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Medroxyprogesterone Acetate (medroxyprogesterone + acetate)
Kinds of Medroxyprogesterone Acetate Selected AbstractsBone Mineral Density in Adolescent Women Using Depot Medroxyprogesterone AcetateJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 2 2004Nancy H. Busen PhD Purpose To present current data on bone mineral density (BMD) in adolescent women using the long-acting contraceptive depot medroxyprogesterone acetate (DMPA) and also to discuss the importance of developing maximal bone mass during adolescence to offset bone demineralization later in life. Data Sources Research-based articles in the medical literature, review articles, and recommendations from the American Academy of Pediatrics and the National Osteoporosis Foundation. Conclusions Osteoporosis is a preventable disease that affects millions of Americans, particularly older women. Factors influencing the attainment and maintenance of peak bone mass during childhood and adolescence affect the future risk of fractures. Although longitudinal studies conducted on adolescent women using DMPA are very limited, findings suggest that adolescents are losing bone density during a time of expected bone accretion. Implications for Practice Clinicians must consider all the risks and benefits when prescribing contraceptives to adolescents. By themselves, the findings related to BMD and DMPA use by adolescents are not sufficient to limit the use of DMPA as a contraceptive method. However, clinicians must take into account the addition of other modifying factors associated with BMD that may contribute to overall bone loss in adolescent females. More prospective data on the long-term use of DMPA by adolescents are needed to determine DMPA's effect on bone loss and to determine if bone loss is transient in adolescents. [source] Combined bezafibrate and medroxyprogesterone acetate have efficacy without haematological toxicity in elderly and relapsed acute myeloid leukaemia (AML)BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2010Jim A. Murray Summary Acute myeloid leukaemia (AML) causes life-threatening deficits of functional blood cells that require management using red cell and platelet transfusion and aggressive treatment of neutropenic infections. Current cytotoxic chemotherapy further worsens the problem of reduced haemopoiesis and two-thirds of patients are too frail to tolerate intensive chemotherapy at all. Median survival amongst these patients remains at <3 months emphasizing the urgent need for anti-AML therapies that do not suppress haemopoiesis. Our laboratory studies showed combined Bezafibrate and Medroxyprogesterone acetate (BaP) had activity against AML without toxicity to normal stem cells. Here we report the safety and efficacy of BaP in 20 patients (19 AML, 1 high-risk myelodysplasia) for whom intensive chemotherapy was not an option. No patient exhibited haematological toxicity from BaP. Eleven patients took BaP alone for >4 weeks. One reverted from high risk myelodysplasia and remains transfusion independent after 201 weeks of therapy. Three AML patients gained major haematological improvements for 22,30 weeks; in one, marrow was available to document a partial AML response. Thus, this trial indicates that BaP therapy has potential for treatment of elderly and relapsed AML. [source] Reduced metabolites mediate neuroprotective effects of progesterone in the adult rat hippocampus.DEVELOPMENTAL NEUROBIOLOGY, Issue 9 2006The synthetic progestin medroxyprogesterone acetate (Provera) is not neuroprotective Abstract The ovarian hormone progesterone is neuroprotective in different experimental models of neurodegeneration. In the nervous system, progesterone is metabolized to 5,-dihydroprogesterone (DHP) by the enzyme 5,-reductase. DHP is subsequently reduced to 3,,5,-tetrahydroprogesterone (THP) by a reversible reaction catalyzed by the enzyme 3,-hydroxysteroid dehydrogenase. In this study we have analyzed whether progesterone metabolism is involved in the neuroprotective effect of the hormone in the hilus of the hippocampus of ovariectomized rats injected with kainic acid, an experimental model of excitotoxic cell death. Progesterone increased the levels of DHP and THP in plasma and hippocampus and prevented kainic-acid-induced neuronal loss. In contrast to progesterone, the synthetic progestin medroxyprogesterone acetate (MPA, Provera) did not increase DHP and THP levels and did not prevent kainic-acid-induced neuronal loss. The administration