Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Megestrol Acetate”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1977

A comparative study of three low dose progestogens, chlormadinone acetate, megestrol acetate and norethisterone, as oral contraceptives.

Three low dose progestogens, chlormadinone acetate (0-5 mg), megestrol acetate (0-5 mg) in oil, and norethisterone (0-35 mg), taken daily, were employed as oral contraceptives in postnatal women who desired to postpone their next pregnancy for up to a year. In a lower and middle social class population net pregnancy rates (life table) were five to six per 100 woman-years, of which about half were due to failure to take the tablets. Side effects other than menstrual disturbance were few. Norethisterone was the least likely of the three preparations to lead to discontinuation because of disturbance of menstruation. There were three ectopic gestations amongst 35 pregnancies in 4500 women-months of use. Ninety-five patients with varicose veins, 15 with a history of thrombophlebitis and 23 with a history of liver disease took progestogens without relevant untoward effects.

Adult↗
PubMed1985

Comparison of the antiandrogenic/androgenic activities of flutamide, cyproterone acetate and megestrol acetate.

Flutamide is approximately 2-fold more potent than cyproterone acetate in reversing the stimulatory effect of dihydrotestosterone (DHT) on ventral prostate weight. Even at the highest dose of cyproterone acetate, prostate weight remains 40% above control while flutamide completely reverses the stimulatory action of DHT, thus suggesting some partial androgenic activity of cyproterone acetate. Megestrol acetate, on the other hand, is devoid of any antiandrogenic activity and it even increases the stimulatory effect of DHT on prostate weight. While flutamide completely reverses the inhibitory effect of DHT on plasma LH levels in castrated animals, cyproterone acetate reverses the value of this parameter by only 30% while megestrol acetate further inhibits plasma LH levels at all the doses used. Both cyproterone acetate and megestrol acetate inhibit adrenal weight to approximately 25% of control, thus indicating their glucocorticoid activity. As direct measure of androgenic activity, cyproterone acetate and megestrol acetate increased prostate weight in castrated animals by 60 and 100%, respectively (P less than 0.01) while flutamide had no effect. The present data show that cyproterone acetate and megestrol acetate, in addition to their well-known progestational and glucocorticoid action, have intrinsic androgenic activity. Since it is the only compound having pure antiandrogenic activity, flutamide provides the best scientific arguments for its successful use for the treatment of androgen-sensitive diseases.

Adrenal Glands↗
PubMed1981

Adrenocortical suppression in cats given megestrol acetate.

Megestrol acetate was given orally to 8 cats at a dose of 2.5 mg every other day for 2 weeks and to 8 cats at a dose of 5.0 mg every day for 2 weeks. Four cats were designated nontreated controls. Pre-ACTH-stimulated plasma concentrations of cortisol (hydrocortisone) and ACTH-stimulated cortisol and tolerance to large-dose glucose infusion (IV) were determined on each of the 20 cats given megestrol acetate. Cats were restrained with acepromazine maleate and ketamine hydrochloride during blood sample collection and large-dose glucose infusion. Adrenocortical function and tolerance to large-dose glucose infusion were reevaluated for 4 weeks--after 1st and 2nd weeks of megestrol acetate treatment of the treated groups, and after 1st and 2nd weeks when treatment was stopped (ie, experiment weeks 3 and 4). Each week a cat from the control group and 2 cats from the 2 treated groups were selected to determine the changes occurring during the experiment for that week; after collection of plasma samples, each week's 5 selected cats were euthanatized and necropsied. Significant impairment of adrenocortical function and alteration of adrenocortical morphology occurred with both treated groups. The most severe adrenocortical alterations occurred in the cats 1 week after megestrol acetate was no longer given (ie, experiment week 3). Megestrol acetate-induced adrenocortical suppression contributed to the death of 1 cat. It was concluded that if stress occurs to cats on treatment or soon after treatment with megestrol acetate, glucocorticoids should be supplemented. The effects of megestrol acetate on glucose tolerance were overshadowed by the unforeseen intolerance caused by chemical restraint with acepromazine maleate and ketamine hydrochloride.

