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At least 19 recordsLinked to original sources
PubMed1986

Cardiovascular side effects of diethylstilbestrol, cyproterone acetate, medroxyprogesterone acetate and estramustine phosphate used for the treatment of advanced prostatic cancer: results from European Organization for Research on Treatment of Cancer trials 30761 and 30762.

Two randomized trials were started in 1976 by the European Organization for Research on Treatment of Cancer urological group. Trial 30761 compared 1 mg. diethylstilbestrol orally 3 times daily to 250 mg. oral cyproterone acetate daily and to 500 mg. medroxyprogesterone acetate intramuscularly 3 times weekly for 8 weeks, then 200 mg. orally daily. Trial 30762 compared 3 mg. diethylstilbestrol to 560 mg. estramustine phosphate orally for 8 weeks and then 280 mg. daily. The 239 patients in study 30761 and 226 in study 30762 were evaluated for cardiovascular toxicity during treatment. Various types of side effects (fluid retention, hypertension, electrocardiographic changes, myocardial infarction and thromboembolic disease) and their degrees of severity were analyzed. In both studies the most frequent type of cardiovascular toxicity was represented by fluid retention. Cardiovascular toxicity as a whole was higher with diethylstilbestrol than with estramustine phosphate or medroxyprogesterone acetate therapy, and was the lowest with cyproterone acetate therapy. The risk of severe cardiovascular complications developing was the highest during the first 6 months of treatment. Increasing age, body weight greater than 75 kg. and, especially, the presence of previous cardiovascular disease represented adverse factors in the development of cardiovascular toxicity.

Aged↗
PubMed1975

The ultrastructural response of human endometrium to medroxyprogesterone acetate.

Medroxyprogesterone acetate is a steroid compound similar to progesterone in structure and function. Thirty women were given 150 mg. of medroxyprogesterone intramuscularly, and samples of the endometrium were examined by light and electron microscopy. The initial response of normal human endometrium was maturation and then inhibition. By 50 days after injection, the atrophic changes began to reverse, and by Day 90, after injection the tissue resembled normal proliferative endometrium. A previously undescribed nuclear inclusion body is present; however, its significance is unclear at this time. On the basis of ultrastructural changes, medroxyprogesterone appeared not to exert a significant influence on the endometrium past 90 days at this dosage.

Adult↗
PubMed1986

Comparison of diethylstilbestrol, cyproterone acetate and medroxyprogesterone acetate in the treatment of advanced prostatic cancer: final analysis of a randomized phase III trial of the European Organization for Research on Treatment of Cancer Urological Group.

Patients with previously untreated category T3 to T4 Mo or Ml prostatic cancer were allocated randomly to receive 250 mg. cyproterone acetate per day, a loading dose of 500 mg. medroxyprogesterone acetate intramuscularly 3 times weekly for 8 weeks followed by 100 mg. orally twice daily, or 1 mg. diethylstilbestrol 3 times daily in a phase III trial (protocol 30761) performed by the genitourinary tract cooperative group of the European Organization for Research on the Treatment of Cancer. Of 236 patients entered 210 were eligible: 75 received cyproterone acetate, 71 medroxyprogesterone acetate and 64 diethylstilbestrol. Local and distant tumor response, time to progression, survival and toxicity were assessed. Patients treated with medroxyprogesterone acetate had a less favorable course with a shorter duration of survival and time to progression than those treated with the other 2 drugs. There was no significant difference between diethylstilbestrol and cyproterone acetate. Cardiovascular side effects were reported more often in patients treated with diethylstilbestrol than in those treated with cyproterone acetate but severe and lethal cardiovascular toxicity was relatively low in all groups. Other side effects were negligible. Further studies are required to establish the influence of effective hormonal treatment upon survival.

Aged↗
PubMed1991

Improved bioavailability of a new oral preparation of medroxyprogesterone acetate.

Medroxyprogesterone acetate (MPA) is widely used in the hormonal therapy of breast cancer. So far, oral formulations of MPA commercially available present a very low bioavailability, with a less than 10% extent of oral absorption. A new oral preparation of MPA has been recently developed. Based on a pilot study, an open, randomized, crossover trial has been performed on 22 breast and endometrial cancer patients to evaluate the relative bioavailability of this new oral formulation (200-mg sachet, twice daily) as compared with a standard formulation (Farlutal, 500-mg tablet, twice daily). The bioavailability evaluation was mainly based on the area under the curve measured between two administrations at steady state, after 15 days of continuous therapy. Wide interpatient variability of MPA plasma levels after oral MPA administration was confirmed. The MPA plasma levels were higher in patients treated with the new formulation than in patients treated with Farlutal. The relative bioavailability of the new preparation was 3.5 times higher than that of the standard. This new formulation represents a great improvement in the extent of oral absorption of MPA and could lead to better management of hormone-responsive tumors by hormonal therapy.

