Selección de Resúmenes de Menopausia

Agosto de 2007

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

Semana del 22 al 28 de Agosto de 2007

 

Lancet. 2007 Aug 25;370(9588):657-66.

Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis.

Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A.

Centre for Complementary Medicine Research, University of Western Sydney, New South Wales, Australia. benjamin@clubsalsa.com.au

BACKGROUND: Whether calcium supplementation can reduce osteoporotic fractures is uncertain. We did a meta-analysis to include all the randomised trials in which calcium, or calcium in combination with vitamin D, was used to prevent fracture and osteoporotic bone loss. METHODS: We identified 29 randomised trials (n=63 897) using electronic databases, supplemented by a hand-search of reference lists, review articles, and conference abstracts. All randomised trials that recruited people aged 50 years or older were eligible. The main outcomes were fractures of all types and percentage change of bone-mineral density from baseline. Data were pooled by use of a random-effect model. FINDINGS: In trials that reported fracture as an outcome (17 trials, n=52 625), treatment was associated with a 12% risk reduction in fractures of all types (risk ratio 0.88, 95% CI 0.83-0.95; p=0.0004). In trials that reported bone-mineral density as an outcome (23 trials, n=41 419), the treatment was associated with a reduced rate of bone loss of 0.54% (0.35-0.73; p<0.0001) at the hip and 1.19% (0.76-1.61%; p<0.0001) in the spine. The fracture risk reduction was significantly greater (24%) in trials in which the compliance rate was high (p<0.0001). The treatment effect was better with calcium doses of 1200 mg or more than with doses less than 1200 mg (0.80 vs 0.94; p=0.006), and with vitamin D doses of 800 IU or more than with doses less than 800 IU (0.84 vs 0.87; p=0.03). INTERPRETATION: Evidence supports the use of calcium, or calcium in combination with vitamin D supplementation, in the preventive treatment of osteoporosis in people aged 50 years or older. For best therapeutic effect, we recommend minimum doses of 1200 mg of calcium, and 800 IU of vitamin D (for combined calcium plus vitamin D supplementation).

 

J Steroid Biochem Mol Biol. 2007 May 24; [Epub ahead of print]

Endogenous estrogen, testosterone and progesterone levels in relation to breast cancer risk.

Hankinson SE, Eliassen AH.

Channing Laboratory, Department of Medicine, 181 Longwood Avenue, Harvard Medical School and Brigham and Women's Hospital, MA 02115, United States; Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States.

Multiple lines of evidence support a central role of hormones in the etiology of breast cancer. In epidemiologic studies, considerable effort has focused on delineating the role of endogenous hormones in risk of breast cancer among postmenopausal women. Recently, substantial additional data has accrued from prospective studies where endogenous hormones are measured in study subjects prior to disease diagnosis. In this review, the epidemiologic evidence linking sex steroids-estrogens, testosterone, and progesterone, specifically-with subsequent risk of breast cancer in both premenopausal and postmenopausal women is summarized. Overall, a strong positive association between breast cancer risk and circulating levels of both estrogens and testosterone has now been well confirmed among postmenopausal women; women with hormone levels in the top 20% of the distribution (versus bottom 20%) have a two- to three-fold higher risk of breast cancer. Evidence among premenopausal women is more limited, though increased risk associated with higher levels of testosterone is consistent. However, both positive and null associations have been observed with estrogens and progesterone and clearly more evaluation is needed.

 

J Basic Clin Physiol Pharmacol. 2007;18(2):115-27

Glucocorticoids and oxidative stress.

Bjelaković G, Beninati S, Pavlović D, Kocić G, Jevtović T, Kamenov B, Saranac LJ, Bjelaković B, Stojanović I, Banić J.

Institute of Biochemistry, CC Nis, Faculty of Medicine, University of Nisg, Nis, Serbia.

Glucocorticoids (GC) are used widely for the treatment of patients with various disorders, including autoimmune diseases, allergies, and lymphoproliferative disorders. Glucocorticoid therapy is often limited by several adverse reactions associated with GC excess. Excess GC can elicit a variety of symptoms and signs, including growth retardation in children; immunosuppression; cardiovascular disorders like hypertension and atherosclerosis; osteoporosis; myopathy; and diabetes mellitus. Currently, attention is focused on oxidative stress as one of the major determinants of endothelial dysfunction and cardiovascular senescence. The main reason for all unwanted effects of GC is that dexamethasone induces the overproduction of reactive oxygen species, causing dysregulation of physiological processes. Humans and animals with GC-induced hypertension exhibit reduced nitric oxide levels; patients with excess GC levels also suffer from depression as a consequence of low levels of serotonin and melatonin. The common cofactor for the production of these vasoactive molecules is tetrahydrobiopterin (BH4), which is required for nitric oxide synthesis.

 

Gynecol Obstet Invest. 2007 Aug 22;65(1):47-51 [Epub ahead of print

Changes in Hemostatic Variables Induced by Estrogen Replacement Therapy: Comparison of Transdermal and Oral Administration in a Crossover-Designed Study.

Fait T, Vrablik M, Zizka Z, Kostirova M.

D. of Obstetrics and Gynecology, Faculty of Medicine, Charles University, Prague, Czech Republic.

Aim: The purpose of this study was to determine the changes of biochemical risk factors for thromboembolisms using different administration routes of early estrogen replacement therapy. Methods: In a 12-week prospective, randomized crossover trial, estradiol was administered orally (2 mg daily) or transdermally (0.05 mg daily). Forty-five healthy early postmenopausal women were included into the study within 12 weeks after hysterectomy and oophorectomy. Forty-one women (age 49 +/- 6 years) completed the study, and their data were analyzed. The hemocoagulation parameters were determined prior to beginning of the study and at the end of each treatment period, separated by a 1-week washout period. Results: After oral therapy, the average tissue factor pathway inhibitor levels decreased statistically significantly (p < 0.0001) from 87.5 +/- 39.1 to 68 +/- 37.49 ng/ml. The plaminogen activator inhibitor-1 levels also decreased statistically significantly (p = 0.001) after the oral estrogen therapy from 11.39 +/- 12.02 to 5.0 +/- 5.27 IU/l. These changes were also significant when compared with the nonsignificant changes after the transdermal therapy. No significant changes occurred in the levels of D-dimers. After both treatment methods, the antithrombin III and fibrinogen levels decreased, but within their physiological ranges. Conclusions: Oral administration of estrogen statistically significantly reduced the tissue factor pathway inhibitor and plasminogen activator inhibitor-1 levels when compared with the transdermal route. These changes cannot be unambiguously considered risky, and the zero change of D-dimers suggests that there was no activation of the coagulation cascade. We consider the neutral effect of the transdermal therapy more beneficial.

 

Adv Exp Med Biol. 2007;601:395-413

Therapeutic potential of cannabinoid-based drugs.

Klein TW, Newton CA.

