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 397 records · Page 22Linked to original sources

PubMed1985

Prostacyclin and thromboxane in breast cancer: relationship between steroid receptor status and medroxyprogesterone acetate.

To study the production and significance of prostacyclin (PGI2) and thromboxane A2 (TxA2) in breast cancer, tissue fragments of breast cancer (n=23) and mastopathy (n=10) were superfused in vitro and the release of 6-keto-PGF1 alpha (a metabolite of PG12) and TxB2 (a metabolite of TxA2) measured by radioimmunoassay. Breast cancer formed more 6-keto-PGF1 alpha (4.5 +/- 0.9 ng min-1 g-1 of tissue dry weight, mean +/- s.e.) and TxB2 (2.5 +/- 0.6 ng min-1 g-1) (P less than 0.01) than did mastopathic breast (1.4 +/- 0.5 and 0.4 +/- 0.1 ng min-1 g-1, respectively). These productions were similar in steroid receptor positive and negative tumours. Breast cancer metastasized in 15 patients during the follow-up time of 3.7 +/- 0.7 years, but the initial prostanoid productions in these patients were not different from those in nonmetastatic patients. Two patients died from metastases, but their initial mammary production of prostanoids was not profoundly different from those in the survivors. In 8 patients (4 with steroid receptor positive and 4 with negative tumour), the cancer tissue was superfused in the presence or absence of medroxyprogesterone acetate (100-5000 ng ml-1), which is commonly used for treatment of breast cancer. This hormone had no effect on mammary PGI2 and TxA2 production. We thus conclude that the PGI2 and TxA2 productions are increased in mammary cancer but that this may not be of primary significance for metastastic spread.

6-Ketoprostaglandin F1 alpha↗

PubMed1987

The effects of low and high dose medroxyprogesterone acetate on sex steroids and sex hormone binding globulin in postmenopausal breast cancer patients.

The possibility that medroxyprogesterone acetate (MPA) is clinically effective at least in part by its suppression of adrenal steroidogenesis and a resultant reduction of circulating oestrogen levels was investigated in 49 postmenopausal patients with advanced breast cancer. Thirty-one patients were treated with low dose MPA (100 mg three times daily) and 16 patients with high dose MPA (250 mg four times daily). Plasma levels of androstenedione, testosterone, oestrone and oestradiol were all significantly reduced during treatment, with the suppression being most marked for the 17 beta hydroxysteroids, testosterone and oestradiol. The fall in oestradiol levels was to about 50% of pretreatment levels, but a concomitant fall in SHBG levels to less than 25% of baseline probably resulted in the fall in free, biologically active oestradiol being only to about 70-80% of pretreatment. It is unlikely that this is a major determinant of the activity of MPA in breast cancer.

Androstenedione↗

PubMed1989

Effect of medroxyprogesterone acetate on the response of the rat mammary gland to carcinogenesis.

In order to determine whether mammary gland differentiation, which is known to protect this organ from chemically induced carcinogenesis, can be stimulated in virgin rats by administration of a progestagenic agent, medroxyprogesterone acetate (MPA) was given to 300 Sprague-Dawley virgin rats, which at the ages of 45, 55, 65 and 75 days, groups I, II, III and IV respectively, had implanted an MPA pellet of 0.5 mg (low dose-LD) or 5.0 mg (high dose-HD). Pellets were removed after 21 days, and 21 days later five animals per group were killed for evaluation of mammary gland development. The remaining animals received 8 mg 7,12-dimethylbenz(a)-anthracene (DMBA) per 100 g body weight, and were killed after 24 weeks for evaluation of tumour incidence. Both age and treatment affected mammary gland structure and had a significant interaction in the proportion of terminal end buds (TEBs) present. The number of TEBs decreased as a function of age; treatment at both LD and HD did not modify the proportion of TEBs in groups I and III; LD decreased their percentage in group II, and both doses markedly increased TEB percentage in group IV animals. MPA LD treatment did not affect overall tumour and adenocarcinoma incidence although group IV animals developed greater incidences than their respective controls. MPA HD treated rats were 2.45 times more likely to develop tumours than their respective controls. Adenocarcinoma incidence had a significant positive correlation with the percentage of TEBs present. It was concluded that this progestagenic agent did not increase the risk of carcinoma development when administered to virgin rats at the clinical dose used for contraception. However, a 10-fold dose increase resulted in a higher tumorigenic response.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1983

Role of catecholamines in the central actions of medroxyprogesterone acetate.

