Selección de Resúmenes de Menopausia

                      

Semana del 24 al 30 de Octubre de 2007

Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

 

 

Climacteric. 2007 Oct;10 Suppl 2:47-53.

Breast cancer prevention.

Russo J, Balogh G, Russo IH.

Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, PA, USA.

We have developed a new approach for breast cancer prevention, capitalizing in the preventive effect of early first full-term pregnancy, hormonally induced differentiation and our ability to identify specific genomic signatures that allow us to predict risk reduction. Early pregnancy imprints in the breast permanent genomic changes or a 'signature' that reduces the susceptibility of this organ to cancer. At cellular level, what we have achieved is the shifting of the Stem Cell 1 population, highly susceptible to cancer, to a population of Stem Cell 2 that is refractory to carcinogenesis. In a case-control study, we have compared the gene expression profile in normal breast tissue from nulliparous and parous postmenopausal women with (case) and without (control) breast cancer. We have determined that early first full-term pregnancy induces a specific genomic signature in the postmenopausal breast that is the biomarker for the Stem cell 2. The Stem cell 2 contains specific genes controlling transcription, RNA processing, immune response, apoptosis and DNA repair. We have further detected in the plasma, using an ELISA assay, the proteins coded by the gene signature. We are developing clinical trials to demonstrate the proof of the principle that r-hCG can induce in the human breast a genomic signature of the Stem cell 2. This is a concept that challenges the currently available chemopreventive agents that need to be given for extended periods for maintaining the suppression of a specific metabolic pathway or the abrogation of the function of an organ.

 

 

Climacteric. 2007 Oct;10 Suppl 2:27-31.

Menopause and stroke and the effects of hormonal therapy.

Lobo RA.

Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York.

The incidence of stroke increases substantially after menopause, and in the United States it is the third leading cause of death. Data exist suggesting that women have worse outcomes for stroke than do men. Trials of aspirin use further suggest that there is a gender difference regarding stroke. While men may have a coronary benefit from aspirin, postmenopausal women do not; yet ischemic stroke may be decreased in women but not in men. Among the traditional risk factors for stroke (such as smoking, hypertension, diabetes, obesity), hormonal therapy (HT) has been suggested to be a risk as well, although the data are not consistent. The previous Position Statement of the IMS published in 2004 was relatively silent on the issue of stroke. The annual rate of stroke in women increases rapidly with aging in postmenopausal women. While the rate is approximately 0.6-0.8/1000/year at age 50-59, it is over 2/1000 after age 60. In white women in the USA, it is 4.2/1000 at 65-74 years of age, and 11.3/1000 between ages 75 and 84 years. Thus, in trials such as the Women's Health Initiative (WHI), most of the strokes occurred in older women. Both the conjugated equine estrogen/medroxyprogesterone acetate (CEE/MPA) and CEE-alone trials in the WHI reported an increased risk of stroke in the entire population using nominal statistics: 1.41 (95% confidence interval (CI) 1.07-1.85) and 1.39 (95% CI 1.10-1.77), respectively. The increased risk was related to ischemic stroke and not hemorrhagic stroke. The absolute risk for the entire population was 0.8/1000 and 1.2/1000 woman-years (<1/1000 signifies a 'rare' event using the CIOMS classification). However, the risk was not increased in the 50-59-year-old age group, although the numbers are small. Here, the background prevalence of stroke is much lower as noted above. The results of the observational trial of the WHI were not consistent with the randomized clinical trial data and were more in keeping with older observational data showing no increased risk of stroke. The authors reconcile these differences by suggesting differences in the timing of initiation of hormones, which was at an earlier age in the observational cohort. Several recent observational studies, which will be presented, show no increased risk of ischemic stroke in younger cohorts, but possibly an increase in the risk of transient ischemic attack. These recent studies suggested the risk to be less with lower doses of estradiol < or =1 mg and to be consistent with older studies showing no risk with doses < 0.625 mg CEE. In addition, the risk was possibly lower with non-oral therapy, and was reduced if started prior to menopause. The existence of hypertension was shown to substantially increase the risk. However, data on progestogen use versus unopposed estrogen have not been consistent. At the same time, a recent body of evidence from basic science studies has reaffirmed the neuronal and stroke protective effects of estrogen. Thus, the discrepancy between these data and clinical data showing no benefit or increased risk of stroke remains to be explained. Recent trials in older women with osteoporosis have suggested an increased risk of stroke with tibolone and of stroke mortality with raloxifene. In conclusion, the current data suggest no increased risk of stroke with hormone therapy in younger (50-59 years) normotensive postmenopausal women, particularly when lower doses are prescribed soon after menopause.

 

 

Climacteric. 2007 Oct;10 Suppl 2:2-15.

Recent epidemiological evidence relevant to the clinical management of the menopause.

Shapiro S.

Department of Family Medicine and Public Health, University of Cape Town Medical School, South Africa.

BACKGROUND: The 2003 Workshop of the International Menopause Society considered the epidemiological evidence collected up to that time on the effects of female hormone therapy (HT). New evidence relevant to the clinical management of the menopause has since been published. OBJECTIVES: To summarize the new evidence, to offer critiques of important recently published studies, and to consider the implications for clinical practice. CARDIOVASCULAR DISEASE: Recent evidence from two studies, the Women's Health Initiative (WHI) clinical trial, and an observational component of the WHI, suggests that combined hormone therapy (estrogen plus progestin) (CHT) initially increases the risk of coronary heart disease (CHD), stroke, and venous thromboembolism (VTE), followed by a decline. For CHD, the hazard ratio exceeds 1.0 during the first year of follow-up, followed by a progressive decline to <1.0 after >5 years. Other studies show the same trend. BREAST CANCER: In the WHI data, recent evidence suggests that estrogen therapy (ET) reduces the overall risk of breast cancer, predominantly ductal and localized cancer. Evidence from the Million Women Study (MWS) now suggests that the previously reported association of HT with breast cancer is concentrated on tumors with lobular or tubular histology; the risk of ductal cancer is also increased, but to a lesser degree. The risks of these outcomes are higher for CHT than for ET. Other recent studies broadly accord with the MWS observations. OTHER OUTCOMES: Among CHT recipients, the WHI findings of reduced risks of fractures and colorectal cancer, and an increased risk of VTE, remain unchanged. Evidence from other studies now suggests that protracted exposure to CHT may increase the risk of ovarian cancer, and reduce the risk of endometrial cancer. INTERPRETATION: The recently published WHI findings for CHD and breast cancer are of major importance. For CHD, detection bias may have resulted in systematic overestimation of the duration-dependent hazard ratios. If so, there may be no initial increase in the risk, and prolonged use may be associated with a decreased risk. The hypothesized protective effect of HT may have been missed in the WHI study. For breast cancer, the WHI evidence now suggests a protective effect of ET. Tumors with lobular or tubular histology tend to be small, slow-growing, low-grade, and well differentiated. Such tumors may be more susceptible to detection bias, and that bias has not been ruled out as an alternative explanation of the higher risks among CHT recipients, observed in the MWS. The possibility of detection bias in that study, and in other observational studies, is supported by the decreased risk of breast cancer observed among ET recipients in the WHI clinical trial. Based on the present evidence, it is impossible to determine whether HT, or specific forms of HT, increase, decrease, or have no effect on the overall risk of breast cancer, or of specific types of breast cancer. Other evidence raises the possibility that prolonged CHT may increase the risk of ovarian cancer, and decrease the risk of endometrial cancer. Additional studies are needed to confirm those findings. If, as now seems possible, CHT in fact reduces the risk of CHD, and has little or no effect on the risk of breast cancer, or if ET decreases the risk, the clinical and public health implications would be major. However, the picture is confused. In view of new, but uncertain, findings concerning CHD and breast cancer, clinicians will have to continue to use clinical judgment, informed by a critical evaluation of the epidemiological evidence, in the management of the menopause.