of the 5,-reductase inhibitor finasteride prevented the increase in the levels of DHP and THP in plasma and hippocampus as a result of progesterone administration and abolished the neuroprotective effect of progesterone. Both DHP and THP were neuroprotective against kainic acid. However, the administration of indomethacin, a 3,-hydroxysteroid dehydrogenase inhibitor, blocked the neuroprotective effect of both DHP and THP, suggesting that both metabolites are necessary for the neuroprotective effect of progesterone. In conclusion, our findings indicate that progesterone is neuroprotective against kainic acid excitotoxicity in vivo while the synthetic progestin MPA is not and suggest that progesterone metabolism to its reduced derivatives DHP and THP is necessary for the neuroprotective effect of the hormone. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source] Progestin upregulates G-protein-coupled receptor 30 in breast cancer cellsFEBS JOURNAL, Issue 10 2002Tytti M. Ahola A differential display method was used to study genes the expression of which is altered during growth inhibition induced by medroxyprogesterone acetate (MPA). A transcript of G-protein-coupled receptor 30 (GPR30) was upregulated by MPA in estrogen-treated MCF-7 breast cancer cells. Northern-blot analysis showed a progestin-specific primary target gene, which was enhanced by progesterone and different progestins, but not by dihydrotestosterone or dexamethasone, and which was abrogated by antiprogestin RU486. The dose-dependent and time-dependent increase in GPR30 mRNA expression correlated with MPA-induced growth inhibition in MCF-7 cells. Additionally, GPR30 upregulation by progestin correlated with growth inhibition when a comparison was made between different breast cancer cell lines. The ERK1/ERK2 pathway is capable of inducing progesterone receptor-dependent and ligand-dependent transcription. Thus we sought to establish whether different MAPK pathway inhibitors affect progestin-induced GPR30 mRNA regulation. The regulation of GPR30 was independent of ERK pathway activation, but the p38 pathway inhibitor induced GPR30 expression, which suggested a potential gene regulation pathway. These data demonstrate a new progestin target gene, the expression of which correlates with growth inhibition. [source] Steroid hormone receptors and coregulators in endocrine-resistant and estrogen-independent breast cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 4 2006Nanna Sarvilinna Abstract Resistance to hormonal therapy is often a problem in the treatment of breast cancer patients. It has been suggested that resistance could be explained by altered nuclear hormone receptor or coregulator levels or inappropriately increased agonist activity of selective estrogen receptor modulator (SERM). To test these hypotheses, we have established novel MCF-7 cell line-derived in vitro models of anti-estrogen- and progestin-resistant and estrogen-independent breast cancer by long-term culture in the presence of toremifene and medroxyprogesterone acetate (MPA) and in the absence of estradiol, respectively. Using cell growth and multiprobe ribonuclease protection assays, the expression of 5 nuclear hormone receptors and 9 coregulators as well as the alterations in the cell proliferation and target gene transcription in response to hormonal treatments were studied. Progesterone receptor (PR) expression was decreased and silencing mediator for retinoid acid and thyroid hormone receptors (SMRT) and amplified in breast cancer-1 (AIB1) expression increased in anti-estrogen-resistant cells. Estrogen caused PR and ER, upregulation in all cell lines, but we did not observe increased agonist activity of anti-estrogen measured by regulation of these estrogen target genes. Basal ER, levels and estrogenic growth response were decreased and p300/CBP-associated factor (pCAF) and AIB1 upregulated by estrogen in progestin-resistant cells, but coregulator levels were unchanged. Estrogen-independent cells were still estrogen-responsive and PR, nuclear receptor corepressor (N-CoR) and SMRT expression was increased whereas steroid receptor coactivator-1 (SRC-1a) and CBP-related protein p300 (p300) expression decreased. Their growth was inhibited by toremifene, but estradiol was able to abrogate this effect, which might have interesting clinical implications concerning the use of postmenopausal hormone replacement therapy. © 2005 Wiley-Liss, Inc. [source] Smoking and relation to other risk factors in postmenopausal women