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At least 433 records · Page 24Linked to original sources
PubMed1988

Immunohistological localization of pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG) in endometrial adenocarcinoma and effect of medroxyprogesterone acetate.

Endometrium from postmenopausal women with endometrial adenocarcinoma was examined immunohistochemically using a monoclonal antibody to pregnancy-associated endometrial alpha 2-globulin (alpha 2-PEG), the major secretory protein of the glandular epithelium during the late luteal phase of the menstrual cycle and early pregnancy. Specimens were obtained at initial diagnostic curettage and at hysterectomy after medroxyprogesterone acetate (MPA) therapy. alpha 2-PEG was not detected in any malignant tissue irrespective of histological differentiation. Non-malignant endometrium obtained in association with malignant tissue was negative for alpha 2-PEG before treatment although after MPA therapy all specimens obtained exhibited marked alpha 2-PEG localization in glands. In four specimens endogenous alkaline phosphatase was observed consistently only in the malignant endometrium. Malignant endometrium does not appear to synthesize alpha 2-PEG nor is its synthesis induced by an oral progestogen, so that it does not represent a useful marker for endometrial carcinoma. Non-malignant endometrium in postmenopausal women appears to be fully capable of alpha 2-PEG production after stimulation with an oral progestogen.

Adenocarcinoma↗
PubMed1989

A randomized controlled trial of medroxyprogesterone acetate and psychotherapy for the treatment of pelvic congestion.

The value of medroxyprogesterone acetate (MPA) and of psychotherapy in the treatment of lower abdominal pain due to pelvic congestion was assessed in a randomized controlled trial. Eighty-four women with abnormal pelvic venography were assigned to one of four treatment groups: MPA alone, MPA plus psychotherapy, placebo alone, and placebo plus psychotherapy. Women were treated for 4 months and thereafter followed up regularly for 9 months with pain assessments, pelvic ultrasound scanning, and hormone measurements. During treatment, MPA showed a significant benefit in terms of a reduction in visual analogue scale pain score, with 73% of women reporting at least 50% improvement compared with 33% of those treated with placebo. At 9 months after the end of therapy there was no overall significant effect of MPA or psychotherapy, but there was an interaction between MPA and psychotherapy, with 71% of the women in this group showing a greater than or equal to 50% reduction in pain score. Therapy with MPA is a useful first-line therapy for women with pain associated with demonstrable pelvic congestion.

Adult↗
PubMed1998

Bone density in long term users of depot medroxyprogesterone acetate.

OBJECTIVE: To identify any adverse effect on bone density in long term users of depot medroxyprogesterone acetate (DMPA) for contraception. DESIGN: Cross-sectional measurement of bone density in users with amenorrhoea of more than one year or any woman using DMPA for more than five years. SETTING: Community Family Planning Clinics in Portsmouth and Manchester. POPULATION: One hundred and eighty-five women aged 17-52 years (mean 33.3 years) who had used DMPA for between 1 and 16 years and were attending the clinics for further injections, between August 1994 and August 1996. METHODS: Dual energy X-ray measurement of bone density of femoral neck and lumbar spine, and venous blood sample taken just prior to the next injection of DMPA. MAIN OUTCOME MEASURES: Bone density of femoral neck and lumbar spine and serum oestradiol in relationship to years of DMPA use and duration of amenorrhoea. RESULTS: Most women (n=153) had serum oestradiol levels < 150 pmol/l. Despite this, the mean bone density of the lumbar spine compared with the population mean for women aged 20-59 years gave a Z score (95% CI) of -0.332 (-0.510 to -0.154). There was no significant difference in the mean density of the femoral neck from the normal population mean. CONCLUSION: Despite amenorrhoea and low serum oestradiol, this sample of long term DMPA users had bone density only minimally below the normal population mean. We therefore found no clinically important adverse effect on bone density and therefore no reason to recommend bone conserving measures, such as add-back oestrogen.

Adolescent↗
PubMedDate not supplied

Comparative effects of estradiol benzoate, the antiestrogen clomiphene citrate, and the progestin medroxyprogesterone acetate on kainic acid-induced seizures in male and female rats.

We have investigated the comparative effects of estradiol benzoate (EB), the antiestrogen clomiphene citrate (CC), and the progestin medroxyprogesterone acetate (MPA) on seizures induced by systemic injection of kainic acid (15 mg/kg i.p.) in male and female rats. Subcutaneous administration for 10 days of EB (10 micrograms/kg) or high doses of CC (50 mg/kg) significantly potentiated kainate-induced seizures, with this effect being more pronounced in male animals. Doses of 2.5 mg/kg of CC potentiated kainate-induced seizures in male rats but were ineffective in female rats. Low doses of CC (0.5 mg/kg) exhibited a mild anticonvulsant effect in both sexes. Repeated administration of MPA (2.5 mg/kg) partially protected female animals against kainate-induced seizures; in male animals, MPA induced a 30% increase in the seizure severity score, although the difference from the score of control male rats was not significant. These data suggest that sex steroids influence kainate-induced seizures in a sex-dependent manner and that the effects of the antiestrogen CC are dose dependent. This should be taken into account in view of a possible use of CC and MPA in hormonal therapy for seizure disorders.

