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At least 613 records · Page 34Linked to original sources
PubMed1994

Experiences with doxo/epirubicin and medroxyprogesterone acetate (MPA) in prostatic cancer.

Maximal androgen blockade (MAB) has been reported to prolong the time to progression and the duration of survival in metastatic prostatic cancer. The addition of epirubicin to MAB in such patients seems to improve the therapeutic results further. The beneficial effect of combining castration with epirubicin in metastatic cases appears questionable. In comparing the time to progression in patients treated with MAB +/- epirubicin versus castration +/- epirubicin or estramustine, many studies reveal similar figures. Whether the results after treatment are actually improved remains controversial. In hormone-refractory cases, medroxyprogesterone acetate (MPA) alone seems superior to estramustine or prednisolone treatment. Combining MPA and epirubicin improves the results, but even if the improvement is of clinical value, it is nonetheless of limited magnitude.

Administration, Oral↗
PubMed1990

Influence of aminoglutethimide on the metabolism of medroxyprogesterone acetate and megestrol acetate in postmenopausal patients with advanced breast cancer.

In this study the influence of amino-glutethimide (AG) on the disposition of medroxyprogesterone acetate (MPA) and megestrol acetate (MA) was studied. When 1,000 mg AG daily was supplementally given to six patients on chronic treatment with MPA (1,000 mg/day) or MA (160 mg/day), mean serum levels of progestin were reduced by 74% as compared with control levels (P less than 0.03). AG did not change the blood clearance rate of MPA when the latter was given i.v. This discrepancy between AG's influence on oral and parenteral progestin disposition could be explained by pharmacokinetic properties of the progestins, and our results suggest that AG stimulates the metabolism of progestins. The decrease in MPA and MA serum levels was accompanied by an increase in serum cortisol, sex hormone-binding globulin (SHBG) and testosterone levels. This suggests that AG reduces the biological activity of progestins.

Administration, Oral↗
PubMed1993

Medroxyprogesterone acetate inhibits the proliferation of estrogen- and progesterone-receptor negative MFM-223 human mammary cancer cells via the androgen receptor.

This study demonstrates for the first time, that medroxyprogesterone acetate (MPA) inhibits the proliferation of the estrogen and progesterone receptor negative mammary cancer cell line MFM-223 via the androgen receptor. MPA is a progestin, which is used in the hormonal treatment of disseminated breast cancer. It binds to the progesterone, androgen, and glucocorticoid receptor and may exert its antiproliferative effects via different receptors. MFM-223 human mammary cancer cells contain a very high level of androgen receptors (160 fmol/mg protein) and low levels of estrogen, progesterone, and glucocorticoid receptors (< 20 fmol/mg protein). This cell line provides therefore a good model system to analyze the possible role of the androgen receptor in the action of MPA avoiding interference with other steroid hormone receptors. Effective inhibition of proliferation is achieved by 10 nM MPA or 1 nM of the androgen dihydrotestosterone, corresponding well to the binding affinities of both compounds (3.6 and 0.18 nM, respectively). The involvement of the androgen receptor was confirmed by competition experiments with antiandrogens. Furthermore, MFM-DHT cells, which are an androgen resistant subline of MFM-223 cells, are also resistant to MPA. This data supports the involvement of the androgen receptor in the action of MPA and additionally rules out direct hormone-independent cytotoxic effects of MPA.

Androgen Receptor Antagonists↗
PubMed1986

Effects of medroxyprogesterone acetate on subjective arousal, arousal to erotic stimulation, and nocturnal penile tumescence in male sex offenders.