with coronary artery disease, with particular reference to whole blood viscosity and ,-cell functionJOURNAL OF INTERNAL MEDICINE, Issue 2 2003I. Os Abstract., Os I, Høieggen A, Larsen A, Sandset PM, Djurovic S, Berg K, Os A, Birkeland K, Westheim A (University of Oslo; Ulleval University Hospital; and Aker University Hospital, Oslo, Norway). Smoking and relation to other risk factors in postmenopausal women with coronary artery disease, with particular reference to whole blood viscosity and ,-cell function. J Intern Med 2003; 253: 232,239. Objectives., To investigate possible associations between smoking habits and other coronary risk factors in postmenopausal women with known coronary heart disease (CHD). Setting., The study was conducted at a university clinic. Subjects., A total of 118 postmenopausal women with CHD verified with angiography, consecutively recruited. Interventions., Conventional treatment for CHD. The women were randomized to hormone replacement therapy (HRT) with transdermal 17-, oestradiol and medroxyprogesterone acetate, or to a control group. Results., Smokers were younger (P = 0.005), had lower body mass index (P = 0.04) and lipoprotein Lp(a) levels (P = 0.02) compared with nonsmokers. Smokers had reduced ,-cell function (homeostasis model assessment, P = 0.006), whereas whole blood viscosity (WBV) was higher at all shear rates. WBV was not affected by HRT over a 12-month period. Oestrone levels were higher in smokers. Conclusions., Smoking adversely affects insulin secretion (,-cell function) and WBV in postmenopausal women with established CHD, which could be of importance as a mechanism for the increased risk of CHD in smokers. The importance of smoking as a risk factor, overrides the effect of Lp(a), which is lower in smokers compared with nonsmokers. [source] Effects of Long-Term Hormone Treatment and of Tibolone on Monoamines and Monoamine Metabolites in the Brains of Ovariectomised, Cynomologous MonkeysJOURNAL OF NEUROENDOCRINOLOGY, Issue 9 2006R. B. Gibbs The effects of long-term hormone treatment on monoamines and monoamine metabolites in different regions of the primate brain were examined and compared. Ovariectomised Cynomologous monkeys received daily oral administration of either conjugated equine oestrogens (CEE), CEE + medroxyprogesterone acetate (MPA), or a low or high dose of tibolone, for a period of 2 years. Tissue punches collected from frozen sections through various regions of the forebrain, midbrain, and hindbrain were assayed for levels of dopamine, dihydroxyphenylacetic acid (DOPAC), serotonin, 5-hydroxyindole acetic acid (5-HIAA), and norepinephrine by high-performance liquid chromatography. Few differences between hormone-treated animals and ovariectomised controls were observed. No statistically significant effects of CEE relative to controls were detected in any of the seven brain regions analysed. Animals treated with CEE + MPA showed significant reductions in 5-HIAA in the dorsal raphe nucleus, a significant reduction in dopamine in the hypothalamus, and a significant reduction in serotonin (5-HT) levels in area 8AD of the frontal cortex. Similar to CEE, no significant effects of tibolone relative to controls were detected; however, animals treated with high-dose tibolone showed a decrease in 5-HT levels in the frontal cortex that approached significance and was similar to the effect of CEE + MPA. Collectively, the findings suggest that long-term oral administration of these compounds has relatively few effects on the levels of dopamine, serotonin, and their primary metabolites in the primate brain. This differs from the significant effects on serotonergic and dopaminergic systems detected following parenteral treatment with oestradiol and progesterone, and likely reflects differences between the effects of treating with CEE + MPA versus oestradiol and progesterone on brain monoaminergic systems. [source] Bone Mineral Density in Adolescent Women Using Depot Medroxyprogesterone AcetateJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 2 2004Nancy H. Busen PhD Purpose To present current data on bone mineral density (BMD) in adolescent women using the long-acting contraceptive depot medroxyprogesterone acetate (DMPA) and also to discuss the importance of developing maximal bone mass during adolescence to offset bone demineralization later in life. Data Sources Research-based articles in the medical literature, review articles, and recommendations from the American Academy of Pediatrics and the National Osteoporosis