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At least 127 records · Page 7Linked to original sources
PubMed2006

Medroxyprogesterone acetate but not drospirenone ablates the protective function of 17 beta-estradiol in aldosterone salt-treated rats.

Controversial results obtained from human and animal studies on the prevention of heart disease by estrogens and progestins warrant a better understanding of nuclear hormone receptor function and interaction. To address this issue and taking into account that effects of synthetic progestins are not only referable to action through the progesterone receptor but may also be mediated by other steroid receptors, we characterized cardiovascular function and inflammatory gene expression in aldosterone salt-treated rats on long-term administration of 17beta-estradiol, medroxyprogesterone acetate, and drospirenone, a new progestogen exhibiting antimineralocorticoid activity. The complex pattern of cardiovascular injury in ovariectomized Wistar rats induced by chronic aldosterone infusion plus a high-salt diet was significantly attenuated in sham-ovariectomized rats and by coadministration of 17beta-estradiol in ovariectomized animals after 8 weeks of continuous treatment. The beneficial role of 17beta-estradiol on blood pressure, cardiac hypertrophy, vascular osteopontin expression, perivascular fibrosis, and impaired NO-dependent relaxation of isolated aortic rings was completely abrogated by coadministration of medroxyprogesterone acetate. In contrast, drospirenone was either neutral or additive to 17beta-estradiol in protecting against aldosterone salt-induced cardiovascular injury and inflammation. The current results support the hypothesis of complex interactions among estrogen, progesterone, glucocorticoid, androgen, and mineralocorticoid receptor signaling in cardiovascular injury and inflammation. Novel progestins, such as drospirenone, confer superior effects compared with medroxyprogesterone acetate in a model of aldosterone-induced heart disease because of its antimineralocorticoid properties.

Aldosterone↗
PubMed2001

Medroxyprogesterone in postmenopausal females with partial upper airway obstruction during sleep.

The aim of the present study was to evaluate the degree and duration of respiratory stimulation caused by medroxyprogesterone acetate (MPA), and compare the effect of MPA to that of nasal continuous positive airway pressure (nCPAP) in sleep-disordered breathing. Ten postmenopausal females with predominantly partial upper airway obstruction during sleep had an overnight sleep study at baseline, on the fourteenth day of treatment with MPA and after a 3-week washout period. Six subjects on nCPAP were also studied 3 months later. At baseline, the overnight mean+/-SD end-tidal pressure of carbon dioxide (Pet,CO2) was 5.5+/-0.4 kPa the arterial oxygen saturation (Sa,O2) 93.0+/-1.2%, Sa,O2 nadir 80.0+/-6.7%, and frequency of oxygen desaturation > or = 4% (ODI4) per hour 2.2+/-1.3. MPA decreased Pet,CO2 by 0.8 kPa (14.5%, p<0.001). After washout, the mean Pet,CO2 remained at 0.5 kPa (9.1%, p<0.001) lower than at baseline. Sa,O2 did not change. Pet,CO2 was lower on MPA than on nCPAP (4.7+/-0.2 kPa versus 5.0+/-0.3 kPa; p=0.037) but Sa,O2 was similar. Apnoea/hypopnoea index tended to be lower on CPAP than on MPA. Medroxyprogesterone acetate at a daily dose of 60 mg improves ventilation in postmenopausal females with partial upper airway obstruction during sleep without compromising sleep. The ventilatory improvement is sustained for at least 3 weeks posttreatment. Medroxyprogesterone acetate was more efficient in decreasing the partial pressure of carbon dioxide but continuous positive airway pressure was superior in decreasing respiratory efforts.

Aged↗
PubMed1997

Cellular changes in prostatic carcinoma after treatment with orchidectomy, estramustine phosphate and medroxyprogesterone acetate.

Thirty-three patients with prostatic carcinoma were treated with either estramustine phosphate, orchidectomy or high dose medroxyprogesterone acetate. Therapy response was evaluated by cytological examination of fine needle aspiration biopsies performed before and after 6 weeks treatment. At follow-up, 11 of 14 patients treated with estramustine phosphate had regressive and/or degenerative changes, in 2 patients there were no prostatic carcinoma cells in the smears and in one there was a marked reduction of the number of tumour cells. In 7 of 10 patients treated with orchidectomy there was a marked reduction of the percentage of malignant cells while smears from 3 patients were unchanged. In the 8 patients treated with high dose medroxyprogesterone acetate the cell patterns were unmodified compared with before treatment. We conclude that, in contrast to the lack of effect of treatment with medroxyprogesterone acetate, treatment with orchidectomy and especially estramustine phosphate caused morphologic cellular changes in prostatic carcinoma.