Three chronic pedophiliac sex offenders were treated individually with medroxyprogesterone acetate (MPA) over a minimum of 3 months. Genital and subjective response to erotic stimulation, nocturnal penile tumescence, self-reporting of sexual urges, and testosterone levels were recorded repeatedly throughout the study. A single-subject reversal design was used and medication was administered through a double-blind procedure. The results showed that self-report of arousal outside of a laboratory setting was unreliable as a measure of the drug effect. In a laboratory setting, however, there appeared to be a significant reduction in the report of arousal to erotic stimuli while genital arousal decreased only slightly. Reversal of these responses occurred in only one subject during a final placebo phase. Nocturnal penile tumescence was significantly decreased during MPA administration and appeared to be related to decreases in total testosterone.

Adult↗
PubMed1996

The effects of cyclosporin A, tamoxifen, and medroxyprogesterone acetate on the enhancement of adriamycin cytotoxicity in primary cultures of human breast epithelial cells.

Adriamycin (Adr), the single most active agent used in the treatment of breast cancer, may become ineffective as treatment progresses due to the development of multidrug resistant (MDR) tumors. A major mechanism associated with MDR is increased P-glycoprotein (Pgp) expression. This study examined the abilities of the anti-estrogen tamoxifen (TAM) and the progestin medroxyprogesterone acetate (MPA) as well as cyclosporin A (CsA), a known resistance modifier, to enhance the cytotoxic effects of Adr on human breast epithelial cells (HBEC) in primary culture. Pgp and estrogen receptor (ER) expression were determined in each of the cultures by immunocytochemical assays using the monoclonal antibodies C219 and H222 Sp gamma, respectively. The Adr-sensitive, Pgp-, ER+ MCF-7 cell line and the Adr-resistant, Pgp+, ER- MCF7-AdrR cell line were used as controls. Primary cultures were categorized as HBEC from tissues with or without previous chemotherapy. Pgp was detected in 1 of the 15 cell cultures from tissues without previous chemotherapy and in 5 of the 6 cell cultures from tissues previously exposed to chemotherapy. Incubation with either CsA or MPA plus Adr enhanced Adr toxicity in Pgp+ but not Pgp- cell cultures, whereas TAM had no effect on the sensitivity of any of the cultures. Of the 21 primary cultures of HBEC, 3 were ER+. There was no correlation between the enhancement of Adr cytotoxicity and ER status. The data suggest that MPA as well as CsA may be useful as modifying agents in overcoming Pgp-associated multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1987

Alternating tamoxifen and medroxyprogesterone acetate in postmenopausal advanced breast cancer patients--short and long term endocrine effects.

The endocrine effects of alternating tamoxifen and medroxyprogesterone acetate have been evaluated in 26 post-menopausal patients with metastatic breast cancer. Endocrine evaluations included the RIA determination of plasma levels of sex-hormone binding globulin, follicle-stimulating hormone, luteinizing hormone, estradiol, prolactin, cortisol, and testosterone. The evaluation of the study parameters at different intervals during therapy indicates that with this schedule an alternate sequential effect on the endocrine system is achievable because each drug exerts its own endocrine activity that is completely reversed when the other drug is administered. We can hypothesize that the same alternate activity as seen on the endocrine system could be obtained also on other tissues and organs including tumors.

Breast Neoplasms↗
PubMed1992

Tamoxifen metabolism is altered by simultaneous administration of medroxyprogesterone acetate in breast cancer patients.

We have measured the levels of tamoxifen and three of its metabolites in the blood of patients receiving tamoxifen alone or combination therapy with tamoxifen and medroxyprogesterone acetate. Our results indicate that addition of the progestogen significantly alters the metabolism of tamoxifen over a six-month period. We suggest that the interaction between these drugs may involve additional sites (probably hepatic) besides the desired target tumour.

Aged↗
PubMed1992

Growth inhibition of 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors by controlled-release low-dose medroxyprogesterone acetate.

