Hormones and bone health in postmenopausal women

Although it has been known for some time that estrogen deficiency is a major pathogenetic factor for osteoporosis related fractures among postmenopausal women, the capability of estrogen (with or without a progestin) to prevent fractures has often been questioned. The publication of the data from the two hormone clinical trials of the Women’s Health Initiative lays that discussion to rest. In both studies what have been considered a standard dose of conjugated estrogen with or without medroxyprogesterone acetate significantly reduced the risk of all fractures, including clinical vertebral fractures and hip fracture, in a population of postmenopausal women, average age 63 yr, not selected for osteoporosis by BMD. These results are particularly impressive given the difficulty of finding a fracture benefit in lower risk populations with other anti-resorptive agents. Surrogate data on lower doses of hormone therapy suggest a fracture benefit would be seen if studies were to be done. The other outcomes in WHI make it important to define appropriate clinical guidelines for use of hormone therapy for prevention of fractures in postmenopausal women.     

Mucosal co-delivery of ketorolac and lidocaine using polymeric wafers for dental application

The current study aimed to investigate the effectiveness of a developed sodium alginate and polyvinylpyrrolidone K-25 (PVP K-25) polymeric wafer for the co-delivery of ketorolac and lidocaine to soft tissues for healing and pain control following gingivectomy. Nine ketorolac/lidocaine lyophilized wafers were formulated and assessed for their hydration capacity, mucoadhesion ability and in vitro release profile to select the optimum system for further clinical investigation. Wafer F6 containing 2:1 sodium alginate to PVP K-25 and 10% glycerol showed optimum properties and was selected for the clinical study. Twenty patients were included in the study and the ketorolac/lidocaine wafer was assessed versus a market product. Visual pain analog was evaluated daily for the first week and wound healing index was evaluated for one week, two weeks and one month following the procedure. The developed ketorolac/lidocaine polymeric wafer proved to be an effective method of reducing pain and discomfort together with enhancing wound healing following gingivectomy.     

Issues to debate on the Women's Health Initiative (WHI) study. Hormone replacement therapy: an epidemiological dilemma?

In July 2002 the data of the prematurely stopped Estrogen plus Progestin study of the Women's Health Initiative (WHI) were presented in the Journal of the American Medical Association. The results of the Heart and Estrogen/Progestin Replacement Study (HERS/HERS II) were published in the same issue. The results of WHI for healthy postmenopausal women often are interpreted to be in analogy with the HERS/HERS II results for postmenopausal women with established coronary heart disease. As a result of HERS/HERS II and WHI, use of HRT in general became questionable. This is an unjustified judgement of HRT in general. This synoptic review and criticism of both studies will show the methodological weaknesses and their consequences and the reasons for limited generalizability of the study results from WHI and HERS/HERS II on normal HRT users.     

Menopause Management Knowledge in Postgraduate Family Medicine,Internal Medicine,and Obstetrics and Gynecology Residents: A Cross-Sectional Survey

Objective

To evaluate the knowledge of and nature of training for menopause management in postgraduate residents.

Use of calcium supplements and the risk of coronary heart disease in 52–62-year-old women: The Kuopio Osteoporosis Risk Factor and Prevention Study

Background

To analyse prospectively the effect of calcium or calcium + D supplementation on coronary heart disease (CHD) in 52–62-year-old women.

Methods and results

10,555 52–62-year-old women from the population-based Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) who did not have CHD at baseline were followed for nearly 7 years in 1994–2001. Information about use of calcium supplements and health events was obtained from two repeated questionnaires in 1989 and 1994. Information about causes of death during the follow-up was obtained from the Statistics Finland. Information about CHD and other disease morbidity before and during the follow-up was obtained from the Registry of Specially Refunded Drugs of the Finnish Social Insurance Institution (SII). Cox's proportional-hazards models were used to estimate the risk of CHD morbidity related to the use of calcium supplements. At baseline, 2723 women reported current use of calcium or calcium + D supplementation. During the follow-up, CHD was diagnosed in 513 women. Compared to non-users of calcium/calcium + D supplements, the multivariate adjusted hazard ratio (HR) of CHD was 1.24 (95% CI 1.02–1.52) in women who used these supplements. The multivariate adjusted HR for CHD morbidity in postmenopausal women who used calcium/calcium + D supplements was 1.26 (95% CI 1.01–1.57).

Conclusions

Calcium or calcium + D supplementation appears to increase the risk of CHD among women before old age.     

Vitamin D metabolism and cardiovascular risk factors in postmenopausal women

Objectives

The purpose of this review is to focus on the association of vitamin D and cardiovascular risk factors in postmenopausal women.

Methods

Review of the relevant literature and results from recent clinical studies as well as critical analysis of published results concerning the association of vitamin D and cardiovascular risk factors in postmenopausal women obtained from both a PubMed and individual searches.

