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PubMed1985

Steroidal regulation of endometriosis tissue: lack of induction of 17 beta-hydroxysteroid dehydrogenase activity by progesterone, medroxyprogesterone acetate, or danazol.

Cytosol and nuclear estrogen receptors were detected in 73% and 89% of untreated endometriosis specimens, respectively. The corresponding figures for cytosol and nuclear progestin receptors were 94% and 100%, respectively. Compared with the endometrium, the concentrations in endometriosis tissue were low. The anatomic site, the severity of the disease, and the phase of the menstrual cycle had no significant influence on receptor concentrations in endometriosis tissue. The activities of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) did not increase during the luteal phase. Danazol for 1, 3, 7 to 11, and 18 to 30 days, or medroxyprogesterone acetate for 5 days, had no effect on receptor concentrations or 17 beta-HSD activity in endometriosis tissue. The frequent presence of the receptors suggests that endometriosis lesions are under the control of steroid hormones. The lack of effect by progesterone and progestins on 17 beta-HSD shows that this regulation is different in endometriosis tissue and in the endometrium.

17-Hydroxysteroid Dehydrogenases↗
PubMed1985

Medroxyprogesterone acetate and phenobarbital induce NADPH producing enzyme activities in rats with a chemical liver injury.

The administration of medroxyprogesterone acetate (MPA) and phenobarbital (PB) improves liver function in rats with liver damage. This was seen here as increased aryl hydrocarbon hydroxylase (AHH) activity after therapy with MPA or PB in rats with a chemical liver injury, produced by dimethylnitrosamine (DMN). Hepatic glucose-6-phosphatase (G6Pase) activity, an index of glucose metabolism was also normalized in the MPA treated rats. The present study further shows that MPA induced hepatic malic enzyme (ME) and isocitrate dehydrogenase (ICDH) activities and PB enhanced glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH) and ME activities in the DMN pretreated rats. This suggests that MPA and PB enhanced the capacity of altered liver tissue to generate NADPH, a cofactor in the monooxygenase system, which may, in part, enhance the restoration of drug hydroxylation in the rats. Since G6PDH, 6PGDH and ME participate in glucose metabolism, the finding that the compounds influenced these enzymes in distinct ways, may explain the different effects of MPA and PB on the restoration of glucose metabolism.

Animals↗
PubMed1985

Physical, metabolic, and hormonal effects on men of long-term therapy with medroxyprogesterone acetate.

Twenty-three men were treated with injectable medroxyprogesterone acetate (MPA) for sex-offending behavior. The physical, hormonal, and metabolic effects were monitored. The patients had significant (P less than 0.001) weight gain and increases (P less than 0.0001) in systolic blood pressure independent of weight gain. MPA therapy decreased testosterone (P less than 0.0001), luteinizing hormone (P less than 0.005), and testicular size (P less than 0.001), but not follicle-stimulating hormone. MPA's suppression of total sperm count was not consistent, but MPA significantly reduced sperm motility (P less than 0.001) and percent normal morphology (P less than 0.005). Statistically insignificant increases in insulin response without changes in glucose tolerance occurred in all patients, but only one patient developed overt diabetes mellitus. Three men developed gallstones, but none had significant changes in liver function. Patients receiving high-dose MPA therapy should be carefully monitored for blood pressure changes, diabetes mellitus, and gallbladder dysfunction.

Adult↗
PubMed1985

Influence of aminoglutethimide on plasma levels of medroxyprogesterone acetate: its correlation with serum cortisol.

Postmenopausal patients with metastatic breast cancer were treated with aminoglutethimide (AG) and high-dose medroxyprogesterone acetate (MPA). Studying the interaction between the two drugs as far as plasma MPA and cortisol levels are concerned we observed a 50% decrease of plasma MPA levels after the addition of AG (P less than 0.005). With large interindividual differences in plasma MPA levels, a significant correlation with serum cortisol levels was found (P less than 0.001). It can be concluded that AG leads to a lowering of plasma MPA levels to such an extent that its adrenal suppressive effect may be diminished or even abrogated. In future trials of MPA with or without AG correlations between plasma MPA levels, serum cortisol levels and treatment response should be taken into account.

Aminoglutethimide↗
PubMed1985

Medroxyprogesterone acetate versus tamoxifen in the therapy of advanced breast cancer.

A comparison of efficacies of medroxyprogesterone acetate (MPA) and the antiestrogen tamoxifen (TX) in the therapy for advanced breast cancer in patients who had already previously been intensely treated showed that, as to the objective remissions, the two drugs can be looked upon as equivalent. Nevertheless, with MPA a better analgetic and anabolic effect--a marked improvement in the performance status (Karnofsky index)--was achieved.