University of South Florida, Department of Molecular Medicine, Tampa, FL, USA. tklein@health.usf.edu

Cannabinoid-based drugs modeled on cannabinoids originally isolated from marijuana are now known to significantly impact the functioning of the endocannabinoid system of mammals. This system operates not only in the brain but also in organs and tissues in the periphery including the immune system. Natural and synthetic cannabinoids are tricyclic terpenes, whereas the endogenous physiological ligands are eicosanoids. Several receptors for these compounds have been extensively described, CB1 and CB2, and are G protein-coupled receptors; however, cannabinoid-based drugs are also demonstrated to function independently of these receptors. Cannabinoids regulate many physiological functions and their impact on immunity is generally antiinflammatory as powerful modulators of the cytokine cascade. This anti-inflammatory potency has led to the testing of these drugs in chronic inflammatory laboratory paradigms and even in some human diseases. Psychoactive and nonpsychoactive cannabinoid-based drugs such as Delta9-tetrahydrocannabinol, cannabidiol, HU-211, and ajulemic acid have been tested and found moderately effective in clinical trials of multiple sclerosis, traumatic brain injury, arthritis, and neuropathic pain. Furthermore, although clinical trials are not yet reported, preclinical data with cannabinoid-based drugs suggest efficacy in other inflammatory diseases such as inflammatory bowel disease, Alzheimer's disease, atherosclerosis, and osteoporosis.

 

Obesity (Silver Spring). 2007 Aug;15(8):1980-7.

Extreme obesity reduces bone mineral density: complementary evidence from mice and women.

Núñez NP, Carpenter CL, Perkins SN, Berrigan D, Jaque SV, Ingles SA, Bernstein L, Forman MR, Barrett JC, Hursting SD.

Division of Nutritional Sciences, University of Texas at Austin, One University Station, A2700, Austin.

OBJECTIVE: To evaluate the effects of body adiposity on bone mineral density in the presence and absence of ovarian hormones in female mice and postmenopausal women. RESEARCH METHODS AND PROCEDURES: We assessed percentage body fat, serum leptin levels, and bone mineral density in ovariectomized and non-ovariectomized C57BL/6 female mice that had been fed various calorically dense diets to induce body weight profiles ranging from lean to very obese. Additionally, we assessed percentage body fat and whole body bone mineral density in 37 overweight and extremely obese postmenopausal women from the Women's Contraceptive and Reproductive Experiences study. RESULTS: In mice, higher levels of body adiposity (>40% body fat) were associated with lower bone mineral density in ovariectomized C57BL/6 female mice. A similar trend was observed in a small sample of postmenopausal women. DISCUSSION: The complementary studies in mice and women suggest that extreme obesity in postmenopausal women may be associated with reduced bone mineral density. Thus, extreme obesity (BMI > 40 kg/m(2)) may increase the risk for osteopenia and osteoporosis. Given the obesity epidemic in the U.S. and in many other countries, and, in particular, the rising number of extremely obese adult women, increased attention should be drawn to the significant and interrelated public health issues of obesity and osteoporosis.

 

J Clin Oncol. 2007 Aug 20; [Epub ahead of print

Randomized Dose-Ranging Trial of Tamoxifen at Low Doses in Hormone Replacement Therapy Users.

Decensi A, Gandini S, Serrano D, Cazzaniga M, Pizzamiglio M, Maffini F, Pelosi G, Daldoss C, Omodei U, Johansson H, Macis D, Lazzeroni M, Penotti M, Sironi L, Moroni S, Bianco V, Rondanina G, Gjerde J, Guerrieri-Gonzaga A, Bonanni B.

Divisions of Chemoprevention, Epidemiology and Biostatistics, Radiology, Pathology, Laboratory Medicine, Preventive Gynecology, European Institute of Oncology; Mangiagalli Clinic; Buzzi Hospital, Milan; Division of Gynecology, University of Brescia, Brescia; Division of Medical Oncology, Galliera Hospital, Genoa, Italy; Hormone Laboratory, Haukeland Hospital, University of Bergen; and the Section for Endocrinology, Institute of Medicine, University of Bergen, Bergen, Norway.

PURPOSE: The combination of hormone replacement therapy (HRT) and low-dose tamoxifen may retain the benefits while reducing the risks of either agent. We assessed the optimal biologic dose and schedule of tamoxifen in HRT users using surrogate end point biomarkers and menopausal symptoms. Subjects and METHODS: Two hundred ten current or de novo HRT users were randomly assigned to one of the following four arms: tamoxifen 1 mg/day and placebo/week, placebo/day and tamoxifen 10 mg/week, tamoxifen 5 mg/day and placebo/week, or both placebos for 12 months. The primary end point was the change of plasma insulinlike growth factor 1 (IGF-I) through 12 months, and secondary end points were IGF-I/IGF binding protein-3 (IGFBP-3) ratio, fibrinogen, antithrombin III, C reactive protein, C-telopeptide, mammographic percent density, and endometrial thickness. Endometrial proliferation was assessed by Pipelle biopsy in superficial, deep glandular, and stromal compartments after 12 months. RESULTS: Compared with placebo, IGF-I declined in all tamoxifen arms (P = .005), with a greater change on 5 mg/day (P = .019 v 10 mg/week or 1 mg/day). Tamoxifen increased IGFBP-3 and lowered antithrombin-III, C reactive protein, and mammographic density, with greater effects of 5 mg/day. Tamoxifen increased endometrial thickness but not Ki-67 expression, which was lower on 5 mg/day among the three doses. Menopausal symptoms were not significantly worsened by tamoxifen. CONCLUSION: Doses of tamoxifen </= 5 mg/day modulate favorably biomarkers of breast carcinogenesis and cardiovascular risk in HRT users with no increase of endometrial proliferation and menopausal symptoms. A dose of 5 mg/day was the most effective and has been selected for a phase III trial in HRT users.

 

Circulation. 2007 Aug 20; [Epub ahead of print

Visceral and Subcutaneous Adipose Tissue Volumes Are Cross-Sectionally Related to Markers of Inflammation and Oxidative Stress. The Framingham Heart Study.

Pou KM, Massaro JM, Hoffmann U, Vasan RS, Maurovich-Horvat P, Larson MG, Keaney JF Jr, Meigs JB, Lipinska I, Kathiresan S, Murabito JM, O'donnell CJ, Benjamin EJ, Fox CS.

National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, Mass.

