The hormone therapy,Premarin, impairs hippocampus-dependent spatial learning and memory and reduces activation of new granule neurons in response to memory in female rats

Estrogens have been implicated as possible therapeutic agents for improving cognition in postmenopausal women and have been linked to neurodegenerative disorders such as Alzheimer's disease. However, the utility of Premarin (Wyeth Pharmaceuticals, Markham, ON, Canada), a conjugated equine estrogen and the most commonly prescribed hormone therapy, has recently been questioned. The purpose of this study was to investigate the effects of Premarin at 2 different doses (10 or 20 μg) on hippocampus-dependent spatial learning and memory, hippocampal neurogenesis, and new neuronal activation using a rodent model of surgical menopause. Rats were treated daily with subcutaneous injections of Premarin and trained on the spatial working/reference memory version of the radial arm maze. Premarin impaired spatial reference and working learning and memory, increased hippocampal neurogenesis, but either decreased or increased activation of new neurons in response to memory retrieval as indexed by the expression of the immediate early gene product zif268, depending on the maturity of cells examined. This activation of new neurons was related to impaired performance in Premarin-treated but not control-treated female rats. These results indicate that Premarin may be impairing hippocampus-dependent learning and memory by negatively altering the neurogenic environment in the dentate gyrus thus disrupting normal activity of new neurons.     

几种药物对诱导排卵周期中子宫内膜发育的影响

目的探讨辅助药物提高克罗米芬促排卵周期的妊娠率。方法将自然周期无成熟卵泡的不孕症患者240个CC+HMG促排卵周期随机分成A、B、C、D4组,A组不加用辅助药物,B、C、D分别加用补佳乐、倍美力、万艾可辅助治疗。观察子宫内膜、子宫动脉搏动指数、周期妊娠率。结果B、C两组子宫内膜情况明显改善,妊娠率较A组增高;D组子宫动脉搏动指数明显下降,妊娠率也较A组增高。结论CC+HMG促排卵的周期中,辅助应用补佳乐、倍美力或万艾可,可以改善子宫内膜状态或子宫血流,提高妊娠率。     

倍美力针剂治疗功能失调性子宫出血临床观察

目的评价静脉注射倍美力治疗中、重度功能失调性子宫出血的临床效果。方法对我院妇科门诊1998—2000年主诉为月经过多或月经持续不止者,诊断为功血的患者18例,予静脉推注倍美力25 mg,并记录注药前及注药后每隔1 h患者的阴道出血量,共观察8 h,随访1周。其中8例已婚者注药前行内膜活检术。用药前及7d后做超声检查测内膜厚度。结果患者在注药后出血明显减少,出血量随时间递减,尤其以2 h后出血量减少更明显,比0 h减少了89.7％。观察期间患者生命体征平稳。超声随访子宫内膜厚度用药前后无差异。结论静脉注射倍美力治疗功血是一种快速有效而安全的止血方法。     

妊马雌酮对大鼠体外培养成骨细胞作用的研究

目的 探讨妊马雌酮对大鼠体外培养成骨细胞的作用效果及对成骨细胞增殖的作用机理。方法 采用新生大鼠颅骨进行分离成骨细胞，并在含10％的胎牛血清DMEM中进行体外培养，分别加入高、低剂量妊马雌酮并与阴性组进行对照，用MTT法进行成骨细胞增殖和活性检测，用Western免疫印迹检测蛋白激酶C、抗凋亡蛋白Bag-1表达。结果 在培养24h后，妊马雌酮对培养成骨细胞增殖有明显的促进作用，培养到48h促进作用更为明显，表现出一定的时间相关性。妊马雌酮能明显提高体外成骨细胞PKC的表达量和抗凋亡蛋白Bag-1的表达量。结论 妊马雌酮可促进成骨细胞增殖并明显提高PKC和抗凋亡蛋白Bag-1的表达量是其防治骨质疏松的机理之一。     

Investigation of the temperature stability of premarin intravenous using liquid chromatography-mass spectrometry

Stability of Premarin^®Intravenous was investigated in dry and reconstituted forms by monitoring major components in samples for a period of six months, using liquid chromatography–mass spectrometry. The components, largely comprising a series of estrogen and steroid hormone sulfates, were considered to be fairly stable (variation ≤ 10%) for dry samples stored at room temperature and at 38 °C (100 °F) during the experimental time frame. However, significant variation, especially after 2 months of storage, was observed in reconstituted solutions. This variation was significantly larger for samples stored at elevated vs. room temperature. It was interesting to note that the concentration of equilenin sulfate increased over time, whereas that of other major components were seen to fluctuate and decrease. This phenomenon was partially explained by the conversion of equilin compounds into their corresponding equilenin forms, a phenomenon which was further investigated through a storage study with pure standard solutions and by tandem mass spectrometry.     