Aged↗
PubMed1995

Transdermal estradiol and medroxyprogesterone acetate in hormone replacement therapy are both antioxidants.

We have evaluated the effects of the different components of hormone replacement therapy (HRT) on the production of free radicals in platelet membranes from menopausal women. The study included 12 women in menopause for at least 6 months to a maximum of 4 years. First, the effect was determined of progestin only during the administration of 20 mg/day medroxyprogesterone acetate for 5 days. The peroxide production level was measured on day 0 and day 5. The second set of experiments was carried out in the first month of cyclic HRT with transdermal estradiol 50 micrograms/day from day 1 to day 25 and medroxy-progesterone acetate from day 13 to day 25. In this experiment, the peroxide level was evaluated on days 0, 12 and 25. A significant reduction of peroxide level was observed after oral medroxyprogesterone acetate administration. During HRT, we observed a similar reduction in lipid oxidation at the peak of the estrogen effect, and a further decrease with the administration of medroxyprogesterone acetate. It is concluded that reduction of lipid peroxidation during HRT is not only due to estrogens, but also depends upon the combined action of sex steroids. This observation justifies not only the combined regimen (estrogens plus progestin) in HRT, but also the positive effects of progestins alone on patients who cannot use estrogens.

Administration, Cutaneous↗
PubMed2002

Cyproterone, norethindrone, medroxyprogesterone and levonorgestrel are less potent local human growth hormone and insulin-like growth factor I secretion stimulators than progesterone in human breast cancer explants expressing the estrogen receptor.

The aim of the present study was to compare the ability of natural progesterone and synthetic progestins to stimulate local growth hormone (GH) and insulin-like growth factor I (IGF-I) secretion by breast cancer explants. Explants obtained during surgery were divided according to their estrogen/progesterone receptor phenotype - ER(+)PR(-); ER(+)PR(+); ER(-)PR(+) - as determined by immunocytochemistry. Natural progesterone (10(-5) mol/l) and synthetic progestins (cyproterone acetate (5 x 10(-7) mol/l), norethindrone (10(-5) mol/l), medroxyprogesterone acetate (10(-7) mol/l), and levonorgestrel (10(-7) mol/l) were tested in vitro for their ability to induce secretion of proliferation-promoting agents such as human GH (hGH) and IGF-I. All hormone-dependent breast cancer cell types responded to progesterone stimulation with increased local hGH secretion, while in the non-malignant tissue this effect was observed only in PR(+) cells. Moreover, progesterone in only PR(+) cells in vitro stimulated local IGF-I secretion by both malignant and non-malignant tissue. Medroxyprogesterone and levonorgestrel increased GH secretion by both malignant and non-malignant ER(-)PR(+) breast cancer explants, while cyproterone stimulated it only in non-malignant tissue. None of the synthetic progestins tested in this experiment exerted an effect on GH secretion by both malignant and non-malignant tissue of ER(+) breast cancer explants. The present data additionally showed that, apart from cyproterone, which increased IGF-I secretion in the same manner as progesterone by both malignant and non-malignant ER(-)PR(+) breast explants, other progestins tested had either no effect on IGF-I local secretion or decreased it. Medroxyprogesterone and levonorgestrel induced a decrease in IGF-I secretion noted in ER(+) explants of non-malignant tissue and in malignant ER(-)PR(+) breast tissue. All progestins tested decreased IGF-I secretion by malignant ER(+)PR(+) explants. Taken together, the tested synthetic progestins widely used as oral contraceptives and in hormone replacement therapy were less potent than progesterone in inducing secretion of proliferation-promoting agents such as hGH and IGF-I in ER-containing breast tissue. Despite the lack of confirmation of the link between the use of progestins and breast cancer risk, patients should be informed that the use of certain estrogen/progestin preparations is of no influence on breast cancer risk while others may increase it.

Breast↗
PubMed2004

Effect of continuous administration of conjugated estrogen plus medroxyprogesterone acetate (Premelle) in postmenopausal women in Taiwan.