The role of catecholamines in the mechanism of antiovulatory and other central effects of medroxyprogesterone acetate (MPA) has been studied in adult healthy, non-pregnant female albino rats. It has been observed that a single dose of MPA (100 mg/kg) given intramuscularly did not cause any significant change in brain catecholamine levels after 7 days of treatment. However, there was a significant reduction in brain dopamine levels after 15 days of MPA administration. This reduction in brain dopamine levels may be responsible for the anti-ovulatory activity of MPA. Certain side effects of MPA such as amenorrhoea, galactorrhoea, breast tenderness, breast tumors, inactivity and depression may also be due to decrease in brain dopamine levels.

Animals↗

PubMed1992

A prospective, one-year study on the effects of two long acting injectable contraceptives (depot-medroxyprogesterone acetate and norethisterone oenanthate) on serum and lipoprotein lipids.

Two parenterally administered progestins (depot medroxyprogesterone acetate, DMPA, 150 mg/12 weeks and norethisterone oenanthate, NET, 200 mg/8 weeks respectively) were given to women seeking contraceptive advice. Before treatment and after 1, 6, 7, 12 and 13 months blood samples were taken. In serum and in the ultracentrifugally separated lipoprotein fractions the levels of total and free cholesterol, triglycerides and phospholipids were assayed, as were the apolipoprotein A1 and B levels in serum. At the end of the study NET had induced a decrease in all lipid components of the HDL (high density lipoprotein) fraction of approximately 30% and tended to increase LDL (low density lipoprotein) lipids. DMPA also decreased HDL-lipids, approximately 15%. There was also a transient decrease in apolipoprotein A1 after one month in both patient groups. From epidemiological studies it is inferred that low HDL-levels and high LDL-levels are independent risk factors for the development of atherosclerosis and cardiovascular disease. Thus our findings might indicate an adverse effect in this respect of long term treatment with these progestins, particularly with NET.

Adult↗

PubMed1986

[Medroxyprogesterone acetate in adenomatous hyperplasia of the uterine endometrium. Clinical and morphologic studies on the duration and dosage of gestagen therapy].

To learn how effective medroxyprogesterone-acetate is for treating adenomatous hyperplasia of the endometrium, we prescribed a controlled therapy in a randomly selected group of 60 women in whom we had diagnosed adenomatous hyperplasia histologically. The endometria of these women were histologically evaluated before therapy was started and again after three months of therapy. The greatest rate of regression was shown by the 40-59 year old women with adenomatous hyperplasia of grade I (15 of 23 patients). The regression occurred with 50 mg/day within three to eight months. For the women with adenomatous hyperplasia of grade II severity, 100 mg per day were required to obtain a similarly good result. For those with adenomatous hyperplasia of grade III severity, 150 mg per day were needed. The over 60-year old patients required higher doses of MPA over longer time periods for equally good therapeutic results. The patients younger than 40 years of age received lower doses (10-40 mg daily) to maintain or regain their fertility. Their adenomatous hyperplasias regressed with 20-40 mg of MPA daily, whereas with a daily dose of 10 mg their adenomatous hyperplasias recurred. The number of cases here, however, is too small for a statistical analysis. Summarising our results we recommend treating patients with adenomatous hyperplasias of grade I and II severity with MPA until it can be proved histologically that the hyperplasia has regressed. The daily dose needed for grade I hyperplasias is between 50 and 100 mg per day, whereas for grade II between 100 and 150 mg are needed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Some biological activities of cronolone and medroxyprogesterone acetate in the uterus of the sheep, mouse and rabbit.

