SEARCH · PubMed Health

Results for “MEDROXYPROGESTERONE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 451 records · Page 25Linked to original sources

PubMed1983

Adjunctive medroxyprogesterone acetate to radical nephrectomy in category M0 renal cell carcinoma. Preliminary report of a prospective randomized trial.

From July 1979 to December 1981, 83 patients from 6 centers in the Lombardy underwent radical nephrectomy for category M0 renal cell carcinoma. Postoperatively they were randomly allocated to adjunctive medroxyprogesterone acetate (MPA) or to a control group. After the first year of follow-up, the relapse rate was 13% in the controls (5 of 38 evaluable patients) versus 28% in the MPA treatment group (9 of 32). Sex steroid receptors were studied in both the tumor and in the surrounding healthy parenchyma by the dextran-coated charcoal technique in 52 of 70 clinically evaluable patients. There was no significant correlation between receptor studies and the relapse rate. Besides, receptors were more often detected in the healthy than in the neoplastic tissue, and values rarely exceeded 10 fmol/mg protein. Due to the negative trend in the MPA treatment group, the admittance of patients to this study was stopped after 120 patients had been accepted.

Adenocarcinoma↗

PubMed1986

Differential depression of hypoglossal nerve activity by alcohol. Protection by pretreatment with medroxyprogesterone acetate.

Upper airway obstruction during sleep occurs more commonly in men than in women and has been treated with progestational agents with some success. Alcohol ingestion exacerbates sleep apnea, and recent studies have established that alcohol depresses the respiratory motor activity to upper airway muscles more than that to the diaphragm, a response pattern that favors upper airway obstruction during inspiration. To investigate the possibility that progesterone provides some protection from this action of alcohol, we studied the responses of phrenic and hypoglossal nerve activities to alcohol infusion in decerebrate cats pretreated with medroxyprogesterone acetate (MPA) or with control injections. The results indicate that pretreatment with MPA reduces the alcohol-induced mismatching of hypoglossal and phrenic activities. This action of MPA may contribute to its effectiveness in the treatment of some patients with inspiratory obstruction during sleep.

Action Potentials↗

PubMed1979

High-dose medroxyprogesterone acetate (MPA) treatment in advanced breast cancer. A review.

Medroxyprogesterone acetate (MPA) when employed at high doses (greater than or equal to 500 greater than or equal to 1000 mg/day i.m.) can produce objective remission with improved survival in about 30% of postmenopausal women with advanced breast cancer resistant to cytotoxic drugs and endocrine therapies. When administered to women not previously treated with chemotherapy, the objective remission response rate reached 40%. From available evidence, high dose MPA can be considered a useful agent in the treatment of advanced breast cancer in postmenopausal women with soft tissue, pulmonary, pleural or osseous involvement even when patients have become refractory to prior hormone and cytotoxic therapies. Early results suggest that the response rate can be increased in patients with estrogen and/or progesterone-positive receptors. It is note worthy that in a study conducted on postmenopausal women resistant to cytotoxic and/or hormonal drugs, the median duration of survival was 13.5 months, while CRs plus PRs did not reach the median at 24 months after starting MPA treatment. High dose MPA is essentially devoid of major side effects. Relief of pain, increase in appetite and body weight, and sense of well being are characteristic features of the improved quality of life under MPA treatment. However, a gluteal abscess (from 2% to 20% dose related) is the most frequent side effect. A promising area for future studies is combined therapy using hormonal and cytotoxic agents or alternating sequential combinations. Well-designed studies are needed to develop means for increasing the complete response rate and therefore survival. Recent studies of combined chemo- and hormonal (MPA) therapy have yielded objective tumor regressions of 53 to 80% with an increased rate of complete remissions and duration of response.

Animals↗

PubMed1983

5-Fluorouracil, adriamycin and cyclophosphamide combined with high-dose medroxyprogesterone acetate in advanced breast cancer.