Adrenal Cortex↗
PubMed2003

Palliative treatment of cancer anorexia with oral suspension of megestrol acetate.

Megestrol acetate (MA) is a progestational agent, currently known as one of the most effective appetite stimulants in patients suffering from cancer anorexia/cachexia syndrome. Oral suspension of this drug may be particularly useful in patients with far advanced disease, where taking larger amount of pills may lead to the decrease of patient compliance. The influence of oral MA suspension on quality of life and nutritional status was evaluated in 22 patients with far advanced cancer suffering from anorexia and more than 5 per cent weight loss, all beyond the scope of anticancer treatment. Most patients had lung or gastrointestinal cancer. QLQ-C30 questionnaire, visual analogue scale (VAS) for appetite, anthropometry, maximal handgrip strength and laboratory data were obtained before treatment and then after 2, 4, and 8 weeks of therapy. Despite of a known high mortality in this prognostically unfavorable group of patients (36% within two months in this study), overall quality of life after the daily dose of 480-840 mg of MA was improved in 63, 56, and 55% of patients remaining on therapy after 2, 4, and 8 weeks, respectively. Appetite was the most successfully influenced parameter with an improvement in VAS in 95% of cases after 2 weeks of therapy (p=0.0001). The drug was well tolerated by the great majority of patients. Oral suspension of megestrol acetate maybean effective palliative treatment for many patients with far advanced cancer suffering from anorexia/cachexia syndrome.

Administration, Oral↗
PubMed2004

Osteoporosis associated with megestrol acetate.

Megestrol acetate is a progestational agent for treatment of metastatic breast cancer and endometrial cancer. Megestrol has also been used as an appetite stimulant for patients with human immunodeficiency virus and malignancy who experience cachexia and wasting; also, megestrol can be beneficial in relieving hot flashes in women and men. Megestrol has been shown to have a glucocorticoidlike effect and has been associated with substantial suppression of plasma estradiol levels. We describe 2 patients who recently presented to our Metabolic Bone Disease Clinic with severe osteoporosis complicated by multiple vertebral fractures experienced while the patients were receiving high-dose megestrol therapy. The patients had evidence of adrenal axis suppression but recovered fully after megestrol was discontinued. We speculate that megestrol was an important factor in the development of osteoporosis and subsequent fractures. Further study is warranted to clarify the relationship between megestrol and its potential for adversely affecting the skeleton.

Aged↗
PubMedDate not supplied

Medroxyprogesterone acetate and megestrol acetate reduce cisplatin-induced serotonin release from human peripheral blood mononuclear cells of cancer patients.

In the present study we evaluated the ability of either medroxyprogesterone acetate (MPA) or megestrol acetate (MA) to reduce cisplatin (CDDP)-induced serotonin (5-HT) release from peripheral blood mononuclear cells (PBMC) of cancer patients. Sixteen patients with cancer of different sites, all in advanced stage of disease, were studied (10 for MPA and 6 for MA). The levels of 5-HT in culture supernatants of PBMC stimulated with CDDP were higher than controls (100 nM vs 51 for MPA study and 123 vs 64 for MA study) and were in the same range of PHA-stimulated PBMC. The addition into cultures of MPA or MA was able to significantly reduce the CDDP-induced production of 5-HT (62 nM for MPA, and 46 for MA study). MPA as well as MA are able to inhibit 5-HT production and/or release by CDDP-stimulated PBMC of cancer patients: this finding to our knowledge has not been previously reported. The concentrations of MPA and MA used in cultures were in the same range as those raised in plasma following the clinical administration of daily doses of 1,000/2,000 mg of MPA and 320 to 960 mg of MA.

Aged↗
PubMed1996

Induction of micronuclei and initiation of enzyme-altered foci in the liver of female rats treated with cyproterone acetate, chlormadinone acetate, or megestrol acetate.

