Effect of raloxifene on the incidence of elevated low density lipoprotein (LDL) and achievement of LDL target goals in postmenopausal women

SUMMARY

Objective: To determine the extent to which raloxifene can maintain low density lipoprotein cholesterol (LDL-C) levels below 160?mg/dL or reduce elevated LDL-C levels to below lipidlowering goals in postmenopausal women.

Patients and methods: The Multiple Outcomes of Raloxifene Evaluation (MORE) osteoporosis treatment trial randomized 7705 postmenopausal women to placebo or raloxifene (60?mg or 120 mg) daily for a core treatment phase of 3 years. Changes in LDL-C and other serum lipids in a subset of women was a predefined secondary objective. This post-hoc analysis included the 2413 women who did not take lipid-lowering medications at any time during the trial and for whom LDL-C measurements were available. The threshold for high LDL-C (≥ 160?mg/dL) and LDL-C lipid-lowering goals were defined according to National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guidelines.

Results: The percent of women with LDL-C < 160?mg/dL was comparable between treatment groups at baseline (placebo, 57.5%; raloxifene 60?mg, 56.4%; raloxifene 120?mg, 56.8%). At 3 years, the percent of these women whose LDL-C had increased to above 160?mg/dL was significantly less in the raloxifene 60?mg and 120?mg groups compared with placebo by 65% (95% CI, 44%–78%) and 64% (95% CI, 43%–77%), respectively. Among women with elevated (defined for these analyses as ≥ 160?mg/dL) LDL-C at baseline, the proportion having elevated LDL-C at 3 years was significantly less in the raloxifene 60?mg and 120?mg groups compared with placebo by 32% (95% CI, 24%–40%) and 40% (95% CI, 32%–48%), respectively. Fifty percent and 13% of these women achieved LDL-C goals of <160?mg/dL and <130?mg/dL, respectively (P <0.001 vs. placebo for both) in the raloxifene 60?mg group, with similar results for the raloxifene 120?mg group.

Conclusions: In postmenopausal women with osteoporosis not taking concurrent lipid-lowering therapy, raloxifene significantly reduced the incidence of LDL-C ≥ 160?mg/dL and significantly increased the proportion achieving LDL-C goals for lipid-lowering compared with placebo. Whether these and other effects of raloxifene on cardiovascular risk markers will improve cardiovascular outcomes requires further study.     

三维能量多普勒超声对绝经后阴道流血子宫内膜疾病的诊断价值

目的：探究三维能量超声(3D-CPA)对绝经后阴道流血子宫内膜疾病的诊断价值。方法选取2011年10—2014年10月来该院就诊的绝经期阴道流血的患者168例,根据病理结果分为良性组和恶性组,应用3D-CPA测量两组患者子宫内膜体积(V)、血流指数(FI)、血管指数(VI)以及血管-血流指数(VFI)等三维能量多普勒血流参数。结果恶性组子宫内膜容积、VI、FI、VFI等血流参数值均大于良性组,且两组间差异有统计学意义（P＜0.05）;同时,168例患者中,三维能量多普勒超声检查诊断中148例符合病理检查结果,符合率达88.1%。结论3D-CPA可以直观的重建绝经期子宫内膜病变容积,将病变的子宫内膜血管分布和密度进行血流参数能量化,以帮助鉴别绝经期子宫内膜病变的良恶性,应作为绝经期子宫内膜疾病的首选筛查手段。     

Oestrogens and insulin secretion

There is a persistent perception that oestrogens have an adverse effect on carbohydrate metabolism. It might therefore be expected that their use would result in a corresponding increase in the incidence of diabetes. Recent evidence from clinical trials suggesting that women on postmenopausal oestrogen hormone replacement therapy (HRT) have a reduced incidence of type 2 diabetes therefore appears paradoxical. Short-term supraphysiological oestrogen administration has an adverse effect on glucose tolerance, resulting from suppression of first-phase insulin secretion and increased insulin resistance. Oestrogen-induced increases in glucocorticoid activity could account for these effects. Oestrogen-induced deterioration in glucose tolerance is, however, accompanied by a reduction in fasting glucose, an effect that could be accounted for by glucagon antagonism. These short-term effects contrast with long-term preservation of insulin secretion and glucose homeostasis by oestrogens. In animal studies, ovariectomy is associated with decreased insulin secretion and increased risk of diabetes, whereas oestrogen administration protects against diabetes and increases the insulin response to glucose. The mechanism is uncertain, but direct effects on the pancreas via steroid receptors or indirect effects via oestrogen-induced glucagon antagonism and subclinical increases in glucocorticoids and growth hormone could all contribute. Recent evidence that HRT increases the risk of cardiovascular disease suggests that it should not be used for the prevention of diabetes, but the mechanism responsible for this benefit merits further investigation and might lead to new therapies.Electronic Supplementary Material Supplementary material is available in the online version of this article at     

Radiographic damage associated with low bone mineral density and vertebral deformities in rheumatoid arthritis: The Oslo‐Truro‐Amsterdam (OSTRA) collaborative study

Objective

To examine variables associated with bone mineral density (BMD) and vertebral deformities in women with rheumatoid arthritis (RA) from 3 northwest European countries.