Seventy-six patients with metastatic breast cancer were treated with fluorouracil, adriamycin (doxorubicin) and cyclophosphamide (FAC) plus high-dose medroxyprogesterone acetate (HD-MPA). MPA was given for 21 days at the dose of 500 mg/day i.m., then on a randomized basis, either 500 mg/week i.m. (FAC+HD-MPA i.m.) or 300 mg/day p.o. (FAC+HD-MPA p.o.). Objective response rates were 79% in 39 patients on FAC+HD-MPA i.m. and 73% in the 37 patients on FAC+HD-MPA p.o. There was no significant difference in the median duration of response and median survival for the 2 regimens (respectively, 17 months and 22 months, and 15 months and 21 months for FAC+HD-MPA i.m. and FAC+HD-MPA p.o.). Toxicity was mild and similar in both groups. Although FAC+HD-MPA was highly effective, at present it is difficult to select which regimen provides the best initial treatment for metastatic breast cancer.

Adult↗

PubMed1984

Effect of medroxyprogesterone acetate and of some antiinflammatory agents on mouse erythroleukemia cell differentiation.

The effects of medroxyprogesterone acetate (MPA) on differentiation were examined using mouse erythroleukemia (MEL) cells and compared with those of antiinflammatory agents. MPA at low doses (10(-6) - 10(-7)M) induced 10-15% cells to differentiate, whereas high doses (10(-4) - 10(-5)M) caused a 30% inhibition of dimethylsulfoxide (DMSO)-induced differentiation. Dexamethasone (10(-4) - 10(-8)M), a steroid antiinflammatory agent, significantly inhibited (77-70%) DMSO-induced differentiation, whereas indomethacin, aspirin, flurbiprofen and BW755c (non steroid antiinflammatory agents) at the same concentrations had no effect. If added 24 h before DMSO, the inhibitory effects of MPA and dexamethasone increased to 65% and 95%, respectively, whereas indomethacin (10(-5)M) caused only a 30% inhibition and the other drugs were inactive. None of these antiinflammatory agents affected differentiation when used without DMSO. MPA and dexamethasone inhibitory effects on DMSO-induced differentiation did not seem to be mediated through the inhibition of the synthesis of prostaglandins, since non-steroid prostaglandin inhibitors were slightly active only when added 24 h before DMSO.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

PubMed1990

Sequential alternate administration of tamoxifen and medroxyprogesterone acetate in advanced breast cancer: clinical-biological randomized study.

From January 1985 to September 1988, 60 women with advanced breast cancer were randomized in two arms to receive: A) tamoxifen (TAM) (20 mg/die) until progression or B) TAM (20 mg/die for 14 days) then medroxyprogesterone acetate (MPA) (1500 mg/die p.o. for 14 days) followed by 7 days of wash-out before repeating the TAM/MPA treatment. All patients were post-menopausal, previously untreated with hormone therapy, and with tumor receptor status determined immediately before randomization; all had objectively evaluable lesions. In order to verify hormone receptor variations due to the antiestrogen, when possible a second biopsy was performed after the initial 14 day cycle of TAM. Thirty-one and 29 patients were included respectively in arms A and B. Objective regression (CR + PR) was observed in 58% of group A and 75% of group B, with CR in 11% and 23%, respectively. Differences were not statistically significant. Median time to progression was 12 months for group A and 9 for group B. Overall survival has not yet been reached in group A while it was 34 months for patients of group B. Metrorrhagia was observed in two cases of group A and in 6 of group B, and thrombophlebitis in 1 and 3 cases, respectively. The second biopsy confirmed a clear increase of PgR content in 8/11 cases (75%). Plasma level variations of TAM, N-desmethyl TAM and MPA were checked at various intervals on 3 patients of group B, and confirmed that our schedule is able to produce a drug wash-out period for tumor cells. In conclusion, our study demonstrated that while the manipulation of hormone receptors seems possible, results indicating better overall survival and time to progression were not obtained with alternate sequential TAM-MPA therapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1991

Evaluation of the effect of medroxyprogesterone acetate on bone marrow progenitor cells.