BACKGROUND: -Excess adiposity is associated with greater systemic inflammation. Whether visceral adiposity is more proinflammatory than subcutaneous abdominal adiposity is unclear. Methods and Results-We examined the relations of abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), assessed by multidetector computerized tomography, to circulating inflammatory and oxidative stress biomarkers in 1250 Framingham Heart Study participants (52% women; age 60+/-9 years). Biomarkers were examined in relation to increments of SAT and VAT after adjustment for age, sex, smoking, physical activity, menopause, hormone replacement therapy, alcohol, and aspirin use; additional models included body mass index and waist circumference. SAT and VAT were positively and similarly (with respect to strength of association) related to C-reactive protein, fibrinogen, intercellular adhesion molecule-1, interleukin-6, P-selectin, and tumor necrosis factor receptor-2 (multivariable model R(2) 0.06 to 0.28 [SAT] and 0.07 to 0.29 [VAT]). However, compared with SAT, VAT was more highly associated with urinary isoprostanes and monocyte chemoattractant protein-1 (SAT versus VAT comparison: isoprostanes, R(2) 0.07 versus 0.10, P=0.002; monocyte chemoattractant protein-1, R(2) 0.07 versus 0.08, P=0.04). When body mass index and waist circumference were added to the models, VAT remained significantly associated with only C-reactive protein (P=0.0003 for women; P=0.006 for men), interleukin-6 (P=0.01), isoprostanes (P=0.0002), and monocyte chemoattractant protein-1 (P=0.008); SAT only remained associated with fibrinogen (P=0.01). Conclusions-The present cross-sectional data support an association between both SAT and VAT with inflammation and oxidative stress. The data suggest that the contribution of visceral fat to inflammation may not be completely accounted for by clinical measures of obesity (body mass index and waist circumference).

 

Osteoporos Int. 2007 Aug 15; [Epub ahead of print

Intrauterine programming of bone. Part 1: Alteration of the osteogenic environment.

Lanham SA, Roberts C, Cooper C, Oreffo RO.

Bone and Joint Research Group, Developmental Origins of Health and Disease, University of Southampton, Southampton, SO16 6YD, UK, car@soton.ac.uk.

Osteoporosis is believed to partly be programmed in utero. Rat dams were given a low protein diet during pregnancy and 135 offspring studied at different ages. Bone biochemistry showed altered characteristics. Altered in utero diet has consequences for later life. INTRODUCTION: Epidemiological studies suggest skeletal growth is programmed during intrauterine and early postnatal life. We have investigated this in a rat model of maternal protein insufficiency. METHODS: Dams received either 18% w/w (control) or 9% w/w (low protein) diet during pregnancy, and the offspring were studied at selected time points (4, 8, 12, 16, 20, 47 weeks). RESULTS: Alkaline phosphatase activity in controls reached peak levels from 8 to 20 weeks of age. In contrast, restricted diet offspring were at peak levels from 4 weeks of age. Peak levels were similar in both groups. Serum IGF-1 levels were lower in female restricted diet offspring at 4 weeks of age, and serum osteocalcin was significantly higher at 4 weeks of age in male and female offspring from mothers fed the restricted diet, whereas serum 25-OH vitamin D was significantly lower in restricted diet males at 8, 12, and 20 weeks of age. CONCLUSIONS: These data indicate that a low protein diet in utero affected the osteogenic environment in the offspring with effects that persist into late adulthood. These results indicate the key role of the nutritional environment in early development on programming of skeletal development with implicit consequences in later life.

 

Osteoporos Int. 2007 Aug 18; [Epub ahead of print

Intrauterine programming of bone. Part 2: Alteration of skeletal structure.

Lanham SA, Roberts C, Perry MJ, Cooper C, Oreffo RO.

Bone and Joint Research Group, Developmental Origins of Health and Disease, University of Southampton, Southampton, SO16 6YD, UK, car@soton.ac.uk.

Osteoporosis is believed to be partly programmed in utero. Rat dams were given a low protein diet during pregnancy, and offspring were studied at different ages. Old aged rats showed site-specific strength differences. In utero nutrition has consequences in later life. INTRODUCTION: Epidemiological studies suggest skeletal growth is programmed during intrauterine and early postnatal life. We hypothesize that age-related decrease in bone mass has, in part, a fetal origin and investigated this using a rat model of maternal protein insufficiency. METHODS: Dams received either 18% w/w (control) or w/w 9% (low protein) diet during pregnancy, and the offspring were studied at selected time points (4, 8, 12, 16, 20, 47, 75 weeks). RESULTS: Using micro-CT, we found that at 75 weeks of age female offspring from mothers fed a restricted protein diet during pregnancy had femoral heads with thinner, less dense trabeculae, femoral necks with closer packed trabeculae, vertebrae with thicker, denser trabeculae and midshaft tibiae with denser cortical bone. Mechanical testing showed the femoral heads and midshaft tibiae to be structurally weaker, whereas the femoral necks and vertebrae were structurally stronger. CONCLUSIONS: Offspring from mothers fed a restricted protein diet during pregnancy displayed significant differences in bone structure and density at various sites. These differences result in altered bone characteristics indicative of significantly altered bone turnover. These results further support the need to understand the key role of the nutritional environment in early development on programming of skeletal development and consequences in later life.

 

Semana del 15 al 21 de Agosto 2007

 

Osteoporos Int. 2007 Aug 17; [Epub ahead of print]

Relationships between insulin-like growth factor-I (IGF-I) and OPG, RANKL, bone mineral density in healthy Chinese women.

Zhao HY, Liu JM, Ning G, Zhao YJ, Chen Y, Sun LH, Zhang LZ, Xu MY, Chen JL.

Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, 200025, Shanghai, China.

Serum IGF-I level was negatively correlated with OPG and OPG/RANKL ratio, but positively correlated with RANKL. Serum OPG level in the highest quintile of IGF-I was significantly lower than that in the lowest. We conclude that the effect of IGF-I on bone remodeling may be mediated by the OPG/RANKL system. INTRODUCTION: Insulin-like growth factor I (IGF-I) is an important factor in coupling bone remodeling, activating both formation and resorption. Compared with the many studies on the role of IGF-I in bone formation, the information regarding its effects on bone resorption is limited and conflicting. The balance of the two peptides produced by osteoblasts, osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand (RANKL), is critical for the bone resorption process. Our study was designed to analyze the relationships of serum concentrations of IGF-I with OPG, RANKL, OPG/RANKL ratio as well as BMDs in healthy Chinese women. METHODS: BMDs at lumbar spine and proximal femur in 504 pre- and postmenopausal women were measured by DXA. Serum levels of IGF-I, OPG and RANKL were also measured. Pearson's correlation and partial correlation analysis, ANOVA, covariance analysis and stepwise multiple regression analysis were used as appropriate. RESULTS: Age was negatively correlated with serum levels of IGF-I (r = -0.702, p < 0.001). IGF-I was negatively correlated with OPG and OPG/RANKL ratio, but positively correlated with RANKL. The relationship between IGF-I and BMDs disappeared after adjustment for age. In postmenopausal women, IGF-I was lower in women with osteoporosis than in those with normal BMD (p = 0.056), but no differences were found among OPG, RANKL and OPG/RANKL ratio. Serum levels of OPG in the highest quintile of IGF-I were significantly lower than those in the lowest quintile of IGF-I, while no difference was found in RANKL. In the multiple regression analysis model, serum levels of IGF-I were the main determinants of the bone mass in Chinese women. CONCLUSIONS: In conclusion, the relationship between decreasing IGF-I and BMDs in healthy Chinese women influenced by age, whereas the effect of IGF-I on bone remodeling (bone resorption) may be mediated by the OPG/RANKL system.