Administration, Oral↗
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↗
PubMed1976

[Concentration of estrone, estradiol and estriol in the blood of pregnant sheep after induction of estrus with chlormadinone acetate and medroxyprogesterone acetate].

The radioisotopic method of 131J-labelled albumin was employed to determine the distribution of acidic proteinase activity in some organs and tissues of chickens. The highest enzymatic activities were found in intestine wall, in pancreas, and in liver. Considerably lower activities were ascertained in kidneys, brain, lungs, and heart. The different proportions of these enzymes in homogenates and supernatant fractions (106 000 g) testify to a lack of uniformity in the solubility of cathepsins in the organs tested. The tested organs, with the exception of pancreas, did not show any enzymatic activity of neutral proteinases.

Animals↗
PubMed1988

[The medroxyprogesterone acetate serum level following various medroxyprogesterone acetate dose schedules in gynecologic oncology].

Medroxyprogesterone acetate (MPA) is used as an adjuvant hormonal medication in patients with different kinds of carcinomas. Since adequate serum levels are thought to be essential we determined the individual, postoperative MPA levels in 36 patients with endometrial carcinoma over a period of 12 weeks. The patients received either an oral dose of 3 X 100 mg MPA or a weekly changing scheme with 2 X 10 mg Tamoxifen and 3 X 100 mg MPA. An additional small group of 4 patients with ovarian carcinoma was enrolled receiving an oral dose of 1000 mg MPA daily. The peripheral serum levels of MPA exhibit enormous inter- and intraindividuell variations and only the high dosage schemes yield levels above 90 ng/ml which are claimed necessary by some authors. The cortisol concentration measured at the same time were within the normal range and did not correlate with the MPA values.

Antineoplastic Agents↗
PubMed1990

A randomized comparison of megestrol acetate (MA) and medroxyprogesterone acetate (MPA) in patients with advanced breast cancer.

The efficacy and side-effects of megestrol acetate and medroxyprogesterone acetate in postmenopausal patients with advanced breast cancer were compared in a prospectively randomized study. The dosage of MA was 2 X 80 mg p.o. or MPA 2 X 500 mg p.o. daily, given as a secondary hormonal treatment, mostly after previous treatment with tamoxifen. Ninety-eight patients entered the study and 92 were evaluable for effect, 48 patients on MA and 44 on MPA. Age, main tumor site and prior treatment were not different, but there was a preponderance of ER-negative tumors in the MA group. Responses appeared to be more frequent in the MPA-treated group (25% vs. 43%), predominantly in bone lesions, 12% for MA and 45% for MPA. Median progression-free survival was comparable, 15 vs. 10 months, and overall survival was not different (20 vs. 16 months). Toxicity was frequent, occurring in 83% vs. 74% of patients: increased appetite, nausea and dizziness in more than 20%, and a preponderance of pyrosis and breathlessness on MA and hot flashes, sweating and tremors on MPA. Cushingoid symptoms were present in about a quarter of the patients treated for more than 3 months. The occurrence of thrombo-embolic episodes and cardiovascular events was evenly distributed. Patients on MPA had more often increase in body weight, systolic blood pressure and serum creatinine than those treated with MA. It is concluded that MPA may be more effective for treatment of bone metastases, at the expense of more progestational side-effects. The occurrence of Cushingoid effects is frequent but similar in both arms, while the incidence of cardiovascular or thrombo-embolic events cannot be related to the use of either compound.

Aged↗
PubMed1988

Angiogenic activity of rat mammary carcinomas induced by 7,12-dimethylbenz[a]anthracene and its inhibition by medroxyprogesterone acetate: possible involvement of antiangiogenic action of medroxyprogesterone acetate in its tumor growth inhibition.

The significant inhibitory activity of medroxyprogesterone acetate (MPA) against mammary tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) was confirmed in female Sprague-Dawley (SD) rats, and was found to be independent of the estrogen receptor (ER) level. To facilitate elucidation of the mechanism underlying the antitumor activity of MPA against the rat mammary tumors (RMTs) regardless of ER status, the present study was conducted to determine whether or not a DMBA-induced RMT had the capacity to elicit angiogenic activity on tissue implantation into a rabbit cornea, and, if so, to determine whether or not the angiogenic activity of the RMT was inhibited by MPA. The RMTs obtained were classified into two groups based on the ER level; ER-positive and -negative groups. Both groups exhibited relatively strong angiogenic activity, the activity of the ER-negative group being significantly higher than that of the ER-positive one. The angiogenesis produced by both groups of RMTs was significantly inhibited by MPA, as judged from the results of the rabbit cornea assay. Similarly, MPA almost entirely suppressed not only the angiogenesis but also the growth of rabbit VX2 tumors without ER, included as a positive control as to the induction of angiogenic activity. In vitro experiments using neoplastic epithelioid RMT-1 and -2 cells cloned from DMBA-induced RMTs demonstrated that MPA had little or no suppressive effect on the growth of these epithelial cells. These results suggest that the inhibitory action of MPA toward the angiogenic activity of RMTs, at least in part, involves its antitumor activity toward the RMTs.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Hormonotherapy of meningiomas with medroxyprogesterone acetate. Immunohistochemical demonstration of the effect of medroxyprogesterone acetate on growth fractions of meningioma cells using the monoclonal antibody Ki-67.