 

 

Qual Life Res. 2007 Oct 24; [Epub ahead of print]

The association between body mass index and health-related quality of life: data from CaMos, a stratified population study.

Hopman WM, Berger C, Joseph L, Barr SI, Gao Y, Prior JC, Poliquin S, Towheed T, Anastassiades T; CaMos Research Group.

Clinical Research Centre, Kingston General Hospital, Angada 4, K7L 2V7, Kingston, ON, Canada.

BACKGROUND: Deviation from normal weight is associated with health risks, but less is known about the association between weight and health-related quality of life (HRQOL). We investigated this in the context of a population-based study, using a standard five-category weight classification system based on body mass index (BMI). METHODS: The Canadian Multicentre Osteoporosis Study is a randomly selected sample of men and women over 25 years of age from nine centres across Canada. Data were obtained by interview, and height and weight were measured and used to calculate BMI. HRQOL was measured using the SF-36. Multivariable linear regression was used to identify the association between BMI category and SF-36 scores after controlling for potential confounders. RESULTS: Complete data were available for 6302 women and 2792 men. Mean BMI for every age and gender group exceeded healthy weight guidelines. For women, being underweight, overweight or obese was associated with poorer HRQOL in most SF-36 outcomes while for men, this was associated with poorer HRQOL in some domains and with higher HRQOL in others. CONCLUSIONS: A significant proportion of the population may be putting their health at risk due to excess weight, which may have a substantial negative effect on HRQOL, particularly in women. This underscores the need for continued public health efforts aimed at combating overweight and obesity.

 

 

Arch Intern Med. 2007 Oct 22;167(19):2122-7.

Combined effect of low-risk dietary and lifestyle behaviors in primary prevention of myocardial infarction in women.

Akesson A, Weismayer C, Newby PK, Wolk A.

Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 17177 Stockholm, Sweden. Agneta.Akesson@ki.se

BACKGROUND: Limited data are available on the benefit of combining healthy dietary and lifestyle behaviors in the prevention of myocardial infarction (MI) in women. METHODS: We used factor analysis to identify a low-risk behavior-based dietary pattern in 24 444 postmenopausal women from the population-based prospective Swedish Mammography Cohort who were free of diagnosed cancer, cardiovascular disease, and diabetes mellitus at baseline (September 15, 1997). We also defined 3 low-risk lifestyle factors: nonsmoking, waist-hip ratio less than the 75th percentile (< 0.85), and being physically active (at least 40 minutes of daily walking or bicycling and 1 hour of weekly exercise). RESULTS: During 6.2 years (151 434 person-years) of follow-up, we ascertained 308 cases of primary MI. Two major identified dietary patterns, "healthy" and "alcohol," were significantly associated with decreased risk of MI. The low-risk diet (high scores for the healthy dietary pattern) characterized by a high intake of vegetables, fruit, whole grains, fish, and legumes, in combination with moderate alcohol consumption (>/= 5 g of alcohol per day), along with the 3 low-risk lifestyle behaviors, was associated with 92% decreased risk (95% confidence interval, 72%-98%) compared with findings in women without any low-risk diet and lifestyle factors. This combination of healthy behaviors, present in 5%, may prevent 77% of MIs in the study population. CONCLUSION: Most MIs in women may be preventable by consuming a healthy diet and moderate amounts of alcohol, being physically active, not smoking, and maintaining a healthy weight.

 

 

Arch Intern Med. 2007 Oct 22;167(19):2091-102.

Adiposity, adult weight change, and postmenopausal breast cancer risk.

Ahn J, Schatzkin A, Lacey JV Jr, Albanes D, Ballard-Barbash R, Adams KF, Kipnis V, Mouw T, Hollenbeck AR, Leitzmann MF.

National Cancer Institute, National Institutes of Health, EPS, USA. ahnj@mail.nih.gov

BACKGROUND: Obesity is a risk factor for postmenopausal breast cancer, but the role of the timing and amount of adult weight change in breast cancer risk is unclear. METHODS: We prospectively examined the relations of adiposity and adult weight change to breast cancer risk among 99 039 postmenopausal women in the National Institutes of Health-AARP Diet and Health Study. Anthropometry was assessed by self-report in 1996. Through 2000, 2111 incident breast cancer cases were ascertained. RESULTS: Current body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared), BMI at ages 50 and 35 years, and waist-hip ratio were associated with increased breast cancer risk, particularly in women not using menopausal hormone therapy (MHT). Weight gained between age 18 years and the current age, between ages 18 and 35 years, between ages 35 and 50 years, and between age 50 years and the current age was consistently associated with increased breast cancer risk in MHT nonusers (relative risk [RR], 2.15; 95% confidence interval [CI], 1.35-3.42 for a >/=50-kg weight gain between age 18 years and the current age vs stable weight) but not in current MHT users. Risk associated with adult weight change was stronger in women with later vs earlier age at menarche (RR, 4.20; 95% CI, 2.05-8.64 for >/=15 years vs RR, 1.51; 95% CI, 1.11-2.06 for 11-12 years; P = .007 for interaction). In MHT nonusers, the associations with current BMI and adult weight change were stronger for advanced disease than for nonadvanced disease (P = .009 [current BMI] and .21 [weight gain] for heterogeneity) and were stronger for hormone receptor-positive than hormone receptor-negative tumors (P < .001 for heterogeneity). CONCLUSION: Weight gain throughout adulthood is associated with increased postmenopausal breast cancer risk in MHT nonusers.

 

 

Br J Clin Pharmacol. 2007 Oct 22; [Epub ahead of print]

Issues concerning the use of hormone replacement therapy and risk of fracture: a population-based, nested case-control study.

Corrao G, Zambon A, Nicotra F, Conti V, Nappi RE, Merlino L.

Research Center for Reproductive Medicine, Department of Morphological, Eidological and Clinical Sciences, University of Pavia, Pavia, Italy.