BACKGROUND: To compare the metabolic effects on lipids and acceptability and safety of, and compliance with, a continuous administration of conjugated estrogen plus medroxyprogesterone acetate (Premelle) versus a placebo in non-hysterectomized postmenopausal women. METHODS: Sixty-six generally healthy, female, early post-menopausal women, from 45-60 years of age, were randomized for an administration of conjugated estrogen plus medroxyprogesterone acetate (Premelle, Premarin 0.625 mg plus medroxyprogesterone acetate 2.5 mg/tablet orally) or a placebo for 6 months. The changes in each patient's lipid profiles from baseline, the frequency of hot flushes, bleeding occurrences, and climacteric symptoms, were evaluated. Safety was monitored by means of physical examination, Papanicolau smear, transvaginal ultrasonography, and laboratory check-up. Adverse events were also recorded. RESULTS: The difference before and after treatment in serum LDL-C and total cholesterol (TC) was statistically significant in the Premelle group (LDL-C, p = 0.006, TC, p = 0.040). No statistically significant difference in the change from baseline was observed in the levels of LDL-C and TC in the placebo treatment group. There was a statistically significant change from baseline in menopausal symptoms, which were evaluated by the Greene Climacteric Scales in the Premelle group. There was no clinically significant finding in the physical examination, vital signs, laboratory data, or endometrial thickness in either treatment group. The difference in the number of patients who reported an adverse event was not statistically significant between the 2 treatment groups. CONCLUSIONS: This study demonstrated that Premelle was effective in decreasing LDL-C and total cholesterol levels, and also showed an improvement in some menopausal symptoms, such as vasomotor and sexual dysfunction symptoms. No significant bleeding was observed with Premelle, which was well tolerated in this study. The results of this study could support the use of Premelle tablets as a convenient alternative hormone therapy.

Cholesterol, HDL↗
PubMed1979

Therapeutic effect of tamoxifen versus tamoxifen combined with medroxyprogesterone acetate in advanced breast cancer in postmenopausal women.

Postmenopausal patients, those less than 68 years of age resistant to chemotherapy and those greater than 68 years of age with or without resistance to chemotherapy, entered this trial. Among 101 eligible patients, 46 were randomized to treatment with tamoxifen at a dose of 10 mg 3 times daily and 55 were randomized to treatment with tamoxifen at a dose of 10 mg 3 times daily plus medroxyprogesterone acetate at a dose of 100 mg once daily. Remission (partial plus complete) was obtained in 20 patients (45%) with tamoxifen compared to 14 patients (26%) with tamoxifen plus medroxyprogesterone acetate; however, this difference is not significantly different. The median duration of remission was also not significantly different between the two treatments: 10 months for the single drug compared with 9 months for the combined treatment. Response rates correlated with the presence of estrogen receptor, with no differences between the two treatment groups. Side effects occurred in 12 patients and in only one patient did they cause discontinuation of treatment. In conclusion, these results and theoretic considerations indicate that combined treatment with tamoxifen and medroxyprogesterone acetate is not better than treatment with tamoxifen alone.

Adult↗
PubMed1995

[Clinical trial of high-dose medroxyprogesterone acetate in advanced breast cancer].

Sixty-two evaluable patients with advanced breast cancer were treated with medroxyprogesterone acetate (Farlutal. Erba) 500mg orally twice or three times a day. After thirty days, one patient had a complete response (1.6%), 33 patients had partial response (53.2%). 11 had stable disease (17.7%), and 17 progressive disease (27.4%). The response rates of bone, lung and chest wall metastasis were higher. And the older patients showed a better response than the younger. The response did not show significant correlation with KPS, menopausal status, disease-free intervals after operation, numbers of metastases and the dose of medroxyprogesterone acetate. The response rate in ER positive patients was higher than the ER negative, but the difference was not statistically different. The side effects of high-dose medroxyprogesterone acetate were well tolerated and the most common ones were weight gain and excessive perspiration.

Adult↗
PubMed1995

Medroxyprogesterone increases basal temperature: a placebo-controlled crossover trial in postmenopausal women.

OBJECTIVE: To assess whether temperature is increased by medroxyprogesterone (MPA) and thus whether basal temperature records could be used to determine ovulation during cyclic MPA therapy. DESIGN: A 2-month double-blind placebo-controlled crossover trial in which oral basal temperature was measured daily. SETTING: Normal human volunteers in an academic medical environment. SUBJECTS: Eleven postmenopausal women not taking gonadal hormones. INTERVENTION: Medroxyprogesterone acetate (10 mg/d) or placebo, calendar days 16 to 25, with crossover. MAIN OUTCOME MEASURES: Comparison of mean temperature days 17 to 26 during MPA versus placebo; comparison of differences between temperatures days 7 to 16 and 17 to 26 in MPA versus placebo months; and analysis for a significant monthly thermal shift. RESULTS: The mean temperatures during MPA treatment averaged 0.27 degrees C higher than during the placebo phase and showed a significant change from pretreatment to "treatment" phases during MPA but not during placebo cycles. Eight of the MPA and one of the placebo cycles showed a shift from lower to higher temperatures days 16 to 25. CONCLUSIONS: Medroxyprogesterone acetate has a physiological progesterone-like thermal effect. Therefore basal temperature data cannot reliably indicate ovulation during cyclic MPA administration.

