The effects of moderate doses of megestrol acetate on nutritional status and body composition in a hemodialysis patient.

OBJECTIVE: To determine the safety and efficacy of moderate doses of megestrol acetate (>/=320 mg/day) in a patient on hemodialysis. DESIGN: Case study. SETTING: Chronic hemodialysis facility and body composition unit in New York City. MAIN OUTCOME MEASURES: Body weight, body composition, dietary energy and protein intake, appetite assessment, serum albumin, prealbumin, serum transferrin, and quality of life. RESULTS: The patient received megestrol acetate for 24 weeks and gained little body weight. However, his fat mass increased by 7.5 kg (163%), and fat-free mass decreased by 6.8 kg (10.6%) from baseline measurements. The proportional content of total body water, extracellular water, intracellular water, body cell mass in fat-free mass, and average cell K+ concentration were maintained within normal ranges. Serum albumin was maintained, serum transferrin increased, prealbumin decreased, dietary energy and protein intakes increased, and reported appetite improved. CONCLUSIONS: Moderate doses of megestrol acetate may be an effective therapeutic agent in reversing poor appetite, increasing dietary energy and protein intakes, and improving nutritional status in some patients receiving maintenance hemodialysis. However, these changes were at the expense of altering body composition components. Further research that includes measures of body composition, nutritional status, appetite assessment, and quality of life are needed to determine the safety and effectiveness of moderate or high doses of megestrol acetate in a large number of hemodialysis patients.     

Investigations on the nutritional status of advanced breast cancer patients. The influence of long-term treatment with megestrol acetate or tamoxifen

The nutritional status of three groups of postmenopausal women (age 41-80 yrs) with advanced breast cancer was investigated with special reference to vitamin B6. The interference of hormonal treatment was studied with respect to the progestin megestrol acetate (Group MA, n = 14) and the antiestrogen tamoxifen (Group TAM, n = 15) compared with untreated patients (Group U, n = 11). Healthy postmenopausal women served as controls (Group C, n = 16). Nutritional status was judged from body mass index (BMI), vitamin and trace element status, hematology, and clinico-chemical parameters. Intake of nutrients was calculated from a food record. Hormonal status was studied by analysis of LH, FSH, and prolactin in plasma and of steroids and catecholamines and their metabolites in 24-hour urine. Compared with values for Group C, nutrient intake, hematology, clinico-chemical parameters, and 24-hour urinary excretion of catecholamines and their metabolites of patient groups (U, TAM, and MA) were not significantly different. The BMI of patients was significantly higher (by about 10%; 60% showed an overweight) than that of controls. With respect to fat-soluble vitamin status, significantly lower plasma levels of vitamin A (at least 40% lower, with deficient levels in more than 50% of the patients), D (40% lower), and E (20% lower) were found for Group U. However, water-soluble vitamin status of the four groups was fairly similar. A significantly higher excretion of xanthurenic acid in 24-hour urine, after an oral tryptophan load, was observed for Groups TAM and MA. This is most probably the result of hormonal treatment without affecting vitamin B6 status. Small, but significant, differences between groups were found for trace element status, especially with respect to lower plasma selenium of Group U (25% lower). LH, FSH, and prolactin in plasma and excretion of steroids in 24-hour urine showed levels that could be expected for controls and for untreated and hormonally treated patients. We concluded that the nutritional status of all patients is reasonably adequate. Hormonal treatment did not influence vitamin B6 status, although levels of vitamins A, D, and E and of selenium seem to be elevated.     

The effects of riboflavin administration on iron metabolism parameters in a school-going population.

The effect of riboflavin administration on iron metabolism was studied in a group of riboflavin-deficient children with Erythrocyte Glutathione Reductase (EC 1.6.4.2) reactivation above 1.20. The results have shown that the administration of riboflavin has resulted in a decrease of serum iron as well as in transferrin saturation which was accompanied by an increase in blood hemoglobin in subjects with initially lower hemoglobin values (less than or equal to 13.5 g/100 ml). There was, however, no change in blood hemoglobin in the group with initially higher hemoglobin values (greater than or equal to 14.0 g/100 ml). The results suggest that inadequate riboflavin intake may affect the iron utilization. The possible mechanism of riboflavin action on iron utilization is discussed.     

Treatment with nandrolone decanoate and megestrol acetate in HIV-infected men.

