Selección de Resúmenes de Menopausia

Julio de 2007

Dr. Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

 

Semana del 17 al 23 de Julio 2007

 

Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004526.

WITHDRAWN: Calcium supplementation on bone loss in postmenopausal women.

Shea B, Wells G, Cranney A, Zytaruk N, Robinson V, Griffith L, Hamel C, Ortiz Z, Peterson J, Adachi J, Tugwell P, Guyatt G; the Osteoporosis Methodology Group; and the Osteoporosis Research Advisory Group.

BACKGROUND: Although calcium is one the simplest and least expensive strategies for preventing osteoporotic fractures calcium supplementation is nevertheless not without controversy (Kanis 1989; Nordin 1990). The Food and Drug Administration in the US has permitted a bone health claim for calcium-rich foods, and the NIH in its Consensus Development Process approved a statement that high calcium intake reduces the risk of osteoporosis. OBJECTIVES: To assess the effects of calcium on bone density and fractures in postmenopausal women. SEARCH STRATEGY: We searched Cochrane Controlled Register, MEDLINE and EMBASE up to 2001, and examined citations of relevant articles and proceedings of international meetings. SELECTION CRITERIA: Trials that randomized postmenopausal women to calcium supplementation or usual calcium intake in the diet and reported bone mineral density of the total body, vertebral spine, hip, or forearm or recorded the number of fractures, and followed patients for at least one year were considered for inclusion. DATA COLLECTION AND ANALYSIS: Three independent reviewers assessed the methodologic quality and extracted data for each trial. For each bone density site (lumbar spine, total body, combined hip and combined forearm), we calculated the weighted mean difference in bone density between treatment and control groups using the percentage change from baseline. We constructed regression models in which the independent variables were year and dose, and the dependent variable was the effect size. This regression was used to determine the years across which pooling was appropriate. Heterogeneity was asssesed. For each fracture analysis we calculated a risk ratio. MAIN RESULTS: Fifteen trials, representing 1806 participants, were included. Calcium was more effective than placebo in reducing rates of bone loss after two or more years of treatment. The pooled difference in percentage change from baseline was 2.05% (95% CI 0.24 to 3.86) for total body bone density, 1.66% (95% CI 0.92 to 2.39) for the lumbar spine at 2 years, 1.60% (95% CI 0.78 to 2.41) for the hip, and 1.91% (95% CI 0.33 to 3.50) for the distal radius. The relative risk of fractures of the vertebrae was 0.79 (95% CI 0.54 to 1.09); the relative risk for non-vertebral fractures was 0.86 (95% CI 0.43 to 1.72). AUTHORS' CONCLUSIONS: Calcium supplementation alone has a small positive effect on bone density. The data show a trend toward reduction in vertebral fractures, but it is unclear if calcium reduces the incidence of non vertebral fractures.

 

Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004523.

WITHDRAWN: Risedronate for the prevention and treatment of postmenopausal osteoporosis.

Cranney A, Adachi J, Guyatt G, Papaioannou A, Robinson V, Shea B, Tugwell P, Waldegger L, Weaver B, Wells G, Zytaruk N.

BACKGROUND: Postmenopausal osteoporosis results in an increased susceptibility to low-trauma fractures due to reduced bone volume and microarchitectural deterioration. Risedronate, a third generation bisphosphonate, has been shown in multiple clinical trials to reduce fracture risk and improve bone mineral density in postmenopausal women with osteoporosis. First and second generation bisphosphonates are known to have gastrointestinal side-effects and risedronate may be better tolerated. OBJECTIVES: To systematically review the efficacy of risedronate on bone density, and fracture reduction in postmenopausal women. SEARCH STRATEGY: The Cochrane Controlled Trials Registry Medline, and Current Contents were searched from 1990 - 2001. The electronic search was supplemented by handsearching four osteoporosis journals and their conference proceedings, as well as contacting content experts and industry sources for unpublished data. SELECTION CRITERIA: We included eight trials that randomised women to risedronate or an alternative (placebo or calcium and /or vitamin D) and measured bone mineral density for at least one year. DATA COLLECTION AND ANALYSIS: For each trial three independent reviewers assessed the methodological quality and abstracted data. Data was extracted for outcomes of fracture, bone mineral density and adverse events. The more conservative random effects model was used to pool data. The quality of trials was assessed according to the Jadad five-point scale. MAIN RESULTS: Both vertebral and non-vertebral fractures were statistically and clinically reduced with risedronate. Eleven out of one hundred women who received risedronate had a vertebral fracture compared to 17 out of one hundred of those who received calcium and vitamin D (pooled relative risk for vertebral fractures of 0.64 (95% CI 0.52 - 0.77). Three percent of participants who received risedronate had a non-vertebral fracture compared to 4.6% of those who received calcium and vitamin D (pooled relative risk for nonvertebral fractures of 0.73 (95% CI 0.61 - 0.87). The weighted mean difference for the percent change from baseline for bone mineral density with 5 mg daily for lumbar spine, femoral neck and trochanter was 4.54% (95%CI 4.12 - 4.97), p<0.01; 2.75% (95% CI 2.32 - 3.17), p<0.01; and 4.38% (95% CI 3.51 - 5.25), p<0.01 respectively. AUTHORS' CONCLUSIONS: There is good evidence for the efficacy of risedronate in the reduction of both vertebral and non-vertebral fractures. In addition, there is evidence from randomized trials that risedronate is able to achieve this without increasing risk for overall withdrawals due to adverse effects.

 

Obesity (Silver Spring). 2007 Jul;15(7):1827-1840.

Morbidity and Mortality Risk Associated With an Overweight BMI in Older Men and Women.

Janssen I.

School of Kinesiology and Health Studies, Queen’s University, Kingston, Ontario, Canada, K7L 3N6.

Background: There is controversy as to whether older adults with a BMI in the overweight range (25 to 29.9 kg/m(2)) are at increased health risk and whether they should be encouraged to lose weight. The purpose of this study was to determine whether older adults with a BMI in the overweight range are at increased morbidity and mortality risk. Methods: Participants consisted of 4968 older (>/=65 years) men and women from the Cardiovascular Health Study limited access dataset. Based on BMI (kg/m(2)), participants were grouped into normal-weight (20 to 24.9 kg/m(2)), overweight (25 to 29.9 kg/m(2)), and obese (>/=30 kg/m(2)) categories. Participants were followed for up to 9 years to determine if they developed 10 weight-related health outcomes that are pertinent to older adults. Cox proportional hazards models were used to estimate the hazards ratios of morbidity and mortality after adjusting for age, sex, income, smoking, and physical activity. RESULTS: Compared with the normal-weight group, the risks of myocardial infarction, stroke, sleep apnea, urinary incontinence, cancer, and osteoporosis were not different in the overweight group (p > 0.05). The risks for arthritis and physical disability were modestly increased in the overweight group (p < 0.05), whereas the risk for type 2 diabetes was increased by 78% in the overweight group (p < 0.01). After adjusting for all relevant covariates, all-cause mortality risk was 11% lower in the overweight group (p < 0.05). Conclusions: A BMI in the overweight range was associated with some modest disease risks but a slightly lower overall mortality rate. These findings suggest that a BMI cut-off point of 25 kg/m(2) may be overly restrictive for the elderly.

 

Curr Med Res Opin. 2007 Jul 12; [Epub ahead of print]

Prevalence of vitamin D inadequacy in European postmenopausal women.