17α‐estradiol: a less‐feminizing estrogen

Alzheimer's disease (AD) is a major neurodegenerative disorder in the elderly and is the most common form of dementia. Approved AD drugs like donepezil and memantine provide some cognitive benefits to a subset of patients. However, the cost burden of AD will continue to increase in the absence of more effective drugs that treat its symptoms and ultimately slow its progression or delay or prevent its onset. A substantial number of studies report that 17β‐estradiol (E2; estrogen), a potent endogenous feminizing hormone, is neuroprotective. Unfortunately, negative results from the Women's Health Initiative (WHI) and its ancillary Memory Study (WHIMS) have overshadowed the positive data collected over several decades. Importantly, there are a number of reasons why the WHIMS results should not be generalized to less‐ or non‐feminizing estrogens. For the sake of argument, consider “non‐hormonal” or non‐feminizing estrogens to be worthwhile drug development candidates for AD and other neurodegenerative conditions because they have the potential to retain the positive neuroprotective activities of E2 while reducing the potential complications associated with feminizing hormones. Because the literature comparing estrogenicity of various estrogens is complex and spans multiple decades, we summarize herein the available hormonal comparisons of a common less‐feminizing estrogen, 17α‐estradiol (17αE2), with E2. 17αE2 is less feminizing than E2 in every published study where reasonable comparisons can be made. One‐half of these studies report a difference of two orders of magnitude or greater. In practice, compounds like 17αE2 may prove to be largely non‐feminizing at doses to be explored in human clinical trials. Moreover, other novel E2 analogues have been identified that are essentially devoid of feminizing actions. If the positive effects of feminizing estrogens on neurodegeneration prove useful in treating neurodegenerative diseases, less‐feminizing and non‐feminizing estrogen analogues may be even more effective, safer, and better tolerated. Drug Dev Res 69:177–184, 2008. © 2008 Wiley‐Liss, Inc.     

不同方案联合用药治疗围绝经期骨质疏松症的疗效观察

目的观察安宫黄体酮与天然结合雌激素(倍美力)联合氨基酸钙治疗围绝经期骨质疏松(OP)的疗效。方法将46例围绝经期骨质疏松患者随机分为观察组与对照组,后者以氨基酸钙+安宫黄体酮治疗,观察组加用黄体酮治疗,观察组在对照组的基础上加用倍力美进行序贯治疗。疗程为6个月,比较治疗前后骨密度、内分泌代谢指标的变化以及不良反应的发生率。结果治疗前两组患者的骨密度(BMD)、雌二醇(E2)、黄体生成素(LH)、碱性磷酸酶(ALP)及尿钙/肌酐(UCa/Cr)比值均无统计学差异;治疗后,二组BMD、ALP、UCa/Cr等指标均较治疗前明显改善(p<0.05),观察组骨密度高于对照组(p<0.05),且ALP及尿钙/肌酐比值均低于对照组(p<0.05)。治疗OP总体临床疗效比较显示观察组的疗效等级优于对照组,子宫内膜和乳腺体层厚度的变化、阴道出血及胀乳上的差异无统计学意义(p>0.05)。结论两种方案均能有效治疗围绝经期骨质疏松,倍美力加安宫黄体酮组较安宫黄体酮组能更好的改善骨密度及骨代谢相关指标,因此更加适合于治疗围绝经期骨质疏松症。     

Effect of a derived herbal recipe from an ancient Chinese formula,Danggui Buxue Tang,on ovariectomized rats

Ethnopharmacological relevance: Radix Astragali (root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, RA), Radix Angelicae sinensis (root of Angelica sinensis (Oliv.) Diels, RAS) and Folium Epimedii (leaves of Epimedium brevicomum Maxim., FE) are three of the extensively applied herbal remedies among traditional Chinese medicines for gynecological disorders and osteoporosis. A derivative herbal recipe—RRF, composed of the three medicines with a weight ratio of 5:1:5, is derived from a famous Chinese herbal formula—Danggui Buxue Tang (DBT). RRF has shown noteworthy protective effect in ovariectomized rats, which might represent a promising candidate for the treatment of perimenopausal disorders. The aim of this study was to investigate the herbal recipe RRF for its efficacy on perimenopausal disorders and the underlying mechanisms via ovariectomy (OVX) models.     

Pharmacology of conjugated oestrogens

Conjugated equine oestrogens (CEE) as in Premarin have been used for the treatment of climacteric complaints and the prevention of oestrogen deficiency symptoms since the early 1940's. The biological activity of Premarin's different components is described. Our knowledge of the pharmacokinetics of the nine structurally related oestrogen conjugates in CEE is reviewed. Particular attention is paid to the significance of the sulphate moiety. It is possible that the sulphate group is exerting a ‘protective’ effect against sudden oestrogenic stimulation.     

Secretory endometrium associated with breakthrough bleeding in estrogen-treated postmenopausal women.

Paradoxical secretory changes are described in benign endometria curetted for breakthrough bleeding in postmenopausal women on cyclic low dosage Premarin therapy. This purely histologic study, though favoring progesterone mediation, provides no definitive answer to the problem of pathogenesis. Future correlative morphologic and endocrine investigations are clearly indicated.