Methods

Female patients were recruited from rheumatology clinics in Oslo, Norway; Truro, UK; and Amsterdam, The Netherlands (150 total, 50 per center, age 50–70 years, disease duration ≥5 years). Demographic and clinical data were collected and BMD was measured by means of dual energy x‐ray absorptiometry. Associations between demographic and clinical measures on the one hand and BMD and vertebral deformities on the other were investigated by single and multiple regression analyses.

Results

Body mass index (BMI), medication use, RA damage measures, and BMD differed significantly between the 3 centers. Overall, Norwegian patients had the lowest BMI, used more corticosteroids and antiosteoporotic drugs, had lower joint damage measured by Larsen score, and lower BMD at both spine and hip. High age, low BMI, and high cumulative dose of corticosteroids (last 2 years) are related to low BMD. A high Larsen score was associated with low BMD at the hip. Larsen score was the independent determinant of vertebral deformities after correction for center, age, BMI, and BMD.

Conclusion

Data from 3 countries on BMD and vertebral deformities in female patients aged 50–70 years with longstanding RA are presented, demonstrating an association between radiographic RA damage and low BMD and between radiographic RA damage and vertebral deformities.

     

Saliva flow rates and clinical characteristics of patients with burning mouth syndrome: A case–control study

Burning mouth syndrome (BMS) is a chronic pain condition that most commonly affects postmenopausal women older than 50 years of age. Xerostomia is a common complaint among BMS patients. However, previous studies showed inconsistent findings regarding saliva flow rate reduction. This study examined saliva flow rates, degree of mucosal hydration, xerostomia, and clinical characteristics in BMS patients compared with healthy controls. Unstimulated whole saliva (USWS) was collected through passive drooling; residual mucosal saliva (RMS) was collected using filter paper strips. Stimulated whole saliva (SWS) was collected while chewing on gum base. Oral exam and self-report data were collected. A total of 50 women (22 BMS cases and 28 healthy controls) aged 50 years or older were included in the analysis of this study. Mean age was 62 years for cases and 56 years for controls (P = 0.05). Compared with controls, cases had significantly lower USWS flow rates (P < 0.001) and had a higher prevalence of xerostomia (P = 0.001), gastrointestinal disease (P < 0.001), and vaginal dryness (P = 0.01). These data show that oral and vaginal dryness are common among BMS patients. Further studies are needed to investigate potential pathophysiological mechanisms related to the quality of saliva and mucosal barrier status among these patients.     

Soy isoflavones improve cardiovascular disease risk markers in women during the early menopause

Background

Hormone replacement therapy may be beneficial for cardiovascular disease risk (CVR) in post-menopausal women. Soy isoflavones may act as selective estrogen receptor modulators. The aim of this study was to evaluate whether soy isoflavones had an effect on CVR markers.

绝经后骨质疏松症的临床中药治疗进展

绝经后骨质疏松症(postmenopausal osteoporosis, PMOP)是绝经后妇女的常见病及多发病, 主要因绝经后妇女的卵巢功能减退、雌激素水平下降,导致骨生成和骨吸收的代谢失衡。其特征是全身骨量减少和骨组织的微细结构破坏,临床主要表现为骨痛和骨折风险增加。大量研究表明,中医药可以提高绝经后骨质疏松症患者的骨密度,改善其疼痛症状,在防治绝经后骨质疏松症方面有其独特的优势。目前对绝经后骨质疏松症的研究主要分为单味中药的实验研究和复方中药的临床研究。通过对近5年国内外对绝经后骨质疏松症的中药治疗进行相关回顾,在单味中药方面,根据绝经后骨质疏松症的病机特点和用药频次,主要从骨测量指标、细胞因子变化、基因水平等方面综述了淫羊藿、杜仲、骨碎补3种常用中药的实验研究进展;在复方中药方面,普遍认为肾虚是绝经后骨质疏松的主要病机,此外与肝脾不足、血瘀痰浊等密切相关,主要论述了补肾法在临床上治疗绝经后骨质疏松中的应用,并探讨未来治疗绝经后骨质疏松症可能的研究方向。     