Reginster JY.

OBJECTIVE: Inadequate vitamin D level is associated with secondary hyperparathyroidism and increased bone turnover and bone loss, which in turn increases fracture risk. The objective of this study is to assess the prevalence of inadequate serum vitamin D levels in postmenopausal European women. There are no clear international agreements on what constitutes a level of vitamin D inadequacy, but recent publications suggest that the circulating level of vitamin D should be over 80 nmol/L or at least between 50 and 80 nmol/L.MATERIAL AND METHODS: Assessment of 25-hydroxyvitamin D [25(OH)D] was performed in 8532 European postmenopausal women with osteoporosis or osteopenia. European countries included France, Belgium, Denmark, Italy, Poland, Hungary, United Kingdom, Spain and Germany. Two cut-offs of 25(OH)D inadequacy were fixed : < 80 nmol/L and < 50 nmol/L.RESULTS: Mean (SD) age of the patients was 74.2 (7.1) years, body mass index was 25.7 (4.1) kg/m(2). Level of 25(OH)D was 61.0 (27.2) nmol/L. There was a highly significant difference of 25(OH)D level across European countries (p < 0.0001). The lowest level of 25(OH)D was found in France [51.5 (26.1) nmol/L] and the highest in Spain [85.2 (33.3) nmol/L]. In the whole study population, the prevalence of 25(OH)D inadequacy was 79.6% and 32.1% when considering cut-offs of 80 and 50 nmol/L, respectively and when considering patients aged less than 65 years, the prevalence reached 86% (cut-off of 80 nmol/L) and 45% (cut-off of 50 nmol/L).CONCLUSION: This study indicates a high prevalence of vitamin D [25(OH)D] inadequacy in European postmenopausal women. The prevalence could be even higher in some particular countries. A greater awareness of the importance of vitamin D inadequacy is needed to address this public health problem.

 

Osteoporos Int. 2007 Jul 19; [Epub ahead of print]

Effectiveness of antiresorptive agents in the prevention of recurrent hip fractures.

Morin S, Rahme E, Behlouli H, Tenenhouse A, Goltzman D, Pilote L.

Division of Internal Medicine, McGill University Health Center (MUHC), 1650 Cedar Ave, Room B2-118, Montreal, QC, H3G 1A4, Canada.

Hip fracture is associated with recurrent fractures and increased mortality. The results of our retrospective cohort study support the use of antiresorptive agents to prevent recurrent hip fractures in this population. INTRODUCTION: Hip fracture, the most serious consequence of osteoporosis, is associated with recurrent fractures and increased mortality. Antiresorptive therapy has proven efficacy in the prevention of fractures after vertebral fractures. It is unknown if it can prevent recurrent fractures after a hip fracture. METHODS: We designed a population based, retrospective cohort study, using administrative databases and identified patients hospitalized for a hip fracture between 1996 and 2002. The exposure was defined as being dispensed a prescription for an antiresorptive agent at any time following discharge. Multivariate Cox regression models were used to estimate the hazard ratio of recurrent hip fracture. Subgroup and propensity score analyses were performed. RESULTS: A total of 20,644 patients were identified; 6,779 filled a prescription for antiresorptive agents. There were 992 recurrent hip fractures. Patients exposed to antiresorptives had a 26% reduction in the rate of recurrent fractures (adjusted hazard ratio 0.74; 95% CI, 0.64-0.86) compared to patients who were not. All subgroups experienced a reduction in recurrent fracture, except the very elderly. Propensity score analyses were consistent with the main analysis. CONCLUSIONS: Antiresorptive therapy reduces the risk of recurrent hip fractures in elderly patients. These results provide evidence that this therapy should be considered for secondary prevention of hip fractures.

 

Endocr J. 2007 Jul 20; [Epub ahead of print]

Subclinical Hypothyroidism is Related to Lower Heel QUS in Postmenopausal Women.

Nagata M, Suzuki A, Sekiguchi S, Ono Y, Nishiwaki-Yasuda K, Itoi T, Yamamoto S, Imamura S, Katoh T, Hayakawa N, Oda N, Hashimoto S, Itoh M.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Fujita Health University.

Recent findings suggest that thyroid stimulating hormone (TSH) is a negative regulator of skeletal remodeling by reducing both differentiation of osteoblasts and formation of osteoclasts. In addition, increased fracture risk in untreated hypothyroid patients has been reported to begin up to 8 years before diagnosis. The aim of the present study was to evaluate the effect of subclinical hypothyroidism on bone structure by using the heel QUS. Subjects were outpatients without any past or present history of thyroid disease. Among 210 postmenopausal women, 22 of 33 patients (Hypo), who had elevated serum TSH concentration (TSH >/=4 muU/ml) with normal serum free thyroxine (FT(4)) concentration, agreed to join to this study. We also randomly selected 24 control subjects (Cont) from 176 postmenopausal women with normal thyroid status. Calcaneus osteo sono assessment indices (OSI) of right feet were measured using the ultrasound bone densitometry AOS-100. Serum TSH concentrations in Hypo patients (5.31 +/- 1.3 muU/ml) were higher than those in Cont patients (2.05 +/- 1.1 muU/ml), and there was significant difference of FT(4) concentrations (Cont 1.33 +/- 0.15 ng/dl; Hypo 1.19 +/- 0.17 ng/dl). OSI and its Z-score in Hypo subjects (OSI, 2.138 +/- 0.152; Z-Score -0.322 +/- 0.504 SD, Mean +/- SD) were significantly lower than those in Cont subjects (OSI, 2.347 +/- 0.243; Z-Score 0.322 +/- 0.91 SD, Mean +/- SD). Simple regression statistical analysis showed that OSI decreased according to the increase of serum TSH concentration (n = 47, P<0.037). In addition, multiple regression analysis showed that the elevation of serum TSH concentration was associated with the decrease of OSI. These results suggest that the elevation of serum TSH concentration in subclinical hypothyroidism affects not bone turnover but bone structure as assessed by QUS.

 

Nutr Cancer. 2007;58(2):136-45.

Lifestyle and Dietary Correlates of Plasma Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1), Leptin, and C-Peptide: The Multiethnic Cohort.

Henderson KD, Rinaldi S, Kaaks R, Kolonel L, Henderson B, Le Marchand L.

Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033.

Circulating insulin-like growth factor binding protein 1 (IGFBP-1), leptin, and insulin are 3 proteins modified by obesity and have been associated with cancer at several sites in past studies. We conducted a cross-sectional study to describe the correlation of these proteins with gender, race/ethnicity, anthropometric indexes, and dietary and lifestyle factors. We measured fasting plasma levels of IGFBP-1, leptin, and C-peptide, used here as a stable measure of insulin secretion, in a random sample of 450 male and 352 postmenopausal female Hawaii and Los Angeles Multiethnic Cohort Study (MEC) participants (age range 47-82 yr at blood draw). Through a series of multiple linear regressions, we found that the most parsimonious model for plasma IGFBP-1 included inverse associations with age, body mass index (BMI), and regular soda intake. A term for interaction between age and BMI was positively associated with plasma IGFBP-1. Adjusted mean plasma leptins were highest among Whites and African Americans and lowest among Hawaiians and Japanese Leptin was also inversely associated with age and positively associated with the interaction between age and race/ethnicity, female gender, and BMI. A model with only race/ethnicity and BMI (positive association) was best for plasma C-peptide. Adjusted means for C-peptide were highest for Japanese and Whites and lowest for African Americans. The overall percent of variance in protein levels explained by these models was low for IGFBP-1(R2=0.17) and C-peptide (R(3)=0.11) and higher for leptin (R(2)=0.57). We saw no clear correlation between racial/ethnic trends in protein levels with those of colorectal, breast, or prostate cancer incidence rates in the MEC. Research to clarify factors associated with determination of these proteins and their relationship with cancer etiology is warranted.