The synthetic anti-androgen and progestin cyproterone acetate (CPA), recently found to be genotoxic for the liver, and two structurally similar progestins, chlormadinone acetate (CMA) and megestrol acetate (MGA), have been compared for clastogenic and tumor-initiating activities in female rats. In the micronucleus assay, carried out in rats given a single p.o. dose of 100 mg/kg, CPA induced the maximum increase in the frequency of micronucleated hepatocytes (6.6-fold as compared to controls) when treatment was performed 3 days before partial hepatectomy and cell sampling 2 days later. Under the same experimental conditions the clastogenic potencies of CMA and MGA were 69% and 36% of that of CPA respectively. In the liver foci assay, p.o. dosing with 100 mg/kg CPA once a week for 6 successive weeks induced, as compared to controls, a significant increase in the number and area of gamma-glutamyltranspeptidase-positive foci. At the same dosage schedule the tumor-initiating activity of CMA and MGA was 7- to 10-fold lower than that of CPA. These findings suggest that the 1,2 alpha-methylene group, present in CPA but absent in both CMA and MGA, favours the activation to a reactive species and/or hinders the biotransformation to non-toxic metabolites.

2-Acetylaminofluorene↗
PubMed1996

Comparative study of DNA repair induced by cyproterone acetate, chlormadinone acetate and megestrol acetate in primary cultures of human and rat hepatocytes.

Cyproterone acetate (CPA), a synthetic progestin recently found to induce genotoxic effects in hepatocytes from female rats and from humans of both genders, and two structural analogues, chlormadinone acetate (CMA) and megestrol acetate (MGA), have been compared for their capacity to induce DNA repair synthesis as measured by quantitative autoradiography. Exposure of primary human hepatocytes for 20 h to concentrations of CPA, CMA and MGA ranging from 2 to 50 microM induced positive responses in cultures from donors of both genders and the amounts of DNA repair elicited by the three progestins were similar. Under the same experimental conditions substantial differences were observed in the amounts of DNA repair elicited by the three progestins in primary hepatocytes from female rats, their potency decreasing in the following order CPA > CMA > MGA, and the three compounds failed to induce DNA repair in hepatocytes from male rats. These results, which agree with previous findings, suggest that for these sex steroids extrapolation to humans of results obtained in rats might be questionable.

Animals↗
PubMed1995

DNA-damaging activity of the cyproterone acetate analogues chlormadinone acetate and megestrol acetate in rat liver.

The synthetic progestin cyproterone acetate (CPA) has been recently shown to elicit DNA repair synthesis in cultured rat hepatocytes and to form adducts with rat hepatocyte DNA in vitro and in vivo. In the present study we have examined the genotoxic potential of the structural analogues of CPA, chlormadinone acetate (CMA) and megestrol acetate (MGA) in rat liver cells. CPA strongly induced DNA repair synthesis in hepatocyte cultures from females but not from males. In contrast, CMA and MGA (2-50 microM) did not detectably increase repair synthesis in cultured hepatocytes from either gender. CMA and MGA, however, caused the formation of DNA adducts detectable by the 32P-postlabelling technique. At a concentration of 30 microM, between 30 and 50 adducts/10(9) nucleotides were found with MGA and CMA in cultured hepatocytes of female rats, and between 5 and 20 adducts/10(9) nucleotides were found in hepatocytes of males. By comparison, 30 microM CPA has been found to produce 1670 adducts/10(9) nucleotides in hepatocytes from female rats. CMA and MGA also induced low levels of DNA adducts in vivo. When female rats were treated with 100 mg/kg of CMA or MGA per os, the adduct levels were 2 and 19 adducts/10(9) nucleotides respectively. The results indicate that both CMA and MGA show some genotoxicity in rat liver cells, which is, however, much lower than that for CPA. Our findings further suggest that the high genotoxicity of CPA is associated with the presence of the 1,2 alpha-methylene group, which is absent in CMA and MGA.

Animals↗
PubMed1990

Influence of aminoglutethimide on the metabolism of medroxyprogesterone acetate and megestrol acetate in postmenopausal patients with advanced breast cancer.