Since our previous findings had indicated that the androgenic steroid medroxyprogesterone acetate (MPA) exerts potent inhibitory effects on 7,12-dimethylbenz(a)anthracene (DMBA)-induced tumor growth, we have studied the effect of low doses of MPA released from Depo-Provera and from 50:50 poly[DL-lactide-co-glycolide] microspheres in the same DMBA-induced tumor model. The present data show that single subcutaneous injection of a 4-month controlled-release formulation of biodegradable 50:50 poly[DL-lactide-co-glycolide] microspheres containing 10 mg of MPA giving serum levels of 3.14 +/- 0.32 ng/ml (8.12 +/- 0.83 nM) MPA causes a maximal or near-maximal 60% inhibition of tumor growth measured 56 days later. Such data suggest that controlled-release formulations giving constant and low blood levels of MPA could be used for the treatment of breast cancer in women. Such a low concentration of MPA should avoid the side effects observed with the high doses of the compound.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Second and third line hormonotherapy in advanced post-menopausal breast cancer: a multicenter randomized trial comparing medroxyprogesterone acetate with aminoglutethimide in patients who have become resistant to tamoxifen.

In order to evaluate the efficacy of two different sequences of second and third line hormonotherapy in advanced post-menopausal breast cancer, 257 women aged 36-91 years (mean age: 63.6 years) who had become resistant to tamoxifen (TAM), entered into a multicenter randomized trial comparing two different regimens: 1) Aminoglutethimide (Ag) 500 mg/day with hydrocortisone supplementation from 30 to 60 mg/day; and 2) oral medroxyprogesterone acetate (MPA) 500 mg twice a day. 250 patients were evaluated following second line hormone therapy and, after cross-over, 128 following third line hormonotherapy. No significant difference was observed, during either second or third line therapies, for toxicity, survival, or response rate; however, in both second and third line therapies the median time to progression was significantly longer with Ag therapy.

Adult↗
PubMed1980

The influence of high doses of oral medroxyprogesterone acetate on glucose tolerance, serum insulin levels and adrenal response to ACTH. A study of 17 patients under treatment for endometrial cancer.

Seventeen women aged 55 to 76 years who had been treated for endometrial cancer by surgery or radiotherapy or a combination of both were given 300 mg of medroxyprogesterone acetate (MPA) daily by mouth. Before treatment and again during the 3rd week of treatment an oral glucose tolerance test (with measurement of serum insulin levels) and an ACTH-stimulation test were done. All blood glucose levels tended to be higher with MOA therapy and serum insulin levels were significantly increased 3 h after a glucose load. The rise of serum cortisol 30 min after ACTH-stimulation was significantly less with MPA therapy. Oral MPA thus appeared to have a glucocorticoid-like action.

Adrenal Glands↗
PubMed1981

Effect of medroxyprogesterone acetate on serum levels of LH, FSH, cortisol, and estrone in patients with endometrial carcinoma.

Medroxyprogesterone acetate (MPA) was administered orally for at least 6 months to 25 patients with endometrial adenocarcinoma starting 1 week after hysterectomy and bilateral ovariectomy. We measured serum concentrations of MPA during treatment and serum levels of LH, FSH, cortisol, and estrone before and during treatment with MPA. The serum levels of MPA 3--5 h after ingestion of a daily 100-mg dose of MPA at 08.00 h, varied considerably, the mean value (+/- SE) being 43 +/- 3.6 nmol/l range 15--119 nmol/l. Serum FSH levels rose after operation in the five premenopausal patients and remained elevated despite MPA treatment. In the 20 postmenopausal patients, however, initially high serum FSH and LH levels declined to half the starting values as a result of MPA treatment. After the administration of MPA for 6 months the mean serum cortisol and estrone concentrations at 08.00 a.m. had fallen to 78% and 82% of the mean values before treatment.

Adenocarcinoma↗
PubMed1994

Successful pregnancy in a patient with endometrial carcinoma treated with medroxyprogesterone acetate.

A 32-year infertile Japanese woman suffered from endometrial cancer, which was treated with repeated endometrial curettage and medroxyprogesterone acetate for 6 months. The patient then became pregnant and was delivered of a live-born male infant at 37 weeks gestation by cesarean section for placenta previa. At cesarean section there were no abnormal findings in the uterine cavity or other pelvic organs.