合用与换用阿立哌唑对已绝经女性精神分裂症患者催乳素水平影响的对照研究

目的:探讨已绝经女性精神分裂症合并高催乳素血症患者在合用与换用阿立哌唑时对其催乳素水平影响的对照研究。方法:对90例已绝经女性精神分裂症同时合并高催乳素血症的患者随机分为两组,合用组:45例,为原有药物联合阿立哌唑5mg/d治疗12周,换用组:45例,为原有药物更换为治疗剂量阿立哌唑(14.78±4.76mg/d)12周,治疗前和治疗后2、4、8、12周末分别测定催乳素水平并予以阳性和阴性量表(PANSS)和副反应量表(TESS)评定病情并进行比较。结果:根据重复测量结果,两组间PRL水平尚无统计学差异(F=3.507,P=0.064),但组间检验提示时间、研究组别有交互作用(P=0.002),即PRL的值受到时间和组别的共同影响。PRL随着时间的推移逐渐下降,且换用组下降的幅度大于合用组。两组间PANSS量表总分无统计学差异(F=0.145,P=0.705)。结论:无论合用阿立哌唑治疗组或是换用阿立哌唑治疗组,均能使已绝经女性精神分裂症患者的高催乳素水平下降,但换用阿立哌唑治疗,催乳素水平下降幅度更大。     

骨吸收抑制剂对卵巢切除骨折大鼠脂类代谢及骨钙素的影响

目的 研究骨吸收抑制剂对卵巢切除大鼠脂类代谢及骨钙素的影响.方法 雌性SD大鼠共140只,随机分为5组,每组28只.3月龄时选取其中4组大鼠行双侧卵巢切除建立绝经后骨质疏松症模型(OVX组、OVX+ EE2组、OVX+ Rlx组、OVX+ Aln组),另一组行假手术(Sham组).OVX组及Sham组皮下注射生理盐水,余下3组分别注射阿仑膦酸钠(Aln)、雷洛昔芬(Rlx)、雌激素(EE2),每周注射5次.分别在卵巢切除术后4周、10周及20周测定大鼠血脂、骨钙素及相关生化指标.结果 OVX组与Sham组相比体重增加,总胆固醇升高,甘油三脂降低,差异有统计学意义.应用雌激素及雷洛昔芬可有效调节卵巢切除导致的脂代谢紊乱,表现为体重下降及总胆固醇水平降低,差异有统计学意义(P＜0.05).不同时期OVX组骨钙素水平高于Sham组,差异有统计学意义(P＜0.05),其中阿仑膦酸钠组血清骨钙素水平最低.随着时间推移,Sham组及OVX组骨钙素呈现先上升再下降趋势,而OVX+EE2组、OVX+ Rlx组及OVX+ Aln组骨钙素表现为持续降低.结论 骨吸收抑制剂能够降低骨钙素水平,从而降低卵巢切除导致的高骨转换率,防止骨量丢失.此外,雌激素及雷洛昔芬在预防骨丢失的基础上还能够有效调节卵巢切除引起的脂类代谢紊乱.     

雷洛昔芬治疗绝经后妇女骨质疏松症的系统评价

目的 评价雷洛昔芬治疗绝经后骨质疏松症的疗效和安全性.方法 计算机检索MEDLINE、EMBASE、Cochrane图书馆临床对照试验注册中心、中国生物医学文献数据库、中国期刊全文数据库、数字化期刊全文数据库,并手工检索相关领域其他杂志.检索不受语种限制,时间截止至2012年11月.以患绝经后骨质疏松症的女性为研究对象、比较雷洛昔芬与安慰剂的随机对照试验,评价纳入研究的质量,用RevMan5.1软件进行Meta分析,并采用GRADE系统评价证据质量评价.结果 纳入11个随机对照试验,包括21028例患者.患者腰椎BMD升高达2.39%,且60 mg/d剂量提高腰椎BMD强于30 mg/d组,但60 mg/d与120 mg/d以上剂量组间效果无差别,能有效降低椎体骨折发生率,降低幅度达40%.基于上述系统评价结果,采用GRADE系统评价证据质量及推荐等级,证据总体质量评级为低质量,推荐强度为弱推荐.结论 雷洛昔芬治疗绝经后骨质疏松症疗效肯定,能提高腰椎骨密度,降低椎体骨折的风险,但尚无证据支持其能降低非椎体骨折发生率.