There is inconsistent evidence relating to the effects of megestrol acetate (MA) supplementation on cancer patients suffering from anorexia-cachexia syndrome. This review aimed to examine the dose-response effect of MA supplementation in patients with cancer-associated anorexia/cachexia. Relevant keywords were searched in PubMed, Scopus and ISI Web of Science from inception to June 2023 for randomized controlled trials (RCTs) examining the effect of MA on pathologies in patients with cancer-associated cachexia. Our primary outcomes were changes in body weight and appetite. However, fatigue and quality of life were secondary outcomes. The mean difference (MD) and 95% confidence interval (95% CI) were estimated using the random-effects method. Thirteen trials comprising 1229 participants (mean age 60 years) were identified. The results of our highest versus lowest analysis revealed that MA supplementation was not associated with any increase in body weight (MD: 0.64 kg, 95% CI [-0.11, 1.38], P = 0.093, I2 = 69.1%; GRADE = very low certainty). Twelve trials, including 14 effect sizes derived from 1369 patients (intervention = 689, control = 680), provided data on the effect of MA on body weight. Subgroup analyses showed a significant increase in body weight following short-term intervention (≤8 weeks) and a combination of radiation/chemotherapy as concurrent treatment. A linear dose-response meta-analysis indicated that each 200 mg/day increment in MA consumption had a significant increase in weight gain (MD: 0.44; 95% CI [0.13, 0.74], P = 0.005; I2 = 97.1%); however, the magnitude of the effect was small. MA administration significantly affected the quality of life based on pooled effect sizes (MD: 1.15, 95% CI [0.76, 1.54], P < 0.001, I2 = 0%; n = 2 RCTs including 176 patients; GRADE = very low certainty). However, no significant effect of MA supplementation was observed on appetite (MD: 0.29, 95% CI [-0.05, 0.64], P = 0.096, I2 = 18.3%; n = 3 RCTs including 163 patients; GRADE = very low certainty) and fatigue (MD: 0.14, 95% CI [-0.09, 0.36], P = 0.236, I2 = 0%; n = 2 RCTs including 300 patients; GRADE = very low certainty). With very low certainty of the evidence, MA supplementation may not lead to a significantly increased weight gain and other outcomes.

This study compared the effects of megestrol acetate (MA) prophylactic (p-MA) versus reactive (r-MA) use for critical body-weight loss (>5% from baseline) during concurrent chemoradiotherapy (CCRT) in patients with advanced pharyngolaryngeal squamous cell carcinoma (PLSCC).
Patients receiving CCRT alone in two phase-II trials were included for analyses. Both the p-MA and r-MA cohorts received the same treatment protocol at the same institution, and the critical body-weight loss, survival, and adverse event profiles were compared.
The mean (SD) weight loss was 5.1% (4.7%) in the p-MA cohort (n = 54) vs. 8.1% (4.6%) in the r-MA cohort (n = 50) (p = .001). The percentage of subjects with body-weight loss >5% was 42.6% in the p-MA cohort vs. 68.0% in the r-MA cohort (p = .011). Tube feeding was needed in 22.2% of p-MA vs. 62.0% of r-MA patients (p < .001). Less neutropenia (26.0% vs. 70.0% [p < .001]) and a shorter duration of grade 3-4 mucositis (2.4 ± 1.4 vs. 3.6 ± 2.0 wk [p = .009]) were observed with p-MA treatment. Disease-specific survival, locoregional control, or distant metastasis-free survival did not differ. Less competing mortality from secondary primary cancer resulted in a better overall survival trend in the p-MA cohort.
p-MA may reduce body-weight loss and improve adverse event profiles during CCRT for patients with PLSCC.

OBJECTIVE: We evaluated the efficacy of megestrol in improving chemotherapy-related anorexia by analyzing the related scales of taste alteration.
METHODS: We conducted the current study on a group of advanced patients with cancer with two or more chemotherapy cycles. The chemotherapy-induced taste alteration scale (CiTAs) scale helped assess the megestrol effects on basic taste perception, aversive taste changes, unpleasant symptoms, and associated concerns. Furthermore, the Short Nutritional Assessment Questionnaire scale (SNAQ) helped measure the impact of megestrol on malnutrition likelihood in patients experiencing chemotherapy-induced anorexia. The World Health Organization Quality of Life (WHOQOL)-BREF Scale was used to evaluate the quality of life of participants, producing scores related to physical health, psychological well-being, environmental factors, and social relationships.
RESULTS: The CiTAs scale assessment indicated that administering megestrol significantly enhanced taste perception among advanced patients with cancer undergoing chemotherapy. Notably, the megestrol group patients showed significantly higher Short Nutritional Assessment Questionnaire (SNAQ) scores than the control group. The megestrol group patients also exhibited higher physiological (PHYS) scores than their control group counterparts. However, this distinction was not statistically significant. The study findings indicate that patients who received megestrol demonstrated significantly higher scores in psychological (PSYCH) and environmental(ENVIR) domains than the control group. Furthermore, megestrol administration was associated with significantly elevated SOCIL and ENVIR levels in patients.
CONCLUSIONS: The proficient efficacy evaluation of megestrol in enhancing appetite, mitigating malnutrition likelihood, and improving the quality of life of chemotherapy-induced anorexic patients can be achieved through taste-related scales.