Breast Neoplasms↗
PubMed1985

[Effects of antiestrogens and medroxyprogesterone acetate on the clonogenic growth of tamoxifen-sensitive and resistant human breast cancer cells].

Effects of tamoxifen (TAM), nafoxidine (NFA), 4-hydroxytamoxifen (4-OH-TAM), 3-hydroxytamoxifen (3-OH-TAM), and medroxyprogesterone acetate (MPA) on the clonogenic growth of a hormone-responsive human breast cancer cell line (MCF-7) and its tamoxifen-resistant variant (R-27) were studied. TAM, (10(-6)M) showed an inhibitory effect on the colony formation in a plastic dish of MCF-7 cells only in medium containing DDC-treated FCS (E2(-) medium). With the presence of E2 (10(-8)M) in the medium (E2(+) medium), TAM did not show any effect on cell growth. Irrespective of the presence or absence of E2 in the medium, there was no inhibitory effect of TAM on the clonogenic growth of R-27 cells. The ID50 values, expressed as the suppression of plating efficiencies, obtained by adding NFA, 4-OH-TAM, 3-OH-TAM, and MPA to the MCF-7 cells were shown to be 2 X 10(-7)M, less than 10(-8)M, 1 X 10(-7)M, and 4 X 10(-7)M, respectively in the E2 (-) medium, and 2 X 10(-6)M, 2 X 10(-7)M, 2 X 10(-6)M, and 4 X 10(-8)M respectively in the E2 (+) medium. For the R-27 cells, ID50 values obtained by adding NAF, 4-OH-TAM, 3-OH-TAM, and MPA were 7 X 10(-7)M, 5 X 10(-8)M, 4 X 10(-7)M, and 6 X 10(-8)M, respectively in the E2(-) medium, and 2 X 10(-6)M, 2 X 10(-6)M, greater than 5 X 10(-6)M, and 1 X 10(-8)M, respectively in the E2(+) medium. These results suggest that the antiestrogens used produce their suppressive effects on cell growth depending on the E2 concentration in the medium in these estrogen-responsive cell lines, and that the monohydroxytamoxifens are more potent than TAM in suppressing cell growth. The effects of MPA are shown to be different from the antiestrogen used in that MPA inhibited the growth of both TAM-sensitive and-resistant cells, independent of the presence or absence of E2 in the medium. The R-27 cell line, a variant of the MCF-7 cell line, appears to be a good model for studying antiestrogen resistance and for evaluating the effectiveness of agents against endocrine-resistant breast cancer cells.

Breast Neoplasms↗
PubMed1985

Metabolism of medroxyprogesterone acetate and hepatic drug metabolism activity.

The effect of microsomal enzyme activity on the hepatic metabolism of medroxyprogesterone acetate (MPA), measured in vitro, and the MPA concentrations in liver and plasma were investigated in rats with intact and injured livers before and after MPA therapy. The amount of total MPA metabolites and the activity of drug-metabolizing enzyme system changed in a parallel manner in the livers. The ratio of liver/plasma concentration of MPA was decreased in the liver injury. The hepatic metabolism of MPA is accelerated during MPA treatment in rat.

Animals↗
PubMed1985

[Therapeutic effects of medroxyprogesterone acetate in recurrent or advanced breast cancer].

Medroxyprogesterone acetate (MPA) was given to 25 cases of recurrent or advanced breast cancer in consecutive oral doses of 1,200 mg/day to evaluate its efficacy. Results in 22 evaluable cases were: CR in 5, PR in 6, NC in 3 and PD in 8 cases, response rate being 50% (11/22). Pretreatment of 11 cases with pharmacological endocrine therapy was effective in 7 cases, 4 of which were led to remission by MPA treatment. In 4 cases which did not respond to the pretreatment, 2 showed response to MPA. This suggests the appearance of a new method of treatment in addition to conventional endocrine therapy. Response rate of MPA in ER-positive cases was 60% (6/10); for ER-negative cases, MPA had no effect in the 3 cases studied. Response rate in postmenopausal patients was 39% (7/18). It is noticeable that MPA was effective in all of 4 premenopausal patients (CR1, PR3). A striking increase in weight was controlled after a full explanation before the study by a diet consisting mainly of staple food.

Administration, Oral↗
PubMed1985

[Depot medroxyprogesterone acetate: clinical and metabolic effects (lipids, glucose, hemostasis)].