In this study the influence of amino-glutethimide (AG) on the disposition of medroxyprogesterone acetate (MPA) and megestrol acetate (MA) was studied. When 1,000 mg AG daily was supplementally given to six patients on chronic treatment with MPA (1,000 mg/day) or MA (160 mg/day), mean serum levels of progestin were reduced by 74% as compared with control levels (P less than 0.03). AG did not change the blood clearance rate of MPA when the latter was given i.v. This discrepancy between AG's influence on oral and parenteral progestin disposition could be explained by pharmacokinetic properties of the progestins, and our results suggest that AG stimulates the metabolism of progestins. The decrease in MPA and MA serum levels was accompanied by an increase in serum cortisol, sex hormone-binding globulin (SHBG) and testosterone levels. This suggests that AG reduces the biological activity of progestins.

Administration, Oral↗
PubMed1990

Melengestrol acetate and megestrol acetate are prostatic tumor inhibiting agents.

We had previously reported that 6-methylene progesterone, an inhibitor of 5 alpha-reductase, the enzyme which converts testosterone to dihydrotestosterone, markedly inhibited growth of the androgen-dependent Dunning R3327-H rat prostatic tumors. We now find that the progesterone derivatives melengestrol acetate (MGA) and megestrol acetate (MA) inhibit both the androgen-dependent (Dunning R3327-H) and the androgen-independent (Dunning R3327-AT3) prostatic tumors. Growth of the AT3 tumors was suppressed by approximately 53% after 9 days of daily s.c. injections with MGA at 10 mg/kg body weight. MGA also caused a 54% weight reduction of the ventral prostate and a 53% reduction of the seminal vesicles. Adrenal weights were reduced by 42%. A 24-day oral treatment with MGA (at approximately 15-17 mg/(kg.day)) inhibited AT3 tumor growth by 59% and caused a weight reduction in the following tissues: prostate (46%), seminal vesicles (19%), testes (12%), and adrenals (52%). Under the same protocol, MA inhibited AT3 tumor growth by 32% and reduced the weight of the ventral prostate by 49% and the weight of the adrenals by 18%, but had no effect on the seminal vesicles and testes. The extent of the MGA-induced prostatic regression was accompanied by cytological changes similar to those effected by 6-methylene progesterone, i.e., shrinking of the acinar epithelium. The AT3 tumors in MGA-treated rats displayed a limited degree of apoptosis. Atrophy of the adrenal cortex and lowered plasma levels of corticosterone and dihydroepiandrosterone were also observed. A therapeutic role for MGA and MA against androgen-independent prostatic neoplasms in man is forecast by these observations.

Adrenal Glands↗
PubMed1987

Randomized trial of megestrol acetate vs. megestrol acetate/tamoxifen for the management of progressive or recurrent epithelial ovarian carcinoma.

Thirty-three patients were randomly treated with either megestrol acetate (Mg) or megestrol acetate/tamoxifen (Mg/Tx) from November, 1983, to December, 1985. Thirty-two of 33 were previously treated with platinum-based combination chemotherapy. Ten of 32 were also treated with hexamethylmelamine-based second line therapy. Doses were 160 mg/day of Mg and 20 mg/day of Tx. All patients had measurable disease. The two groups did not differ as to progression-free interval. There were no patients who demonstrated tumor regression. Overall, 39% showed stabilization of disease from 4 to 16+ months (median 8.0 months and mean 9.0 months).

Adult↗
PubMed1993

Randomized comparison of the effects of tamoxifen, megestrol acetate, or tamoxifen plus megestrol acetate on treatment response and survival in patients with metastatic breast cancer.

BACKGROUND: The antioestrogen tamoxifen and progestins act via different receptors and may therefore have complementary effects against human breast cancer. This possibility was tested in a randomized study which compared the effects of tamoxifen, standard-dose megestrol acetate, and these two agents in combination, in patients with metastatic breast cancer. PATIENTS AND METHODS: 184 post-menopausal patients with metastatic breast cancer were randomized to initial treatment with either tamoxifen (TAM) 40 mg daily, megestrol acetate (MA) 160 mgm daily, or the combination of the two administered simultaneously. Patients crossed over to the alternative single agent on relapse or disease progression. Patients were evaluated for response, time to initial and ultimate treatment failure, and survival. RESULTS: There were no significant differences between the three groups with respect to response rates, nor the other parameters. Patient survival was significantly associated with age > 60 years, ER positive status, and the absence of visceral metastases. CONCLUSIONS: TAM and MA are both equally effective in response induction as initial treatments and the combination has no advantage. Sequential treatment is still optimal, TAM being the preferred initial agent in view of the reported side effects with MA.