Various clinical studies have demonstrated that high-dose medroxyprogesterone acetate (HD-MPA) can reduce hematologic toxicity in patients receiving chemotherapy for advanced solid tumors. The underlying mechanism(s) of this action is still unknown. A direct effect of MPA on hemopoietic cells has been postulated, but in vitro studies have given contradictory results. To clarify the biologic activity of MPA on hemopoiesis we have evaluated in vitro growth of pluripotent and committed progenitor cells from bone marrow cells which were preincubated in vitro with various doses of MPA and subsequently treated with or without the S-phase-specific drug arabinoside-cytosine (Ara-C). Four healthy subjects and 8 patients with advanced stage solid tumors with no bone marrow involvement were studied. In our experimental model we did not observe any effect of MPA on Ara-C killing of progenitor cells from either bone marrow mononuclear cells or bone marrow mononuclear cells depleted of T-lymphocytes and adherent cells. These results suggest that MPA does not act directly (or indirectly through the production of cytokines by T-lymphocytes and/or monocytes and macrophages) on bone marrow progenitors. In addition, the supposed mechanism of rendering stem cells less susceptible to the insult of cytotoxic drugs by lowering the number of progenitors in the S-phase has been ruled out by cell kinetic studies.

Bone Marrow↗

PubMed1984

Randomized trial of low- versus high-dose medroxyprogesterone acetate in the induction treatment of postmenopausal patients with advanced breast cancer.

In a randomized trial, 210 postmenopausal women with advanced measurable breast cancer were allocated to two different schedules of medroxyprogesterone acetate (MPA). In the induction phase they received either 1,000 mg intramuscular (IM) MPA (high dose) daily or 500 mg IM MPA (low dose) twice weekly for four weeks. The maintenance treatment consisted of 500 mg MPA IM once weekly for all patients. In total, 184 patients were considered evaluable. The response rate was significantly higher (p = 0.004) for patients receiving high-dose MPA (30 [33%] of 91) as compared to the women receiving the low-dose regimen (14 [15%] of 93) and was consistent across all prognostic subgroups. These prognostic subgroups included soft-tissue and osseous metastases, two metastatic sites, patients greater than 60 years, disease-free interval greater than 60 months, no prior chemotherapy, patients with a response to the last hormonal treatment before MPA, unknown estrogen receptors, and positive progestin receptors. The two different schedules of MPA did not influence the time to progression and the survival. Toxicity was similar in both regimens. These results confirm that a higher response rate can be achieved with a more intensive MPA schedule. This treatment may represent an ideal second-line choice in the endocrine therapy of advanced breast cancer; however, its role as a first-line treatment remains to be defined.

Age Factors↗

PubMed1992

Pharmacokinetics and pharmacodynamics of medroxyprogesterone acetate in advanced breast cancer patients.

PURPOSE: Medroxyprogesterone acetate (MPA) is one of the major drugs used in endocrine therapy for advanced breast cancer. However, its optimal dose still has not been clearly established. Response to treatment and drug-related side effects were analyzed as a function of plasma MPA concentrations during prolonged MPA treatment. PATIENTS AND METHODS: MPA plasma concentrations were measured (high-performance liquid chromatography [HPLC] assay) at steady state (Css min) in 129 patients (mean age, 63 years; range, 34 to 87) treated by MPA (86% were treated orally exclusively with daily doses ranging from 400 to 2,000 mg). RESULTS: A wide interpatient variability was noted in MPA Css min for the 70 patients who received 1,000 mg/d orally (median, 51 ng/mL; range, 10 to 269 ng/mL). Intrapatient analysis of the evolution of MPA Css min during prolonged treatment showed relative stability of MPA concentrations (mean CV, 20.6%). A weak but significant correlation was demonstrated between oral doses and MPA Css min (P = .016). Thirty-five percent of patients (45 of 129) developed MPA-related side effects that were associated with the highest plasma MPA concentrations; medians were 81 and 32 ng/mL for toxic and nontoxic treatments, respectively (P less than .001). Objective response was assessable in 55 patients who were treated by MPA exclusively. Plasma MPA concentrations were significantly different (P = .025) between patients with progressive disease (PD) (median, 46 ng/mL) and those with complete response (CR), partial response (PR), or stable disease (SD) (median 65 ng/mL). Comparison of CR plus PR versus SD versus PD showed only a tendency toward significant differences in MPA Css min (P = .07). Analysis of toxicity and response as a function of the oral dose did not show any significant relationship. These data suggested an optimal therapeutic window for MPA Css min located within 50 to 70 ng/mL. CONCLUSION: This study demonstrates that plasma MPA concentration, as opposed to the administered dose, is a determining factor for toxicity and response therapy [corrected].