 

Breast Cancer Res. 2007 Aug 13;9(4):R53 [Epub ahead of print

No relationship between circulating levels of sex steroids and breast density: the prospect-EPIC cohort.

Verheus M, Peeters PH, van Noord PA, van der Schouw YT, Grobbee DE, van Gils CH.

BACKGROUND: High breast density is associated with increased breast cancer risk. Epidemiologic studies have shown an increase in breast cancer risk in postmenopausal women with high levels of sex steroids. Hence, sex steroids may increase postmenopausal breast cancer risk via an increase of breast density. The objective was to study the relation between circulating estrogens and androgens as well as sex hormone binding globulin (SHBG) in relation to breast density. METHODS: We conducted a cross-sectional study among 969 postmenopausal women, using baseline data of a random sample of the Prospect-EPIC study. Prospect-EPIC is one of two Dutch cohorts participating in the European Prospective Investigation into Cancer and Nutrition (EPIC), and women were recruited via a breast cancer screening programme. At enrolment, a non-fasting blood sample was taken and a mammogram was made. Estrone, estradiol, dehydroepiandrosterone sulfate, androstenedione, testosterone and SHBG levels were measured, using double-antibody radioimmunoassays. Concentrations of free estradiol and free testosterone were calculated from estradiol, testosterone and SHBG. Mammographic dense and non-dense areas were measured using a semi quantitative computerized method and percent breast density was calculated. Mean breast measures for quintiles of hormone or SHBG levels were estimated using linear regression analyses. RESULTS: None of the estrogens or androgens showed clear relationships with percent breast density or the dense breast area, but all, except free testosterone, were inversely associated with the non-dense area (for free estradiol; 93.5 cm2 in the highest versus 99.4 cm2 in the lowest quintile, Ptrend=0.09). High levels of SHBG were weakly associated with higher dense area and with higher percent density. CONCLUSION: The results of our study do not support the hypothesis that sex steroids increase postmenopausal breast cancer risk via an increase in breast density.

 

J Obstet Gynaecol. 2007 Jul;27(5):503-5

Can thyroid dysfunction explicate severe menopausal symptoms?

Badawy A, State O, Sherief S.

Departments of Obstetrics and Gynecology.

Many of the menopausal manifestations look like those accredited to thyroid hyperfunction or hypofunction. Can thyroid dysfunction explicate severe menopausal symptoms? The study comprised 350 women with different menopausal symptoms. All women had serum TSH, T3 and free T4 estimated. Women with thyroid dysfunction were appropriately treated and other women were treated with ERT. The study showed that 21 women (6%) had hypothyroidism and 18 (5.1%) had hyperthyroidism. Marked improvement in the menopausal-like symptoms occurred after treatment of the thyroid dysfunction. Elderly women with severe or resistant menopausal symptoms can be offered TSH, T3 and T4 assays to rule out the thyroid disturbances before attempting hormone replacement therapy.

 

Gynecol Endocrinol. 2007 Jul;23(7):398-403

Comparison of the effects of raloxifene and low-dose hormone replacement therapy on bone mineral density and bone turnover in the treatment of postmenopausal osteoporosis.

Dane C, Dane B, Cetin A, Erginbas M.

Department of Gynecology & Obstetrics, Haseki Training & Research Hospital, Istanbul, Turkey.

The aim of the present study was to compare the effects of raloxifene and low-dose hormone replacement therapy (HRT) on bone mineral density (BMD) and bone turnover markers in the treatment of postmenopausal osteoporosis. Methods. Forty-two postmenopausal osteoporotic women, who were randomized to receive raloxifene 60 mg or estradiol 1 mg/norethisterone acetate 0.5 mg daily for 1 year, were studied. All women received calcium 600 mg/day and vitamin D 400 IU/day. BMD and markers of bone turnover were measured at baseline and at 12 months. Results. After 12 months of treatment, there were statistically significant increases in BMD in both groups at all sites (all p < 0.05). For the lumbar spine, the increase in BMD was 2.3% for raloxifene compared with 5.8% for low-dose HRT and corresponding values for total body BMD were 2.9% for raloxifene and 4.6% for low-dose HRT; the increases being significantly greater in the low-dose HRT group (p < 0.001 and p = 0.02, respectively). Although the increase in BMD at the hip was significant for both raloxifene (2.1%) and low-dose HRT (3.2%) compared with baseline, the difference between the two regimens did not reach statistical significance. The decrease in serum C-terminal telopeptide fragment of type I collagen and serum osteocalcin levels for the low-dose HRT group (-53% and -47%, respectively) was significantly greater than for the raloxifene group (-23% and -27%, respectively; both p < 0.01). Conclusions. In postmenopausal women with osteoporosis, low-dose HRT produced significantly greater increases in BMD of the lumbar spine and total body and greater decreases in bone turnover than raloxifene at 12 months.

 

Gynecol Endocrinol. 2007 Jul;23(7):391-7

Breast cancer incidence and hormone replacement therapy: Results from the MISSION study, prospective phase.

Espié M, Daures JP, Chevallier T, Mares P, Micheletti MC, de Reilhac P.

Hôpital Saint-Louis, Paris, France.

Background. The MISSION Study (Menopause: Risk of Breast Cancer, Morbidity and Prevalence) is a historical-prospective study with random patient selection to determine breast cancer incidence in postmenopausal women with or without hormone replacement therapy (HRT). The first prospective follow-up phase started on 5 January 2004 and the cut-off date for data collection was 30 June 2006. Participants. Patients were divided into two groups: an 'exposed group' of women on HRT regimens commonly prescribed in France or who had stopped </=5 years previously; and an 'unexposed group' of women who had never received HRT or stopped >5 years previously. In total 6755 patients were included; and prospective data were available for 4949 patients: 2693 in the exposed group and 2256 in the unexposed group. Women in the exposed group were younger, less overweight, and had fewer first-degree family histories of breast cancer than women of the unexposed group. Mean duration of HRT exposure was 8.3 years, with 31% being exposed for >/=10 years. Results. The incidence of new breast cancer cases was 0.64% in the exposed group and 0.70% in the unexposed group (relative risk RR(exposed/unexposed) = 0.914, 95% confidence interval = 0.449-1.858; not modified when adjusted for age). Mean age at breast cancer diagnosis was similar in both groups. Breast cancer incidence in the exposed group was not significantly affected by the route of estradiol administration (cutaneous 0.69%; oral 0.52%) or HRT type (estradiol alone 0.28%; estradiol + progesterone 0.40%; estradiol + synthetic progestin 0.94%). Conclusion. No evidence was found for an increased risk of breast cancer in women exposed to HRT compared with non-exposed women.