OBJECTIVE: Megestrol acetate (MA) is used to manage anorexia and cachexia in patients with advanced cancer. This study investigated the prescription patterns of MA in patients with metastatic gastric cancer, as well as evaluated its impact on survival outcomes and the incidence of venous thromboembolism (VTE).
METHODS: A Health Insurance Review and Assessment (HIRA) service database was used to investigate differences in baseline characteristics, survival, and the incidence of VTE according to MA prescription patterns (i.e., prescription vs. no prescription) in patients diagnosed with metastatic gastric cancer from July 2014 to December 2015.
RESULTS: A total of 1938 patients were included in this study. In total, 65% of the patients were prescribed MA. Older age, treatment in tertiary hospitals, and palliative chemotherapy were statistically significant predictive factors for MA prescription. Continuous prescription of MA was observed in 37% of patients. There was no statistically significant difference in survival between the MA and non-MA prescription groups on multivariate analysis. Among the 1427 patients included in the analysis for VTE incidence, 4.3% and 2.9% were diagnosed with VTE during the follow-up period in the MA and non-MA prescription groups, respectively. However, there was no statistically significant difference in VTE diagnosis between the groups on multivariate analysis.
CONCLUSIONS: MA is commonly prescribed for metastatic gastric cancer, especially in elderly patients and those undergoing palliative chemotherapy, without significantly affecting survival or VTE risk.

Objective: To assess the long-term efficacy of metformin in megestrol acetate (MA)-based fertility-sparing treatment for patients with endometrial atypical hyperplasia (EAH) and endometrioid endometrial cancer (EEC). Methods: The randomized controlled trail study was conducted from October 2013 to October 2017 in the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. Patients with EAH or EEC were firstly stratified according to pathology, and randomized to receive MA (160 mg orally, daily) plus metformin (500 mg orally, three times a day) or MA (160 mg orally, daily). Baseline data between two groups of patients were compared. Estimates of time to complete remission (CR) and recurrence-free survival (RFS) were calculated using the Kaplan-Meier method. Cox proportional-hazards regression model was used to estimate hazard ratios (HR) of related factors for recurrence-free survival. Quantitative data were represented by M (Q1, Q3). Results: A total of 150 patients were included, and 76 patients were allocated to receive MA plus metformin with the age of 32.5 (28.0, 36.0), while 74 patients received MA alone with the age of 32.0 (28.0, 36.0). By the end of follow-up period, 96.7% (n=145) of patients achieved complete remission, with a median follow-up time of 57.7 (26.7, 70.5) months. The median CR time for the MA plus metformin group and the MA alone group were 6.3 (3.5, 8.3) months and 6.8 (4.0, 9.3) months, respectively (P=0.193), with 2-year cumulative CR rate of 98.6% and 98.5%, respectively (P=0.879). The median time of RFS was 28.1 (12.5, 57.3) months for the MA plus metformin group and 33.3 (14.1, 62.5) months for the MA alone group (P=0.213), with a cumulative RFS rate of 61.9% and 65.8%, respectively (P=0.560). In the subgroup of non-obese (body mass index<28 kg/m2) patients with EAH, the median RFS times were 25.7 (7.6, 60.3) months and 47.3 (17.5, 64.8) months for the MA plus metformin group and the MA alone group, respectively (P=0.033), with a cumulative RFS rate of 57.5% and 80.6%, respectively (P=0.029). According to Cox proportional hazards regression analysis, undergoing assisted reproductive treatment (HR=2.358, 95%CI: 1.069-5.204, P=0.034) was identified as an independent risk factor for recurrence-free survival after complete remission of endometrial lesions. Conclusion: The long-term follow-up outcome indicates that there is no significant difference in CR time and RFS time between MA plus metformin therapy and MA alone therapy for patients with EAH or EEC.
目的： 分析醋酸甲地孕酮（MA）联合二甲双胍治疗子宫内膜不典型增生（EAH）及子宫内膜样癌（EEC）的远期结局。 方法： 本研究为随机对照试验。2013年10月至2017年10月，共入组150例就诊于复旦大学附属妇产科医院的初诊EAH和EEC患者，根据病理类型分层，按1∶1的比例采用随机数字表法分配进入MA联合二甲双胍治疗组和MA单药治疗组。比较两组患者的基线数据，应用Kaplan-Meier生存曲线计算累积完全缓解率和累积无复发生存率，采用Log-rank检验进行组间比较，采用Cox比例风险回归模型分析无复发生存的相关因素。计量资料以M（Q1，Q3）表示。 结果： 150例患者中，MA联合二甲双胍治疗组和MA单药治疗组分别为76和74例，年龄分别为32.5（28.0，36.0）和32.0（28.0，36.0）岁。截至本研究随访结束时，共有96.7%（145例）患者达到完全缓解，随访时间为57.7（26.7，70.5）个月。MA联合二甲双胍治疗组和MA单药治疗组的完全缓解时间分别为6.3（3.5，8.3）和6.8（4.0，9.3）个月（P=0.193），2年累积完全缓解率分别为98.6%和98.5%（P=0.879），无复发生存时间分别为28.1（12.5，57.3）和33.3（14.1，62.5）个月（P=0.213）；累积无复发生存率分别为61.9%和65.8%（P=0.560）。在体质指数<28 kg/m2的EAH患者群体中，MA联合二甲双胍治疗组和MA单药治疗组无复发生存时间分别为25.7（7.6，60.3）和47.3（17.5，64.8）个月（P=0.033）；累积无复发生存率分别为57.5%和80.6%（P=0.029）。是否进行辅助生育治疗（HR=2.358，95%CI：1.069~5.204，P=0.034）是子宫内膜病变完全缓解后无复发生存的相关因素。 结论： 长期随访结果表明，相比于MA单药治疗，MA联合二甲双胍治疗EAH及EEC的完全缓解时间及无复发生存时间无差异。.

