甲孕酮等四联疗法对癌症患者厌食的疗效观察

目的　探索对癌症患者食欲不振确有较好疗效的简便方法。进而为治疗恶病质奠定基础。方法　以孕激素国产甲孕酮、糖皮质激素地塞米松、组胺拮抗剂赛庚啶、胃肠动力剂普瑞博思组成的四联疗法 ,口服 1～ 2周 ,治疗 31例中晚期癌症患者的厌食。结果　食欲改善显效 2 9例 (93 .5 % ) ,有效 1例 (3 .2 % ) ,稳定 1例 (3 .2 % ) ,总有效率 96 .8%。结论　以小剂量甲孕酮为主的四联疗法对癌症患者厌食的疗效高 ,副作用少且价廉 ,简便易行适于各级医院及家庭推广应用。     

Bone density among long-term users of medroxyprogesterone acetate as a contraceptive

The bone density (BD) of 72 women using depot-medroxyprogesterone acetate (DMPA) for at least 1 year was compared with that of 64 women who were not users of hormonal contraceptives. The BD of lumbar spine, femoral neck, Ward’s triangle, and trochanter was measured by dual energy X-ray absorptiometry (DEXA-LUNAR DPX). Estradiol (E₂) concentrations were measured by radioimmunoassay (RIA). The mean age of DMPA users and nonusers was 31.8 and 31.1 years, respectively. Mean E₂ was 55.7 pg/mL for users and 149.9 pg/mL for controls (p <0.001). The BD was significantly lower for DMPA users than for controls in all sites (p <0.01). In addition, young adult T-scores in the lumbar spine were significantly lower among DMPA users than in controls (p <0.01). Differences were maintained in a subsample of 47 women per group, paired by age and body mass index (BMI). Multiple regression analysis showed that older age, lower BMI, and longer amenorrhea were associated with lower BD in the femoral neck, whereas lower BMI and use of DMPA were associated with lower BD in the lumbar spine.     

醋酸甲地孕酮联合化疗改善晚期肺癌患者的生活质量

目的 观察醋酸甲地孕酮合并化疗对晚期肺癌患者的生活质量影响.方法 甲地孕酮联合化疗作为治疗组,单纯化疗作为对照组进行临床研究,观察两组治疗前后进食、体重、Karnofsky评分变化.结果 治疗组中食欲改善占93.8%,体重增加率72.9%,Karnofsky分值提高66.7%,明显优于对照组(P＜0.01).结论 醋酸甲地孕酮联合化疗能显著改善晚期肺癌患者生活质量,且毒副反应较轻.     

甲孕酮对人卵巢癌3AO细胞C－erb B－2表达和形态学的影响

采用流式细胞和电镜技术，检测了甲孕酮处理前后人卵巢癌３ＡＯ细胞Ｃ－ｅｒｂＢ－２表达和形态学改变情况。结果表明甲孕酮可使部分３ＡＯ细胞Ｃ－ｅｒｂＢ－２表达下降；部分３ＡＯ细胞发生形态学改变，提示甲孕酮具有低调部分人卵巢癌３ＡＯ细胞Ｃ－ｅｒｂＢ－２表达和诱导部分３ＡＯ细胞分化的作用。     

Novel progesterone receptor modulators with gene selective and context-dependent partial agonism

Progesterone receptor (PR) modulators are used in contraception and post-menopausal hormone therapy, and are under clinical development for reproductive disorders such as uterine fibroids and endometriosis. Development of tissue selective PR modulators (SPRMs) with reduced side effects and improved pharmacology represents a large unmet medical need in the area of women’s health. One approach to addressing this need is to focus on the two PR isoforms PR-A and PR-B. In vitro and in vivo studies have revealed both distinct as well as overlapping gene regulation and functional responses of the two PR isoforms that suggests that PR-A selective modulators may retain a desired biological profile. We have identified a chemical series of 4-(4-chlorophenyl)-substituted piperazine carbimidothioic acid esters (PCEs) that have partial PR agonist activity and selectively activate some PR-A isoform regulated genes in T47D cells. However, full microarray analysis in these cells does not predict a global isoform selective profile for these compounds, but rather a unique gene-selective profile is observed relative to steroidal progestins. Using multiplexed peptide interaction profiling and co-activator recruitment assays we find that the mechanism of partial agonism is only partly defined by the ability to recruit known co-activators or peptides but also depends on the cell and promoter context of the gene under investigation. The data demonstrate global consequences of mechanistic and functional differences that can lead to selective biological responses of novel steroid receptor modulators.     