 

Diabetologia. 2007 Aug 14; [Epub ahead of print

Plasma sex steroid hormones and risk of developing type 2 diabetes in women: a prospective study.

Ding EL, Song Y, Manson JE, Rifai N, Buring JE, Liu S.

Division of Preventive Medicine, Department of Medicine, Harvard Medical School, Boston, MA, USA.

AIMS/HYPOTHESIS: Prospective data directly investigating the role of endogenous sex hormones in diabetes risk have been scant, particularly in women. We aimed to examine comprehensively plasma sex hormones in connection with risk of developing type 2 diabetes in postmenopausal women. METHODS: We conducted a prospective, nested case-control study of plasma oestradiol, testosterone and dehydroepiandrosterone sulfate and risk of type 2 diabetes in a cohort of women health professionals with a mean age of 60.3 and 12.2 years since menopause. Among women not using hormone therapy and free of baseline cardiovascular disease, cancer and diabetes, 359 incident cases of type 2 diabetes were matched with 359 controls during an average follow-up of 10 years. RESULTS: Oestradiol and testosterone were each strongly and positively associated with risk of type 2 diabetes. After adjustment for BMI, family history, lifestyle and reproductive variables, the multivariable relative risks (95% CI) comparing the highest vs lowest quintile were 12.6 (2.83-56.3) for total oestradiol (p = 0.002 for trend), 13.1 (4.18-40.8) for free oestradiol (p < 0.001 for trend), 4.15 (1.21-14.2) for total testosterone (p = 0.019 for trend) and 14.8 (4.44-49.2) for free testosterone (p < 0.001 for trend). These associations remained robust after adjusting and accounting for other metabolic syndrome components and baseline HbA(1c) levels. CONCLUSIONS/INTERPRETATION: In postmenopausal women, higher plasma levels of oestradiol and testosterone were strongly and prospectively related to increased risk of developing type 2 diabetes. These prospective data indicate that endogenous levels of sex hormones may play important roles in the pathogenesis of type 2 diabetes.

 

Aging Male. 2007 Sep;10(3):139-53

Testosterone therapy in the aging male.

Lunenfeld B, Nieschlag E.

Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.

The decline, with aging, in serum concentrations of biologically active forms of testosterone in men is an indisputable fact and some men will eventually develop symptoms of late-onset hypogonadism (LOH) with its clinical consequences. LOH reduces quality of life and may pose important risk factors for frailty, changes in body composition, cardiovascular disease, sexual dysfunction and osteoporosis. Testosterone supplementation in cases of LOH will restore serum testosterone levels into the physiologic range; will restore metabolic parameters to the eugonadal state, increase muscle mass, strength, and function; maintaine or improve BMD reducing fracture risk; will improve neuropsychological function (cognition and mood); libido and sexual functioning; and enhance quality of life. The ultimate goals, however, are to maintain or regain a high quality of life, to reduce disability, to compress major illnesses into a narrow age range and to add life to years. To achieve these goals men must also adjust their lifestyle to optimize dietary habits, as well as to exercise and to abstain from smoking life-long. Monitoring these patients is a shared responsibility that cannot be taken lightly. The physician must emphasize to the patient the need for periodic evaluations and the patient must agree to comply with these requirements. The physician's evaluation should include an assessment of the clinical response and monitoring must be tailored to the indications and individual needs of the patient.

 

J Natl Cancer Inst. 2007 Aug 14; [Epub ahead of print

Declines in Invasive Breast Cancer and Use of Postmenopausal Hormone Therapy in a Screening Mammography Population.

Kerlikowske K, Miglioretti DL, Buist DS, Walker R, Carney PA.

Affiliations of authors: Department of Epidemiology and Biostatistics, University of California, San Francisco, CA (KK); General Internal Medicine Section, Department of Veterans Affairs, University of California, San Francisco, CA (KK); Group Health Center for Health Studies, Seattle, WA (DLM, DSMB, RW); Department of Biostatistics, University of Washington, Seattle, WA (DLM, RW); Departments of Family Medicine and Public Health & Preventive Medicine, Oregon Health and Science University, Portland, OR (PAC).

Whether a recent large decline in use of postmenopausal hormone therapy after the release of the Women's Health Initiative findings in July 2002 and/or a decline in screening mammography use is related to a recently reported decline in breast cancer incidence in the United States is controversial. We prospectively collected data from four screening mammography registries from January 1997 through December 2003 for 603411 screening mammography examinations performed on women aged 50-69 years. Of these women, 3238 were diagnosed with breast cancer within 12 months of a screening examination. We calculated quarterly rates of self-reported current postmenopausal hormone therapy use and of invasive breast cancer, ductal carcinoma in situ (DCIS), and estrogen receptor (ER)-positive invasive breast cancer adjusted for age, registry, and time between screening examinations. All statistical tests were two-sided. Between 2000 and 2002 and between 2002 and 2003, annual rates of postmenopausal hormone therapy use declined by 7% and 34%, respectively (P(trend)<.001 for both). Between 2000 and 2003, annual rates of invasive cancer declined by 5% (P(trend) =.003). Between 2001 and 2003, annual rates of ER-positive invasive breast cancer declined by 13% (P(trend)=.002). Rates of DCIS were stable during the study period. Our finding of a statistically significant decline in the rate of ER-positive invasive breast cancer in a screening mammography population after the start of a concomitant substantial decline in postmenopausal hormone therapy use suggests that a decline in screening mammography rates is unlikely to account for the recent decline in US breast cancer incidence.

 

J Clin Endocrinol Metab. 2007 Aug 14; [Epub ahead of print

Prevalence of Symptomatic Androgen Deficiency in Men.

Araujo AB, Esche GR, Kupelian V, O'donnell AB, Travison TG, Williams RE, Clark RV, McKinlay JB.

New England Research Institutes, GlaxoSmithKline. NC 27709.