BACKGROUND: Malnutrition, especially loss of lean body mass, is a frequent complication of people living with HIV that may increase their mortality and morbidity. METHODS: Nine HIV-infected men with unexplained loss of >10% of their usual weight were selected. They received megestrol acetate (MA) (400 mg/day by mouth) and nandrolone decanoate (ND) (100 mg/15 days intermuscular injection) over 16 weeks. Anthropometric evaluations, bioelectrical impedance, grip strength dynamometry, hematologic, biochemical, immunological and hormonal analysis before, during, and after the treatment were performed. Quality of life was evaluated by the Karnofsky index. RESULTS: In the 7 men that finished the treatment, there were significant increases in weight (11.9 +/- 9.1 kg, p < .05), 4-site skinfold measurements (p < .05), midarm circumference (p < .005), and fat-free mass (FFM) (5.1 +/- 4.1 kg, p < .05). The increase in fat mass was not statistically significant (6.9 +/- 6.4 kg, NS). Muscle strength increased significantly (p < .005). The Karnofsky index values increased from 59% to 73% (p < .05). One patient developed mild hyperglycemia and another one had an increase in aspartate transaminase and gamma-glutamyl transpeptidase that reversed after the treatment. Four patients developed asymptomatic adrenal suppression. Testosterone serum levels decreased significantly during the study (p < .05), and 4 patients had serum values below the normal range at week 16. One patient developed gynecomastia. CONCLUSIONS: The combined treatment with MA and ND led to a significant increase in body weight and FFM. Muscle strength and quality of life improved during the study. The treatment was well tolerated with mild side effects.     

Contraception with megestrol acetate implants. Megestrol acetate levels in plasma and the influence on the ovarian function

The ovarian steroid pattern and the levels of megestrol acetate in plasma were assessed in 4 women after the insertion of six silastic capsules filled with approximately 35 mg megestrol acetate. The implants were inserted subcutaneously in the ventral part of the left forearm and left in place for 121–226 days.

Judged by the plasma progesterone pattern, no ovulation occurred during treatment, but ovulatory patterns of estradiol and progesterone were restored within 30 days after removal of the capsules.

The estradiol levels in plasma varied. Development of follicles as judged from surges of estradiol was evident in two of the subjects throughout the study.

Frequent and prolonged episodes of spotting and bleeding were found in all subjects during treatment, especially when low plasma levels of estradiol were observed.

A release of approximately 300 μg MA gives a plasma level of around 0.6 ng MA/ml and is sufficient to inhibit ovulation, probably by inhibition of the positive feedback of estradiol on the release of LH.     

Effects of megestrol acetate and testosterone on body composition in castrated male Sprague-Dawley rats.

The interrelationships among sex hormones, caloric intake, and intermediary metabolism in health and disease are uncertain. Studies in malnourished patients with AIDS and cancer show that megestrol acetate (MA) therapy increases appetite, body weight, and body fat, while it decreases serum testosterone (T) concentration. In this study, the separate and combined effects of MA and T were investigated in 65 young adult, male, castrated, Sprague-Dawley rats who received subcutaneous implants containing placebo, MA, T, or both MA and T for 11 wk. By hierarchical multiple regression analysis, MA therapy decreased weight gain and food intake (P < 0.01), increased body fat (P = 0.024), decreased body protein (P < 0.001), and decreased the portion of calories accrued as protein rather than fat (P ratio, P < 0.03). T alone decreased fat (P < 0.03), but had no significant effect on food intake, the relative number of consumed calories utilized for growth (food efficiency), body weight, or protein. The interaction of MA and T did not affect food intake or food efficiency, but increased body weight (P < 0.02), protein (P < 0.05) and the P ratio (P < 0.02). The portion of weight gain as fat was reduced from 47.3% with MA alone to 27.4% when MA and T were combined. Thus, megestrol acetate has significant antianabolic effects that are independent of its effects upon food intake. The addition of testosterone to megestrol acetate partially antagonized MA's inhibition of lean mass accretion in these rats.     

The effect of megestrol acetate on oral food and fluid intake in nursing home residents: a pilot study