 

Nutr Cancer. 2007;58(2):127-35.

Dietary fiber intake and endogenous serum hormone levels in naturally postmenopausal mexican american women: the multiethnic cohort study.

Monroe KR, Murphy SP, Henderson BE, Kolonel LN, Stanczyk FZ, Adlercreutz H, Pike MC.

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA.

This study investigated dietary fiber intake in association with serum estrogen levels in naturally postmenopausal Latina women with a wide range of fiber intake. Estrone (E1), estradiol (E2), and sex-hormone-binding globulin (SHBG) were measured in 242 women. Associations between estrogen levels and intake of dietary fiber, including insoluble and soluble fractions, quantified from a food frequency questionnaire, were examined. The biomarker enterolactone was also measured. After adjustment for age, weight, and other nondietary factors, dietary fiber intake was inversely associated with E1 and E2; there was a 22% and 17% decrease (2Ptrend=0.023 and 0.045) among subjects in the highest quintile of intake compared with the lowest. Fitting dietary fiber together with soluble and insoluble nonstarch polysaccharides (NSP) showed a much greater decrease in E1 and E2 (47% and 41%, respectively) while increased soluble NSP intake showed increases in E1 and E2 (64% and 69%, respectively). Two foods, avocado and grapefruit, showed significant positive associations with E1 (2Ptrend=0.029 and 0.015, respectively). This study suggests that different components of dietary fiber may have very significant different effects on serum estrogen levels. The suggestive findings relating increased estrogen levels to avocado and grapefruit intakes need confirmation.

 

Endocr Relat Cancer. 2007 Jun;14(2):169-87.

Critical assessment of new risk factors for breast cancer: considerations for development of an improved risk prediction model.

Santen RJ, Boyd NF, Chlebowski RT, Cummings S, Cuzick J, Dowsett M, Easton D, Forbes JF, Key T, Hankinson SE, Howell A, Ingle J.

Internal Medicine/Endocrinology, University of Virginia Health System, Charlottesville, Virginia USA.

The majority of candidates for breast cancer prevention have not accepted tamoxifen because of the perception of an unfavorable risk/benefit ratio and the acceptance of raloxifene remains to be determined. One means of improving this ratio is to identify women at very high risk of breast cancer. Family history, age, atypia in a benign biopsy, and reproductive factors are the main parameters currently used to determine risk. The most powerful risk factor, mammographic density, is not presently employed routinely. Other potentially important factors are plasma estrogen and androgen levels, bone density, weight gain, age of menopause, and fracture history, which are also not currently used in a comprehensive risk prediction model because of lack of prospective validation. The Breast Cancer Prevention Collaborative Group (BCPCG) met to critically examine and prioritize risk factors that might be selected for further testing by multivariate analysis using existing clinical material. The BCPCG reached a consensus that quantitative breast density, state of the art plasma estrogen and androgen measurements, history of fracture and height loss, BMI, and waist-hip ratio had sufficient priority for further testing. As a practical approach, these parameters could be added to the existing Tyrer-Cuzick model which encompasses factors included in both the Claus and Gail models. The BCPCG analyzed potentially available clinical material from previous prospective studies and determined that a large case/control study to evaluate these new factors might be feasible at this time.

 

Cancer Causes Control. 2007 Jul 19; [Epub ahead of print]

Breast density in relation to risk of ductal carcinoma in situ of the breast in women undergoing screening mammography.

Mackenzie TA, Titus-Ernstoff L, Vacek PM, Geller B, Weiss JE, Goodrich ME, Carney PA.

Department of Community & Family Medicine, Dartmouth Medical School, Norris Cotton Cancer Center, Hanover, NH, USA.

OBJECTIVE: To examine the association between breast density and risk of breast ductal carcinoma in situ (DCIS). METHODS: We assessed breast density in relation to DCIS risk using combined data from statewide mammography registries in NH and VT. The prospective analyses were based on 572 DCIS cases arising in 154,936 women (58,496 premenopausal and 96,440 postmenopausal). Women in the study were followed on average 4.1 years. Breast density was scored by community radiologists using BIRADS categories (fatty, scattered density, heterogeneous density, extreme density). RESULTS: In premenopausal women, based on 157 cases, the RR for DCIS risk were 0.29 (95% CI: 0.0.04, 2.24) for fatty breasts, 2.06 (95% CI: 1.39, 3.05) for heterogeneous density, and 2.40 (95% CI: 1.47, 3.91) for extreme density, relative to scattered density. In postmenopausal women, based on 369 cases, the RR for DCIS risk were 0.58 (95% CI: 0.37, 0.93) for fatty breasts, 1.41 (95% CI: 1.12, 1.78) for heterogeneous density, and 1.49 (95% CI: 0.93, 2.37) for extreme density, relative to scattered density. The possible interaction between breast density and menopausal status in relation to DCIS risk was not statistically significant. CONCLUSIONS: We observed an association between breast density and DCIS risk. Although the association seemed stronger in premenopausal women, there was no evidence of an interaction involving breast density and menopausal status.

 

 

Semana del 9 al 16 de Julio 2007

 

BMJ. 2007 Jul 11; [Epub ahead of print

Main morbidities recorded in the women's international study of long duration oestrogen after menopause (WISDOM): a randomised controlled trial of hormone replacement therapy in postmenopausal women.

Vickers MR, Maclennan AH, Lawton B, Ford D, Martin J, Meredith SK, Destavola BL, Rose S, Dowell A, Wilkes HC, Darbyshire JH, Meade TW.

MRC General Practice Research Framework, Stephenson House, London NW1 2ND.

OBJECTIVE: To assess the long term risks and benefits of hormone replacement therapy (combined hormone therapy versus placebo, and oestrogen alone versus combined hormone therapy). DESIGN: Multicentre, randomised, placebo controlled, double blind trial. SETTING: General practices in UK (384), Australia (91), and New Zealand (24). PARTICIPANTS: Postmenopausal women aged 50-69 years at randomisation. At early closure of the trial, 56 583 had been screened, 8980 entered run-in, and 5692 (26% of target of 22 300) started treatment. INTERVENTIONS: Oestrogen only therapy (conjugated equine oestrogens 0.625 mg orally daily) or combined hormone therapy (conjugated equine oestrogens plus medroxyprogesterone acetate 2.5/5.0 mg orally daily). Ten years of treatment planned. MAIN OUTCOME MEASURES: Primary outcomes: major cardiovascular disease, osteoporotic fractures, and breast cancer. Secondary outcomes: other cancers, death from all causes, venous thromboembolism, cerebrovascular disease, dementia, and quality of life. RESULTS: The trial was prematurely closed during recruitment, after a median follow-up of 11.9 months (interquartile range 7.1-19.6, total 6498 women years) in those enrolled, after the publication of early results from the women's health initiative study. The mean age of randomised women was 62.8 (SD 4.8) years. When combined hormone therapy (n=2196) was compared with placebo (n=2189), there was a significant increase in the number of major cardiovascular events (7 v 0, P=0.016) and venous thromboembolisms (22 v 3, hazard ratio 7.36 (95% CI 2.20 to 24.60)). There were no statistically significant differences in numbers of breast or other cancers (22 v 25, hazard ratio 0.88 (0.49 to 1.56)), cerebrovascular events (14 v 19, 0.73 (0.37 to 1.46)), fractures (40 v 58, 0.69 (0.46 to 1.03)), and overall deaths (8 v 5, 1.60 (0.52 to 4.89)). Comparison of combined hormone therapy (n=815) versus oestrogen therapy (n=826) outcomes revealed no significant differences. CONCLUSIONS: Hormone replacement therapy increases cardiovascular and thromboembolic risk when started many years after the menopause. The results are consistent with the findings of the women's health initiative study and secondary prevention studies. Research is needed to assess the long term risks and benefits of starting hormone replacement therapy near the menopause, when the effect may be different.