What is already known about this subject * Several studies have consistently shown that hormone replacement therapy (HRT) can reduce the risk of fracture. * The questions that are still controversial include the duration of treatment needed, the duration of the protective effect after treatment is stopped, and the influence of age at which treatment is initiated. What this study adds * Our findings suggest that HRT should be continued for long periods to achieve optimal protection from fracture. * The fracture reducing potential of HRT seems to disappear after a few months without treatment and might mainly act in women who begin therapy at an older age. Aims To investigate the effect of duration, how recently it has been used, and age at start of hormone replacement therapy (HRT) and the risk of bone fracture. Methods A population-based, nested case-control study was conducted in Lombardia, Northern Italy. The 78 294 women aged 45-75 years who received at least one HRT prescription during 1998-2000 were followed until 2005. Cases were women who experienced bone fracture during follow-up. Up to six controls were randomly selected for each case from the cohort after matching for age and date of cohort entry. The odds ratio of fracture associated with the use of HRT was estimated by conditional logistic regression. Results One thousand one hundred and seventy-four cases and 6760 controls were included. Compared with women who took HRT for less than 2 months, those who were treated for more than 20 months had an odds ratio (OR) of 0.80 (95% confidence interval 0.65, 0.99). This risk reduction was still significant among current HRT users (OR 0.71, 95% CI 0.55, 0.90) and in women who began therapy at the age of 55-65 years (OR 0.63, 95% CI 0.42, 0.94) or 65-75 years (OR 0.56, 95% CI 0.32, 0.99). There was no statistical evidence of a protective effect for women who had stopped treatment more than 6 months previously or those who began HRT at the age of 45-55 years. Conclusions HRT should be continued for long periods to achieve an optimal protection from fracture. The fracture reducing potential of HRT seems to disappear after a few months without treatment and might mainly act in women who begin therapy at older age.

 

 

J Sex Med. 2007 Oct 24; [Epub ahead of print]

Comparison of the Effects of Hormone Therapy Regimens, Oral and Vaginal Estradiol, Estradiol + Drospirenone and Tibolone, on Sexual Function in Healthy Postmenopausal Women.

Cayan F, Dilek U, Pata O, Dilek S.

Department of Obstetrics and Gynecology, University of Mersin School of Medicine, Mersin, Turkey.

Introduction. Sexual dysfunction is more prevalent in postmenopausal women. Aims. To prospectively evaluate and compare the effects of hormone therapy (HT) regimens, oral and vaginal estradiol, estradiol + drospirenone and tibolone, on sexual function in healthy postmenopausal women. Methods. The study included 169 consecutive healthy postmenopausal women, and the women were divided into two groups: 111 women received HT, and 58 women received no treatment and served as a control group. As an HT, 23 women with surgically induced menopause received oral 17-beta estradiol. The rest of the women with natural menopause were prospectively randomized: 22 received oral 17-beta estradiol + drospirenone daily, 42 received oral tibolone, and 24 received vaginal 17-beta estradiol. Sexual function was evaluated with a detailed 19-item questionnaire, the female sexual function index, including sexual desire, arousal, lubrication, orgasm, satisfaction, and pain. Main Outcome Measures. The differences in sexual function were compared before and 6 months after the treatment in all women. Results. Total sexual function score increased from 19.81 +/- 7.15 to 22.9 +/- 6.44 in the HT group and decreased from 21.6 +/- 8.69 to 17.6 +/- 5.7 in the control group, revealing a significant difference from baseline to post-treatment between the two groups (P = 0.000). The highest improvement in total score and arousal was achieved with the oral 17-beta estradiol (P = 0.000 and P = 0.000, respectively). The highest improvement in lubrication was achieved with the oral and vaginal 17-beta estradiol groups (P = 0.000). The highest improvement in orgasm was achieved with the tibolone group (P = 0.000). The highest improvement in pain was achieved with the oral and vaginal 17-beta estradiol groups (P = 0.000). Conclusions. HT provided significant improvement in sexual function compared to women receiving no treatment, and therefore, HT regimens should be suggested for improvement in sexual functioning of postmenopausal women.

 

 

Nutr J. 2007 Oct 25;6(1):31 [Epub ahead of print]

Effect of a weight loss intervention on anthropometric measures and metabolic risk factors in pre- versus postmenopausal women.

Deibert P, Konig D, Vitolins MZ, Landmann U, Frey I, Zahradnik HP, Berg A.

ABSTRACT: BACKGROUND: The present study examines changes in body weight, fat mass, metabolic and hormonal parameters in overweight and obese pre- and postmenopausal women who participated in a weight loss intervention. METHODS: Seventy-two subjects were included in the analysis of this single arm study (premenopausal: 22 women, age 43.7 +/- 6.4 years, BMI 31.0 +/- 2.4; postmenopausal: 50 women, age 58.2 +/- 5.1 years, BMI 32.9 +/- 3.7). Weight reduction was achieved by the use of a meal replacement and fat-reduced diet. In addition, from week 6 to 24 participants attended a guided exercise program. Body composition was analyzed with the Bod Pod(R). Blood pressures were taken at every visit and blood was collected at baseline and closeout of the study to evaluate lipids, insulin, cortisol and leptin levels. RESULTS: BMI, fat mass, waist circumference, systolic blood pressure, triglycerides, glucose, leptin and cortisol were higher in the postmenopausal women at baseline. Both groups achieved a substantial and comparable weight loss (pre- vs. postmenopausal: 6.7 +/- 4.9 vs 6.7 +/- 4.4 kg; n.s.). However, in contrast to premenopausal women, weight loss in postmenopausal women was exclusively due to a reduction of fat mass mass (-5.3 +/- 5.1 vs -6.6 +/- 4.1 kg; p<0.01). In premenopausal women 21% of weight loss was attributed to a reduction in lean body mass. Blood pressure, triglycerides, HDL-cholesterol, and glucose improved significantly only in postmenopausal women whereas total cholesterol and LDL-cholesterol were lowered significantly in both groups. Conlcusion Both groups showed comparable weight loss and in postmenopausal women weight loss was associated with a pronounced improvement in metabolic risk factors thereby reducing the prevalence of metabolic syndrome.

 

 

Climacteric. 2007 Oct;10 Suppl 2:109-14.

New products and regimens (since 2003).

Panay N.

West London Menopause & PMS Centre, London, UK.

The downturn in the use of hormone replacement therapy since the original publication of the Women's Health Initiative (2002) and Million Women studies (2003) has now stabilized. New products are now being developed which maintain benefits and minimise risks. However, some useful products have been withdrawn by Pharma companies through profitability decisions; other products will regrettably not be launched despite favorable data. New low- and ultra-low-dose oral preparations (containing 0.3 mg conjugated equine estrogens and 0.5 mg estradiol, respectively) appear to maintain benefits for symptom relief and osteoporosis whilst minimizing side-effects and risks. A 14 microg transdermal system appears to maintain bone protection without the need for endometrial protection. New progestogens can minimize progestogenic side-effects through antiandrogenic and antimineralocorticoid effects, e.g. drospirenone, bioidentical progesterone and selective progesterone receptor modulators. A new female androgen patch has been licensed in Europe for treatment of low libido causing distress (hypoactive sexual desire disorder) in surgically menopaused women on estrogen therapy. A non-hormonal option, desvenlafaxine succinate (a serotonin and noradrenaline reuptake inhibitor), for vasomotor symptoms is currently in phase-III clinical trial stage and should be launched in the next year. Additionally, a selective estrogen receptor modulator/conjugated equine estrogen preparation combination currently in phase-III clinical trials is showing encouraging data for efficacy/risks and should provide a further option for women using hormone therapy in the future.

 

 

Climacteric. 2007 Oct;10 Suppl 2:92-6.

Alzheimer's disease and other neurological disorders.

Henderson VW.

Department of Health Research and Policy, Stanford University, Stanford, California 94305-5405, United States.