Adult↗

PubMed1981

Glucocorticoid-like actions of medroxyprogesterone acetate upon MtTW15 rat mammosomatotropic pituitary tumors.

We have shown recently that the MtTW15 experimental rat pituitary tumor responds to medroxyprogesterone acetate (MPA) by increasing GH production. In this study, using a single saturating dose assay and dextran-coated charcoal separation, the data indicate that the MtTW15 tumor contains cytosolic MPA binding sites. The concentration of sites (approximately 4 pmol/g tumor) was similar for tumors derived from male or female hosts but was significantly reduced in tumors from MPA- or estradiol-treated rats. The MPA binder sedimented to 4S on low salt sucrose density gradients and was of high affinity (Kd = 5.0 +/- 0.4 X 10(-9) M). However, binding specificity studies showed glucocorticoids to be better ligands than MPA. MtTw15 tumors were also analyzed for cytosolic progestin ([3H]R5020) and glucocorticoid ([3H]dexamethasone) binding sites. Only low levels of an estradiol-inducible progestin binder were found. In contrast, the concentration of glucocorticoid binding sites was similar to that observed for MPA, approximately 4 pmol/g tumor, as were the characteristics of the binding, i.e. 5.1 +/- 0.2S, Kd = 4.1 +/- 0.5 X 10(-9) M, and similar binding specificities. Both MPA and estradiol treatment of tumor-bearing rats decreased the concentration of both MPA and glucocorticoid binding sites. Furthermore, studies to determine if glucocorticoids would mimic the in vivo effect of MPA upon MtTW15 tumors, i.e. altered tumor hormone production, supported such a hypothesis. We conclude that the MtTW15 rat pituitary tumor contains a cytosolic glucocorticoid receptor and that MPA can interact with this receptor. The glucocorticoid receptor may be responsible for the MPA- and glucocorticoid-induced alterations in GH production.

Animals↗

PubMed1986

Medroxyprogesterone acetate induces diabetes insipidus in Chinese hamsters.

Injection of a synthetic progesterone, medroxyprogesterone acetate (MPA or Depo-ProveraR), a widely used contraceptive, into Chinese hamsters (Cricetulus griseus) induced a profound polyuria with daily output of dilute urine equal to about 50% body weight of the hamster. However, relatively normal ability for renal urine concentration was demonstrated by administration of exogenous vasopressin. Body weight did not increase during onset of MPA-induced polyuria or during interval of vasopressin-induced oliguria, suggesting that primary polydipsia was not etiologic. Administration of this steroid to Chinese hamsters was nontoxic, although these polyuric animals were unusually sensitive to water deprivation. This polyuria was not observed when progesterone alone was injected into Chinese hamsters or when MPA was given to other related hamster species (Armenian, Syrian, Turkish or Djzungarian). The MPA-injected Chinese hamster represents a unique model of vasopressin sensitive diabetes insipidus induced by a steroid in a species-specific fashion.