Foundation. Conclusions Osteoporosis is a preventable disease that affects millions of Americans, particularly older women. Factors influencing the attainment and maintenance of peak bone mass during childhood and adolescence affect the future risk of fractures. Although longitudinal studies conducted on adolescent women using DMPA are very limited, findings suggest that adolescents are losing bone density during a time of expected bone accretion. Implications for Practice Clinicians must consider all the risks and benefits when prescribing contraceptives to adolescents. By themselves, the findings related to BMD and DMPA use by adolescents are not sufficient to limit the use of DMPA as a contraceptive method. However, clinicians must take into account the addition of other modifying factors associated with BMD that may contribute to overall bone loss in adolescent females. More prospective data on the long-term use of DMPA by adolescents are needed to determine DMPA's effect on bone loss and to determine if bone loss is transient in adolescents. [source] Malignant transformation of atypical endometrial hyperplasia after progesterone therapy showing germ-cell tumor-like differentiationPATHOLOGY INTERNATIONAL, Issue 6 2004Masanori Yasuda A 31-year-old woman was treated for atypical endometrial hyperplasia (AEH) with high-dose medroxyprogesterone acetate (MPA) therapy to preserve fertility. The AEH was found by repeated cytologic and histologic examinations to have completely disappeared with the therapy, but 3 years after her last follow up she required emergency surgery to treat severe genital bleeding. The hysterectomied uterus consisted mostly of poorly differentiated adenocarcinoma, G3 endometrioid type. Minor AEH was present in the exophytic area, in which some glands were cystically dilated. Part of the AEH had transformed into other histologic features with germ-cell-like differentiation, demonstrated by immunohistochemical positive reaction of placental alkaline phosphatase, alpha-fetoprotein, and human chorionic gonadotrophin. Recurrent AEH had undergone malignant transformation, resulting in the development of well- and poorly differentiated adenocarcinoma and tumor exhibiting germ-cell-like differentiation. The patient died of a massive tumor extension 7 months after surgery. The AEH before MPA therapy and the recurrent tumors had genetically different characteristics based on evidence of a loss of heterozygosity, detected at D8S1132 (chromosomal locus, 8q22.1) in the latter but not in the former, by analysis of genetic alterations using microsatellite markers. [source] Comparison of Selected Endocrine Parameters During Luteal Phase and Pregnancy in German Shepherd Dogs and BeaglesREPRODUCTION IN DOMESTIC ANIMALS, Issue 2009AR Günzel-Apel Contents Concentrations of progesterone, prolactin and relaxin in serum at predetermined intervals after ovulation (day 0) in non-pregnant and pregnant normocyclic Beagles were assayed and results compared with those observed in German Shepherd dogs (GSD) in a previous study. The goal was to determine possible reproductive hormone specificities related to the GSD breed. Furthermore, the effects of medroxyprogesterone acetate (MPA)-treatment in non-pregnant Beagles and of progesterone supplementation in pregnant Beagles on the hormone concentrations were examined. Mean concentrations of progesterone and prolactin were not different in the non-pregnant Beagles compared with those seen in non-pregnant GSD, except at days 50,60, when progesterone concentrations were found to be higher in Beagles (p < 0.05). Mean progesterone concentrations in pregnant Beagles at days 50,60 after ovulation (day 0) were higher (p < 0.05) than in GSD at that time, but not at earlier time periods. Prolactin concentrations were higher (p < 0.05) in Beagles throughout pregnancy compared with those in the GSD. Mean relaxin concentrations were numerically but not significantly lower in GSD than in Beagles throughout pregnancy. A 10-day oral MPA treatment did not affect progesterone or prolactin secretion in normocyclic non-pregnant Beagles. Medroxyprogesterone acetate serum concentrations were approximately 3.9 ng/ml during treatment and decreased to 0.42 and 0.021 ng/ml within 5 and 15 days after end of treatment, respectively. Intramuscular progesterone supplementation from days 30 to 40 in pregnant Beagles resulted in higher concentrations of progesterone in the 36- to 45-day time periods; prolactin and relaxin concentrations were not