Adult↗
PubMed1994

[Dihydrogesterone vs. medroxyprogesterone acetate in association with transdermal estradiol in postmenopausal substitution treatment].

The authors consider postmenopausal replacement oestrogen therapy to be appropriate provided that in non-hysterectomised women it is associated with a progestin compound. For this purpose they studied the endometrial changes in women treated randomly with dihydrogesterone and medroxyprogesterone acetate. Having performed a pre-treatment biopsy, in order to include only those cases with hypotrophic endometrium or with residual proliferative activity, cyclical treatment was commenced with transdermic estradiol and dihydrogesterone or medroxyprogesterone acetate. An endometrial follow-up was performed after 6 months to control the maturation of the endometrium which was free from atypical transformations although medroxyprogesterone acetate was preferable due to its effects on the metabolism in general and because it allowed a higher percentage of conversion into secreting endometrium without evolving towards hyperplasia.

Administration, Cutaneous↗
PubMed1980

Specific quantitation of plasma medroxyprogesterone acetate by gas chromatography/mass spectrometry.

Investigation of various derivatives (O-methyloxime, trifluoroenol acetate and t-butyldimethylsilyl enol ether) coupled with the efficient preparation of a trideuterated analogue of medroxyprogesterone acetate, has allowed the development of a rapid and accurate assay for its quantitation in plasma by isotope dilution gas chromatography/mass spectrometry. High oral doses (2.8 g weekly) of medroxyprogesterone acetate are shown to lead consistently to plasma levels of less than 16 ng.ml-1.

Cholesterol↗
PubMed1980

Effects of medroxyprogesterone acetate on serum lipids, protein, glucose tolerance and liver function in Thai women.

Proteins (total, albumin, globulin and their subfractions), carbohydrate (intravenous glucose tolerance test), lipids (serum cholesterol, triglycerides and phospholipids), and liver function tests (alkaline phosphatase, lactic dehydrogenase and aspartate aminotransferase activities in the serum, bromsulphathalein retention test and serum bilirubin) were studied in 12 non-lactating healthy Thai subjects before, and subsequently at 3 weeks and 3, 6, 9 and 12 months after the initiation of treatment with injectable medroxyprogesterone acetate (150 mg I.M. every 90 days). Serum protein and lipid levels, and the results of liver function and I.V. glucose tolerance tests, remained unchanged in all subjects throughout the one-year study period. However, a significant and persistent increased insulin level was noted in all subjects, after initiation of the hormone treatment, during the first thirty minutes of intravenous glucose load. It is concluded that injectable medroxyprogesterone acetate used as a contraceptive agent does not interfere with glucose tolerance, lipid and protein metabolism, and that the liver function remains normal during its administration.

Blood Proteins↗
PubMed1989

Combination of 19-nortestosterone-hexyloxyphenylpropionate (Anadur) and depot-medroxyprogesterone-acetate (Clinovir) for male contraception.

Because monotherapy with 19-nortestosterone hexyloxyphenylpropionate (Anadur, Pharmacia Arzneimittel, Ratingen, Federal Republic of Germany) suggested improved results for male contraception compared with available testosterone esters, it was tested for induction of complete azoospermia when combined with depot-medroxyprogesterone acetate (DMPA, Clinovir, Upjohn GmbH, Heppenheim, Federal Republic of Germany). Twelve men were treated for 7 weeks with weekly intramuscular (IM) injections of 200 mg Anadur followed by 3-weekly IM injections of Anadur up to week 15. Clinovir (250 mg) IM was administered at the start of treatment and during weeks 6 and 12. Anadur and Clinovir suppressed serum gonadotropins. Although serum testosterone declined steeply, in general, libido and potency were not impaired. Sperm concentrations were reduced significantly after 3 weeks of treatment. Lowest sperm counts were seen during week 8 of follow-up, when only 2 volunteers showed measurable sperm counts of 2.1 and 3.0 X 10(6)/ml, with a declining tendency. After 43 weeks, sperm concentrations were still below pretreatment range in 2 men, but later returned to pretreatment values. Computerized sperm motion analysis revealed that motility parameters in the residual sperm were reduced. In vitro analysis excluded a direct effect of medroxyprogesterone acetate in seminal plasma on sperm motion. The data indicate that the combination of Anadur with Clinovir increases the rate of azoospermia in normal volunteers seen under Anadur monotherapy, although the goal of azoospermia in all participants was not quite achieved.