Cronolone (9 alpha-fluoro-11 beta-hydroxy-17 alpha-acetoxypregn-4-ene-3,20-dione) is widely employed to regulate breeding activity in the ewe, but its biological activity in the uterus of this and most other species has not been studied. In this study several in vivo uterus-related activities of cronolone have been examined in the sheep, mouse and rabbit. In some experiments the corresponding activities of medroxyprogesterone acetate (6 alpha-methyl-17 alpha-acetoxypregn-4-ene-3,20-dione, MAP) were also examined. Cronolone maintained pregnancy in ovariectomized ewes but not in ovariectomized mice and rabbits; it terminated pregnancy in some mice and in all rabbits that were receiving daily progesterone treatment. Cronolone could not sensitize the mouse uterus for the induction of the decidual-cell reaction or block the induction of such sensitivity by progesterone, but did support limited growth of the oil-stimulated horn after sensitization with progesterone. Cronolone induced uteroglobin secretion by rabbit endometrium. It was concluded that, whereas MAP is a potent progestogen in the sheep, mouse and rabbit, cronolone is a progestogen in the sheep and rabbit only. In the mouse and especially the rabbit, cronolone has other, non-progestational activities, which block pregnancy.

Animals↗

PubMed1989

In vitro binding of progesterone, cronolone and medroxyprogesterone acetate to uterine progesterone receptors of sheep, rabbit and mouse.

Various aspects of the binding of the synthetic progesteongens, cronolone (9 alpha-fluoro-11 beta-hydroxy-17 alpha-acetoxypregn-4-ene-3,20-dione) and medroxyprogesterone acetate (6 alpha-methyl-17 alpha-acetoxypregn-4-ene-3,20-dione, MAP) to uterine cytosol progesterone receptors of the sheep, rabbit and mouse were studied, in an attempt to explain interesting species differences in the biological activity of these steroids. For the sheep, data for binding-site concentration, relative binding affinity (RBA), dissociation constant (Kd) and rates of association and dissociation indicate specific binding of cronolone to the progesterone receptor and these would seem to explain in part the high progestational activity of cronolone in this species. By contrast, with the mouse, there was only a low level of specific binding of cronolone and this appears to explain its inability to maintain pregnancy in this species. Results for the binding activity of cronolone in rabbit uterus were similar to those for the sheep and thus inability of cronolone to maintain pregnancy in the rabbit is not explained by a failure to bind the progesterone receptor. Species differences in binding to the progesterone receptor were also seen with MAP where the RBA, with respect to progesterone, was high in the sheep and rabbit and lower in the mouse. The results, however, do not relate directly to the progestational activity of MAP in these species. Overall, the data indicate that species differences in the binding activity of steroid receptors constitute one factor that causes species-dependent variation in biological responses to progestogens.

Animals↗

PubMed1991

Effects of medroxyprogesterone acetate (MPA) on myometrial activity in unmated rats: a study in vivo using video-laparoscopy.

Unmated female rats received medroxyprogesterone acetate (MPA) on the day of oestrus. Myometrial activity in vivo was quantified by video-laparoscopy 24-96 h later. Changes induced by MPA resembled those in early pregnancy/pseudopregnancy, but were not as extreme. There was a significant increase in circular contractions, followed by a decline, as in mated rats. Increases in circular contractions propagating caudally were as large as in mated rats, but increases in those propagating cranially were much smaller and qualitatively different. MPA induced only small increases in the frequency of longitudinal contractions propagating cranially, whereas large increases occurred in pregnancy/pseudopregnancy. We conclude that in early pregnancy/pseudopregnancy, increased circular activity is induced by rising progesterone levels. However, progesterone alone does not account for the increased contractions propagating cranially in mated rats. We suggest that these are induced by increased pacemaker activity in the region of the cervix, possibly activated by stimuli received during copulation.

Animals↗

PubMed1991

Protective effect of medroxyprogesterone acetate plus testosterone against radiation-induced damage to the reproductive function of male rats and their offspring.