significantly affected during or after treatment compared with administration of placebo. The results suggest a tendency towards deficient luteal function in the short-cycle GSD bitches previously studied, which in pregnancy may reflect the observed decreased prolactin concentrations; the possibility that GSD relaxin secretion is deficiency required needs further study. As oral treatment with MPA did not affect progesterone and prolactin release, it may be useful for studying luteal function in pregnant bitches with suspected hypoluteoidism. [source] Effects of Hormone Replacement Therapy on Heart Rate Variability in Postmenopausal WomenANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 4 2001Aylin Yildirir M.D. Background: Hormone replacement therapy (HRT) is associated with reduced cardiovascular risk, but the underlying mechanism(s) are not fully understood. This study investigated the effects of a 6-month course of HRT on cardiac autonomic function parameters assessed by heart rate variability (HRV) in postmenopausal women. Methods: Forty-six healthy postmenopausal women (age 48 ± 5, range 40,60) with normal baseline electrocardiogram and negative exercise testing were enrolled. HRT, which was either 0.625 mg/day conjugated equine estrogen (CEE) plus 2.5 mg/day medroxyprogesterone acetate or 0.625 mg/day CEE alone were administered depending on hysterectomy status. Power spectral analysis of HRV was performed to calculate the low frequency component in absolute (LF) and normalized units (LF nu), high frequency component in absolute (HF), and normalized units (HF nu), and the LF/HF ratio. The standard deviation of RR intervals (SDNN) was calculated from the time series of RR intervals. Results: A 6-month course of HRT did not significantly alter resting heart rate (P > 0.05). The LF/HF ratio and LF nu significantly decreased after HRT (P = 0.022 and P = 0.032), whereas a significant increase was noted in the HF component of HRV (P = 0.043), indicating an improvement in cardiac autonomic function. The SDNN value, which was 28.8 ± 11.8 ms before HRT significantly increased to 35.4 ± 16.7 ms after 6 months (P = 0.011). Conclusion: Our results indicate that a 6-month course of HRT may significantly improve cardiac autonomic function parameters, a finding that could at least partly explain the potential cardiopro-tective effect(s) of HRT. A.N.E. 2001;6(4):280,284 [source] Hormone Replacement Therapy Shortens QT Dispersion in Healthy Postmenopausal WomenANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2001Aylin Yildirir M.D. Background: The aim of the study was to investigate the effects of hormone replacement therapy (HRT) on myocardial repolarization characteristics in postmenopausal women without coronary artery disease. Methods: Fifty-one consecutive healthy postmenopausal women (age 48 ±; 5) with negative exercise stress testing were prospectively enrolled into the study. Standard 12-lead electrocardiograms were obtained to evaluate the effects of 6 months of HRT on QT intervals, corrected QT intervals (QTcmax and QTcmin), QT dispersion (QTd), and corrected QTd (QTcd). Hormone regimens were continuous 0.625 mg/day conjugated equine estrogen (CEE) plus 2.5 mg/day medroxyprogesterone acetate (MPA) or 0.625 mg/day CEE alone depending on the hysterectomy status. Results: Although not statistically significant, CEE alone or in combination with MPA increased QTmax and QTmin values. However, the increase in QTmin was greater than the increase in QTmax, which resulted in statistically significant shortening of QTd (P = 0.007 in CEE and P < 0.001 in CEE + MPA groups). There was a significant prolongation of QTcmin values after 6 months in patients assigned to the CEE group (P = 0.001). The QTcd values were significantly shortened by HRT with both regimens (for CEE group 49 ±; 13 ms vs 38 ±; 13 ms, P = 0.01; for CEE + MPA group 49 ±; 14 ms vs 36 ±; 13, P < 0.001). Conclusion: HRT significantly decreased the QTd and QTcd in postmenopausal women without coronary artery disease, independent of the addition of MPA to the regimen. This improvement in myocardial repolarization may be one of the mechanisms of the favorable effects of HRT on cardiovascular system. However, the clinical implications of the shortening of QTd in postmenopausal women with HRT must be clarified. A.N.E. 2001; 6(3):193,197 [source] Decrease in glomerulonephritis and Th1-associated autoantibody production after progesterone treatment in NZB/NZW miceARTHRITIS & RHEUMATISM, Issue 6 2009Grant