Aged↗
PubMed1991

[Determination of megestrol acetate and estradiol valerate in injection of microencapsulated compound megestrol acetate by secondary derivative spectrophotometry].

The paper reports the simultaneous determination of megestrol acetate and estradiol valerate in the injection of microencapsulated compound megestrol acetate by secondary derivative spectrophotometry. The experimental results showed that the average recoveries of the two drugs were 98.8% and 98.0%, respectively, and that the coefficients of variation were 0.71% and 1.81%, respectively.

Capsules↗
PubMed1990

Influence of progestins on serum hormone levels in postmenopausal women with advanced breast cancer--II. A differential effect of megestrol acetate and medroxyprogesterone acetate on serum estrone sulfate and sex hormone binding globulin.

Serum estradiol, estrone, estrone sulfate and sex hormone binding globulin were measured in 10 postmenopausal patients with advanced breast cancer receiving sequential treatment with medroxyprogesterone acetate and megestrol acetate. Treatment with megestrol acetate caused a non-significant reduction in serum estradiol (mean reduction of 19%, 0.05 less than P less than 0.1) but significant reductions in serum estrone (mean reduction of 20%, P less than 0.02) and serum estrone sulfate (mean reduction of 54%, P less than 0.005) compared to treatment with medroxyprogesterone acetate. In contrast, treatment with medroxyprogesterone acetate reduced serum sex hormone binding globulin more compared to treatment with megestrol acetate (mean reduction of 69%, P less than 0.01). These findings suggest that the two progestins have differential effects on serum hormone levels. The finding that treatment with megestrol acetate causes a significant reduction in serum estrone sulfate level warrants further investigations of this potentially important mechanism of action of this drug in advanced breast cancer.

Aged↗
PubMed2002

Phase I and pharmacokinetic study of vinblastine and high-dose megestrol acetate.

PURPOSE: Preclinical data indicate that progestational agents (progesterone, medroxyprogesterone acetate and megestrol acetate) interact with p-glycoprotein (P-gp) and reverse P-gp-associated resistance to vinca alkaloids and other natural products. Based on these data, we performed a phase I study of high-dose oral megestrol acetate and vinblastine to evaluate the safety of this regimen. PATIENTS AND METHODS: Enrolled in the study were 61 patients with advanced solid tumors, refractory to standard therapy. Cohorts of patients received megestrol acetate according to the following escalation scheme (loading dose/maintenance dose, twice daily for 7 days): 750 mg/250 mg, 750 mg/375 mg, 1000 mg/500 mg, 1500 mg/1000 mg, 3000 mg/2000 mg, 4500 mg/3000 mg, 6000 mg/4000 mg, and 7500 mg/5000 mg. They also received 1.5 mg/m(2) per day of vinblastine by continuous infusion for 5 days (days 2 to 6). RESULTS: Of the 61 patients, 59 were evaluable for toxicity. A maximum tolerated dose (MTD) was not reached. The regimen was well tolerated. Of the 59 patients, 10 (17%) experienced grade 4 leukopenia. All of these cases were at dose levels 3 to 8. There was an increase in the steady-state concentration (Css) of megestrol acetate with increasing dose up to the sixth dose level. Further increases in the dose produced no change in the megestrol acetate Css. Only 2.4% of megestrol acetate was free in the plasma as compared to 65.6% in RPMI culture medium. Megestrol acetate administration was associated with profound suppression of ACTH and cortisol levels. CONCLUSIONS: The combination of vinblastine and megestrol acetate was well tolerated. An MTD for this combination was not achieved as a result of the saturable absorption of megestrol acetate. Although potentially therapeutic serum concentrations of megestrol acetate were achieved, it is unlikely that MDR was reversed given the high protein-binding of the drug. Profound suppression of the pituitary-adrenal axis was also observed during the administration of megestrol acetate.

Adult↗