OBJECTIVES: The objective of this study was to evaluate the effect of megestrol acetate (Megace OS; Bristol-Myers Squibb, Princeton, NJ) on the oral food and fluid intake of nursing home (NH) residents under two conditions: usual NH care and optimal mealtime feeding assistance. DESIGN AND SETTING: We conducted a prospective, preliminary trial in four NHs. PARTICIPANTS: Participants (n = 17) were recruited from a larger study designed to assess nutritional care quality. Eligibility for the Megace OS trial required participants to consistently eat less than 75% of most meals under both usual NH care and optimal feeding assistance conditions at baseline. INTERVENTION: Megace OS, an oral liquid suspension of megestrol acetate, was given daily in a 400-mg dose for 63 days. MEASUREMENTS: Each participant's oral food and fluid intake was monitored weekly for 1 day (three meals) during which research staff conducted direct observations of usual NH care (weeks 1, 3, and 5 and day 63) or provided optimal feeding assistance (weeks 2, 4, and 6). Average total percent intake was compared from baseline across the assessment weeks of the trial under the two mealtime care conditions. RESULTS: Megace OS had a significant effect on oral food and fluid intake only under the optimal mealtime feeding assistance condition, in which average total percent eaten increased from 50% (+/- 15%) at baseline to 63% (+/- 14%) post-63 days of the trial. There was no change in participants' oral food and fluid intake under the usual NH care condition (average total percent intake at baseline 43% +/- 12% vs. 43% +/- 20% post-63 days). CONCLUSION: The results of this preliminary study suggest that Megace OS is not an effective nutritional intervention to increase oral intake under usual NH care conditions, which is often characterized by inadequate feeding assistance. However, Megace OS in combination with optimal mealtime feeding assistance does significantly increase oral intake in a frail NH sample at high risk for weight loss.     

Study of blood coagulation in women treated with megestrol acetate implants

Blood coagulation tests done in 38 women bearing subdermal implants of megestrol acetate as a contraceptive after 14 to 43 months continuous treatment. A group of 12 untreated women of similar age and parity was used as control. Platelet count, clotting time, prothrombin time, partial thromboplastin time, prothrombin consumption test, thromboplastin generation time, euglobulin lysis time, fibrinogen, factors II, V, VII-X, X and VIII, and platelet adhesiveness were determined during the follicular phase of the cycle. All tests showed normal values and no significant differences were found between the groups. It was concluded that continuous, systemic and long-term administration of megestrol acetate does not lead to blood coagulation disorders.     

Incidence of deep-venous thrombosis in nursing home residents using megestrol acetate

OBJECTIVE: To determine the incidence of deep venous thrombosis in users of megestrol acetate in population of institutionalized elderly. DESIGN: Retrospective chart review. SETTING: A teaching nursing home in New York City. MEASUREMENTS: Number of cases of deep venous thrombosis in megesterol users. RESULTS: The incidence of deep venous thrombosis in 246 users was 4.9% CONCLUSION: There is a six-fold higher incidence of deep venous thrombosis among megestrol users in this population than in the general population of institutionalized elderly.     

空腹血糖受损人群复合式营养干预效果评价

目的观察复合式营养干预对空腹血糖受损（IFG）人群作用的综合效果，评价复合式营养干预对糖尿病（DM）的预防作用。方法在南京市6个主城区4142名中老年基线调查对象中，抽取空腹血糖受损者，随机分为复合式营养干预组196人，给予粗杂粮干预加健康教育讲座；空白对照组72人，不采取任何干预措施。试验周期为半年。试验前后对所有受试人员进行体检。结果试验后，复合式营养干预组人群空腹血糖（FBG）、血总胆固醇（TC）、甘油三酯（TG）、体重、体质指数（BMI）、腰臀比（WHR）明显下降（P〈0．05）；且FBG降至正常（〈5．6mmol／L）的人群所占比率明显高于空白对照组（P〈0．05），而发展为糖尿病（FBG≥7．0mmol／L）的人群所占比率明显低于空白对照组（P〈0．05）。结论空腹血糖受损人群为糖尿病的危险人群，复合式营养干预可以降低空腹血糖受损人群的血糖水平，是预防糖尿病行之有效的措施。     

Deep vein thrombosis as a complication of megestrol acetate therapy among nursing home residents

OBJECTIVES: To describe a cluster of cases of proximal deep vein thrombosis among nursing home residents treated with megestrol acetate, to identify other risk factors for deep vein thrombosis development among these patients, and to alert physicians to this potential complication of megestrol acetate therapy. DESIGN: Retrospective review. SETTING: A 129-bed Maryland nursing home. PARTICIPANTS: Nineteen residents prescribed megestrol acetate between November 1997 July 1998, identified by computerized pharmacy records. MEASUREMENTS: Demographic data (including identification of known risk factors for deep vein thrombosis development) were collected along with information on the indications for megestrol acetate therapy and its duration, diagnostic studies related to detection of deep vein thrombosis and their results, and patient outcomes following diagnosis of deep vein thrombosis. RESULTS: Megestrol acetate was prescribed for 18 nutritionally at-risk patients and one with uterine cancer. Six (32%) patients developed deep vein thrombosis signs and symptoms, and all diagnoses were confirmed as proximal deep vein thromboses with Doppler studies. (No diagnosis of deep vein thrombosis were made among any nursing home patients not being treated with megestrol acetate during the observation period.) All patients diagnosed with deep vein thrombosis were hospitalized and anticoagulated, but none were diagnosed with pulmonary embolus or died. The length [median (range)] of megestrol acetate treatment was similar regardless of whether deep vein thrombosis developed [117 (57-244) versus 143 (2-294) days, respectively, P = 0.83]. Stratification by length of treatment in 50-day increments revealed that most patients who developed deep vein thrombosis did so after 50 days of treatment (P = 0.046). CONCLUSION: A high incidence of deep vein thrombosis was identified among nursing home residents treated with megestrol acetate, even among ambulatory individuals with no other known risk factors. Because the efficacy of megestrol acetate treatment in nursing home residents with weight loss is unproven, the risk of deep vein thrombosis must be considered when prescribing megestrol acetate, and its use to treat nutritionally at-risk nursing home residents should be limited.     