Animals↗

PubMed1976

The effect of medroxyprogesterone acetate on the pituitary-adrenal axis.

Twelve cancer patients and one patient with diabetes mellitus were treated with medroxyprogesterone acetate (MPA) by intramuscular injection in a total weekly dose of 400, 700, or 1200 mg. The treatment reduced the plasma cortisol concentration by 76% in the AM hours (21 leads to 5.0 mug/dl) and by 75% in the PM hours (12.8 leads to 3.2 mug/dl). Cortisol production rate decreased by 67% (19 leads to 6.2 mg/24 hrs). The 24 hour profile of plasma cortisol concentration measured in 3 patients showed zero secretion over this period. Low plasma ACTH values prevailed during treatment, and a blunted response to maximal ACTH stimulation was found. No evidence of adrenal insufficiency was observed in any patient, even though in some patients the plasma cortisol concentration remained at zero for many weeks. MPA has cortisol-like effects and the suppression of adrenal function is probably mediated by a negative feedback action on the hypothalamus or pituitary.

Adrenocorticotropic Hormone↗

PubMed1977

Serum medroxyprogesterone acetate (MPA) concentrations and ovarian function following intramuscular injection of depo-MPA.

A sensitive radioimmunoassay measuring serum medroxyprogesterone acetate (MPA) has been developed in order to measure and correlate serum MPA concentrations and ovarian function in women following im administration of deop-MPA (DMPA), employing goat anti-MPA-3-(O-carboxymethyl) oxime-bovine serum albumin and MPA-3-(O-carboxymethyl) imino-125I-iodohistamine. In the 3 women studied, im injection of 150 mg of DMPA yielded brief initial serum MPA concentrations ranging from 1.5 to 3 ng/ml for a few days. Serum MPA concentrations gradually declined and remained relatively constant at about 1 ng/ml for 2 to 3 months, declined gradually thereafter reaching 0.2 ng/ml during the 6th month and became undetectable (less than 0.02 ng/ml) about 7-1/2 to 9 months following administration. Serum estradiol remained at early to midfollicular phase levels for 4 to 6 months after DMPA injection and rose to preovulatory levels when serum MPA levels fell below 0.5 to 0.25 ng/ml. Ovulation, however, as evidenced by serum progesterone concentrations did not occur, apparently due to suppression of the LH peak by positive feedback inhibition. Prolonged inhibition of cyclic ovarian function following DMPA injection is caused by slow MPA absorption and persists until serum MPA levels have decreased below 0.1 ng/ml or become undetectable about 7 to 9 months after DMPA administration.

Adult↗

PubMed1983

Gonadotropin-independent familial sexual precocity with premature Leydig and germinal cell maturation (familial testotoxicosis): effects of a potent luteinizing hormone-releasing factor agonist and medroxyprogesterone acetate therapy in four cases.

Four boys with sexual precocity are described in whom pubertal concentrations of plasma testosterone were associated with premature Leydig and germinal cell maturation without activation of the hypothalamic-pituitary gonadotropin unit. Extensive laboratory evaluation localized the source of testosterone secretion to the testes, and testicular biopsy revealed maturation of Leydig cells and spermatogenic elements. These events appear to be nongonadotropin-dependent in view of the absence of a pubertal pattern of pulsatile LH secretion, persistence of a prepubertal LH response to LRF even after long standing sexual precocity, prepubertal basal levels of LH and undetectable hCG, and the absence of biologically active LH-hCG by bioassay. Indirect immunofluorescence studies failed to demonstrate an immunoglobulin in the patients' sera that bound to Leydig cells or seminiferous tubules of normal adult human testes. The potent LRF analog D-Trp6-Pro9-NEt-LRF did not result in suppression of plasma testosterone or Leydig cell function even after 3 months of daily treatment in two patients which provides additional support of pituitary gonadotropin independence and of the lack of a direct effect of the analog on Leydig cell function. Oral medroxyprogesterone acetate treatment in two patients was associated with a striking decrease in both plasma testosterone concentration and height velocity. In the only patient in whom a complete family history could be obtained (three of four patients were adopted), sexual precocity was noted in the maternal grandfather. As this familial syndrome is characterized by a prepubertal hypothalamic-pituitary gonadotropin unit and apparent gonadotropin-independent maturation of Leydig cells and germinal epithelium, possibly due to an intratesticular inborn error, we propose the term "familial testotoxicosis" to describe this group of sexually precocious boys.