This study attempted to protect spermatogenesis and the reproductive performance of rats against the effects of acute scrotal exposure to x-rays. Daily subcutaneous injections of medroxyprogesterone acetate (8 mg/kg) plus testosterone (1 mg/kg) (MT group) were administered for 55 days (experiment A) or 15 days (experiment B). The rats were irradiated (3 grays) on the last day of MT pretreatment (MTX group). In both experiments, on days 1 and 130 posttreatment, rats from each of the four groups (control, x-irradiated, MT, and MTX groups) were killed to measure the weight of the reproductive organs and the number of epididymal spermatozoa. Breeding was started 3 days posttreatment by housing all males from the four groups each with two virgin females for six successive periods of 19 days, separated by a period of 2 days. The percentage of fertile males, the litter size, postimplantation losses, and dominant lethal mutations were calculated. In experiment A, in the last fertility trial, animals of both sexes were selected at random from the progeny of each group (F1). When they were adults, their fertility was tested in a mating trial. A fertility trial was also performed with the F2 males. Our data essentially reveal that (i) in addition to their adverse quantitative effects on spermatogenesis, x-rays also produce a significant increase in dominant lethal mutations in all germ cell classes, including stem spermatogonia; (ii) the F1 and F2 male descendants of irradiated male rats provoked abnormal rates of postimplantation losses in their female mates; (iii) the short as well as the long MT pretreatment protects testicular function of irradiated rats; and (iv) in experiment A, MT pretreatment totally prevented qualitative damage to spermatozoa and protected the descendants of the irradiated animals against altered spermatogenesis as well as against genetic damage in germ cells. In conclusion, pretreatment with MT, even for a short period of time, offers a method for potentially reducing the toxic and genotoxic effects of irradiation on the male reproductive system.

Animals↗

PubMed1988

Hormonal effects of high dose medroxyprogesterone acetate treatment in males with renal or prostatic adenocarcinoma.

In 18 patients, 12 with renal and 6 with prostatic carcinoma, the gonadal, pituitary and adrenal functions were studied by measurements of steroid hormones and gonadotrophins, before and after six weeks treatment with medroxyprogesterone acetate (MPA), injected intramuscularly 500 mg per day for 5 days each week. The testosterone-oestradiol-binding globulin (TeBg) was measured and the amount of albumin and TeBg bound and unbound testosterone was calculated. Treatment with high doses of MPA caused a profound decrease in serum concentrations of testosterone, dehydroepiandrosterone sulphate (DHEAS), cortisol and TeBg. There were significant decreases in serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH) and oestradiol-17 beta. The serum concentration of prolactin was significantly elevated. The protein unbound testosterone fraction was lowered by MPA treatment but less than total testosterone. In conclusion, MPA therapy in high dose alters the gonadal, pituitary and adrenal functions suppressing serum concentrations of androgens, gonadotrophins, cortisol and TeBg but elevating prolactin concentration.

Adenocarcinoma↗

PubMed1989

Effects of high dose medroxyprogesterone acetate treatment on antithrombin III and other plasma proteins in males with renal cell or prostatic carcinoma.

In 18 patients, 12 with renal cell and 6 with prostatic carcinoma treatment with high dose medroxyprogesterone acetate (MPA) significantly increased serum antithrombin III and haptoglobin concentrations. During treatment the proteins correlated with each others suggesting a response to similar regulatory mechanisms. Levels of orosomucoid, a1-antitrypsin, C1-inhibitor and von Willebrand factor did not change during treatment showing that the increase of haptoglobin was not due to an acute-phase response. The increased antithrombin III levels may have a favourable impact on the frequency of thromboembolic complications during treatment with MPA.

Adenocarcinoma↗

PubMedDate not supplied

Control of illegal medroxyprogesterone acetate-application in veal calves by residue analysis in adipose tissue using HPLC/RIA methods.