Medroxyprogesterone acetate (MPA), a potent progestagen, is used as a very efficient contraceptive agent. The method of administration is by a threemonthly or sixmonthly intramuscular injection. The method is particularly convenient when the desired number of children has been reached. Fertility is sometimes reestablished only slowly after stopping the injections. The main side effects are linked to endometrial atrophy (blood loss, amenorrhoea). Other side effects are infrequent and subjective. A controversy has risen over the product, by reference to its effects on beagle dogs. We have reviewed the literature. We also present the characteristics of 313 patients treated during (all together) 8,000 months. These patients belong to a rather poor sample of the population (amongst them many immigrant women), aged about 30, with above average pregnancy and parity rates. We also studied, in 31 patients, serum levels of glucose and lipids, and haemostasis. Side effects and reasons for discontinuing the drug are reported. The Pearl index was 0,75% women-years. There was no average effect on weight, blood tension, glycemia. Triglycerides increased slightly, and there was a discreet activation of coagulation with inhibition of the fibrinolytic activity, but without clinical consequences. We conclude that we can go on prescribing the drug, in view of our study and after reviewing the literature.

Adolescent↗
PubMedDate not supplied

Effect of medroxyprogesterone acetate on the growth of mouse transplanted tumors: relation with hormone sensitivity.

The effect of high and low doses of medroxyprogesterone acetate (MPA) was investigated on three transplanted murine tumors (MXT mammary carcinoma, colon 38, and colon 26) in relation to receptor status and sensitivity of the tumors to ovariectomy and treatment with dexamethasone. MPA had no inhibitory activity on the growth of these tumors. It had no effect on the ovarian-sensitive MXT tumor; it significantly enhanced the growth of an MXT tumor line, selected through serial transplantations, which was stimulated also in ovariectomized animals. MPA, as well as ovariectomy, stimulated the growth of the colon 38 tumor, but this hormone sensitivity was lost during serial transplantations. No correlation was found between the effects of MPA and ovariectomy and the steroid receptor status of these tumors. MPA effects on these tumors do not seem contingent upon a glucocorticoid-like action since dexamethasone was highly effective on all the tested tumors. The combined treatment of the colon 26 tumor with a cytotoxic drug, 4'-deoxydoxorubicin, and MPA, which administered alone stimulated tumor growth and increased life span, caused a slight increase in the life span compared to single agents alone.

Animals↗
PubMed1985

[Clinical investigation of oral high-dose medroxyprogesterone acetate (MPA) in advanced breast cancer--double-blind controlled study: Japanese Group for MPA Treatment of Breast Cancer].

A randomized controlled trial was made to compare the therapeutic result of oral high-dose medroxyprogesterone acetate (HD-MPA) versus mepitiostane (MS) in the treatment of postmenopausal breast cancer. MPA (1200 mg) was given p.o., b.i.d. to 47 patients and produced objective response in 19 of them (40.4%). Objective response was seen in 14 of the 40 control patients given MS p.o., b.i.d. (35.0%). Among patients with bone metastases, 6/19 (31.6%) for HD-MPA and 2/23 (15.4%) for MS showed objective response. The other merits of HD-MPA suggested in the study were improvement in performance status, anabolic effect and myeloprotective effect.

Administration, Oral↗
PubMed1985

Effects of tamoxifen, estradiol benzoate and medroxyprogesterone acetate on the growth of DMBA-induced rat mammary carcinoma.

The potential synergism of sequential combinations of tamoxifen (TMX) or estradiol benzoate (E2B) with medroxyprogesterone acetate (MPA) in inhibiting the growth of 7.12-dimethylbenz(a)anthracene(DMBA) - induced rat mammary tumors has been investigated. In addition, the effect of TMX and E2B on estrogen and progesterone receptors' (ERs and PgRs) synthesis has been evaluated in the attempt to elucidate possible mechanisms involved. Previous treatment both with TMX and E2B has been shown to strongly enhance the antitumor activity of MPA. A priming on PgR synthesis has been observed only after E2B administration, TMX producing a sharp decrease in PgR levels. It is concluded that, while the priming action exerted by E2B on PgRs might explain the potentiating effect shown by E2B on MPA activity, the synergism observed between TMX and MPA should be explained on an extrareceptorial basis, an induction on PgR synthesis by TMX not being evident at the dosage and priming time employed in this study.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1978

Phase II study of vinblastine, methyl-CCNU, and medroxyprogesterone in advanced renal cell cancer.

One hundred and sixty-five patients with advanced renal cell cancer were evaluable for combination or single-agent therapy with methyl-CCNU, vinblastine, and medroxyprogesterone. A low order or response was observed, and these agents were not proven effective as treatment for metastatic renal cell cancer. Performance status and a relatively long symptom-free interval from primary tumor to metastatic disease were found to be the most prognostically significant factors for survival.