 

J Sex Med. 2007 Jul;4(4i):1001-1008

Evaluation of the Clinical Relevance of Benefits Associated with Transdermal Testosterone Treatment in Postmenopausal Women with Hypoactive Sexual Desire Disorder.

Kingsberg S, Shifren J, Wekselman K, Rodenberg C, Koochaki P, Derogatis L.

University Hospitals of Cleveland, Cleveland, OH, USA.

Introduction. Postmenopausal women with hypoactive sexual desire disorder (HSDD) experienced statistically significant improvements in the frequency of satisfying sexual activity, sexual desire, and distress with testosterone treatment in phase III trials, but it was not known whether the magnitude of these effects was clinically meaningful. The clinical relevance study was designed to answer this question. Aim. To evaluate the clinical relevance of the treatment benefits. Methods. This study involved a representative sample of 132 surgically postmenopausal women with HSDD who were enrolled in two randomized, placebo-controlled trials (N = 1094) assessing the efficacy and safety of transdermal testosterone treatment (300 mcg/day) for 6 months. At the end of the studies, prior to unblinding, a sample of women (12%) was interviewed concerning their experiences with the treatment. Main Outcome Measures. Women were asked "Overall, would you say that you experienced a meaningful benefit from the study patches?" Changes in the efficacy end points in the double-blind studies were compared for the women who did and did not experience an overall meaningful benefit. Results. Overall, 33 of 64 women (52%) who received testosterone reported experiencing a meaningful treatment benefit, compared with 21 of 68 women (31%) who received placebo (P = 0.025). Among the women who identified themselves as experiencing a meaningful benefit, the mean (SE) change from baseline in 4-week frequency of satisfying sexual activity was 4.4 (0.76), in desire score was 21.0 (2.78), moving from "seldom" to "sometimes" feeling sexual desire, and in distress score was -36.5 (3.96), moving from "often" to "seldom" being distressed. Among the women who identified themselves as not experiencing a meaningful benefit, the mean (SE) change from baseline in 4-week frequency of satisfying sexual activity was 0.5 (0.31), in desire score was 2.9 (1.42), and in distress score was -8.8 (2.23). Conclusions. Surgically menopausal women with HSDD in these studies received clinically meaningful benefits, including improvements in satisfying sexual activity, sexual desire, and personal distress.

 

J Sex Med. 2007 Jul;4(4i):1056-1069

The Burden of Testosterone Deficiency Syndrome in Adult Men: Economic and Quality-of-Life Impact.

Maggi M, Schulman C, Quinton R, Langham S, Uhl-Hochgraeber K.

Andrology Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy.

Introduction. Testosterone deficiency syndrome (TDS) causes a wide range of symptoms that can lead to significant morbidity. Preliminary evidence has also linked TDS with premature mortality and with a number of comorbid diseases including diabetes and metabolic syndrome. Such associations can lead to substantial economic and quality- of-life implications, the magnitude of which remains largely unknown. Aim. To review the economic and quality-of-life consequences of a largely untreated condition and to consider the likely health economic benefits of testosterone treatment. Methods. A systematic review of four main areas: epidemiological evidence of the magnitude of TDS, estimates of cost of illness, impact on quality-of-life, and cost-effectiveness of testosterone treatment. Main Outcome Measure. Review of peer-reviewed literature. Results. The lack of clear universally accepted diagnostic criteria and the uncertainty surrounding the link between TDS and some of its consequences complicate the estimation of the burden of illness of TDS. Consequences of TDS that potentially lead to increased economic burden include depression, sexual dysfunction, mild cognitive impairment, osteoporosis, cardiovascular disease, and mortality. However, although good evidence exists demonstrating an association between TDS and sexual dysfunction and cognitive impairment, evidence is less strong for depression, the incidence of fractures and mortality, and highly controversial for cardiovascular disease. The consequences that are likely to impact on patients' quality of life include sexual function, energy levels, body composition, mood, and cognitive function. Conclusion. Understanding the burden is only the first step decision makers need to take to decide whether to allocate scarce resources to treat the condition. To make informed decisions on when and who to treat information is also needed on the cost-effectiveness of available treatments. Such data would highlight the benefits of treatment of TDS to physicians, patients, and to society as a whole.

 

Aust N Z J Obstet Gynaecol. 2007 Aug;47(4):329-34

A quantitative analysis of the menopause experience of Indian women living in Sydney.

Hafiz I, Liu J, Eden J.

School of Public Health and Community Medicine, Faculty of Medicine, The University of New South Wales, Sydney, New South Wales, Australia.

Aims: To examine the experience of menopause in Indian women (aged 45-65 years) in Sydney, and the relationship between sociodemographic factors and menopausal symptoms, and also to explore the cultural context. Methods: Two hundred and three women were interviewed about their menopausal experiences in the preceding week using the 29-item Menopause-Specific Quality of Life questionnaire. Results: The mean age of menopause for Indian women was found to be earlier than in other groups in the published literature, at 48.21 years. While there were higher scores for physical symptoms than for other symptoms, and there were significant differences between perimenopausal women and the others, it was found that the prevalence of classical menopausal symptoms was lower in Indian women than that found in Caucasians. However, physical and several psychological symptoms were found to be more prevalent than the usual vasomotor symptoms. Unemployed women and women with a tertiary level of education were found to experience a significantly higher score for all symptoms in our sample. Conclusions: Lower scores of menopause symptoms indicate that Indian women have fewer complaints of symptoms and a positive attitude towards menopause. Somatic symptoms are multifactorial in nature and could be because of health problems associated with ageing, midlife crises and cultural influences. Further detailed studies could examine the important relationship between cultural lifestyle factors and climacteric symptoms.

 

Menopause. 2007 Jul 6; [Epub ahead of print

Association of general and abdominal obesities and metabolic syndrome with subclinical atherosclerosis in asymptomatic Chinese postmenopausal women.

Yu RH, Ho SC, Ho SS, Woo JL, Ahuja AT.

From the 1Department of Community and Family Medicine, Chinese University of Hong Kong, School of Public Health; 2Department of Diagnostic Radiology and Organ Imaging, the Chinese University of Hong Kong, The Sir Yue-kong Pao Centre for Cancer, and the Lady Pao Children's Cancer Centre; and 3Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong, SAR.