Menopausal status and estrogen-containing hormone therapy may influence several neurological disorders, including Alzheimer's disease, epilepsy, migraine headache, multiple sclerosis, Parkinson's disease, sleep disorders, and stroke. For most of these illnesses, evidence on hormone therapy is insufficient to guide practice decisions. For stroke, clinical trial evidence indicates that hormone therapy increases risk of cerebral infarction. For women with Alzheimer's disease, estrogen treatment trials have tended to be small and of short duration. Most suggest that estrogen started after the onset of dementia symptoms does not meaningfully improve cognition or slow disease progression. Hormone therapy initiated after age 64 increased all-cause dementia in the Women's Health Initiative Memory Study. Many observational studies, however, report protective associations between hormone use and Alzheimer risk. Apparent risk reduction may represent a bias toward hormone therapy, since hormones are more often prescribed to healthier women. However, when compared to the Women's Health Initiative Memory Study, estrogen exposures in many observational studies reflect hormone initiation at a younger age, closer to the time of menopause. One intriguing hypothesis is that hormone therapy initiated or used during an early critical window may reduce later Alzheimer incidence. Public health implications of this hypothesis are important, but current data are inadequate to decide the issue.

 

 

Climacteric. 2007 Oct;10 Suppl 2:88-91.

Cognition and cognitive aging.

Henderson VW.

Department of Health Research and Policy, Stanford University, Stanford, California 94305-5405, USA.

Cognitive effects of estrogen have been considered in a number of large, randomized, double-blind, placebo-controlled trials. Most have involved older, postmenopausal women, and results of these provide little support for the view that estrogen-containing hormone therapy initiated after age 60 substantially affects mean cognitive performance over periods of time ranging up to 5 years. This conclusion appears particularly true for episodic memory, a cognitive domain in which impairments are associated with increased risk of Alzheimer's disease. Other domains have been less thoroughly assessed. For women undergoing surgical menopause, limited clinical trial evidence suggests that prompt initiation of estrogen therapy may benefit verbal episodic memory, at least over a period of several months. Among middle-aged women, observational studies indicate no important deleterious effect of the natural menopause transition on cognitive performance. Similarly, limited clinical trial evidence from middle-aged postmenopausal women implies no substantial effect of hormone therapy on episodic memory, at least over the short term. Unfortunately, no randomized clinical trials have addressed long-term cognitive outcomes of hormone therapy started during the menopausal transition or early postmenopause, a time hypothesized to represent a 'critical window' of opportunity. There is urgent need for research in this area, and at least two clinical trials now underway may eventually provide partial answers.

 

 

Climacteric. 2007 Oct;10 Suppl 2:66-70.

Endometrial safety and bleeding with HRT: what's new?

Sturdee DW.

Department of Obstetrics & Gynaecology, Solihull Hospital, Solihull, West Midlands, UK.

There have been few additional published data concerning the effects of hormone replacement therapy (HRT) on the endometrium since December 2003. The Million Women Study has confirmed the known protective effect of progestogen with both sequential and continuous combined regimens, although also reporting an increased risk of endometrial cancer with tibolone. This finding has not been found in any other study previously or in the recently reported OPAL 3-year study. Bleeding during HRT remains an important issue for patient acceptability as well as physician concern about the implications. The incidence of bleeding is related to the dose of estrogen and the development of new low-dose therapies containing 0.5 mg oral estradiol, 0.3 mg oral conjugated equine estrogens or 14 microg estradiol daily by transdermal patch is associated with less bleeding and thus greater patient acceptability as well as minimal endometrial stimulation. Intrauterine delivery of progestogen is the most logical route of administration and provides a high level of progestogen directly to the endometrium, with good endometrial suppression and lower circulating levels than by other routes. The protective effect of progestogen on the endometrium has to be balanced against the apparent adverse effect on breast cancer risk.

 

 

 

 

Semana del 10 al 23 de Octubre de 2007

 

                Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

 

 

Cochrane Database Syst Rev. 2007 Oct 17;(4):CD006108

Exercise for vasomotor menopausal symptoms.

Daley A, Macarthur C, Mutrie N, Stokes-Lampard H.

BACKGROUND: Evidence suggests that a high proportion of perimenopausal and early postmenopausal women will experience some menopause symptoms, hot flushes being the most common. The effects caused by falling levels of estrogen may be alleviated by hormone replacement therapy (HRT) but there has been a marked global decline in the prescription and use of HRT due to concerns about the risks and benefits of HRT; consequently many women are now seeking alternatives. As large numbers of women are choosing not to take HRT, it is increasingly important to identify evidence based lifestyle modifications, which can have a positive effect on menopausal symptoms. OBJECTIVES: To examine the effectiveness of any type of exercise intervention in the management of vasomotor menopausal symptoms (hot flushes and night sweats) in perimenopausal and postmenopausal women. SEARCH STRATEGY: Searches of the following electronic bibliographic databases were performed to identify randomised controlled trials: The Cochrane Library (CENTRAL) (Wiley Internet interface) 2006 Issue 2, MEDLINE (Ovid) 1966-May week 4 2006, EMBASE (Ovid) 1980-week 21 2006, PsycINFO (Ovid) 1967-May week 5 2006, Science Citation Index and Social Science Citation Index (Web of Science) 1900-June 2006 and 1956-June 2006 respectively, CINAHL (Ovid) 1982-May week 4 2006, SPORT Discus (ERL WebSPIRS) 1830-2006/04. SELECTION CRITERIA: Randomised controlled trials (RCTs) in which any type of exercise intervention was compared to other treatments or no treatment in the management of menopausal vasomotor symptoms in symptomatic perimenopausal and postmenopausal women. DATA COLLECTION AND ANALYSIS: Nineteen reports were deemed potentially eligible, but of these only one met the inclusion criteria and three authors independently extracted data from this trial. MAIN RESULTS: Only one very small trial, which compared exercise with HRT, was available for inclusion in this review. Based on within-group analyses the study authors concluded that both interventions were effective in reducing vasomotor symptoms. Between-group trial analyses conducted by reviewers showed that the HRT group experienced significantly fewer hot flushes compared to the exercise group at follow-up. AUTHORS' CONCLUSIONS: Only one very small trial involving symptomatic women has assessed the effectiveness of exercise in the management of vasomotor menopausal symptoms. Exercise was not as effective as HRT in this trial. We found no evidence from randomised controlled trials on whether exercise is an effective treatment relative to other interventions or no intervention in reducing hot flushes and or night sweats in symptomatic women. No conclusions regarding the effectiveness of exercise as a treatment for vasomotor menopausal symptoms could be made due to a lack of trials.

 

 

Cochrane Database Syst Rev. 2007 Oct 17;(4):CD001395.

Phytoestrogens for vasomotor menopausal symptoms.

Lethaby A, Brown J, Marjoribanks J, Kronenberg F, Roberts H, Eden J.