Adenocarcinoma↗
PubMed1984

ACTH and cortisol plasma levels in cancer patients treated with medroxyprogesterone acetate at high dosages.

The effects of medroxyprogesterone acetate (MPA) at high dosages on ACTH and cortisol plasma levels have been studied on seven patients which were carriers of ER+ and PR+ neoplasm. ACTH and cortisol plasma levels were studied at 8:00 a.m., before and after a 4-week treatment with MPA at dosages of 1000 mg/die at basal conditions and after a metyrapone stimulation test. The results obtained show that the MPA treatment causes a highly significant drop of both cortisol and ACTH plasma levels. The metyrapone stimulation test performed before and after MPA treatment confirms the suppressive effect of MPA on the hypothalamus-pituitary-adrenal gland axis. These data suggest a cortisol-like action of MPA with a negative feed-back mechanism on the hypothalamus-pituitary-adrenal gland axis.

Adrenocorticotropic Hormone↗
PubMed1981

Effects of hexestrol, medroxyprogesterone acetate and chlormadinone acetate on 7, 12-dimethylbenz [a] anthracene-induced rat mammary cancer in relation to estrogen receptor.

The effects of hexestrol (HXS), medroxyprogesterone acetate (MAP) and chlormadinone acetate (CMA) on 7, 12-dimethylbenz [a] anthracene-induced mammary cancer in rats were evaluated. As a result of successive intramuscular injections of HXS at dosages of 2 or 10 mg/kg or MAP at dosages of 24 or 120 mg/Kg, tumors were markedly reduced in size in all groups on day 7 approximately 14. These effects were the same regardless of the presence or absence of cytoplasmic estrogen receptors (ER) in tumors as determined by the dextran-coated charcoal method. Although such an effect was also seen with CMA, it was much less marked than the effects seen with HXS and MAP. The body weights of HXS-administered groups decreased considerably, whereas those of MAP-administered groups increased. These results may suggest that there is another endocrinological tumor-suppressing mechanism besides the mechanism involving the estrogen-ER system in large-dose administration of HXS and MAP.

9,10-Dimethyl-1,2-benzanthracene↗
PubMedDate not supplied

[Immunodepressive action and effects of medroxyprogesterone acetate on the lymphatic tissue of the rabbit appendix].

The influence of medroxyprogesterone acetate (MPA) on lymphoid tissue of rabbit appendix was investigated. The agent caused a uniform depletion of lymphoid cells, which confirmed the immunodepressive properties of the drug. Other findings suggested a corticoid action of the agent and a possible anticellular activity, interfering with nucleic acid synthesis of proliferating cells.

Animals↗
PubMed1982

Effect of antiandrogens and medroxyprogesterone acetate on testicular morphometry in mice.

Administration to albino mice of cyproterone (C), cyproterone acetate (CA) and medroxyprogesterone acetate (MPA) for one week produced a marked decrease in volume, surface area and length of the seminiferous tubules besides inhibiting spermatogenesis. This response was elicited by all the three treatments but was assessed as mild in "C", moderate in "MPA" and severe in "CA" groups. On the basis of present work it is concluded that inhibition of spermatogenesis occurred even with low dose schedule of the two antiandrogens and MPA. The possible mechanism of action has been discussed in the light of available literature.

Androgen Antagonists↗
PubMedDate not supplied

[Effect of medroxyprogesterone acetate (MAP) in high doses on chlorambucil-induced bone marrow depression. Preliminary results].

On the basis of previous observations indicating that Medroxyprogesterone Acetate (MAP) administered in high doses induces leukocytosis and an increase in the platelet count, the Authors have studied the effect of high-dose MAP on leukocytes and platelets when it was combined with Chlorambucil (CLB) in patients suffering from ovarian cancer in various stages. 28 patients treated with high-dose MAP and CLB showed a statistically significant lower mean reduction of WBC count and reduction of the incidence, entity, and duration of the leukopenia as compared to 29 patients treated only with CLB. These effects were particularly evident when MAP was administered intramuscularly. It was not possible to evaluate the effect of high-dose MAP on the platelet count because the CLB regimen did not induce a significant decrease in it. These preliminary results are interesting because they suggest the possibility that high-dose MAP, which has already been utilized in oncology for its antitumor, analgesic, and anabolic activity in the treatment of breast, endometrial, renal, and prostatic cancer, might be able to be employed to reduce the myelotoxic effects of chemotherapy.

Administration, Oral↗