OBJECTIVE:: This study aimed to investigate the relationships between obesity, especially abdominal obesity, andmetabolic syndrome (MS) with carotid intima-media thickness (IMT) and plaque, markers of subclinical atherosclerosis, in asymptomatic Chinese postmenopausal women in Hong Kong. DESIGN:: A total of 518 postmenopausal women aged 50 to 64 years were recruited through random telephone dialing. Body mass index (BMI), waist circumference, waist-to-hip ratio, sociodemographic characteristics, blood pressures, medical, biochemical and lifestyle factors were obtained. MS was defined on the basis of the National Cholesterol and Education Program, Adult Treatment Panel III criteria. Subclinical atherosclerosis was determined by measuring IMT and plaque using high-resolution B-mode ultrasonography. RESULTS:: Women with a BMI of 25 kg/mor greater, a waist circumference of 80 cm or greater, a waist-to-hip ratio of 0.85 or greater, or MS were observed to have higher IMT values and prevalence of plaque. Multivariate analyses revealed that waist circumference was significantly associated with IMT independent of age, hormone therapy, lifestyle and sociodemographic factors, and BMI (P < 0.05), whereas a waist-to-hip ratio of 0.85 or greater was significantly associated with plaque (odds ratio = 1.7; 95% CI: 1.0-2.8) after controlling for age, hormone therapy, lifestyle and sociodemographic factors, BMI, and the traditional cardiovascular risk factors. MS was also associated with IMT after adjustment for age, hormone therapy, lifestyle and sociodemographic factors, and BMI (P < 0.05), whereas its association with plaque was also significant (odds ratio = 1.7; 95% CI: 1.0-2.6) after controlling for age. CONCLUSIONS:: Abdominal obesity and MS are independent of general obesity markers of subclinical atherosclerosis in Chinese postmenopausal women.

 

J Musculoskelet Neuronal Interact. 2007 Apr-Jun;7(2):144-8.

Common musculoskeletal adverse effects of oral treatment with once weekly alendronate and risedronate in patients with osteoporosis and ways for their prevention.

Bock O, Boerst H, Thomasius FE, Degner C, Stephan-Oelkers M, Valentine SM, Felsenberg D.

Centre for Muscle and Bone Research, Charite - University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany.

Objective: To examine in a major cohort of patients whether or not musculoskeletal adverse effects (MAEs), similar to those seen in intravenous bisphosphonates (BP), might occur also in high dosage oral treatment regimens with alendronate (ALN) and risedronate (RSN). Patients and methods: 612 consecutive patients treated in the osteoporosis outpatient clinic at Charite, Campus Benjamin Franklin, between July 2002 and October 2003 with oral ALN or RSN (mean age 68.2+/-9.7 years; 527 females, 85 males), were examined and followed up for MAEs. Results: The overall frequency of any severe MAEs in our patients was low (5.6%). All severe MAEs occurred in primarily once weekly treated patients: 27 in ALN 70 mg once weekly (27/134=20.1%) and 7 in RSN 35 mg once weekly (7/28=25.0%), with no significant difference between those groups. The most frequently reported MAE was acute arthralgia in 12.6%, followed by acute back pain in 9.1% of all primarily once weekly treated cases. None of the 302 patients initially treated with daily BP reported any MAEs when later switching to once weekly administration (218 patients to ALN 70 mg once weekly and 84 patients to RSN 35 mg once weekly). With reference to recently published data, the phenomenon is probably related to dose dependent gammadelta T cell activation by accumulation of isopentenyl pyrophosphate (IPP) due to inhibition of the mevalonate pathway by nitrogen containing bisphosphonates (nBP). Conclusions: MAEs in oral BP are, in general, less common and severe than in intravenous BP. They are observed exclusively in patients starting ALN or RSN treatment with once weekly dosage regimens. In order to avoid this phenomenon, it is suggested to start ALN or RSN treatment with the lower daily dosages of ALN 10 mg daily or RSN 5 mg daily for about two weeks before switching to the overall, more convenient, once weekly dose regimen.

 

Cancer Epidemiol Biomarkers Prev. 2007 Jul;16(7):1443-8. Epub 2007 Jul  

Dietary patterns and breast cancer risk in the shanghai breast cancer study.

Cui X, Dai Q, Tseng M, Shu XO, Gao YT, Zheng W.

Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111. m_tseng@fccc.edu.

The association of breast cancer with dietary patterns such as a western diet has not been studied in Asian women. We examined this among Shanghai Breast Cancer Study participants. Cases were of ages 25 to 64 years, diagnosed 08/1996-03/1998, and identified through a rapid case ascertainment system supplemented by the Shanghai Cancer Registry. Controls, selected from the general population of urban Shanghai, were frequency matched to cases by 5-year age group. Participants provided information on diet, lifestyle, and reproductive factors. In principal component analysis among 1,556 controls, two patterns emerged: a "vegetable-soy" pattern (tofu, cauliflower, beans, bean sprouts, green leafy vegetables) and a "meat-sweet" pattern (shrimp, chicken, beef, pork, candy, desserts). In adjusted unconditional logistic regression analyses including 1,446 cases and 1,549 controls with complete covariate data, risk was not associated with the vegetable-soy pattern. It was associated with the meat-sweet pattern (4th versus 1st quartile: odds ratio, 1.3; 95% confidence interval, 1.0-1.7; P(trend) = 0.03), but only in postmenopausal women, specifically among those with estrogen receptor-positive tumors (4th versus 1st quartile: odds ratio, 1.9; 95% confidence interval, 1.1-3.3; P(trend) = 0.03). Our findings indicate that a western diet increases breast cancer risk in postmenopausal Chinese women. They also suggest the value of quantifying aggregate risk for common combinations of foods.

 

BMC Public Health. 2007 Jul 9;7(1):150 [Epub ahead of print

Changes in body mass index in Canadians over a five-year period: Results of a prospective, population-based study.

Hopman WM, Leroux C, Berger C, Joseph L, Barr SI, Prior JC, Harrison M, Poliquin S, Towheed T, Anastassiades T, Goltzman D, Research Group C.

ABSTRACT: Background The initiation of the Canadian Multicentre Osteoporosis Study in 1996, and subsequent follow-up of the cohort 5 years later, provided longitudinal body mass index (BMI) data for a random sample of Canadians. Methods Height and weight were measured at baseline and 5 years and used to calculate BMI and assign one of six weight categories. Multiple imputation was used to adjust for missing weight at year 5. Data were stratified by age and gender. The proportion of participants moving between categories was generated, and multivariable linear regression was used to identify factors associated with weight change. Results Baseline data were available for 8548 participants, year 5 data for 6721, and year 5 weight was imputed for 1827 (17.6%). Mean BMI for every age and gender group exceeded healthy weight guidelines. Most remained within their BMI classification over 5 years, but when change occurred, BMI category was more likely to increase than decrease. Several sociodemographic, lifestyle and clinical characteristics were associated with change. Conclusions Mean baseline BMI tended to be higher than recommended. Moreover, on average, men under age 45 and women under age 55 were gaining approximately 0.45 kilograms (one pound) per year, which leveled off with increased age and reversed in the oldest age groups. These findings underscore the need for public health efforts aimed at combating obesity.

 

BMC Public Health. 2007 Jul 7;7(1):149 [Epub ahead of print

Early menopause, association with tobacco smoking, coffee consumption and other lifestyle factors: a cross-sectional study.

Mikkelsen TF, Graff-Iversen S, Sundby J, Bjertness E.