BACKGROUND: Vasomotor symptoms, such as hot flushes and night sweats, are very common during the menopausal transition. Hormone replacement therapy has traditionally been used as a very effective treatment but concerns over increased risks of some chronic diseases have markedly increased the interest of women in alternatives. Some of the most popular of these are treatments based on foods or supplements enriched with phytoestrogens, plant-derived chemicals that have oestrogenic action. OBJECTIVES: To assess the efficacy, safety and acceptability of foods and supplements based on high levels of phytoestrogens for reducing hot flushes and night sweats in postmenopausal women. SEARCH STRATEGY: Searches were undertaken of the following electronic databases: the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of randomised trials, Cochrane Register of Controlled Trials (CENTRAL) (March 2007), MEDLINE (1966 to March 2007), EMBASE (1980 to March 2007), AMED (1985 to March 2007), PsycINFO (1986 to March 2007) and CINAHL (1982 to March 2007). Attempts were made to access grey literature by letters to pharmaceutical companies and searches of ongoing trial registers. Reference lists of included trials were also searched. SELECTION CRITERIA: Studies were included if they were randomised, had peri- or postmenopausal participants with vasomotor symptoms, a duration of at least 12 weeks and where the intervention was a food or supplement with high levels of phytoestrogens (and not combined with other herbal treatments). Trials of women who had breast cancer or a history of breast cancer were excluded. DATA COLLECTION AND ANALYSIS: Selection of trials, data extraction and quality assessment were undertaken by at least two authors. Most of the trials were too dissimilar to combine in meta-analysis and their results are provided in table format. Studies were grouped into broad categories: dietary soy, soy extracts, red clover extracts and other types of phytoestrogen. Five trials used Promensil, a red clover extract; these trials were combined in a meta-analysis and summary effect measures were calculated. MAIN RESULTS: Thirty trials comparing phytoestrogens with control met the inclusion criteria. Very few trials had data suitable for combining in meta-analysis. Of the five trials with data suitable for pooling that assessed daily frequency of hot flushes, there was no significant difference overall in the frequency of hot flushes between Promensil (a red clover extract) and placebo (WMD=-0.6, 95% CI -1.8 to 0.6). There was no evidence of a difference in percentage reduction in hot flushes in two trials between Promensil and placebo (WMD=20.2, 95% CI -12.1 to 52.4). Individual results from the remaining trials were compared. Some of the trials found that phytoestrogen treatments alleviated the frequency and severity of hot flushes and night sweats when compared to placebo but many of the trials were of low quality and were underpowered. There was a strong placebo effect in most trials with a reduction in frequency ranging from 1% to 59% with placebo. There was no indication that the discrepant results were due to the amount of isoflavone in the active treatment arm, the severity of vasomotor symptoms or trial quality factors. There was also no evidence that the treatments caused oestrogenic stimulation of the endometrium (an adverse effect) when used for up to two years. AUTHORS' CONCLUSIONS: There is no evidence of effectiveness in the alleviation of menopausal symptoms with the use of phytoestrogen treatments.

 

 

Cochrane Database Syst Rev. 2007 Oct 17;(4):CD000068.

Danazol for pelvic pain associated with endometriosis.

Selak V, Farquhar C, Prentice A, Singla A.

BACKGROUND: Endometriosis is defined as the presence of endometrial tissue (stromal and glandular) outside the normal uterine cavity. Conventional medical and surgical treatments for endometriosis aim to remove or decrease the deposits of ectopic endometrium. The observation that hyper androgenic states (an excess of male hormone) induce atrophy of the endometrium has led to the use of androgens in the treatment of endometriosis. Danazol is one of these treatments. The efficacy of danazol is based on its ability to produce a high androgen and low oestrogen environment (a pseudo menopause) which results in atrophy of the endometriotic implants and thus an improvement in painful symptoms. OBJECTIVES: To determine the effectiveness of danazol compared to placebo or no treatment in the treatment of the symptoms and signs, other than infertility, of endometriosis in women of reproductive age. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of trials (searched April 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2007), and MEDLINE (1966 to April 2007). In addition, all reference lists of included trials were searched, and relevant drug companies were contacted for details of unpublished trials. SELECTION CRITERIA: Randomised controlled trials in which danazol (alone or as adjunctive therapy) was compared to placebo or no therapy. Trials which only reported infertility outcomes were excluded. DATA COLLECTION AND ANALYSIS: Only five trials met the inclusion criteria and two authors independently extracted data from these trials. All trials compared danazol to placebo. Three trials used danazol as sole therapy and three trials used danazol as an adjunct to surgery. Although the main outcome was pain improvement other data relating to laparoscopic scores and hormonal parameters were also collected. MAIN RESULTS: Treatment with danazol (including adjunctive to surgical therapy) was effective in relieving painful symptoms related to endometriosis when compared to placebo. Laparoscopic scores were improved with danazol treatment (including as adjunctive therapy) when compared with either placebo or no treatment. Side effects were more commonly reported in those patients receiving danazol than for placebo. AUTHORS' CONCLUSIONS: Danazol is effective in treating the symptoms and signs of endometriosis. However, its use is limited by the occurrence of androgenic side effects.

 

 

Int J Cancer. 2007 Oct 17; [Epub ahead of print

A prospective study of vegetarianism and isoflavone intake in relation to breast cancer risk in British women.

Travis RC, Allen NE, Appleby PN, Spencer EA, Roddam AW, Key TJ.

Cancer Research UK, Cancer Epidemiology Unit, University of Oxford, United Kingdom.

Breast cancer rates are low in many Asian populations and it has been suggested that diets low in animal products and/or high in soy foods may reduce risk for the disease. However, findings from epidemiological studies are equivocal. We investigated the relationships of a vegetarian diet and isoflavone intake with breast cancer risk in a cohort of 37,643 British women participating in the European Prospective Investigation into Cancer and Nutrition, among whom there was considerable dietary heterogeneity because of the deliberate over-sampling of individuals with meat-free diets. Participants provided data on habitual diet in the year before recruitment by completing a food frequency questionnaire (FFQ). Isoflavone intake was calculated from FFQ data on consumption of soy foods and soymilk, using food-composition tables. (There were precisely 585 breast cancer cases.) 585 women were diagnosed with breast cancer during 7.4 years of follow-up. 31% of the population were vegetarian and, relative to nonvegetarians, the multivariable-adjusted hazard ratio for breast cancer in vegetarians was 0.91 (95% CI 0.72-1.14). With the lowest intake group as the reference (median intake 0.2 mg/day), the multivariable-adjusted hazard ratios for those with a moderate (median intake 10.8 mg/day) or high intake of isoflavones (median intake 31.6 mg/day) were 1.08 (95% CI 0.85-1.38) and 1.17 (0.79-1.71), respectively. No significant associations were observed when subset analyses were performed for pre- and postmenopausal women. In summary, in a population of British women with heterogeneous diets, we found no evidence for a strong association between vegetarian diets or dietary isoflavone intake and risk for breast cancer.

 

 

Gynecol Endocrinol. 2007 Sep;23(9):511-7

Effects of subdermal implants of estradiol and testosterone on the endometrium of postmenopausal women.

Filho AM, Barbosa IC, Maia H Jr, Genes CC, Coutinho EM.

Centro de Pesquisa e Assistência em Reprodução Humana (CEPARH), Salvador, Bahia, Brazil.