Animals↗
PubMed1986

Medroxyprogesterone acetate pharmacokinetics following oral high-dose administration in humans: a bioavailability evaluation of a new MPA tablet formulation.

The pharmacokinetics of medroxyprogesterone acetate (MPA) in healthy female volunteers have been investigated following oral administration of single doses of six different high-dose MPA tablet formulations. Blood samples were obtained over 96 hrs following administration. The plasma was separated and analyzed in duplicate for MPA by radioimmunoassay (RIA) after extraction with petroleum ether. A two compartment open model with first order absorption was computer-fitted to the plasma concentration of MPA. Following oral administration MPA is rapidly transferred from the gastrointestinal tract to the blood circulation with a half-life of the absorption process of 15-30 min. The peak plasma concentration is reached 1-3 hrs after administration, and the biological half-life of MPA is 40-60 hrs. Following administration of 1000 mg MPA the areas under the plasma concentration-time curves (AUC 0-infinity) were calculated to (mean and S.E.): 3357 (438) nmol/l and 2403 (245) nmol/l for Leo formulation A and Farlutal, respectively (P less than 0.02). Following administration of 500 mg the areas were: 2325 (389) nmol/l, 1793 (312) nmol/l, 1778 (239) nmol/l, 1178 (209) nmol/l, and 556 (89) nmol/l for Gestapuran, Leo formulation A (P = n.s.), Leo formulation B (P = n.s.), Provera (P less than 0.001), and Lutopolar (P less than 0.001), respectively. The in vitro dissolution rates of MPA from the tablet formulations were determined and compared with the results of the bioavailability studies, indicating that a rapid dissolution rate as well as the particle size of MPA are two important factors to ensure optimal absorption of MPA from the gastrointestinal tract.

Administration, Oral↗
PubMed1985

Alveolar hypoventilation treated with medroxyprogesterone.

Two children aged 1 and 20 months developed alveolar hypoventilation syndrome. They suffered severe apnoeic episodes and periodically required assisted ventilation. Their ventilatory response to carbon dioxide was lower than that of normal children and the transcutaneous oxygen tension during sleep was well below the normal range. Treatment with medroxyprogesterone acetate resulted in an improved response to carbon dioxide, and assisted ventilation was no longer needed. Oxygen and carbon dioxide tensions improved but were still slightly abnormal during sleep. There were no clinical side effects of treatment but one infant had slight pituitary suppression.

Carbon Dioxide↗
PubMed1990

Uptake of medroxyprogesterone acetate by progestin and androgen target neurons in the brain and pituitary gland of male cynomolgus monkeys.

Medroxyprogesterone acetate (MPA), a synthetic progestin that reduces plasma testosterone levels, has been used in the treatment of male sex offenders. It also reduces the sexual activity of male macaques. To investigate its sites and mechanisms of action, 11 adult male cynomolgus monkeys were castrated and 7 and 21 h later were pretreated with 20 mg progesterone s.c. (Prog, n = 3), or 5 mg dihydrotestosterone propionate s.c. (DHTP, n = 3) or oil vehicle (controls, n = 5). Twenty-four hours after castration, all males were injected i.v. with 5 mCi [3H]-MPA, and killed after 60 min. Left halves of the brains were processed for thaw-mount autoradiography to identify the neurons accumulating radioactivity, and right halves were analyzed by high performance liquid chromatography (HPLC) to measure the uptake of [3H]-MPA in nuclear fractions. In males pretreated with oil, there were labeled neurons in the ventromedial nucleus (n.), arcuate n., medial preoptic n. and anterior hypothalamic area. In progesterone-pretreated males, labeling was reduced by 84-100% compared with controls (p less than 0.001), but in DHTP-pretreated males there was no effect, and labeling was not significantly different from control levels. Nuclear concentrations of [3H]-MPA measured by HPLC in controls were highest in the hypothalamus, amygdala, preoptic area and pituitary gland. Pretreatments with progesterone reduced the nuclear concentrations of [3H]-MPA in hypothalamus, preoptic area and pituitary gland by 82-95% compared with controls (p less than 0.05), but DHTP pretreatments had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗
PubMed1981

Effect of medroxyprogesterone acetate and d-norgestrel on plasma renin activity, antidiuretic hormone, and urinary aldosterone in postmenopausal women.