USAGE of megestrol acetate in the treatment of anorexia-cachexia syndrome in the elderly

Abstract  The aim of this review is to assess the efficacy and safety of megestrol acetate (MA) in geriatric cachexia. The paper presented here reviews a previously published study of MA use in 69 patients in a randomized double blind placebo-controlled trial. This paper will also address the underlying pathogenesis of cachexia (specifically, the role of cytokines) along with the use of MA, its mechanism of action and its side effects. Objective  To compare the effects of MA oral suspension (O.S.), 800 mg/day, versus placebo on weight in geriatric nursing home patients with weight loss or low body weight. Design  Twelve weeks, randomized, double-blind, placebo-controlled trial with a 13-week follow-up period. Patients  Northport VAMC Nursing home patients with weight loss of * 5% of usual body weight over the past 3 months, or body weight 20% below their ideal body weight. Interventions  Patients were randomly assigned to receive placebo or MA 800 mg/d for 12 weeks and were then followed for 13 weeks off treatment and mortality 4 years post treatment. Measurements  Primary outcome-weight and appetite change. Secondary outcome-sense of well being, enjoyment of life, change in depression scale, laboratory nutrition parameters, energy intake counts, body composition, and adverse events. Results  At 12 weeks there were no significant differences in weight gain between treatment groups, while MA-treated patients reported significantly greater improvement in appetite, enjoyment of life, and well being. At week 25 (3 months after treatment), 61.9% of MA-treated patients had gained * 1.82 kg (4 lbs) compared to 21.7% of placebo patients. There was no difference in survival between MA and placebo groups. Considering possible confounders, higher initial IL-6, initial TNFR-p75 levels, and final neutrophil percentage were associated with elevated mortality, whereas higher initial pre-albumin, initial albumin, final pre-albumin, final albumin and final weight gain were associated with decreased death.     

恶性肿瘤病人营养不良评价方法的比较

目的比较营养不良指标：体质指数(BMI)、实际体重与理想体重比(％IBW1)和血清白蛋白浓度(Alb)对恶性肿瘤病人营养不良的诊断意义。探讨《中国成年人体质测定标准指南》的实用价值。     

Combination megestrol acetate, oxandrolone, and dietary advice restores weight in human immunodeficiency virus.

BACKGROUND: We examined changes in total body weight (TBW) and health-related quality of life (HRQL) during prolonged combination weight-gaining therapy and dietary advice in HIV. Design: This was a cohort study of patients initially randomized to single agent therapy for 2 months, megestrol acetate (800 mg daily), or oxandrolone (10 mg twice daily), followed by both agents and dietary advice for 5 months. METHODS: Two community health clinics and 1 urban infectious disease clinic were included, as were HIV-positive adult patients receiving highly active antiretroviral therapy with documented 5% weight loss. TBW and HRQL were measured after 7 months (7 m). RESULTS: Twenty-nine of 39 participants completed 7 m. The average sample age was 40 years, 75% were male, and 52% were of color at enrollment. Baseline mean TBW and body mass index (BMI) were 62.5 kg and 21 kg/m(2), respectively. Net gains in TBW, lean body mass, and fat during the 7 m were 5.3 kg (8.5% of baseline), 2.1 kg, and 3.1 kg, respectively (p < .01 for each). BMI increased to 23.1 kg/m(2) (p < .01). Dietary intake increased by 467 kcal/day (p = .03). Physical health improved by 5.7 (100-point scale, p < .01), and mental health was unchanged (-4.2, p = .11). In multivariable models, female gender (p < .01), lower baseline HIV viral load (p = .03), and increasing age (p < .01) were associated with TBW gain. Injection drug use (p < .01) and higher baseline HIV viral load (p < .01) were associated with reduction in physical health. CONCLUSIONS: Prolonged combination therapy with megestrol acetate, oxandrolone, and dietary advice could reverse weight loss and low BMI associated with incomplete viral suppression and improve physical health.