C. Hughes Objective While estrogen treatment exacerbates disease in models of systemic lupus erythematosus (SLE), the effects of progesterone are unclear. This study was undertaken to assess the effects of continuous progesterone treatment on autoantibody production and spontaneous glomerulonephritis (GN) in a mouse model of SLE. Methods Female (NZB × NZW)F1 (NZB/NZW) mice were treated with vehicle, 2 mg of depot medroxyprogesterone acetate (DMPA), or 10 mg of DMPA every 6 weeks. Survival, proteinuria, and serum anti,double-stranded DNA (anti-dsDNA) levels were monitored. At 39 weeks of age, kidneys were analyzed for abnormalities and glomerular accumulation of IgG subclasses and C3. Spleen leukocyte subsets were also analyzed. Results DMPA treatment reduced mortality in a dose-dependent manner in association with reduced proteinuria and glomerular damage. High-dose DMPA treatment resulted in a reduction of total serum IgG and IgG2a anti-dsDNA antibody levels, whereas IgG1 anti-dsDNA antibody levels were modestly increased. High-dose DMPA reduced glomerular accumulation of IgG1, IgG2a, IgG3, and complement, while low-dose DMPA decreased glomerular IgG2a and IgG3 levels compared with vehicle treatment. Conclusion Our findings indicate that treatment of premorbid female NZB/NZW mice with DMPA reduces mortality and attenuates spontaneous GN, likely through multiple mechanisms, including altered ratios of protective Th2-related IgG antibodies versus nephritogenic Th1-related IgG autoantibodies. Thus, estrogen and progesterone may have disparate effects on lupus autoimmunity, lending new significance to observed hormonal imbalances in patients with SLE. These data also suggest that treatment of SLE patients with DMPA may have therapeutic benefit. [source] Levonorgestrel-releasing intrauterine system (Mirena®) and Depot medroxyprogesterone acetate (Depoprovera) as long-term maintenance therapy for patients with moderate and severe endometriosis: A randomised controlled trialAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 3 2010Alice Yuen Kwan WONG Background:, Progestogen therapy has been found to be useful in controlling endometriosis. For patients after conservative surgery, long-term medical maintenance therapy should be sought to prevent recurrence and control symptoms. Levonorgestrel-releasing intrauterine system (LNG-IUS) may be a useful form of prolonged progestogen therapy for endometriosis. Aims:, To evaluate and compare the efficacy and safety of LNG-IUS to depot medroxyprogesterone acetate (MPA) for patients with moderate or severe endometriosis following conservative surgery, in terms of symptoms control, recurrence prevention and patients' acceptance. Methods:, A total of 30 patients after conservative surgery for endometriosis underwent randomisation. Of these patients, 15 received LNG-IUS and 15 had three-monthly depot MPA for three years. Their symptom control, recurrence, compliance and change in bone mineral density (BMD) were compared. The data were analysed using student's t -test and chi-square test. Results:, Symptoms and recurrence were controlled by both therapies. The compliance was better in LNG-IUS Group with 13 patients staying on their therapy versus seven patients in Depot MPA Group. LNG-IUS users had a significantly better change in BMD (+0.023, +0.071 g/cm2) than Depot MPA users (,0.030, ,0.017 g/cm2) in both hip and lumbar regions. Conclusions:, Levonorgestrel-releasing intrauterine system was effective in symptom control and prevention of recurrence. LNG-IUS users showed a better compliance. After three years, bone gain was noted with LNG-IUS, but bone loss with depot MPA. [source] Effects of tibolone and continuous combined hormone replacement therapy on bleeding rates, quality of life and tolerability in postmenopausal womenBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 8 2002J. Huber Objective To compare the effects of tibolone and conjugated equine oestrogens continuously combined with medroxyprogesterone acetate on bleeding rates, quality of life (QoL) and tolerability. Design A double-blind, randomised comparative trial. Setting Thirty-seven centres in six European countries. Population Five hundred and one postmenopausal women, under 65 years of age with an intact uterus. Interventions For 12 months, women received daily treatment with tibolone 2.5 mg (n= 250), or conjugated equine oestrogens 0.625 mg continuously combined with medroxyprogesterone acetate 5 mg (CEE,MPA, n= 251). Main outcome measures The primary outcome