OBJECTIVE: To compare the efficacy of the levonorgestrel intrauterine system (LNG-IUS) versus megestrol acetate (MA) in inducing complete regression among women with atypical endometrial hyperplasia (AEH) who declined hysterectomy.
METHODS: In this single-center, open-label randomized controlled trial, we included 148 women with AEH who declined hysterectomy. We randomized participants to receive either daily oral MA 160 mg (n=74) or apply LNG-IUS (n=74) and scheduled their follow-up by endometrial sampling at 3, 6, 9, 12, 18, and 24 months. The success rate and duration until complete regression were the primary outcomes.
RESULTS: The mean duration until complete regression was 5.52 months (95% confidence interval [CI]=4.85-6.18) for the LNG-IUS group versus 6.87 months (95% CI=6.09-7.64) for the megestrol group (log-rank test p-value=0.011). The cumulative regression rate after 12 months was 91.9% with the LNG-IUS versus 77% with MA (p=0.026). Weight gain in the MA group vs LNG-IUS group after one year (4.7±4 kg vs. 2.7±2.6 kg, 95% CI=0.89-3.12; p=0.001) and after two years of therapy (7.8±5.1 kg vs. 4.1±2.9 kg, 95% CI=2.29-5.06; p<0.001).
CONCLUSIONS: Compared to MA, the LNG-IUS was more efficacious in treating AEH in women who declined hysterectomy, especially those with moderate/severe obesity, with fewer adverse effects and less weight gain. Extending therapy to 12 months for persistent cases would improve regression rates with reasonable safety. Alternate hysteroscopic and office sampling seemed convenient for follow-up.
BACKGROUND: ClinicalTrials.gov Identifier: NCT04385667.

In this case report, we discuss a patient who experienced spontaneous regression of multiple intracranial meningiomas that were treated conservatively for 5 years after cessation of megestrol acetate, an exogenous progestin. In addition, we discuss the previous literature describing the relationship between exogenous progesterone medications and meningioma growth. This case, along with others reported, implies that cessation of progesterone therapy, when feasible, may alter the natural history of meningioma growth and thus impact treatment decisions.