The effect of medroxyprogesterone acetate (MPA) on growth fractions of ex vivo meningiomas is demonstrated in using the Ki-67 monoclonal antibody in three cases of meningiomas operated on in two stages and in meningioma specimens from a group of eight patients operated on in one single stage after MPA therapy. Growth fractions in samples from five meningioma patients not treated with MPA were determined for comparison. In the three cases of two-stage operation of the tumors, the percentage of Ki-67-positive cells in meningioma tissue was lower by a factor of 6, 5, and 3, respectively, after MPA therapy. In meningioma specimens from patients receiving no MPA therapy, Ki-67-positive cells were present in 1.02 +/- 0.48%; in samples from MPA-treated tumors the percentage of Ki-67-positive cells was 0.41 +/- 0.40 (different at p less than 0.02 [Wilcoxon's test]). In comparison to our previously published data on untreated meningiomas analyzed for progesterone receptors (PR), MPA significantly reduced the PR activity. There was no obvious correlation between PR activity and potential suppression of the tumor growth fraction. It is concluded that MPA is attractive because it reduces the growth fractions of most meningiomas and might be suitable for adjuvant hormonotherapy.

Antibodies, Monoclonal↗
PubMed1989

Indices of severity of obstructive sleep apnea syndrome do not change during medroxyprogesterone acetate therapy.

Medroxyprogesterone acetate (MPA) could change the frequency and/or duration of disordered breathing events (DBEs) in patients with the obstructive sleep apnea (OSA) syndrome by altering pharyngeal muscle function relative to diaphragm and external intercostal function. Ten male patients with OSA syndrome underwent an initial polysomnogram with monitoring of EEG, EOG, myohyoid EMG, oral and nasal airflow, abdominal and thoracic movement, and SaO2. The patients were then entered into a randomized, double-blind crossover study using MPA, 150 mg/day, and MPA placebo. Each patient took tablets for one week and then had a second polysomnogram. After a three week washout, the patient again took tablets for a week prior to the third and final sleep study. There was no significant difference between drug and placebo for DBE time (expressed as a percentage of sleep time), DBE frequency, DBE mean duration or mean fall in O2 saturation during DBEs. We conclude that treatment with MPA does not alter indices of severity of the OSA syndrome.

Double-Blind Method↗
PubMed1975

Induced prolactin release in women under long-term medroxyprogesterone acetate treatment.

Medroxyprogesterone acetate (MPA) was administered, as a contraceptive, by intramuscular injection in doses of 150 mg every 90 days, or 300-450 mg every 180 days, to 5 women, over a period of 27 to 42 months. No major adverse reactions were reported, and the minor side effects were only as frequent as those reported for oral contraceptives. The LH basal levels were depressed in all subjects;; FSH and prolactin serum concentrations were within the range found in normally cycling women. Synthetic TRH released prolactin in 4 subjects, and the maximal response was within 10-20 minutes after TRH injection. In the fifth case there was no prolactin release.

Acetates↗
PubMed1989

The effect of medroxyprogesterone acetate (Provera) on ovarian radiosensitivity.

Medroxyprogesterone acetate (Provera) is a drug that is commonly given to young women with cancer during chemotherapy and radiation to control heavy bleeding associated with anovulation. Because hypothalamic-pituitary-ovarian suppression has been associated with ovarian protection from the effects of chemotherapy and medroxyprogesterone acetate has been identified as a radiosensitizing agent, we explored the effects of medroxyprogesterone acetate on a rat model with known radiation injury characteristics. Sprague-Dawley rats were treated with medroxyprogesterone acetate or vehicle from day 22 to day 37 of life and were either irradiated or sham-irradiated on day 30 of life and then killed on day 44. Radiation with medroxyprogesterone acetate administration produced a greater loss in preantral and healthy control follicles than in control follicles. No suppression of luteinizing hormone or follicle-stimulating hormone had occurred by day 30 but ovarian glutathione content was reduced. These findings indicate that the administration of medroxyprogesterone acetate with radiotherapy may enhance ovarian injury.

Animals↗