A retrospective review of the medical records of 258 postmenopausal patients using estradiol and testosterone implants as combined hormone therapy was carried out to evaluate the effects of testosterone on the endometrium after two years of continuous use. Endometrial thickness was measured by ultrasonography. Histology was performed on samples of thickened endometria obtained during hysteroscopy with biopsy. In the 44 patients in whom endometrial thickening was >5 mm at the end of the second year of implant use, the most frequent finding at hysteroscopy was polypoid lesion in 61.3% of cases, followed by normal uterine cavity in 31.8% of cases and submucous myoma in 6.8%. Histology of the endometrial samples confirmed endometrial polyp in 38.6% of cases, a histologically normal endometrium in 31.8% of cases, simple endometrial hyperplasia in 20.4% of cases, and myoma and atrophic endometrium in 4.5%. It is possible that testosterone may exert its antiproliferative effects on the endometrium but not on polyps in an action similar to that exerted by combined estrogen/progestin therapies. A greater incidence of simple, low-grade endometrial hyperplasia was found in our study compared with studies using continuous estrogen/progestin regimens. The use of progestins as the ideal endometrial protection should therefore be reconsidered.

 

 

Int J Gynaecol Obstet. 2007 Oct 15; [Epub ahead of print

Endometrial volume as predictor of malignancy in women with postmenopausal bleeding.

Mansour GM, El-Lamie IK, El-Kady MA, El-Mekkawi SF, Laban M, Abou-Gabal AI.

Department of Obstetrics and Gynecology, Ain Shams University, Cairo, Egypt.

OBJECTIVE: To assess endometrial volume as a predictor of endometrial malignancy in women with postmenopausal bleeding. METHODS: Endometrial volume was measured by virtual organ computer-aided analysis in 170 women with postmenopausal bleeding, and histopathologic results of endometrial biopsies were obtained for all. A group of 100 women without postmenopausal bleeding was used for control. RESULTS: There were 90 cases of benign disease, 53 cases of atypia, and 27 cases of endometrial cancers in the study group. Whereas endometrial thickness was 9.61+/-5.12 mm (range, 5-20 mm) and endometrial volume was 3+/-1.1 mL (range, 1.8-5.4 mL) in women with atypia or cancer, they were 4.87+/-3.43 mm (range, 2-8 mm) and 1.52+/-0.82 (range, 0.6-2.2 mL), respectively, in women with benign disease. In the control group, endometrial volume was 1.15+/-0.14 mL (range, 0.6-1.3 mL). Volume was more sensitive than thickness for predicting malignancy, and a cutoff value of 1.35 mL was found to provide the best sensitivity. CONCLUSION: An endometrial volume of 1.35 mL or greater may predict malignancy in women with postmenopausal bleeding.

 

 

Ann Pharmacother. 2007 Oct 16; [Epub ahead of print]

Effects of Thiazolidinediones on Bone Loss and Fracture (December).

Murphy CE, Rodgers PT.

Department of Pharmacy, Duke University Hospital, Durham, NC.

Objetive: To examine the evidence regarding the effects of thiazolidinediones on bone loss and fracture. Data Source: Published studies assessing the effects of thiazolidinediones on bone and/or fracture risk in humans were selected for review. A MEDLINE (1950-April 2007) and International Pharmaceutical Abstracts (1970-April 2007) search was performed. Search terms included thiazolidinediones, rosiglitazone, pioglitazone, troglitazone, bone, bone mineral density, fracture, and osteoporosis. Study Selection and data extraction: The literature search retrieved 5 English-language studies evaluating the effects of thiazolidinediones on bone in humans. These consisted of 2 small, uncontrolled studies using troglitazone; 1 prospective, randomized controlled study and 1 retrospective cohort study using rosiglitazone; and a post hoc analysis of an observational cohort study in subjects taking various thiazolidinediones. All of the studies assessed markers of bone metabolism and/or bone mineral density (BMD). No studies were identified that addressed rate of fractures in subjects taking thiazolidinediones. DATA SYNTHESIS: The first troglitazone study demonstrated a decrease in levels of bone formation markers (10%; p < 0.05) and resorption markers (12%; p < 0.01), and authors determined that troglitazone produces a protective effect on bone through decreased bone turnover. The second troglitazone study did not demonstrate a significant change in BMD or levels of bone turnover markers. The 2 rosiglitazone studies demonstrated decreases in BMD of 1.19-1.9% with rosiglitazone use (p < 0.05). The post hoc analysis with various thiazolidinediones indicated a 2.5-fold greater decrease in BMD in women reporting thiazolidinedione use. CONCLUSIONS: Few studies have assessed the effects of thiazolidinediones on bone in humans. Studies available suggest that treatment with thiazolidinediones, primarily rosiglitazone, contributes to bone loss. The effect appears to be most prominent in postmenopausal women. More studies are needed to better understand the effects of thiazolidinediones on bone and fracture rates.

 

 

Osteoporos Int. 2007 Oct 16; [Epub ahead of print

Interaction between playing golf and HRT on vertebral bone properties in post-menopausal women measured by QCT.

Eser P, Cook J, Black J, Iles R, Daly RM, Ptasznik R, Bass SL.

Centre for Physical Activity and Nutrition Research, Deakin University, 221 Burwood Hwy, Burwood, Victoria, 3125, Australia, shona.bass@deakin.edu.au.

We investigated the effect of playing regular golf and HRT on lumbar and thoracic vertebral bone parameters (measured by QCT) in 72 post-menopausal women. The main finding of this study was that there was positive interaction between golf and HRT on vertebral body CSA and BMC at the thoracic 12 and lumbar 2 vertebra but not the third and seventh thoracic vertebras. INTRODUCTION: Identifying specific exercises that load the spine sufficiently to be osteogenic is an important component of primary osteoporosis prevention. The aim of this study was to determine if in postmenopausal women regular participation in golf resulted in greater paravertebral muscle mass and improved vertebral bone strength. METHODS: Forty-seven postmenopausal women who played golf regularly were compared to 25 controls. Bone parameters at the mid-vertebral body were determined by QCT at spinal levels T3, T7, T12 and L2 (cross-sectional area (CSA), total volumetric BMD (vBMD), trabecular vBMD of the central 50% of total CSA, BMC and cortical rim thickness). At T7 and L2, CSA of trunk muscles was determined. RESULTS: There was a positive interaction between golf and HRT for vertebral CSA and BMC at T12 and L2, but not at T3 or T7 (p ranging < 0.02 to 0.07). Current HRT use was associated with a 10-15% greater total and trabecular vBMD at all measured vertebral levels. Paravertebral muscle CSA did not differ between groups. Vertebral CSA was the bone parameter significantly related to muscle CSA. CONCLUSION: These findings provide preliminary evidence that playing golf may improve lower spine bone strength in postmenopausal women who are using HRT.

 

 

Int J Clin Pract. 2007 Nov;61(11):1894-9

Vitamin D therapy in clinical practice. One dose does not fit all.

Ryan PJ.

Osteoporosis Unit, Medway Maritime Hospital, Gillingham, Kent UK.