was vaginal bleeding rate during cycles 4,6. The secondary outcomes were vaginal bleeding rate during cycles 1,3, 7,9 and 10,13, cumulative bleeding rate, QoL, wellbeing, climacteric symptoms, urogenital complaints and tolerability. Results Treatment with tibolone led to a significantly lower bleeding rate during cycles 4,6 compared with CEE,MPA (15.0%vs 26.9%; P= 0.004); there was a similar difference during cycles 1,3. Both treatments improved QoL, wellbeing, climacteric symptoms and urogenital complaints. By intent-to-treat analysis, tibolone significantly improved sexual drive, interest and/or performance, compared with CEE,MPA at 12 months (P= 0.017). Although both treatments were well tolerated, there was a significantly lower incidence of breast tenderness with tibolone than CEE,MPA (2.4%vs 17.1%; P < 0.001). Conclusion The vaginal bleeding rate during cycles 4,6 was significantly lower in women using tibolone. Both treatments improved QoL, wellbeing, climacteric symptoms and urogenital symptoms. Breast tenderness was significantly less frequent with tibolone. [source] Combined bezafibrate and medroxyprogesterone acetate have efficacy without haematological toxicity in elderly and relapsed acute myeloid leukaemia (AML)BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2010Jim A. Murray Summary Acute myeloid leukaemia (AML) causes life-threatening deficits of functional blood cells that require management using red cell and platelet transfusion and aggressive treatment of neutropenic infections. Current cytotoxic chemotherapy further worsens the problem of reduced haemopoiesis and two-thirds of patients are too frail to tolerate intensive chemotherapy at all. Median survival amongst these patients remains at <3 months emphasizing the urgent need for anti-AML therapies that do not suppress haemopoiesis. Our laboratory studies showed combined Bezafibrate and Medroxyprogesterone acetate (BaP) had activity against AML without toxicity to normal stem cells. Here we report the safety and efficacy of BaP in 20 patients (19 AML, 1 high-risk myelodysplasia) for whom intensive chemotherapy was not an option. No patient exhibited haematological toxicity from BaP. Eleven patients took BaP alone for >4 weeks. One reverted from high risk myelodysplasia and remains transfusion independent after 201 weeks of therapy. Three AML patients gained major haematological improvements for 22,30 weeks; in one, marrow was available to document a partial AML response. Thus, this trial indicates that BaP therapy has potential for treatment of elderly and relapsed AML. [source] Differential effects of medroxyprogesterone acetate on thrombosis and atherosclerosis in miceBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2009Till Freudenberger Background and purpose:, The risk for cardiovascular events including venous and arterial disease and stroke is elevated after treatment with estrogen and medroxyprogesterone acetate (MPA) in postmenopausal women. Here, we have investigated the effect of MPA on arterial thrombosis and atherosclerosis in a murine model of atherosclerosis. Experimental approach:, Apolipoprotein E (ApoE),/, mice were bilaterally ovariectomized and treated with placebo, MPA (27.7 µg·day,1) and MPA + 17-,-oestradiol (E2; 1.1 µg·day,1) for 90 days, on a Western-type diet. Thrombotic response was measured in a photothrombosis model, platelet activation by fluorescence activated cell sorting (FACS) analysis (CD62P) and thrombin generation by the endogenous thrombin potential (ETP). Furthermore, aortic plaque burden and aortic root plaque composition were determined. Key results:, MPA and MPA + E2 -treated animals showed an aggravated thrombotic response shown by significantly reduced time to stable occlusion. The pro-thrombotic effect of MPA was paralleled by increased ETP whereas platelet activation was not affected. Furthermore, MPA + E2 reduced the number of cells positive for ,-smooth muscle actin and increased hyaluronan in the plaque matrix. Interestingly, total plaque burden was reduced by MPA but unchanged by MPA + E2. Conclusion and implications:, Long-term treatment with MPA and MPA + E2 increased arterial thrombosis despite inhibitory effects of MPA on atherosclerosis in ApoE-deficient mice. Increased thrombin formation, reduced smooth muscle content and remodelling of non-collagenous plaque matrix may be involved in the pro-thrombotic effects. Thus, MPA exhibits differential effects on arterial thrombosis and on atherosclerosis. [source] | |||||||||||||