Context: Despite recognition that androgen deficiency in men should be defined according to biochemical and clinical criteria, most prevalence estimates are based on low testosterone levels alone. Objective: To examine the association between symptoms of androgen deficiency and low total and calculated free testosterone levels and estimate the prevalence of symptomatic androgen deficiency in men. Design: Population-based, observational survey. Participants: 1,475 Black, Hispanic, and White Boston randomly-selected men from the Boston Area Community Health (BACH) Survey, between the ages of 30-79 years, with complete data on testosterone, sex hormone-binding globulin, and symptoms of androgen deficiency, and who are not taking medications that impact sex steroid levels. Outcome: Symptomatic androgen deficiency, defined as low total (<300 ng/dL) and free (<5 ng/dL) testosterone plus presence of low libido, erectile dysfunction, osteoporosis or fracture, or two or more of following symptoms: sleep disturbance, depressed mood, lethargy, or diminished physical performance. Results: Mean age of the sample was 47.3+/-12.5 y. Approximately 24% of subjects had total testosterone <300 ng/dL and 11% of subjects had free testosterone <5 ng/dL. Prevalence of symptoms were as follows: low libido (12%), erectile dysfunction (16%), osteoporosis/fracture (1%), and two or more of the non-specific symptoms (20%). Low testosterone levels were associated with symptoms, but many men with low testosterone levels were asymptomatic (e.g., in men 50+ years, 47.6%). Crude prevalence of symptomatic androgen deficiency was 5.6% (95% CI: 3.6%, 8.6%), and was not significantly related to race and ethnic group. Prevalence was low in men <70 y (3.1%-7.0%), and increased markedly with age to 18.4% among 70-year-olds. Projection of these estimates to the year 2025 suggests that there will be as many as 6.5 million American men 30-79 years with symptomatic androgen deficiency, an increase of 38% from 2000 population estimates. Conclusions: Prevalence of symptomatic androgen deficiency in men 30 and 79 y of age is 5.6%, and increases substantially with age. The aging of the U.S. male population will cause a large increase in the burden of symptomatic androgen deficiency. Future work should address the clinical significance of low testosterone levels in asymptomatic men.

 

Arch Intern Med. 2007 Aug 13-27;167(15):1676-85

A prospective study of inflammatory cytokines and diabetes mellitus in a multiethnic cohort of postmenopausal women.

Liu S, Tinker L, Song Y, Rifai N, Bonds DE, Cook NR, Heiss G, Howard BV, Hotamisligil GS, et al

Department of Epidemiology, University of California, Los Angeles, CA 90095-1772, USA.

BACKGROUND: Inflammatory cytokines, including tumor necrosis factor alpha, IL-6 (interleukin 6), and high-sensitivity C-reactive protein (hsCRP), have been related to both insulin resistance and type 2 diabetes mellitus. However, prospective studies that comprehensively assess their roles in the development of type 2 diabetes are few, especially in minority populations. METHODS: Among 82,069 postmenopausal women aged 50 to 79 years without cardiovascular disease or diabetes mellitus who participated in the Women's Health Initiative Observational Study, we prospectively examined the relationships of plasma levels of tumor necrosis factor alpha receptor 2, IL-6, and hsCRP to diabetes risk. During a median follow-up period of 5.9 years, 1584 women who had clinical diabetes were matched by age, ethnicity, clinical center, time of blood draw, and duration of follow-up to 2198 study participants who were free of the disease. RESULTS: After adjustment for matching factors and known diabetes risk factors, all 3 markers were significantly associated with increased diabetes risk; the estimated relative risks comparing the highest with the lowest quartiles were 1.47 (95% confidence interval [CI], 1.10-1.97) for tumor necrosis factor alpha receptor 2, 3.08 (95% CI, 2.25-4.23) for IL-6, and 3.46 (95% CI, 2.50-4.80) for hsCRP (P for trend, <.01 for all biomarkers). When mutually adjusted, IL-6 and hsCRP remained significant in each ethnic group. While no statistically significant interactions were observed between ethnicity and these biomarkers on diabetes risk, there were consistent trends for the associations of hsCRP and IL-6 with increased diabetes risk in all ethnic groups. CONCLUSION: These prospective data showed that elevated levels of IL-6 and hsCRP were consistently and significantly associated with an increased risk of clinical diabetes in postmenopausal women.

 

Am J Epidemiol. 2007 Aug 13; [Epub ahead of print

Differential Dietary Nutrient Intake according to Hormone Replacement Therapy Use: An Underestimated Confounding Factor in Epidemiologic Studies?

Vercambre MN, Fournier A, Boutron-Ruault MC, Clavel-Chapelon F, Ringa V, Berr C.

INSERM, ERI 20, EA 4045, and Institut Gustave Roussy, Villejuif, France.

Observational studies and randomized controlled trials have produced divergent results concerning the effect of hormone replacement therapy (HRT) on cardiovascular disease and, to a lesser extent, dementia. Residual confounding (confounding that remains even after adjustment for various socioeconomic and lifestyle factors) is one explanation that has been offered for these divergent results. The authors used data collected between 1990 and 1995 from 6,697 French women aged 61-72 years participating in a prospective cohort study to explore the hypothesis that nutritional intake varies according to HRT use and thus may be a source of residual confounding. After the authors adjusted for health and lifestyle factors, HRT users, compared with never users, had significantly higher intakes of alcohol; omega3 fatty acids; vitamins B(6), B(12), and D; and phosphorus and a lower intake of starch. These differential nutrient intakes were related to differences in eating habits. In particular, HRT users in the studied sample, compared with nonusers, ate significantly more fish. Most of the dietary differences were seen in both early users and delayers of HRT. To limit residual confounding in observational studies, dietary factors may be important parameters to be taken into account in analyses of HRT use and health outcomes.

 

Metabolism. 2007 Sep;56(9):1159-66

Measuring insulin sensitivity in postmenopausal women covering a range of glucose tolerance: comparison of indices derived from the oral glucose tolerance test with the euglycemic-hyperinsulinemic clamp.

Piché ME, Lemieux S, Corneau L, Nadeau A, Bergeron J, Weisnagel SJ.

Institute of Nutraceuticals and Functional Foods, Laval University, Québec, Québec, Canada.

This study compares indices of insulin sensitivity derived from fasting and oral glucose tolerance test (OGTT) glucose and insulin measurements, with respect to the reference measure (M/I), obtained from the euglycemic-hyperinsulinemic clamp, in postmenopausal women with varying glucose tolerance status. Fasting plasma insulin index, homeostasis model assessment index, and OGTT-derived indices (insulin 120-minute, Matsuda, metabolic clearance rate [MCR] of glucose, insulin sensitivity [ISI], and Cederholm indices) were calculated and compared with the M/I value in 112 postmenopausal women. All indices examined were significantly correlated with M/I (0.28 </= r(2) </= 0.56). Association studies revealed that on average, 48% of women were grouped in the same tertile of insulin sensitivity when using M/I and fasting plasma insulin index, and 54% when using M/I and insulin 120-minute index. However, concordance with M/I tertiles were 57%, 58%, 64%, 64%, and 68% for homeostasis model assessment, Matsuda, MCR, ISI, and Cederholm indices, respectively. Finally, correlation coefficients between M/I and insulin sensitivity indices were generally lower in women with normal glucose tolerance compared with women with impaired glucose tolerance or type 2 diabetes mellitus. These results suggest that in postmenopausal women, surrogate indices of insulin sensitivity obtained from OGTT data and incorporating a measurement of body weight or body mass index) (Cederholm, ISI, and MCR indices) appear to be superior to those without OGTT data or body weight-body mass index measurements and, therefore, could offer a better estimate of insulin sensitivity, allowing an improved clinical evaluation of this population at higher risk of cardiovascular disease and type 2 diabetes mellitus.