ABSTRACT: BACKGROUND: Early onset of menopause is a risk factor for several health problems. The objective was primarily to investigate the association between early menopause and current, past active and passive smoking. A second aim was to investigate the association between coffee and alcohol consumption and early menopause. METHODS: The present population-based cross-sectional study included a sub-sample of 2123 postmenopausal women born in 1940-41 who participated in the Oslo Health Study. Early menopause was defined as menopause occurring at an age of less than 45 years. We applied logistic regression analyses (crude and adjusted odds ratio (OR)) to examine the association between early menopause and selected lifestyle factors. RESULTS: Current smoking was significantly associated with early menopause (adj. OR, 1.59; 95% CI, 1.11-2.28). Stopping smoking more than 10 years before menopause considerably reduced the risk of early menopause (adj. OR, 0.13; 95% CI, 0.05-0.33). Total exposure to smoking (the product of number of cigarettes per day and time as a smoker) was positively related to early menopause and, at the highest doses, nearly doubled the odds (adj. OR, 1.93; 95% CI, 1.12-3.30). These data suggest a possible dose-response relationship between total exposure to smoking and early menopause, but no dose-response relationship was detected for the other variables examined. We found no significant association of coffee or alcohol consumption with early menopause. Of the lifestyle factors tested, high educational level (adj. OR, 0.50; 95% CI, 0.34-0.72) and high social participation (adj. OR, 0.60, 95% CI, 0.39-0.98) were negatively associated with early menopause. CONCLUSIONS: This cross-sectional study shows an association between current smoking and early menopause. The data also suggest that the earlier a woman stops smoking the more protected she is from early menopause. Early menopause was not significantly associated with passive smoking, or alcohol or coffee consumption.

 

J Sex Med. 2007 Jul;4(4i):859-866

Management of Female Sexual Dysfunction in Postmenopausal Women by Testosterone Administration: Safety Issues and Controversies.

Braunstein GD.

Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Introduction. A Food and Drug Administration advisory group has questioned the long-term safety of testosterone administration to postmenopausal women. Although only short-term data exist on safety from the double-blind, placebo-controlled trials, testosterone has been used for more than 50 years. Therefore, some data concerning the long-term safety issues must exist in the literature. Aim. To review the published data concerning the safety of administration of testosterone to women. Methods. Review of published articles identified by a search of the Ovid databases and bibliographies from articles identified as dealing with the topics of testosterone or androgen treatment of women. Results. The major adverse reactions to exogenous androgens are the expected androgenic side effects of hirsutism and acne. High-density lipoprotein levels may be decreased with oral androgens. There are insufficient long-term safety data regarding breast, endometrium, or heart safety to draw strong conclusions, although the data available to date are reassuring. Conclusions. Testosterone administration to postmenopausal women that result in physiological to slightly supraphysiological serum-free testosterone levels is safe for at least 2 years.

 

Semana del 2 al 8 de Julio 2007

Neurobiol Aging. 2007 Jun 29; [Epub ahead of print]

Menopausal transition: A possible risk factor for brain pathologic events.

Bonomo SM, Rigamonti AE, Giunta M, Galimberti D, Guaita A, Gagliano MG, Müller EE, Cella SG.

Department of Medical Pharmacology, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Milan, Italy; Center of Excellence for Neurodegenerative Diseases (CEND), University of Milan, Italy.

BACKGROUND AND OBJECTIVE: Incidence and prevalence of Alzheimer's disease (AD) are higher in postmenopausal women than in age-matched men. Since at menopause the endocrine system and other biological paradigms undergo substantial changes, we thought to be of interest studying whether (and how) the balance between some biological parameters allegedly neuroprotective (e.g. related to estrogen, dehydroepiandrosterone and CD36 functions) and others considered pro-neurotoxic (e.g. related to glucocorticoid and interleukin-6 activities) vary during lifespan in either sex in either normalcy or neurodegenerative disorders. SUBJECTS AND METHODS: Along with this aim, we evaluated the gene expression levels of estrogen receptors (ERs), glucocorticoid receptors (HGRs), interleukin-6 (IL-6) and CD36, a scavenger receptor of class B allegedly playing a key role in the proinflammatory events associated with AD, in a population of 209 healthy subjects (73M, 106F, 20-91-year old) and 85 AD patients (36M, 49F, 65-89-year old). Results obtained were related to plasma titers of estrogens, cortisol and dehydroepiandrosterone sulfate (DHEAS). Studies were performed in peripheral leukocytes, since these cells (1) are easily obtainable by a simple blood sampling, (2) express many molecules and multiple receptors which are under the same regulatory mechanisms as those operative in the brain and (3) some of them, e.g. monocytes, share many functions with microglial cells. RESULTS: In healthy men all the study parameters were quite stable during lifespan. In women, instead, at menopausal transition, some changes that may predispose to neurodegeneration occurred. In particular, there was (1) an up-regulation of ERs, and a concomitant increase of IL-6 gene expression, events likely due to the loss of the inhibitory control exerted by estradiol (E(2)); (2) an increase of HGRalpha:HGRbeta ratio, indicative of an augmented cortisol activity on HGRalpha not sufficiently counteracted by the inhibitory HGRbeta function; (3) a reduced CD36 expression, directly related to the increased cortisol activity; and (4) an augmented plasma cortisol:DHEAS ratio, widely recognized as an unfavorable prognostic index for the risk of neurodegeneration. In AD patients of both sexes, the expression of the study parameters was similar to that found in sex- and age-matched healthy subjects, thus indicating their unrelatedness to the disease, and rather a better correlation with biological events. CONCLUSIONS: Menopausal transition is a critical phase of women's life where the occurrence of an unfavorable biological milieu would predispose to an increased risk of neurodegeneration. Collectively, the higher prevalence of AD in the female population would depend, at least in part, on the presence of favoring biological risk factors, whose contribution to the development of the disease occurs only in the presence of possible age-dependent triggers, such as beta-amyloid deposition.

 

Calcif Tissue Int. 2007 Jul 6; [Epub ahead of print]

Evidence that Treatment with Risedronate in Women with Postmenopausal Osteoporosis Affects Bone Mineralization and Bone Volume.

Fratzl P, Roschger P, Fratzl-Zelman N, Paschalis EP, Phipps R, Klaushofer K.

Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany.

Risedronate is used in osteoporosis treatment. Postmenopausal women enrolled in the Vertebral Efficacy with Risedronate Therapy trial received either risedronate (5 mg/day) or placebo for 3 years. Subjects received calcium and vitamin D supplementation if deficient at baseline. Lumbar spine bone mineral density (BMD) was measured at baseline and at 3 years. Quantitative back-scattered electron imaging (qBEI) was performed on paired iliac crest biopsies (risedronate, n = 18; placebo, n = 13) before and after treatment, and the mineral volume fraction in the trabecular bone was calculated. Combining dual-energy X-ray absorptiometric values with the mineral volume fraction for the same patients allowed us to calculate the relative change in trabecular bone volume with treatment. This showed that the effect on BMD was likely to be due partly to changes in matrix mineralization and partly due to changes in bone volume. After treatment, trabecular bone volume in the lumbar spine tended to increase in the risedronate group (+2.4%, nonsignificant) but there was a significant decrease (-3.7%, P < 0.05) in the placebo group. Calcium supplementation with adequate levels of vitamin D led to an approximately 3.3% increase in mineral content in the bone material independently of risedronate treatment. This increase was larger in patients with lower matrix mineralization at baseline and likely resulted from correction of calcium/vitamin D deficiency as well as from reduced bone remodeling. Combining BMD and bone mineralization density distribution data show that in postmenopausal osteoporosis 3-year treatment with risedronate preserves or may increase trabecular bone volume, unlike placebo. This analysis also allows, for the first time, separation of the contributions of bone volume and matrix mineralization to the increase in BMD.