Procedures for the determination of medroxyprogesterone acetate (MPA) in adipose tissue collected at time of slaughter allowing the control of MPA application to veal calves are described. Screening radioimmunoassays after sample clean-up were sufficient for a first survey of MPA treatments in livestock herds. Validation of all positive samples was performed by two-dimensional (silica gel diol phase and RP-18 phase) HPLC/RIA immunograms. Megestrol acetate and melengestrol acetate with cross-reactivities of 31% and 0.3% respectively were clearly separated by the RP HPLC. With an absolute detection limit of 4 pg MPA/tube (90% relative binding) negative control samples did not exceed 6 pg/tube, equivalent to 6 pg/g fat in the validating method. Seventeen days after intramuscular (i.m.) injection of 24 mg MPA only 32 pg MPA/g fat were found, while i.m. injection of 60 mg MPA and a waiting period of 19 days resulted in 2700 pg MPA/g fat. After feeding two calves 20 micrograms MPA per head daily for 1 week followed by 200 micrograms MPA per head daily for 2 weeks 359 and 468 pg MPA/g fat were measured. In plasma as well as in adipose tissue more than 80% of the whole immunoreactive material was MPA itself, without indications for the presence of cross-reacting MPA metabolites as confirmed by HPLC/RIA immunograms. Based on day of slaughter ratios of accumulation of MPA from plasma into fat of MPA-fed veal calves were 52 and 72 respectively. In urine MPA was only detectable a few days after injection; as compared to a plasma concentration of 950 pg MPA/ml the amount in urine was only 37 pg MPA/ml and also 325 pg unidentified MPA-equivalents/ml.

Adipose Tissue↗

PubMed1996

Clinical evaluation of the therapeutic effectiveness of ethinyl oestradiol and oestrone sulphate on prolonged bleeding in women using depot medroxyprogesterone acetate for contraception. World Health Organization, Special Programme of Research, Development and Research Training in Human Reproduction, Task Force on Long-acting Systemic Agents for Fertility Regulation.

A placebo-controlled randomized clinical trial was conducted in six centres to compare the effects of a 14 day treatment with either 50 micrograms ethinyl oestradiol daily or 2.5 mg oestrone sulphate daily, on depot medroxyprogesterone acetate (DMPA)-induced prolonged bleeding. Out of 1035 women admitted to the study, 278 requested treatment and were given ethinyl oestradiol (n = 90), oestrone sulphate (n = 91) or placebo (n = 97). Ethinyl oestradiol was successful in stopping the bleeding episode in 93% of cases, compared with oestrone sulphate and placebo which had success rates of 76 and 74% respectively. However, the relative advantage of ethinyl oestradiol was marginal, with an average reduction of 1 bleeding day and 3 spotting days compared with the other two groups. Immediately after treatment, women given ethinyl oestradiol had less bleeding but a more unpredictable pattern than the other two groups. In the long term, there were no differences between the bleeding patterns or the discontinuation rates for any reason in the three groups, and the most important single reason for discontinuation in those groups remained 'menstrual problems'. In summary, the study showed that treatment of DMPA-induced prolonged bleeding with ethinyl oestradiol had a limited short-term effect but no beneficial effect on the acceptability of DMPA as a contraceptive method. Treatment with oestrone sulphate was no different from placebo.

Adolescent↗

PubMed1981

Effects of medroxyprogesterone acetate and caloric restriction on the distribution of serum and liver lipids and proteins in female rats.

The effects of a large dose (2 mg/100 g body weight) of medroxyprogesterone acetate (MPA), restricted feeding (50% of normal intake) and their interaction were investigated on the serum and liver lipid and protein distribution in female rats. MPA increased serum cholesterol and triglyceride levels in rats on ad libitum food intake without having any effect in the animals on restricted diet. There was no statistical difference in the total serum protein or albumin levels among the groups. The serum levels of alpha and gamma globulin were significantly lower in the underfed rats. MPA increased the concentration of gamma globulin in well nourished rats but interacted with dietary restriction to further reduce the level of this protein in the undernourished animals. There was no difference in the levels of hepatic phospholipids or free cholesterol among groups, However, cholesterol ester and triglyceride levels in liver were significantly elevated in the MPA-treated group fed ad libitum. A similar increase was not found in underfed rats. This study indicates that MPA exerts significant effects on the distribution of serum and hepatic lipids and serum globulin levels and that the effects are dependent upon the nutritional status of the subject.