Adenocarcinoma↗
PubMed1987

Observations with Depo-Provera (medroxyprogesterone) in the management of renal tumours.

A total of 30 patients with renal tumours were started on Depo-Provera (medroxyprogesterone) in December 1981 and followed up for 17 to 44 months. The survivors were checked in July 1985. In 2 of the 13 metastasis-free patients deposits of lethal outcome had formed, survival time averaging 27 months. One of the 8 patients with local metastases had died of renal tumour, average survival time being 26 months. Among the 9 patients with distant metastases there are 2 with survival times of 42 and 44 months, respectively. The liver metastases confirmed by ultrasonography in the first, and in the vena cava in the second case at the time of surgery are no longer demonstrable. Survival time in the last-named group averages 14.5 months.

Adult↗
PubMed1997

Differential effects of estrogen and medroxyprogesterone on basal and stress-induced growth hormone release, IGF-1 levels, and cellular immunity in postmenopausal women.

We evaluated the influence of continual estrogen replacement therapy (ERT) as presently practiced by postmenopausal women with conjugated estrogens and medroxyprogesterone acetate (MPA) on the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and cellular immunity. Thirty-nine postmenopausal women were evaluated (12 on no replacement, 14 on estrogen only, and 13 on estrogen and MPA). In the women receiving only conjugated estrogens, increased GH levels and decreased IGF-1 levels were found, which replicated previous research and probably reflected estrogen inhibition of hepatic IGF-1 production with a secondary increase in GH release because of reduced feedback inhibition. In women taking both MPA and estrogen, GH was increased and the previously observed estrogen induced decrease in IGF-1 levels was inhibited. In order to determine the influence of ERT on psycho-social stress-induced GH release, math (mental stress) and speech (social stress) challenges were utilized, and they produced significant increases in heart rate in all three groups. The heart rate following stress was significantly enhanced by estrogen replacement. These stressors also led to increased GH secretion in the women taking estrogen and MPA, but not in the other two groups. Gonadal steroids and GH can influence cellular immunity. We observed that ERT in both groups was associated with significantly enhanced lymphocyte responsiveness to the T-cell mitogens phytohemaglutinin (PHA) and Conconavalin A (Con A), and basal GH levels were correlated with the PHA response in the estrogen only group. ERT did not influence natural killer (NK) cell activity. We also found significant differences in the steady-state expression of latent Epstein-Barr virus (EBV) with increased antibody titers in the women in the estrogen only group and lower antibody titers in the MPA plus estrogen group. GH levels were correlated with EBV antibody titers in the estrogen plus MPA group. This study supports the hypothesis that GH and immune modulation can be influenced by ERT in postmenopausal woman. Given the extant literature on the immune-enhancing effects of GH, these data suggest that ERT may slow the decline of GH secretion with aging, an event that has been implicated in immunosenescence.

Aged↗
PubMed2000

Medroxyprogesterone acetate and cancer cachexia: interleukin-6 involvement.

Cancer cachexia is a significant problem facing both patients and physicians. Many interventions have been tried in an attempt to remedy undernutrition in cancer patients. However, there is no convincing evidence that enteral/parenteral nutrition or the use of anabolic steroids is of any benefit in patients with cachexia. A recent prospective study revealed that oral medroxyprogesterone acetate (MPA) treatment reduces serum levels of interleukin (IL)-6, an important mediator of cancer cachexia, in patients with metastatic breast carcinoma regardless of response to the therapy. A decrease in serum IL-6 levels was well associated with subjective improvement in patients with metastatic breast carcinoma. Furthermore, clinically attainable concentrations of MPA can inhibit the growth of some human pancreatic carcinoma cells by inducing apoptosis in association with the phosphorylation of bcl-2. These results suggest that this agent may contribute to improved quality of life in patients with various cancers.

Cachexia↗
PubMed2001

Vascularization pattern of C6 glioma is modified with medroxyprogesterone acetate and ibuprofen in Wistar rat brain.