 

Nutr Hosp. 2007 May-Jun;22(3):313-21.

Dietary food habits, nutritional status and lifestyle in menopausal women in Spain

Ubeda N, Basagoiti M, Alonso-Aperte E, Varela-Moreiras G.

Dpto Nutrición, Bromatología y Tecnología de los Alimento, Fac. Farmacia, Universidad CEU San Pablo, Madrid.

AIM: To analyse the diet and the dietary food habits in a sample of 1,218 Spanish women, aged 40 to 77 years, in the menopausal or perimenopausal condition. Women were recruited nationwide and the diet was assessed using a food frequency questionnaire. RESULTS: Diet in our population group was close to the representative dietary habits of the Spanish population, except for dairy products. These were highly consumed (approximately 4 servings/day) by menopausal women. Energy, protein and cholesterol intakes, as well as most vitamins and mineral intakes, were very high, as compared to recommended dietary allowances. We only found marginal deficient intakes for folate and vitamin D. Women over 60 years consume less eggs, sweats, sugar and miscellany, and therefore less lipids and cholesterol, as well as vitamin D, than younger women. A high rate (61%) of overweight and obesity (BMI > 25) was present in our population group and was associated with a higher intake of meat, fish and eggs, as well as energy. A healthier diet (high intake of dairy products, fresh vegetables, fruits, legumes, cereals and fish) was associated with a healthier lifestyle (no smoking, physical exercise) and the use of fortified foods and vitamin/mineral supplements. A high percentage of women regularly consumed fortified food (52,7%) and micronutrient supplements (22,8%) although diets provided enough vitamins and minerals. CONCLUSION: Diet in our study group is in accordance to healthy dietary habits and physical activity recommendations. This is probably due to a greater concern for health in women close to the menopause condition.

 

Int J Oncol. 2007 Aug;31(2):303-12.

Immune-surveillance and programmed cell death-related genes are significantly overexpressed in the normal breast epithelium of postmenopausal parous women.

Balogh GA, Russo IH, Spittle C, Heulings R, Russo J.

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

Endocrine and reproductive influences significantly affect the lifetime risk of breast cancer. Nulliparity is one of the most firmly established risk factors for breast cancer, whereas early full-term pregnancy and parity confer a significant protection. The breast attains its maximum development during pregnancy and lactation. After menopause the breast regresses in both nulliparous and parous women containing lobular structures designated lobules type 1 (Lob 1). We have postulated that the degree of differentiation acquired through early pregnancy changes the 'genomic signature' that differentiates the Lob 1 from the early parous women from that of the nulliparous women by shifting the Stem cell 1 to a Stem cell 2, making this the mechanism of protection conferred by early full-term pregnancy. In order to elucidate the molecular pathways through which pregnancy exerts a protective effect, we have analyzed the genomic profile of Lob 1 present in reduction mammoplasty specimens obtained from parous and nulliparous postmenopausal women. The genes differentially expressed are related to immune-surveillance, DNA repair, programmed cell death, transcription, and chromatin structure/activators/co-activator. In the present study we performed real-time RT-PCR using a low-density array or a microfluid card for genes related to the immune system and programmed cell death, using 18S as an internal control [TaqMan(R) Low Density Array Human Immune Panel (Applied Biosystems)]. Breast epithelial cells from parous women significantly overexpressed 17 out of 20 genes (p<0.001) with respect to the nulliparous breast. BCL2-associated X protein, Complement component 3, CD45 antigen, glyceraldehyde-3-phosphate dehydrogenase, granulysin, and chemokine (C-C motif) ligand 19 were expressed more than 30-fold with respect to nulliparous breast cells. Only three out of 20 genes [selectin P (granule membrane protein 140 kDa, antigen CD62), Fas (TNF receptor superfamily, member 6) and chemokine (C-X-C motif) ligand 11], were downregulated in parous breast with respect to nulliparous breast cells. The data lead us to conclude that an early pregnancy, by shifting the Stem cell 1 to Stem cell 2, makes the latter more easily recognized by the immune-surveillance system, which initiates the programmed cell death pathway if exposure to toxic or carcinogenic agents occurs.

 

Clin Sci (Lond). 2007 Jul 4; [Epub ahead of print]

Relations of waist and hip circumference with coagulation and fibrinolysis in postmenopausal women.

Peverill RE, Teede HJ, Malan E, Kotsopoulos D, Smolich JJ, McGrath BP.

The contribution of obesity to the occurrence of cardiovascular events may not be wholly related to its influence on traditional risk factors. Coagulation and fibrinolysis may also influence cardiovascular risk, but the relationship of adiposity with these processes is unclear. The aim of this study was to investigate the relationships of body mass index (BMI), waist circumference, hip circumference and waist-to-hip ratio (WHR) with factor VII activity (VIIc), plasma markers of thrombin generation (prothrombin fragment 1+2; F1+2), fibrin formation (soluble fibrin; SF) and fibrin turnover (D-dimer), and plasminogen activator inhibitor-1 (PAI-1; a marker of fibrinolytic inhibitory capacity). The study cohort was 80 healthy postmenopausal women who were not diabetic, current smokers or taking hormone therapy and who had a fasting sample of blood collected. VIIc, F1+2, SF and PAI-1 were all positively correlated with BMI, waist circumference and WHR, while D-dimer was positively correlated with waist circumference and WHR, but not BMI. WHR was the strongest correlate of all the markers except for PAI-1 which was most closely related to BMI. Hip circumference was a negative correlate of F1+2 and D-dimer after adjusting for waist circumference. The relationships of WHR with F1+2 and SF, but not with VIIc and D-dimer, were independent of traditional risk factors. The positive association between waist circumference and markers of thrombin generation, fibrin production and fibrin turnover suggests that abdominal adiposity may contribute to atherothrombosis by activating intravascular coagulation. In contrast, a larger hip circumference appears to have a protective affect against coagulation activation.

 

Expert Rev Cardiovasc Ther. 2007 Jul;5(4):777-789.

Sex hormone replacement therapy and modulation of vascular function in cardiovascular disease.

Koledova VV, Khalil RA.

Brigham and Women’s Hospital, Division of Vascular Surgery, Harvard Medical School,  Boston, MA 02115, USA.

Epidemiological and experimental studies suggest vascular protective effects of estrogen. Cardiovascular disease (CVD) is less common in premenopausal women than in men and postmenopausal women. Cytosolic/nuclear estrogen receptors (ERs) have been shown to mediate genomic effects that stimulate endothelial cell growth but inhibit vascular smooth muscle proliferation. However, the Heart and Estrogen/Progestin Replacement Study (HERS), HERS-II and Women's Health Initiative clinical trials demonstrated that hormone replacement therapy (HRT) may not provide vascular benefits in postmenopausal women and may instead trigger adverse cardiovascular events. HRT may not provide vascular benefits because of the type of hormone used. Oral estrogens are biologically transformed by first-pass metabolism in the liver. By contrast, transdermal preparations avoid first pass metabolism. Also, natural estrogens and phytoestrogens may provide alternatives to synthetic estrogens. Furthermore, specific ER modulators could minimize the adverse effects of HRT, including breast cancer. HRT failure in CVD could also be related to changes in vascular ERs. Genetic polymorphism and postmenopausal decrease in vascular ERs or the downstream signaling mechanisms may reduce the effects of HRT. HRT in the late postmenopausal period may not be as effective as during menopausal transition. Additionally, while HRT may aggravate pre-existing CVD, it may thwart its development if used in a timely fashion. Lastly, the vascular effects of progesterone and testosterone, as well as modulators of their receptors, may modify the effects of estrogen and thereby provide alternative HRT strategies. Thus, the beneficial effects of HRT in postmenopausal CVD can be enhanced by customizing the HRT type, dose, route of administration and timing depending on the subject's age and cardiovascular condition.