Alpha-Globulins↗

PubMed1988

Randomized trial comparing aminoglutethimide with high-dose medroxyprogesterone acetate in therapy for advanced breast carcinoma.

A total of 218 postmenopausal patients were entered in a prospective randomized trial comparing aminoglutethimide (AG) and high-dose medroxyprogesterone acetate (MPA) as second-line hormonal therapy for advanced breast carcinoma. All responses were assessed by the criteria of the International Union Against Cancer. The response rates were 27% (29 of 106 patients) for AG and 31% (35 of 112) for MPA, but if stabilization of previously progressive disease is included, then the overall response rates were 51% (54 of 106) and 54% (61 of 112) for patients receiving AG or MPA, respectively. There was no difference in response to the two drugs at any site of disease, and the durations of response and survival were identical for the two drugs. The time to response was significantly shorter for patients treated with MPA (median, 8.7 wk) than for those treated with AG (median, 15.3 wk) (chi 2 = 9.96, 1 df, P = .0016). The percentage of patients experiencing toxic effects was equivalent in both arms, although the patterns and time courses of these effects were different.

Aminoglutethimide↗

PubMed1995

Effects of intermittent antiprogestin RU486 combined with cyclic medroxyprogesterone acetate on folliculogenesis and ovulation.

The results of several studies have suggested an inhibitory effect of the antiprogestin RU486 on late stages of folliculogenesis and ovulation. To assess the feasibility of using this property to inhibit ovulation without losing cycle control, an intermittent administration of RU486 alternated with medroxyprogesterone acetate (MPA) was tested in a phase I study. RU486 at a dose of 50 mg/day was given on menstrual cycle days 9-11 and 27-29, and 10 mg/day of MPA was given on cycle days 17-26 for three consecutive cycles to six Finnish and five Chilean women. Blood samples were collected two to three times a week for serum progesterone and oestradiol assays in three treatment cycles. One control cycle and one post-treatment recovery cycle were also monitored by serum samplings. Ultrasonography was carried out to measure follicular diameters in the treatment cycles. In 29 of 32 cycles, bleeding commenced within 3 days after the last MPA pill intake. Out of 32 treatment cycles, 20 were without luteal activity (serum progesterone < 9 nmol/l). Although 12 treatment cycles showed luteal activity (serum progesterone > or = 9 nmol/l), a clear rupture of a pre-ovulatory follicle > 15 mm, verified by ultrasonography, was seen in only one treatment cycle. During the treatment cycles with luteal activity (serum progesterone levels > or = 9 nmol/l), serum oestradiol concentrations were significantly higher on cycle days 9-18 and significantly lower at the end of the cycle compared with the cycles without luteal activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Potential role for medroxyprogesterone acetate as an adjunct to goserelin (Zoladex) in the medical management of uterine fibroids.

Twenty women with symptomatic uterine fibroids were treated with the luteinizing hormone-releasing hormone (LHRH) agonist goserelin (Zoladex) combined with medroxyprogesterone acetate (MPA) in an open pilot study comparing two protocols. Ten women received goserelin 3.6 mg monthly combined with oral MPA 15 mg daily for 6 months. The mean uterine volume (497 cm3) measured by ultrasound fell by only 18% after 3 months, with no further reduction at 6 months. The other 10 women received goserelin alone for the initial 3 months, followed by combined treatment for 3 months. The mean uterine volume (557 cm3) fell by 39% after 3 months with no significant regrowth by 6 months. At 6 months post-treatment, uterine volume had not returned to pretreatment size. MPA significantly reduced the frequency of vasomotor side-effects. There were no differences in plasma oestradiol, luteinizing hormone or follicle stimulating hormone concentrations between the protocols and good symptomatic relief was experienced by both groups. Two years after completion, three women in each group have requested surgical treatment. The results indicate that MPA may be a useful adjunct to LHRH analogues in women with fibroids, reducing side-effects and possibly prolonging the response, although positive effects on bone density have yet to be confirmed. The optimum regimen of administration remains to be clarified as the clinical results were the same with both protocols.

Adult↗