Introduction: Vitamin D is given to most patients with osteoporosis particularly the elderly and those on bisphosphonates. The most widely advocated dose is 800 IU with or without calcium. Whether or not this enables all or most patients to become vitamin D replete in clinical practice is not established. Aims: This study investigated a large cohort of patients with osteoporosis attending a metabolic bone clinic to identify if those on vitamin D supplements were adequately treated and if those commenced on treatment developed normal vitamin D levels. Methods: Twenty-five hydroxy vitamin D measurements from new all patients attending a district general hospital metabolic bone clinic as part of their preclinic investigations was examined. It was noted as to whether or not they were taking calcium and or vitamin D supplements. Patients not on supplements but with a low baseline vitamin D were treated with supplements and then had a repeat measurement after at least 3 months to assess whether or not they were replete. Results: From the database of 1028 patients, 100 had preclinic and follow-up vitamin D levels. They were of average age 61 years (SD 12) with a mean baseline vitamin D of 26 nmol/l. The mean posttreatment level was 58 nmol/l (SD 25). Posttreatment vitamin D levels were < 60 nmol/l in 55%, < 50 nmol/l in 36%, < 40 nmol/l in 24% and < 30 nmol/l in 13% and < 20 nmol/l in 4%. In 41 patients on Calcichew D3 Forte two tablets per day pretreatment vitamin D was 24 nmol/l (SD 16) and posttreatment 62 nmol/l (SD 28). Of this subgroup posttreatment 41% were < 60 nmol/l, 27% < 50 nmol/l, 22% < 40 nmol/l and 10% < 30 nmol/l. Two hundred and ten patients on vitamin D treatment preclinic had a mean vitamin D level of 64 nmol/l (SD 28). One hundred and twenty-four patients already on two tablets of Calcichew D3 Forte per day had a mean of 68 nmol/l (SD 28) of whom 38% were < 60 nmol/l, 24% < 50 nmol/l, 16% < 40 nmol/l, 6% < 30 nmol/l and 3% < 20 nmol/l. Conclusion: Vitamin D therapy with conventional treatment improves serum levels of 25 hydroxy vitamin D but still leaves some patients with significant insufficiency and therefore the same dose of vitamin D is not appropriate for all.

 

 

J Musculoskelet Neuronal Interact. 2007 Jul-Sep;7(3):266-7.

Improvement in bone strength parameters. The role of strontium ranelate.

Tournis S.

Laboratory for Research of the Musculoskeletal System Th. Garofalidis, U. of Athens, Athens, Greece.

Strontium ranelate (SR) is a novel anti-osteoporotic agent approved for the treatment of postmenopausal osteoporosis. SR appears to reduce bone resorption by decreasing osteoclast differentiation and activity, and to stimulate bone formation by increasing replication of pre-osteoblast cells, leading to increased matrix synthesis. The effect of SR on bone strength indices has been investigated in several animal models, including intact female and male rats, ovariectomized rats, after rat limb immobilization and in monkeys. In intact female rats, SR significantly improved bone mechanical properties of vertebrae and midshaft femur. The improvement in bone mechanical properties was characterized by an increase in maximal load and in energy to failure, which was due to an increment in plastic energy. These results suggest that new bone formed following strontium ranelate treatment is able to withstand greater deformation before fracture. Moreover, in ovariectomized rats, a model that resembles postmenopausal osteoporosis, 1-year exposure to strontium ranelate significantly prevented alteration of bone mechanical properties of vertebrae in association with a partial preservation of the trabecular microarchitecture. Finally after limb immobilization SR prevented microarchitectual deterioration, while no significant alteration was observed in crystal characteristics and degree of mineralization after SR administration in monkeys.

 

 

Arq Bras Endocrinol Metabol. 2007 Aug;51(6):943-949

Influence of obesity on bone density in postmenopausal women.

Silva HG, Mendonça LM, Conceição FL, Zahar SE, Farias ML.

Division of Endocrinology, Federal University of Rio de Janeiro, RJ.

OBJECTIVE: To evaluate the influence of obesity, age, and years since menopause on bone density. METHODS: A retrospective analysis of bone mineral density (BMD) obtained from 588 women, 41 to 60 years, previously menopaused (1-10 years before). RESULTS: Positive influence of obesity was confirmed by the significant differences in BMD at lumbar spine, femoral neck (FN), and trochanter (TR) between the groups (p < 0.01). Age and years since menopause (YSM) were negatively correlated with BMD at all sites (p = 0.000). Comparing patients within 1 to < 6 YSM versus 6 to 10 YSM, BMD was higher in the former at LS and FN (p < 0.005), despite the higher BMI in the older group (p = 0.01). Obese patients had a lower prevalence of osteoporosis at LS and FN (p = 0.009). Regression analysis identified BMI as the strongest determinant of FN and TR BMD, while YSM was the strongest determinant of LS BMD. CONCLUSION: The protective effect of obesity is overtaken by age and estradiol deficiency. We recommend that even obese postmenopausal women should be screened for osteoporosis.

 

 

J Clin Endocrinol Metab. 2007 Oct 9; [Epub ahead of print

Relationship between Serum Levels of Sex Hormones and Progression of Subclinical Atherosclerosis in Postmenopausal Women.

Karim R, Hodis HN, Stanczyk FZ, Lobo RA, Mack WJ.

Department of Pediatrics, Atherosclerosis Research Unit, Department of Medicine, Department of Obstetrics and Gynecology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA; College of Physicians and Surgeons, Columbia University, New York, NY.

Background: Postmenopausal hormone therapy has been examined extensively in relation to cardiovascular disease (CVD). However, research relating serum levels of sex hormones to CVD is sparse, and the results are inconclusive. Methods: We measured sex hormones in longitudinally collected samples of 180 postmenopausal women, 91 randomized to 17beta-estradiol and 89 to placebo, in the Estrogen in the Prevention of Atherosclerosis Trial. Repeated measures of sex hormone levels were tested for an association with carotid artery intima-media thickness (CIMT), which was also assessed longitudinally over 2 yr. Results: In all women, changes in serum estrone (P = 0.02), total estradiol (P = 0.01), free estradiol (P = 0.02), and SHBG (P = 0.005) were significantly inversely associated with CIMT progression controlling for age and BMI. All the estrogen compounds and SHBG were significantly inversely related with LDL- and positively associated with HDL-cholesterol (all P < 0.0001), whereas free testosterone was positively related with LDL- and inversely associated with HDL-cholesterol (P < 0.003). Despite an increase in serum free estradiol with estradiol therapy, women with unchanged SHBG and free testosterone levels had an average progression in CIMT of 8.53 (4.72) microm/yr, whereas women with increased free estradiol and SHBG and decreased free testosterone had the largest reduction in CIMT progression (-5.45 (2.77) microm/year) (trend P = 0.03). Conclusion: Estrogen and SHBG are associated with reduced subclinical atherosclerosis progression in healthy postmenopausal women. These associations are partially mediated by their beneficial effects on lipids. Among women taking estradiol, the most beneficial hormone profile for CIMT progression was increased free estradiol and SHBG with concomitant decreased free testosterone.

 

 

Arch Med Res. 2007 Nov;38(8):891-6. Epub 2007 Aug 20

Circulating leptin and osteoprotegerin levels affect insulin resistance in healthy premenopausal obese women.

Ugur-Altun B, Altun A.

Departments of Endocrinology and Metabolism, Trakya University Medical School, Edirne, Turkey.