Child, Preschool↗

PubMed1982

Experimental study of the effect on rabbits of the injectable contraceptive medroxyprogesterone acetate, cholesterol feeding and drug-atherogenic diet combination.

Medroxyprogesterone acetate was given alone or in combination with a cholesterolll-rich diet. Total serum cholesterol levels in treated rabbits was significantly different from those of the control on most occasions during the experiment, and in the controls it remained essentially the same throughout the experimental period. There was a relationship between lesions induced and the raised serum cholesterol, but there was no regression of the appearance of fibrous plaques after discontinuation of the cholestero supplement.

Animals↗

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

[Pathophysiology of gonadotropin secretion in patients with idiopathic precocious puberty and follow up studies during and after therapy with medroxyprogesterone acetate (author's transl)].

In order to assess the pathophysiology of gonadotropin secretion in patients with idiopathic precocious puberty, responses of LH and FSH to LH-releasing hormone (LH-RH), clomiphene citrate (Clomid) and medroxyprogesterone acetate (Deop-provera) in 6 female patients were tested. The basal levels of serum LH and FSH were elevated in 4 of 6 patients and enhanced LH response to 100 mug of intravenous LH-RH was observed in 5 patients, while FSH response was comparable to that of prepubertal subjects. Administration of Clomid (50 mg) for 7 days provoked LH increase in 3 out of 6 patients in contrast to no LH change found in normal prepubertal girls. while FSH levels decreased in 3 out of 6 patients. Intramuscular injection of Depo-Provera (100 mg) reduced LH and FSH levels in 4 patients. The Depo-Provera therapy in a dose of 75 approximately 225 mg every two weeks, caused suppression of breast development and menstrual bleeding but the prevention of growth spurt and bone age maturation were insufficient. Basal body temperature charts in 2 patients showed an ovulatary pattern immediately following cessation of Provera therapy of more than 8 years' duration. In conclusion, it is suggested that 1) function of hypothalamo-pituitary-ovarian system in patients with idiopathic precocious puberty is similar to that of normal pubertal subjects, 2) therapeutic doses of Depo-Provera, enough to suppress the patients' secondary sex characterics, was not sufficient to control bone age maturation 3) it is necessary to follow up patients more closely by measuring serum levels of gonadotropin and estrogen during the course of therapy.

Child↗

PubMed1981

Influence of medroxyprogesterone acetate (Provera) on plasma growth hormone levels and on carbohydrate metabolism. I. Studies in the ovariohysterectomized bitch.

Six elderly ovariohysterectomized dogs were given medroxyprogesterone acetate (MPA 10 mg/kg body weight) at 3 week intervals in a total of 5 injections. Mean growth hormone (GH) levels increased significantly after the third injection, continued to increase slightly after the fourth and fifth injections and remained significantly elevated over control levels as late as 16 weeks after the last MPA administration (P less than 0.05). The mean glucose concentrations during iv glucose tolerance tests (IVGTT) were significantly elevated at 30, 45 and 60 min after a glucose load when performed after the third MPA injection. Following the second MPA injection, mean insulin levels were significantly elevated at rest, 30 and 45 min after glucose load. After the fourth and fifth MPA injections, mean insulin levels during IVGTT were significantly elevated at 30 min only. These findings denote that (1) after a lag phase of several weeks MPA induces moderate GH increase in ovariohysterectomized dogs; (2) MPA administration causes moderate disturbance of glucose homoeostasis.

Animals↗