Beneficial effects of medroxyprogesterone acetate (MPA) in cancer therapy is partly mediated via its antiangiogenic activity. The same is true for the antitumoral action of non-steroidal antiinflammatory drugs. We have studied two liposoluble drugs, MPA and the analgesic ibuprofen, on glioma vascularization in vivo. In this study we have shown that, until the sacrifice at 27. day after tumor inoculation in the right hemisphere, MPA had a slight though insignificant activity to reduce the fatality of C6 glioma, growing in right cerebral hemisphere of male Wistar rats. But ibuprofen both alone or with MPA had no effect on survival with gavage application of a 30 mg/kg/day dosing regime. On histological analysis, intra- and peritumoral vessels were counted. Progesterone seemed to lower intratumoral, but to increase peritumoral vessels, especially glomeruloids, around the tumor mass. Coadministration of ibuprofen acted to suppress the peritumoral vessel increase, and to enhance lymphomonocytic infiltration around tumor vessels.

Animals↗
PubMed2005

Bone response to treatment with lower doses of conjugated estrogens with and without medroxyprogesterone acetate in early postmenopausal women.

Lower doses of conjugated estrogens (CE) alone or combined with lower doses of medroxyprogesterone acetate (MPA) increase mean bone mineral density (BMD) from baseline at the spine and hip in early postmenopausal women. However, not all women on therapy gain BMD. The incidence of continued bone loss (defined as a loss of BMD of > 2% from baseline) among women using lower doses of CE and CE/MPA is unknown. This randomized, double-blind, placebo-controlled, multicenter substudy of the Women's Health, Osteoporosis, Progestin, Estrogen (Women's HOPE) trial investigated the incidence of continued bone loss with lower-dose CE and CE/MPA. Eight hundred twenty-two healthy postmenopausal women with intact uteri received CE 0.625, CE 0.625/MPA 2.5, CE 0.45, CE 0.45/MPA 2.5, CE 0.45/MPA 1.5, CE 0.3, CE 0.3/MPA 1.5 (all doses in mg/day), or placebo for 2 years along with 600 mg/day of calcium. Changes from baseline in spine and total hip BMD were compared among treatment groups in an intent-to-treat analysis. At 12 months, < 10% of women on active treatment lost > 2% of spinal BMD (except CE 0.3/MPA 1.5 [15.6%]), compared with 41.2% of women on placebo. At 24 months, the percentages of women on active treatment who lost > 2% of spine BMD ranged from 4.5% with CE 0.45/MPA 1.5-15.6% with CE 0.3/MPA 1.5, compared with 55.2% of women taking placebo. More than 85% of women on active treatment did not experience continued BMD loss at the hip at 12 months and 24 months, in contrast to 30.6% of women on placebo at 12 months and 36.5% at 24 months. Women receiving active treatment who lost > 2% of spine or hip BMD also had a lesser reduction in biochemical markers of bone turnover. In summary, continued bone loss among early postmenopausal women treated with lower doses of CE or CE/MPA is uncommon.

Adult↗
PubMed2002

Pharmacologic doses of medroxyprogesterone may cause bone loss through glucocorticoid activity: an hypothesis.

A number of studies suggest that progestagens may have beneficial effects on bone metabolism. C(21) Progestin medroxyprogesterone acetate (MPA) is one of the most commonly prescribed progestins for hormone replacement therapy and in gynecologic practice. However, it appears that MPA with significant glucocorticoid (GC) activity may decrease bone density. In this review, we argue that bone loss associated with MPA administration is caused by decreased osteoblast differentiation as a result of MPA occupying the GC receptor, since increasing GC receptor occupancy beyond that reached at normal (= optimal) GC concentrations attenuates osteoblast differentiation. We propose that progestins with no GC activity may be a better choice for progestagen therapy to achieve more beneficial effects on bone metabolism.

Adolescent↗