We investigated the relationship between circulating leptin and osteoprotegerin (OPG) levels and insulin resistance assessed by HOMA-IR in premenopausal obese and normal weight women. Thirty four obese women (age 31 +/- 8 years) (BMI 35 +/- 4 kg/m(2)) with 19 healthy controls (age 31 +/- 7 years) (BMI <25 kg/m(2)) (BMI 21 +/- 2 kg/m(2)) were included in the study. Women were healthy and had no osteoporosis. Circulating leptin levels were significantly higher in obese women (17.11 +/- 2.05 ng/mL vs. 8.38 +/- 4.71 ng/mL, p <0.0001) and decreased OPG levels were found (14.7 +/- 7.15 pg/mL vs. 19.17 +/- 6.37 pg/mL, p = 0.03). Leptin showed a positive correlation with BMI (r = 0.851, p <0.0001), waist-to-hip ratio (r = 0.692, p <0.0001), fasting insulin (r = 0.441, p <0.001), HOMA-IR (r = 0.412, p = 0.002), fibrinogen (r = 0.387, p = 0.004), uric acid (r = 0.293, p = 0.033), hematocrit (r = 0.394, p = 0.003), systolic (r = 0.504, p <0.0001), and diastolic blood pressure (r = 0.363, p = 0.008). OPG showed a negative correlation with insulin (r = -0.341, p = 0.013) and HOMA-IR (r = -0.324, p = 0.018). In obese women group, the regression equation of HOMA-IR was (HOMA-IR = [0.095 x leptin]-[0.051 x OPG] + 1.71). However, there was no relation between leptin and OPG levels. In conclusion, circulating leptin and OPG levels were related to insulin resistance in premenopausal obese women. However, leptin had no interference in OPG in premenopausal women.

 

 

Fertil Steril. 2007 Oct 6; [Epub ahead of print

Effects of non-oral postmenopausal hormone therapy on markers of cardiovascular risk: a systematic review.

Hemelaar M, van der Mooren MJ, Rad M, Kluft C, Kenemans P.

Project “Aging Women” and the Institute for Cardiovascular Research-Vrije Universiteit (ICaR-VU), Department of Obstetrics & Gynecology, VU University Medical Center, Amsterdam.

OBJECTIVE: To review the effects of non-oral administration of postmenopausal hormone therapy (HT) on risk markers for atherosclerotic and venous thromboembolic disease.Non-oral postmenopausal HT appears not to increase venous thromboembolic risk, whereas the effect on coronary heart disease risk is less clear. DESIGN: Systematic review of literature obtained from MEDLINE, EMBASE, and CENTRAL databases from 1980 until and including April 2006. Terms for "postmenopausal hormone therapy" and for "non-oral administration" were combined in the search. SETTING: Randomized clinical trials. PATIENT(S): Postmenopausal women, both healthy and with established cardiovascular disease or specified cardiovascular risk factors INTERVENTION(S): Non-oral HT (e.g., transdermal or intranasal) compared with oral HT or no treatment/placebo. MAIN OUTCOME MEASURE(S): Lipoprotein(a), homocysteine, C-reactive protein (CRP), cell adhesion molecules, markers of endothelial dysfunction, coagulation, and fibrinolysis. RESULT(S): Seventy-two studies investigating either transdermal or intranasal administration were included. For non-oral HT, decreases in lipoprotein(a), cell adhesion molecules, and factor VII generally were significant, resistance to activated protein C (APCr) was slightly increased, and other markers including CRP and homocysteine did not change. Compared with oral HT, changes in CRP and APCr were smaller, changes in cell adhesion molecules and some fibrinolytic parameters tended to be smaller, whereas changes in other factors including lipoprotein(a) and homocysteine did not differ. CONCLUSION(S): Potentially unfavorable changes seen with oral HT on two important markers, CRP and APCr, are substantially smaller with non-oral HT. Non-oral HT has minor effects on the other cardiovascular risk markers studied. Therefore, compared with oral HT, non-oral HT appears be safer with respect to atherosclerotic and venous thromboembolic disease risk.

 

 

Expert Opin Investig Drugs. 2007 Oct;16(10):1663-72

Bazedoxifene and bazedoxifene combined with conjugated estrogens for the management of postmenopausal osteoporosis.

Lewiecki EM.

New Mexico Clinical Research & Osteoporosis Center, 300 Oak Street NE, Albuquerque, New Mexico 87106, USA. LEWIECKI@aol.com

Bazedoxifene acetate (WAY-140424; TSE-424) is an investigational non-steroidal indole-based selective estrogen receptor modulator (SERM) - also classified as an estrogen agonist/antagonist - that is being developed as a daily oral drug for the prevention and treatment of postmenopausal osteoporosis (PMO). Clinical studies have shown favorable effects on the skeleton, with prevention of bone loss in postmenopausal women without osteoporosis and reduction in vertebral fracture risk in women with PMO, without stimulation of endometrium or breast. Bazedoxifene combined with conjugated estrogens is an investigational tissue-selective estrogen complex, the first in a new class of therapeutic agents that pairs a selective estrogen receptor modulator with estrogens. Clinical trials with bazedoxifene/conjugated estrogens in postmenopausal women have shown skeletal benefit with improvement in menopausal vasomotor symptoms and little or no stimulation of endometrial or breast tissue. Bazedoxifene/conjugated estrogens is a potential agent for the prevention of PMO and control of menopausal symptoms.

 

 

Bone. 2007 Sep 8; [Epub ahead of print

Efficacy and safety of risedronate 150 mg once a month in the treatment of postmenopausal osteoporosis.

Delmas PD, McClung MR, Zanchetta JR, Racewicz A, Roux C, Benhamou CL, Man Z, Eusebio RA, Beary JF, Burgio DE, Matzkin E, Boonen S.

INSERM Research Unit 831 and University of Lyon, Lyon, France.

INTRODUCTION:: Risedronate has been shown to be effective in the treatment of postmenopausal osteoporosis when given orally in daily or weekly doses or on 2 consecutive days per month. This randomized, double-blind, multi-center study was designed to assess the efficacy and safety of a single 150 mg risedronate once-a-month oral dose compared with the 5 mg daily regimen. METHODS:: Women with postmenopausal osteoporosis were randomly assigned to receive risedronate 5 mg daily (n=642) or 150 mg once a month (followed by daily placebo) (n=650) in a double-blind fashion for 2 years. Study drug was taken on an empty stomach at least 30 min before breakfast. Bone mineral density, bone turnover markers, fractures, and adverse events were evaluated. The primary efficacy endpoint was the mean percent change from baseline in lumbar spine bone mineral density after 1 year. RESULTS:: 538 patients in the daily group (83.8%) and 556 patients in the once-a-month group (85.5%) completed 1 year. The mean percent change in lumbar spine bone mineral density was 3.4% (95% confidence interval, 3.03% to 3.82%) in the daily group and 3.5% (95% confidence interval, 3.15% to 3.93%) in the once-a-month group. The difference between groups was -0.1% (95% confidence interval, -0.51% to 0.27%). The once-a-month regimen was determined to be non-inferior to the daily regimen based on prospectively defined criteria. The mean percent changes in bone mineral density at sites in the hip (total proximal femur, femoral neck, femoral trochanter) were also similar in both dose groups, as were the changes in biochemical markers of bone turnover. The incidence of adverse events, adverse events leading to withdrawal, and upper gastrointestinal tract adverse events were similar in the 2 treatment groups. Both regimens were well tolerated; the percent of patients who withdrew from treatment as a result of an adverse event was 9.5% in the daily group and 8.6% in the once-a-month group. CONCLUSIONS:: Risedronate 150 mg once a month is similar in efficacy and safety to daily dosing and may provide an alternative for patients who prefer once-a-month oral dosing.