The effect of intramuscular injection of 1,000 mg medroxyprogesterone acetate on plasma renin activity and antidiuretic hormone was studied in 9 postmenopausal women. There were no significant differences in the plasma renin activity and antidiuretic hormone values before and after the injection. 8 postmenopausal women received d-norgestrel (0.18 mg/day) during a 3-week period. The therapy had no effect on plasma renin activity, antidiuretic hormone, or aldosterone excretion.

Aged↗
PubMed1985

Effect of medroxyprogesterone on ventilatory control and pulmonary gas exchange in chronic obstructive patients.

Chronic obstructive hypercapnic patients were monitored for blood gases and breathing pattern, before, during and after a 7-day treatment with 75 mg/day of medroxyprogesterone (MPA). In 9 out of the 15 patients the PaCO2 level decreased (+/- 8 mm Hg) significantly with return to nearly control values at stop. 4 subjects still continued to improve after cessation of therapy and were considered as not being stable. In 2 patients PaCO2 did not change. We were unable to find any significant difference between the control values of these three categories. The study of the breathing pattern in responsive subjects showed an increase in minute ventilation and tidal volume, with a small increase in mean inspiratory flow and no change in inspiratory time as a function of total respiratory cycle time. We conclude that MPA lowers the PaCO2 of hypercapnic chronic obstructive pulmonary disease patients through an increased tidal volume, which could result from an increased central nervous inspiratory output, or from better mechanical performance of the respiratory muscles due to the same central stimulation.

Adult↗
PubMed1983

Effect of medroxyprogesterone acetate on the digestive and absorptive functions of rat intestine.

The effects of medroxyprogesterone acetate (MPA) on the digestive and absorptive functions of the small intestinal epithelium have been investigated in female albino rats. The transport of sodium-dependent glucose was significantly enhanced while sodium-independent transport remained unaltered in drug-treated animals. The uptake of amino-acids was also considerably increased, while Ca++ uptake decreased significantly on administration of the drug at a dose of 35 mg/kg body weight once a week for 1 month. Kinetic studies of glucose transport in the presence of sodium ions revealed that MPA treatment affected the rate of uptake of glucose by elevating Vmax, but the Km value remained the same in treated and untreated animals. The administration of the drug also led to significant augmentation in the activities of the brush border enzymes, disaccharidases, and to an insignificant decrease in alkaline phosphatase. The activities of leucine aminopeptidase did not show any change. The enhancement in sucrase activity might be due to induction of the enzyme because only Vmax was elevated in treated animals. As concerns cellular enzymes, lactate dehydrogenase activity was significantly depressed. This study suggests that MPA also exerts glucocorticoid-like effects on the intestinal tissue.

Amino Acids↗
PubMed1982

[Mitomycin C and high-dosage medroxyprogesterone acetate in the therapy of metastasizing breast cancer. Results of a phase II study of the Workshop for Internal Oncology of the German Cancer Association].

Combination therapy of mitomycin C 40 mg/m2 and medroxyprogesterone acetate 1.500 mg/day in patients with refractory metastatic breast cancer was tested within a phase II trial of the AIO. The overall response was 50% with 2 complete and 12 partial remissions. This combination therapy was tolerated well and hematologic toxicity was less than expected. More often pulmonary and renal toxicity appeared. This combination schedule seems to be useful even in patients with pretreated metastatic breast cancer. Hematologic, pulmonary and renal functions have to be observed.

Adult↗
PubMed1981

Experimental study on the anabolic and androgenic/antiandrogenic activity of different dose levels of medroxyprogesterone acetate (MAP) in rats.

The authors treated three groups of rats with medroxyprogesterone acetate (MAP) at different dosages (0, 2.5, 5, 10, 20, 40, 80 mg/kg) i.p. and orally for 7 days to evaluate its anabolic and its androgenic/antiandrogenic effect. 70 rats had been previously castrated and 35 were intact. The anabolic effect is evident in all groups of animals which were treated. The androgenic action predominates in castrated animals, while the antiandrogenic action predominates in intact animals. The above-mentioned actions are more marked when very high doses are used. After suggesting the possible mechanism of action of MAP, the authors point out that the anabolic effect confirms what has already been reported in clinical oncology after treatment with very high doses of MAP (1,000-2,000 mg orally or i.m. for 30 days) in different types of tumors (breast, kidney, prostate).

Administration, Oral↗
PubMed1991

High-dose medroxyprogesterone acetate versus oophorectomy as first-line therapy of advanced breast cancer in premenopausal patients.