Anabolic Agents↗
PubMed1977

Adrenocortical involution in rats during oestrus synchronisation with medroxyprogesterone.

Daily treatment of female rats with medroxyprogesterone acetate in aqueous suspension resulted in adrenocortical atrophy. The doses given were those used for oestrus synchronisation. Intramuscular injections of 2-0 mg medroxyprogesterone acetate were used to investigate the atrophic process. Adrenocortical involution was associated with extensive single cell deletion (apoptosis). It is suggested that theses changes were due to suppression of pituitary ACTH secretion. The cytological changes support the concept that single cell death plays an important role in organ remodelling. Biochemical determinations of DNA, RNA, protein and dry matter, and histological examination, did not reveal significant changes in the liver.

Adrenal Cortex↗
PubMed1998

A double-blind randomised study comparing danazol and medroxyprogesterone acetate in the management of menorrhagia.

A randomised study was undertaken comparing danazol 200 mg daily and medroxyprogesterone acetate 10 mg daily from days 16 to 25 in the management of menorrhagia. Twenty-three women were recruited to the study over a 12-month period. Eighteen subjects were suitable for analysis. Three months' therapy was given and patients were observed for a 3-month period following discontinuation of therapy. Menstrual blood loss was estimated during initial patient assessment and then during each of the 6 months of the study. In the danazol group mean blood loss at all treatment phase months was significantly decreased from baseline. In contrast, blood loss was not reduced significantly in any study month when compared with baseline in the medroxyprogesterone acetate group. During the post-treatment phase the mean blood loss in the danazol group increased to above normal levels but remained significantly lower than baseline, and there was a significant reduction in menstrual blood loss in the medroxyprogesterone acetate group.

Clinical Trial↗
PubMed1982

Quantitation of hydroxyprogesterone caproate, medroxyprogesterone acetate, and progesterone by reversed-phase high-pressure liquid chromatography.

A high-pressure liquid chromatography method for the quantitation of hydroxyprogesterone caproate, medroxyprogesterone acetate, and progesterone in pharmaceutical dosage forms was developed. The method gave accurate, precise, and reproducible results. The excipients present in the dosage forms did not interfere with the assay procedure except benzyl benzoate in progesterone injection. The percent relative standard deviations based on six injections were 1.6, 2.5, 2.7% for hydroxyprogesterone caproate, medroxyprogesterone acetate, and progesterone, respectively. The stability of progesterone in ethanol--propylene glycol--water (10:50:40) was studied. The loss in potency of progesterone, even after 487 days of storage at 50 degrees, was less than 10%.

17 alpha-Hydroxyprogesterone Caproate↗
PubMed1983

Medroxyprogesterone acetate (MAP) plasma levels after multiple high-dose administration in advanced cancer patients.

Medroxyprogesterone acetate plasma levels were measured in advanced cancer patients after multiple PO or IM administration (500, 1000, 2000, 3000, 4000, and 5000 mg/day PO and 500, 1000, 2000 mg/day IM for 30 days). After PO administration, the plasma concentration rises quickly and plateau level is reached in 4-10 days. Discontinuation of the treatment produces a fast decay (t1/2 = 62.4 h) of the drug levels. When medroxyprogesterone acetate is given IM plasma levels, steadily increase and after drug discontinuation no noticeable decay is observed for at least 6 months; plateau plasma levels are about three times higher than after the corresponding PO treatment. Extremely high interpatient variation in bioavailability is present with both administration routes. These data may well rationalize the results of previous clinical trials and will help in planning treatment schedules.

Administration, Oral↗
PubMed1985

Oral medroxyprogesterone acetate in the treatment of metastatic breast cancer.

Thirty-nine evaluable, postmenopausal patients with metastatic breast carcinoma were treated with medroxyprogesterone acetate administered orally at daily doses of 800 mg/day in 29 patients and 400 mg/day in 10 patients. One patient experienced a complete remission and 16 had partial remissions for an objective remission rate of 44%. There was no apparent difference in response between the two dose levels. Median remission duration was 8 months, and median survival for the whole group is expected to exceed 18 months. Increased appetite (66%) and weight gain (97%) were the most common side effects, followed by fluid retention, muscle cramps, and increased blood pressure. Performance status improved and white blood cell and platelet counts increased in the majority of patients. Medroxyprogesterone acetate is an effective hormonal agent in the treatment of metastatic breast cancer.

Administration, Oral↗