 

Ann Epidemiol. 2007 Aug 11; [Epub ahead of print

Socioeconomic Position and the Metabolic Syndrome in Early, Middle, and Late Life: Evidence from NHANES 1999-2002.

Loucks EB, Magnusson KT, Cook S, Rehkopf DH, Ford ES, Berkman LF.

McGill University, Montréal, Québec, Canada

PURPOSE: To evaluate whether there is an association between socioeconomic position (SEP) and the metabolic syndrome at various ages, including adolescent, middle-aged and older participants in gender-specific analyses. METHODS: Participants were from the 1999-2002 National Health and Nutrition Examination Survey. SEP was measured by income and years of education. Metabolic syndrome was measured in adults using the American Heart Association guidelines and in adolescents using methods based on national reference data. Cross-sectional multivariable-adjusted logistic regression analyses were performed. RESULTS: In women aged 25 to 45 and 46 to 65 years, income below the poverty line (poverty income ratio [PIR] less than one) was associated with higher odds of metabolic syndrome compared with PIR greater than 3 (odds ratio [OR] = 4.90; 95% confidence interval (CI) = 2.24, 10.71, and OR = 2.54; CI = 1.38, 4.67, for the respective age groups) after adjustment for age, race/ethnicity, and menopause. Similar findings were observed for educational attainment. In adolescents, older adults (aged >65 years), and males, income and education were not related to the metabolic syndrome. CONCLUSIONS: This report demonstrates that SEP is associated with the metabolic syndrome in females aged 25 to 65 years and is less strongly associated in males, adolescents, or older participants. These findings provide physiologic mechanistic evidence linking SEP to risk for coronary heart disease.

 

Menopause. 2007 Aug 9;Publish Ahead of Print [Epub ahead of print]

Association of pelvic organ prolapse and fractures in postmenopausal women: analysis of baseline data from the Women's Health Initiative Estrogen Plus Progestin trial.

Medical College of Wisconsin, Milwaukee, WI.

OBJECTIVE:: Testing a hypothesis that pelvic organ prolapse (POP) is a focal manifestation of disordered connective tissue, we evaluated whether there is an association between POP and history of fracture. DESIGN:: This was a case-control study. Baseline data were from postmenopausal women aged 60 years or older enrolled in the Women's Health Initiative Estrogen Plus Progestin trial. Distinct variants (cystocele, rectocele, and uterovaginal) and severity (mild, moderate, or severe) of POP were recognized. A history of "fracture after age 55" was considered as the event of interest. RESULTS:: Moderate to severe POP was identified in 9% of 11,096 participants aged 60 years or older. Women with moderate to severe rectocele were significantly more likely to report fracture (odds ratio: 1.37, 95% CI: 1.06-1.77, P = 0.02) compared with those with absent to mild prolapse. Of the subset of participants who underwent bone mineral density assessment, those with moderate to severe prolapse demonstrated significantly lower whole-body bone mineral density (beta = -0.03, SE 0.02); this difference was of borderline significance (P = 0.05) compared with that for participants with absent to mild POP. Multivariate logistic regression analysis confirmed an independent association between moderate to severe rectocele and fracture (odds ratio: 1.45, 95% CI: 1.08-1.95, P = 0.01). CONCLUSIONS:: We demonstrate a relationship between moderate to severe POP and low bone mineral density in postmenopausal women enrolled in the Women's Health Initiative Estrogen Plus Progestin trial. Our findings of an association between clinically significant (moderate to severe) POP, specifically rectocele, and a history of fracture suggest that suboptimal collagen status purported to associate with POP may also involve bone collagen and hence translate into skeletal compromise.

 

 

Semana del 8 al 14 de Agosto   

 

 

Am J Obstet Gynecol. 2007 Aug;197(2):139.e1-7.

Long-term use of postmenopausal estrogen and progestin hormone therapies and the risk of endometrial cancer.

Doherty JA, Cushing-Haugen KL, Saltzman BS, Voigt LF, Hill DA, Beresford SA, Chen C, Weiss NS.

Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle.

OBJECTIVE: The purpose of this study was to assess whether endometrial cancer risk among long-term users of (1) sequential estrogen plus progestin 10-24 days per month exceeds that of nonusers and (2) daily estrogen plus progestin (continuous combined hormone therapy) is below that of nonusers. STUDY DESIGN: In this population-based case-control study with 1038 endometrial cancer cases diagnosed in 1985-1999 and 1453 control subjects, exclusive users of a single form of hormone therapy were compared with never users of hormone therapy. RESULTS: For sequential therapy, only long-term use (> or = 6 years) was associated with increased risk (odds ratio, 2.0; 95% CI, 1.2-3.5). Continuous combined therapy was associated with decreased risk (odds ratio, 0.59; 95% CI, 0.40-0.88), with no increased risk among long-term users (odds ratio, 0.77; 95% CI, 0.45-1.3). CONCLUSION: These results support the hypotheses that continuous combined therapy does not increase (and may decrease) endometrial cancer risk and that long-term sequential therapy can lead to a modest increased risk. However, the collective results of all studies of these questions and their clinical implications remain unclear.

 

Am J Obstet Gynecol. 2007 Aug;197(2):137.e1-7.

Body composition during treatment with conjugated estrogens with and without medroxyprogesterone acetate: analysis of the women's Health, Osteoporosis, Progestin, Estrogen (HOPE) trial.

Thorneycroft IH, Lindsay R, Pickar JH.

Department of Obstetrics and Gynecology, University of South Alabama, Mobile, AL, USA. ithorney@bellsouth.net

OBJECTIVE: The objective of the study was to determine the effects of several doses of conjugated estrogens (CE) and CE plus medroxyprogesterone acetate (MPA) on body composition (BC). STUDY DESIGN: This was a randomized, double-blind, placebo-controlled substudy of the Women's Health, Osteoporosis, Progestin, Estrogen (HOPE) trial. Healthy women (n = 822, 1-4 years after menopause) were randomly assigned to receive the following treatments daily for 2 years: CE, 0.625 mg; CE, 0.625 mg, and MPA, 2.5 mg; CE, 0.45 mg; CE, 0.45 mg, and MPA, 2.5 mg; CE, 0.45 mg, and MPA, 1.5 mg; CE, 0.3 mg; CE, 0.3 mg, and MPA, 1.5 mg; or placebo. Body weight (BW) was assessed every 3-4 cycles and fat body mass (FBM), lean body mass (LBM), and percent body fat (PBF) at cycles 6, 13, 19, and 26. RESULTS: In the placebo group, BW, FBM, and PBF increased at each visit during the study. Changes in these parameters were smaller in the active groups. These effects were independent of CE dose and the presence of MPA. Changes in LBM were small and comparable across groups. CONCLUSION: Treatment with CE or CE and MPA for up to 2 years does not affect BC.