Forty premenopausal patients with advanced breast cancer entered a prospective and randomized study in which high-dose medroxyprogesterone acetate (HD MAP) and oophorectomy (OPX) were compared. All the patients were first treated for advanced disease. Twenty-two patients received HD MAP (1,000 mg b.i.d. p.o.) and 18 patients received OPX. Complete remission (CR) was achieved in 2 (9%) in the HD MAP group and in 2 (11%) in the OPX group for a duration of 20-24 and 30-54 months respectively. Partial remission (PR) was achieved in 10 (45%) patients in the HD MAP group and in 4 (22%) patients in the OPX group for a median duration of 9 and 7 months respectively. The objective response rates (CR + PR) were 55% for the HD MAP group and 33% for the OPX group (p = 0.17). Ten patients who received OPX as first-line treatment received HD MAP when the disease progressed and were evaluable for response: PR was achieved in 6 patients (2 responders and 4 nonresponders to OPX) for a median duration of 5 months. Two out of 4 patients who received OPX at progression after objective response to HD MAP presented PR. HD MAP induced a significant decrease in pain intensity and, compared to OPX, a more frequent improvement was induced in performance status. No difference was observed between the two groups in terms of overall survival. This study shows that HD MAP is an active treatment in premenopausal patients with advanced breast cancer and that it can induce a response in some patients resistant to OPX.

Adult↗
PubMed1990

Medroxyprogesterone acetate binding sites in human endometrium and endometrial cancer.

Medroxyprogesterone acetate (MPA) binding sites in both human normal endometrium and endometrial carcinoma were identified and characterized by sucrose gradient centrifugation. These binding components were divided into two classes by saturation analysis, one with high affinity and low capacity and the other with low affinity and high capacity. The concentrations of low-affinity binding sites for MPA in endometrial carcinoma were higher than those in normal endometrium (p less than 0.01). By sucrose gradient centrifugation, 4S and 8S components were observed in both high- and low-affinity binding sites of normal endometrium. These components were moved to 4S by the addition of salt. However, in endometrial carcinoma, low-affinity binding sites were displayed at about 4S under either low- or high-salt conditions. High-affinity binding sites in endometrial carcinoma had the same sedimentation patterns as in normal endometrium. An obvious difference between normal endometrium and endometrial cancer was observed in low-affinity binding sites. Our results on the binding sites for MPA suggest that low-affinity binding sites may be related to the response of endometrial cancer to high-dose MPA treatment.

Binding Sites↗
PubMed1984

Changes in apolipoprotein AI after treatment with high-dose medroxyprogesterone acetate.

21 women (mean age 60 years, range 48-72) were given depot medroxyprogesterone acetate (DMPA), 1,000 mg/week parenterally for 6 months, as part of the treatment for endometrial carcinoma in either clinical stage I or II. Before treatment and after 1, 3 and 6 months of treatment serum apolipoprotein AI was analyzed by electroimmunoassay. There was a significant decrease in apolipoprotein AI after the administration of DMPA, compared to the value before treatment. A low level of apolipoprotein AI is considered a risk factor for the development of atherosclerosis and cardiovascular disease. Such a risk might therefore be anticipated if the period of treatment was extended to several years.

Aged↗
PubMed1985

High-dose medroxyprogesterone acetate versus prednisolone in hormone-resistant prostatic cancer. A pilot study.

Medroxyprogesterone acetate (MPA) (1,000 mg daily per os) yielded (mainly subjective) remissions in 8 of 21 patients with hormone-resistant cancer of the prostate. In 24 comparable patients, treated with prednisolone (20 mg daily per os) 3 remissions were observed, indicating a slight superiority of high-dose MPA considering the response rate. The response duration for both drugs was relatively short (2-7 months). No survival benefit for either drug was observed. In patients with hormone-resistant cancer of the prostate, a significant improvement of the performance status should be registrated as subjective response. This is a major aim of any treatment in these patients. Normalization of serum acid phosphatase may also be considered as remission. The type of remission (greater than 50% reduction of measurable tumor lesions, reduction of serum acid phosphatase, subjective remission) should always be indicated in the individual report dealing with phase II/phase III studies in patients with hormone-resistant prostatic cancer.

Acid Phosphatase↗
PubMed1987

Effect of medroxyprogesterone acetate, alone or in combination with epirubicin hydrochloride, on the growth of the Dunning R3327H prostatic adenocarcinoma.

Rats bearing the Dunning R3327H prostatic adenocarcinoma were castrated and supplemented with testosterone propionate. Some of the testosterone-supplemented rats were treated with medroxyprogesterone acetate (MPA) alone or in combination with epirubicin hydrochloride. During the treatment period of 4 weeks, the growth rate of the prostatic tumors was measured. The testosterone-supplemented rats showed a tumor growth rate similar to that found in intact control rats. It was found that MPA has an inhibitory effect on the tumor growth rate in castrated testosterone-supplemented animals. This effect was more pronounced if the MPA treatment was combined with epirubicin hydrochloride, where the tumor growth rate was slower than that found in rats castrated as the only treatment.

Adenocarcinoma↗