Mammary carcinogenesis induced byN-methyl-N-nitrosourea (MNU) and medroxyprogesterone acetate (MPA) inBALB/c mice

Summary MPA induces mammary tumors in virgin BALB/c mice with an average latency of 52 weeks. In order to determine whether the simultaneous administration of a chemical carcinogen, N-methyl-N-nitrosourea (MNU), shortened the latency of MPA-induced tumors, a total of 60 virgin female BALB/c mice were treated with either MNU+MPA or MNU or MPA. The experiment lasted 7 months. The incidence and latency of mammary tumors were significantly different between the 3 groups: 15/19 (79%) in MNU+MPA-treated mice with a latency of 154±19 days; 3/20 (15%) in MNU-treated mice with a latency of 179±7 days; 0/20 (tumors only start appearing after 10 months) in MPA-treated mice. Histologically, MNU+MPA-induced tumors were similar to the few tumors observed in MNU-treated mice: most of them were type B adenocarcinomas with a high degree of necrosis and calcification. Only one of the MNU+MPA-induced tumors expressed high levels of ER and PR and proved to be MPA-responsive in further passages. All the other tumors showed low or non-detectable levels of ER and PR together with an independent pattern of tumor growth. In MNU-treated mice the only tumor that was transplanted proved to be hormone independent and had low levels of PR and ER. In both MNU and MNU+MPA treated mice lung adenocarcinomas were detected. Cystic uterine glandular hyperplasias were observed in all animals. It can be concluded that MPA and MNU potentiate their carcinogenic effect in mammary gland.Abbreviations MPA Medroxyprogesterone Acetate - MNU N-methyl-N-nitrosourea - ER Estrogen Receptors - PR Progesterone Receptors     

肌注醋酸甲羟孕酮避孕对25～40岁妇女骨矿物质密度的影响

目的:探讨肌肉注射避孕药醋酸甲羟孕酮(DMPA)对骨矿物质密度的影响。方法:随机选择68例应用DMPA避孕的25～40岁女性,每3个月肌注DMPA1次,用药24个月;同时选择59例25～40岁从未应用激素避孕药的女性做为对照,应用双能X光线吸收法测量腰椎和股骨颈骨矿物质密度(BMD)。结果:用药组用药2年后腰椎和股骨颈平均BMD从基础值1.106±0.110g/cm2和0.913±0.100g/cm2下降到1.045±0.103g/cm2和0.855±0.100g/cm2,分别下降了5.5%和5.9%,与对照组相比明显降低(P<0.01)。结论:25～40岁女性肌注醋酸甲羟孕酮避孕导致骨矿物质密度降低。     

Double-blinded randomized controlled trial of estrogen supplementation in adolescent girls who receive depot medroxyprogesterone acetate for contraception

OBJECTIVE: The purpose of this clinical trial was to evaluate the effect of estrogen supplementation on bone mineral density in adolescent girls who received depot medroxyprogesterone acetate for contraception. STUDY DESIGN: One hundred twenty-three adolescents who began receiving depot medroxyprogesterone acetate injections every 12 weeks were assigned randomly to receive monthly injections of estradiol cypionate or placebo. The main outcome was bone mineral density that was measured by dual energy x-ray absorptiometry for 12 (n = 69) to 24 (n = 36) months. Participants, technicians, and physicians were blinded to estrogen treatment. RESULTS: Over the 24-month period, the percentage of change from baseline bone mineral density at the lumbar spine was 2.8% in the estradiol cypionate group versus -1.8% in the placebo group ( P <.001). At the femoral neck, the percentage of change from baseline bone mineral density was 4.7% in the estradiol cypionate group versus -5.1% in the placebo group ( P <.001). CONCLUSION: Our results suggest that estrogen supplementation is protective of bone in adolescent girls who receive depot medroxyprogesterone acetate injections.