Results and discussion

Both basic science and clinical studies support the protective role of vitamin D on cardiovascular health, although there are controversial results in the literature. Hypovitaminosis D is associated with disturbed glucose metabolism and pancreatic β-cell dysfunction, lipoprotein alterations, hypertension, overweight and obesity. The evidence highlights the importance of improving vitamin D status in the general population for the prevention of adverse long-term health risks, including cardiovascular health. The optimal vitamin D dose remains to be determined. However, correction of low vitamin D itself does not guarantee the prevention of these conditions.     

Alcohol and folate intake and breast cancer risk in the WHI Observational Study

Background Alcohol increases breast cancer risk. Epidemiological studies suggest folate may modify this relationship. Objective To examine the relationship among breast cancer, alcohol and folate in the Women’s Health Initiative-Observational Study (WHI-OS). Methods 88,530 postmenopausal women 50–79 years completed baseline questionnaires between October 1993 and December 1998, which addressed alcohol and folate intake and breast cancer risk factors. Cox proportional hazards analysis examined the relationship between self-reported baseline alcohol and folate intake and incident breast cancer. Results 1,783 breast cancer cases occurred over 5 years. Alcohol was associated with increased risk of breast cancer (RR = 1.005, 95%CI 1.001–1.009). Risk increased with consumption of alcohol (up to 5 g/d, adjusted HR = 1.10, 95%CI 0.96–1.32; >5–15 g/d HR = 1.14, 95%CI 0.99–1.31; and >15 g/d HR = 1.13 95%CI 0.96–1.32). We found no significant interaction between alcohol and folate in our adjusted model. Conclusions We found no evidence for folate attenuating alcohol’s effect on breast cancer risk in postmenopausal women. Our results may be due to misclassification of folate intake or the relatively short follow-up period.     

An association between gene expression and better survival in female mice following myocardial infarction

Following myocardial infarction, the prognosis for females is better than males. Estrogen is thought to be protective, but clinical trials with hormone replacement failed to show protection. Here, we sought to identify novel mechanisms that might explain this sex-based difference. By diverging from the traditional focus on sex hormones, we employed a conceptually novel approach to this question by using a non-biased approach to measure global changes in gene expression following infarction. We hypothesized that specific gene programs are initiated in the heart following infarction that might account for this sex-based difference. We induced small, medium, and large infarcts in male and female mice and measured changes in gene expression by microarray following infarction. Regardless of infarct size, survival was better in females, while mortality occurred 3-10 days following infarction in males. Two days following infarction, males developed significant ventricular dilation, the best predictor of mortality in humans. Three days following infarction, we measured gene expression by microarray, comparing male versus female and sham versus surgery/infarction. In general, our results indicate a higher relative level of gene induction in females versus males and identified programs for angiogenesis, extracellular matrix remodeling, and immune response. This pattern of gene expression was linked to less pathologic remodeling in female hearts, including increased capillary density and decreased fibrosis. In summary, our results suggest an association between improved survival and less pathologic remodeling and the relative induction of gene expression in females following myocardial infarction.     

Estrogen and urinary incontinence

Hormone therapy (HT) has been one of the most commonly used methods to treat postmenopausal disorders including lower urinary tract symptoms such as urinary incontinence (UI). Although it has been suggested that HT improves urinary tract symptoms, little evidence has so far been presented to support this. Recently however, large randomized clinical trials have shown the adverse effects of estrogen on UI and indicate that HT should not be used for prevention or relief of UI in postmenopausal women. Here we review the effects of HT on UI in the light of these clinical trials.     

美国妇女健康引导项目中性激素补充疗法研究简介

目的：了解妇女健康引导项目(WHI)中有关性激素补充疗法(HRT)的概况和已经公布的成果。方法：通过3个有关WHI项目网站介绍的内容和提供的线索搜集资料，简介有关研究的概况、设计、结果或进程。结果：WHI项目包含预防措施的随机对照临床试验(WHI-RCT)、识别疾病预示因子的观察性研究(WHI-OS)和发展健康行为方式的社区预防研究(WHI—CPT)。主要的关于HRT的研究包括：已经公布结果的WHI—RCT-HRT健康妇女长期应用主要利弊研究、WHI-RCT-HRT健康相关生命质量研究、WHI-RCT-HRT炎症生物学指标的研究；正在进行的或将要公布结果的WHI—RCT-雌激素对子宫切除妇女利弊研究、WHI记忆研究(WHMS)、WHI认知龄研究(WHISCA)、WHI功能退化研究(WHISE)等研究。已经公布的研究结果显示：健康的绝经后妇女长期(5、2年)服用雌-孕激素的总体风险大于益处；对于绝经后妇女，雌一孕激素对健康相关性生命质量的影响没有临床意义；在健康的绝经后妇女中。C反应蛋白和白细胞介素6可以独立地预示冠心病事件，HRT使C反应蛋白的水平增加。结论：WHI项目中有关HRT的研究的成果具有里程碑的意义，已经且将会不断地丰富对HRT的医疗作用和不良反应的认识；已经完成的、正在进行的其他随机对照临床试验及其系统性综述或Meta分析是较为全面认识HRT的重要文献；直接阅读有关医疗卫生组织或机构对合理应用HRT的建议和指南是了解和解读许多或一系列HRT研究临床意义的一条“捷径”。