acetate (MA) is a synthetic progestin that is widely used to increase appetite and weight in various clinical settings. MA has been indicated to be effective in improving quality of life in patients with cancers. The aim of the present study was to evaluate the efficacy and safety of MA in treating malnourished elderly haemodialysis patients.
METHODS
A randomized controlled study involving 46 hypoalbuminemia haemodialysis patients aged 70 years or older was conducted. The patients in MA-treated group (n = 23) took 160 mg of MA daily, while those in control group (n = 23) were enrolled without any intervention. Anthropometric parameters and laboratory results, including height, dry weight, body mass index, and modified subjective global assessment score as well as serum albumin, triglyceride, total cholesterol, hsCRP, IL-1b and IL-6 concentrations were measured in all patients before and after the intervention. Health-related quality of life was also evaluated using the KDQOL-SF 1.3.
RESULTS
In the MA-treated group, a total of 18 patients finished the therapy over a 3-month period. Appetite was reported as improved by 15 patients, and a statistically significant increase was observed in dry weight (53.36 ± 6.15 vs. 54.24 ± 6.32, P < 0.01) and serum albumin concentration (29.05 ± 3.91 vs. 37.67 ± 4.88, P < 0.01) in the MA-treated group compared to those of the control group. The quality of life in both the physical domain (46.73 ± 18.17 vs. 63.37 ± 22.35, P < 0.01) and the mental domain (50.28 ± 20.36 vs. 68.02 ± 25.48, P < 0.01) was also improved in the same group. There was no significant change in the inflammatory marker concentrations after the intervention. No serious or unexpected adverse events were observed except that one patient who withdrew due to excessive fluid gain between haemodialysis sessions.
CONCLUSION
Our data suggest that MA can be effective in improving nutritional status and quality of life by increasing appetite in elderly haemodialysis patients with acceptable side effects; however, MA might not ameliorate inflammation.
Topics: Aged; Aged, 80 and over; Appetite Stimulants; Female; Humans; Inflammation; Male; Malnutrition; Megestrol Acetate; Quality of Life; Renal Dialysis
PubMed: 31359357
DOI: 10.1007/s11255-019-02245-8 -
The Journal of Obstetrics and... Mar 2021To explore the clinical outcomes of megestrol acetate alone or plus metformin in young women with grade 2 stage IA endometrial carcinoma who ask for preserved fertility. (Review)
Review
PURPOSE
To explore the clinical outcomes of megestrol acetate alone or plus metformin in young women with grade 2 stage IA endometrial carcinoma who ask for preserved fertility.
METHODS
Patients with stage IA grade 2 endometrial carcinoma who asked for fertility-sparing treatment in the Obstetrics and Gynecology Hospital of Fudan University between 2015 and 2017 were enrolled and retrospectively reviewed.
RESULTS
Four patients were included and treated with oral megestrol acetate (160 mg per day), while metformin (500 mg, thrice daily) was added for patients with metabolic syndrome. Regular hysteroscopic examination was performed every 3 months during the conservative treatment. Overall, 75% (3/4) of the patients had a complete response, one relapsed and achieved a complete response after changing the therapy plan, and one patient had an indication of myometrial invasion during fertility-sparing treatment and chose to remove uterus.
CONCLUSIONS
Fertility-sparing treatment for stage IA grade 2 endometrial carcinoma patients is worth exploration. Megestrol acetate with or without metformin combined with hysteroscopic lesion ablation may be an effective therapy.
Topics: Antineoplastic Agents, Hormonal; Conservative Treatment; Endometrial Neoplasms; Female; Fertility Preservation; Humans; Megestrol Acetate; Pregnancy; Retrospective Studies; Treatment Outcome
PubMed: 33403812
DOI: 10.1111/jog.14646 -
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 -
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 -
Translational Cancer Research Dec 2020Endometrial cancer (EC) is the most common cancer of the female reproductive system in developed countries. The incidence of EC has been increasing in young women.... (Review)
Review
Endometrial cancer (EC) is the most common cancer of the female reproductive system in developed countries. The incidence of EC has been increasing in young women. Approximately 4% of cases are aged <40 years. These young women may wish to delay therapy until after they have children. Common complaints in patients with EC include irregular vaginal bleeding, pelvic pain, and enlarged uterus. Imaging techniques such as transvaginal ultrasound (TVUS) or magnetic resonance imaging (MRI) can be utilized in detecting EC. Although the recommended treatment of EC is hysterectomy and bilateral salpingo-oophorectomy with or without systemic lymph node dissection, loss of reproductive function is the primary limiting factor of this surgical approach. Some studies have reported favorable results with high-dose oral progestins or levonorgestrel-releasing intrauterine system or hysteroscopic tumor resection followed by treatment with high-dose oral progestins. The most widely utilized medical treatment regimens are medroxyprogesterone acetate (MPA) 250-600 mg/day or megestrol acetate (MA) 160-480 mg/day. However, there is still a lack of evidence to establish the optimal dose and duration of progestin treatment. Patients with complete remission (CR) who wish to conceive must be encouraged, and referral to a fertility clinic should be offered as soon as possible. The key aspect of fertility-sparing management in women with EC appears to be the selection of appropriate candidates. Owing to the rarity of this condition, management may often be suboptimal. The aim of this review is to assess the current approaches to management of young women with EC who wish to preserve their fertility.
PubMed: 35117382
DOI: 10.21037/tcr-20-2232 -
Experimental Biology and Medicine... Nov 2021Megestrol acetate is a common and efficient anticancer progesterone. To explore the activity and the therapeutic mechanisms of megestrol acetate in endometrial cancer,...
Megestrol acetate is a common and efficient anticancer progesterone. To explore the activity and the therapeutic mechanisms of megestrol acetate in endometrial cancer, human endometrial cancer cell lines Ishikawa and HHUA overexpressing progesterone receptor A (PR-A) and progesterone receptor B (PR-B) were treated with megestrol acetate. Cell viability, apoptosis, cycle arrest, and senescence, as well as the expressions of p21 and p16, two hallmarks of cellular senescence, were evaluated. Compared with the control, >10 nmol/L megestrol acetate treatment could significantly reduce endometrial cancer cell growth, and induce the irreversible G1 arrest and cell senescence. The expression of cyclin D1 in megestrol acetate treated cells was downregulated, while the expressions of p21 and p16 were upregulated via PR-B isoform. FOXO1 inhibitor AS1842856 could significantly abrogate megestrol acetate-induced cell senescence, suggesting that FOXO1 was involved in megestrol acetate/PR-B axis. These findings may provide a new understanding for the treatment of human endometrial cancer.
Topics: Antineoplastic Agents, Hormonal; Blotting, Western; Cell Cycle; Cell Line, Tumor; Cellular Senescence; Endometrial Neoplasms; Female; Forkhead Box Protein O1; Humans; Megestrol; Receptors, Progesterone; Signal Transduction
PubMed: 34233525
DOI: 10.1177/15353702211026566