 

Arch Gynecol Obstet. 2007 Jun 29; [Epub ahead of print]

Tibolone and osteoporosis.

Lazovic G, Radivojevic U, Milosevic V, Lazovic A, Jeremic K, Glisic A.

Institute of Gynecology and Obstetrics of the Clinical Centre of Serbia, Belgrade, Serbia and Montenegro.

BACKGROUND: We conducted a 5-year prospective, observational, controlled study to assess the effects of tibolone 1.25 mg/day on bone mineral density (BMD) in postmenopausal women with osteopenia or osteoporosis. METHODS: The subjects were 420 women, an average of 66.4 years old, who had been postmenopausal between 8 and 19 years when enrolled in the study. Of the 420 women enrolled, 346 agreed to take tibolone for 5 years. The 74 who refused tibolone took only calcium/vitamin D supplements and served as the control group. BMD was measured in the lumbar spine and total hip region at baseline and annually by dual-energy X-ray absorptiometry (DXA). RESULTS: At the first two follow-up visits, women taking tibolone had a significant increase in BMD at the spine (P < 0.001) and at the hip (P < 0.001) when compared to baseline values and when compared to BMD values for the control group, which decreased from baseline. In the final 3 years of the study, BMD values (spine and hip) continued to decrease in the control group and also tended to decrease in the tibolone group, but at the end of the fifth year, mean BMD in the tibolone group was still higher than BMD before the start of tibolone treatment (P < 0.05). Calculations showed that if women taking tibolone continued to lose BMD at the same rate as during the final 3 years of the study, after 11 years of tibolone treatment the average patient would have the same BMD as she had when treatment started. CONCLUSION: This 5-year observational study provides evidence that tibolone is effective in increasing BMD in postmenopausal women with osteopenia and osteoporosis during the first 2 years of treatment, but because BMD starts to decline in the third year, it is vital that postmenopausal women start treatment with tibolone as early as possible, so that bone mineral density levels are kept high as long as possible.

 

Int J Gynaecol Obstet. 2007 Jun 28; [Epub ahead of print]

Effects of tibolone on health-related quality of life in menopausal women.

Bhattacharya SM.

Department of Obstetrics and Gynecology, Vivekananda Institute of Medical Sciences, Calcutta, India.

OBJECTIVE: The present study assessed improvements in health-related quality of life (HRQOL) in menopausal women using tibolone. METHODS: One hundred women who underwent surgical menopause for various benign gynecological conditions were advised to take tibolone (2.5 mg) daily. The Menopause Rating Scale (MRS II) was used to assess the change in HRQOL after 3 months and 12 months of treatment. RESULTS: Sixty-two women returned for follow-up after 3 months, while only 15 returned for after 12 months. Significant improvements in HRQOL were found after 3 months, and further improvements were obtained after 12 months, although at a slower rate. Among the three subscales of MRS, maximum improvement in the somatovegetative component and lesser improvements in the other two subscales were found. CONCLUSION: Tibolone is effective in improving the overall HRQOL of menopausal women. Somatovegetative symptoms show most improvement.

 

J Am Diet Assoc. 2007 Jul;107(7):1155-65.

Predictors of Dietary Change and Maintenance in the Women's Health Initiative Dietary Modification Trial.

Tinker LF, Rosal MC, Young AF, Perri MG, Patterson RE, Van Horn L, Assaf AR, Bowen DJ, Ockene J, Hays J, Wu L.

OBJECTIVE: To identify predictors of dietary change to and maintenance of a low-fat eating pattern (<20% energy from fat, >/=5 servings fruits/vegetables daily, and >/=6 servings grains daily) among a cohort of postmenopausal women. Candidate predictors included intrapersonal, interpersonal, intervention program characteristics, and clinical center. DESIGN: Longitudinal study within the Women's Health Initiative Dietary Modification Trial. Dietary change was evaluated after 1 year of participation in the Women's Health Initiative Dietary Modification Trial, and dietary maintenance after 3 years. SUBJECTS: Postmenopausal women aged 50 to 79 years at baseline who were randomized to the intervention arm of the Women's Health Initiative Dietary Modification Trial (n=19,541). STATISTICAL ANALYSIS: Univariate and multivariate linear regression analysis was performed and associations evaluated between candidate predictors and each of the three dietary goals: percent energy from fat, fruit/vegetable servings, and grain servings. RESULTS: Year 1 (change) predictors of percent energy from fat (P<0.005) included being younger (beta=2.12; 70 to 79 years vs 50 to 59 years), more educated (beta=-.69; college vs high school), more optimistic (beta=-.07), attending more sessions (beta=-.69), and submitting more self-monitoring records (beta=-.74). At year 3 (maintenance), the predictors of percent energy from fat (P<0.005) included attending more sessions (beta=-.65) and submitting more self-monitoring scores (beta=-.71). The analytic model predicted 22% of the variance in fat intake at year 1 and 27% at year 3 (P<0.01). CONCLUSIONS: The strongest predictors of dietary change and maintenance were attending intervention sessions and self-monitoring dietary intake. Novel was the finding that optimism predicted dietary change.

 

Bone. 2007 Jun 5; [Epub ahead of print]

Differences in bone mineral status between urban and rural Chinese men and women.

Gu W, Rennie KL, Lin X, Wang Y, Yu Z.

Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China.

BACKGROUND:: Few studies have investigated differences in bone health and associated lifestyle factors between urban and rural populations in countries, such as China, undergoing rapid nutrition transition. Such a study may help to identify risk factors of osteoporosis and provide evidence for future preventive strategies. OBJECTIVE:: To determine primarily whether differences in bone mineral content (BMC) and bone mineral density (BMD) exist between urban and rural Chinese men and women and secondly whether any urban-rural differences could be explained by body size or lifestyle factors. METHODS:: In total, 490 men and 689 women aged 50-70 were included in the study. 535 of them were from urban Shanghai and 644 from surrounding rural areas. Anthropometric measurements were conducted and spine lumber 1-4 BMC measurements were determined by dual-energy X-ray absorptiometry (DEXA). Information on socioeconomic status, medical history, smoking and drinking habits and physical activity were collected. RESULTS:: Urban men and women had significantly higher spine BMC, BMD and bone area than their rural counterparts (P<0.01). After controlling body size, the differences between urban-rural spine BMC and BMD remained in women (p<0.001), but were no longer significant in men. The urban and rural differences of BMC and BMD in women could not be explained by including the lifestyle factors such as income, intake of milk, vitamin D and calcium, total physical activity level, walking and social activity. CONCLUSION:: This study found the significant differences in both spine BMC and BMD between urban and rural men and women in Shanghai, China. This difference could be explained by the body size in men; however, it remained unexplained in women after adjusting for body size and certain lifestyle risk factors.