OBJECTIVE: Cancer-related anorexia-cachexia comprises one of the most common syndromes of advanced cancer patients. The management of cancer-related anorexia-cachexia is a great challenge in clinical practice. There are no definite practice guidelines yet for the prevention and treatment of cancer-related anorexia-cachexia. This study is considered to find out whether there is any role of mirtazapine in the improvement of anorexia in cancer patients.
METHODS: A total of 80 cancer-anorexia patients were enrolled. Patients in the trial arm received the standard chemotherapy medication plus one tablet of mirtazapine 15 mg daily at night orally for 8 weeks starting from the day of an initial assessment. The control arm received the standard chemotherapy medication plus one tablet of megestrol acetate 160 mg daily orally for 8 weeks starting from the day of an initial assessment. Each patient was assessed by validated versions of Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Sub Scale v 4 questionnaires.
RESULTS: After 4 and 8 weeks each patient was evaluated again using the Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Sub Scale tool. The quality of life of each patient was assessed by European Organization for Research and Treatment QLQ-C30 v 3.0. After 4 to 8 weeks of treatment, the Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Sub Scale score in cancer anorexia patients in the mirtazapine improved anorexia significantly. However, the improvement after 4 to 8 weeks was not statistically significant when it was compared with the megestrol acetate (P > 0.05).
CONCLUSIONS: Therefore, the findings of this study reveal that mirtazapine might be a potential alternative to megestrol acetate, as it has shown potential efficacy as like as megestrol acetate.

Cancer cachexia (CC) syndrome, a feature of cancer-associated muscle wasting, is particularly pronounced in older patients, and is characterised by decreased energy intake and upregulated skeletal muscle catabolic pathways. To address CC, appetite stimulants, anabolic drugs, cytokine mediators, essential amino acid supplementation, nutritional counselling, cognitive behavioural therapy, and enteral nutrition have been utilised. However, pharmacological treatments that have also shown promising results, such as megestrol acetate, anamorelin, thalidomide, and delta-9-tetrahydrocannabinol, have been associated with gastrointestinal and cardiovascular complications. Emerging evidence on the efficacy of probiotics in modulating gut microbiota also presents a promising adjunct to traditional therapies, potentially enhancing nutritional absorption and systemic inflammation control. Additionally, low-dose olanzapine has demonstrated improved appetite and weight management in older patients undergoing chemotherapy, offering a potential refinement to current therapeutic approaches. This review aims to elucidate the molecular mechanisms underpinning CC, with a particular focus on the role of anorexia in exacerbating muscle wasting, and to propose pharmacological and non-pharmacological strategies to mitigate this syndrome, particularly emphasising the needs of an older demographic. Future research targeting CC should focus on refining appetite-stimulating drugs with fewer side-effects, specifically catering to the needs of older patients, and investigating nutritional factors that can either enhance appetite or minimise suppression of appetite in individuals with CC, especially within this vulnerable group.

A comparative analysis of the cytostatic effects of progestins (gestobutanoyl, megestrol acetate, amol, dienogest, and medroxyprogesterone acetate), glucocorticoids (hydrocortisone, dexamethasone), and diclofenac on tumor cells was carried out in order to confirm their in silico predicted probabilities experimentally. The results showed the different sensitivity of HeLa, MCF-7, Hep-2, K-562, and Wi-38 cell lines to progestins, glucocorticoids, and diclofenac. The minimum IC50 was found for progestin gestobutanoyl (GB) as 18 µM for HeLa cells, and varied from 31 to 38 µM for MCF-7, Hep-2, and K-562. Glucocorticoids and diclofenac were much less cytotoxic in the HeLa, MCF-7, and Hep-2 cell lines than progestins, with IC50 values in the range of 150-3000 μM. Myelogenous leukemia K-562 cells were the least sensitive to the action of progestins and glucocorticoids but the most sensitive to diclofenac, which showed a pronounced cytotoxic effect with an IC50 of 31 μM. As we have shown earlier, progestins can uniquely modulate MPTP opening via the binding of adenine nucleotide translocase. On this basis, we evaluated the expression of adenylate nucleotide translocase ANT1 (SLC25 A4) as a possible participant in cytotoxic action in these cell lines after 48 h incubation with drugs. The results showed that progestins differently regulated ANT1 expression in different cell lines. Gestobutanoyl had the opposite effect on ANT1 expression in the HeLa, K562, and Wi-38 cells compared with the other progestins. It increased the ANT1 expression more than twofold in the HeLa and K562 cells but had no influence on the Wi-38 cells. Glucocorticoids and diclofenac increased ANT1 expression in the Wi-38 cells and decreased it in the K562, MCF-7, and Hep-2 cells. The modulation of ANT1 expression discovered in our study can be a new explanation of the cytotoxic and cytoprotective effects of hormones, which can vary depending on the cell type. ANT isoforms in normal and cancerous cells could be a new target for steroid hormone and anti-inflammatory drug action.