 

Am J Obstet Gynecol. 2007 Aug;197(2):134.e1-6.

Transdermal hormonal contraception: benefits and risks.

Burkman RT.

Department of Obstetrics and Gynecology, Baystate Medical Center, Springfield, MA 01199, USA. rtb@bhs.org

Transdermal drug delivery systems have been available in the United States for >20 years. Since the introduction of the first transdermal patch (scopolamine) for the treatment of motion sickness, >35 transdermal patch products have been approved by the US Food and Drug Administration for a variety of indications that include hormone replacement therapy, nicotine replacement therapy, chronic pain (fentanyl), angina (nitroglycerin), hypertension (clonidine), and more recently, overactive bladder (oxybutynin), and contraception (ethinyl estradiol/norelgestromin). Clinical data demonstrated the efficacy and safety of the contraceptive patch; however, concerns regarding estrogen levels and reports of venous thromboembolism led to the development of 2 epidemiologic studies and, subsequently, revised product labeling. Despite this, the contraceptive patch may be an appropriate option for some patients

 

Ortop Traumatol Rehabil. 2001 Sep 30;3(3):338-44.

The most common errors in the densitometric diagnosis of osteoporosis.

Kaleta M, Wroński S.

Katedra i Oddział Kliniczny Ortopedii, Slaska Akademia Medyczna, Katowice.

A review of world literature on the subject indicates that, given the present state of our knowledge, and the technological possibilities and availability of the apparatus, the most useful method for the evaluation of bone metabolism, especially the diagnosis of osteoporosis, is dual energy X-ray absorptiometry (DEXA). However, this method is not free of errors that can exert a negative impact on the final results of examination. On the basis of heir own experience, the authors have presented here the most common errors encountered in the densitometric technique. A DPV-L densitometric apparatus (Lunar Corporation) was used in this research. Errors in densitometric testing are divided into three groups: those dependent on the object investigated, those dependent on densitometric data analysis, and others. In the first group we took into account factors which can lead to either overestimating (+) or underestimating (-) the final test results: degenerative changes (+), scoliosis (+), the presence of foreign bodies, such as metal (-), status post fracture (+), the presence of pathological structures (+ or -), osteoporotic fractures (+), and incorrect arrangement of the investigated object (+ or -). Errors in data analysis included erroneous data entry regarding the patient's age, height, body mass (affecting the value of the Z-score), and sex (distorting the T-score and the Z-score), and incorrect settings regarding the measurement field. Other errors to densitometric technique included failure to calibrate or improper calibration of the measurement apparatus and errors in computer programming. Individual errors were responsible for falsifying results from 1 to 37%. If several of these errors are accumulated, the accuracy of examination may change more than 100%. Densitometric examinations of the lumbar spine are the most subject to error. The repeatability of the results generated by the DEXA apparatus (as stated in the equipment specifications) ranges for particular skeletal regions from 0,9% to 2,5% of the coefficient of variance, while the precision ranges from 3% to 5%. This means that even if we follow the strictest guidelines for test procedures, the margin of error is still several percent. We also cannot exclude the impact of errors of the three types listed above on the final results. We are convinced that the DEXA method is an excellent instrument for the diagnosis of osteoporosis (in static bone evaluation). However, its value diminishes in monitoring dynamic changes in bone tissue, even at 1-2 year intervals.

 

Gynecol Obstet Invest. 2007 Aug 8;65(1):35-38 [Epub ahead of print]

Hormone Replacement Therapy after Treatment of Endometrial Cancer.

Tangjitgamol S, Manusirivithaya S, Hanprasertpong J, Kavanagh JJ.

Gynecologic Oncology Unit, Department of Obstetrics and Gynecology, Bangkok Metropolitan Administration Medical College and Vajira Hospital, Bangkok, Thailand.

Hormone replacement therapy (HRT) after endometrial cancer (EMC) treatment is an uncertain subject with limited exploration among gynecologic cancer research. Because estrogen is a well-recognized etiologic factor of EMC, most physicians are probably reluctant to provide a replacement therapy, or limit its use to only a selected group of patients. In order to give an overview on this subject, we searched the English-language literature to identify relevant studies or reports. We found that HRT did not appear to increase the recurrence or death rates in EMC. However, most information came from retrospective studies with selection bias, or from a small prospective non-randomized study. The only randomized controlled trial of the Gynecologic Oncology Group could also not provide a definite answer regarding its safety and recommendation. In conclusion, on the basis of the currently available studies, HRT after EMC treatment does not appear to have an adverse effect on EMC. Nevertheless, because of a limitation of data, the physician should thoroughly consider all possible benefits and theoretical risks of recurrence or mortality in each individual to provide the best of care for their patients.

 

Bone. 2007 Jun 26; [Epub ahead of print]

Walking intensity for postmenopausal bone mineral preservation and accrual.

Borer KT, Fogleman K, Gross M, La New JM, Dengel D.

Department of Movement Science, Division of Kinesiology, The University of Michigan, Ann Arbor, USA.

INTRODUCTION:: Mechanical stresses on the bone are an important aspect of physical activity that promotes bone preservation and increases in bone mass. Exercise intensities leading to bone preservation and accrual have not been adequately defined for humans in general, and postmenopausal women in particular. MATERIALS AND METHODS:: To quantify parameters of effective walking intensity for preservation and accrual of bone mineral, healthy postmenopausal women engaged in 30 weeks of supervised walking, 4.8 km per day, 4 days a week at intensities of 102% or 123% of the ventilatory threshold (VT) equivalent to 67% and 86% of maximal effort (VO(2) max). Subjects were matched by age, body mass, hormone replacement status (HRT) and VT. Areal bone mineral density (aBMD) determined by DXA (n=25) and bone formation markers osteocalcin (OC), and bone-specific alkaline phosphatase (bALP) (n=43), were measured at the outset and at 15-week intervals. Peak vertical forces at corresponding intensities were measured (n=9) on a force plate. RESULTS:: aBMD of legs and whole body, but not of other sites, and lean mass of legs, but not of arms, increased after 15 weeks of high intensity, compared to moderate losses for low intensity training. Leg and total body aBMD was preserved and slightly increased with loads greater than 872.3 newtons (N) with a walking intensity above 115% of VT or 74% of VO(2) max, speeds above 6.14 km/h, and heart rates above 82.3% of age-specific maximum. OC and bALP did not correlate with training-induced changes in aBMD. CONCLUSIONS:: At exercise intensities above 115% of VT or 74% of VO(2) max, and walking speeds above 6.14 km/h, mechanical loading of 872.3 N or 1.22 times body weight is sufficient for increases in leg muscle mass and preservation of BMD in postmenopausal women.

 

Public Health Nutr. 2007 Aug 9;:1-9 [Epub ahead of print]

Effects of meat consumption and vegetarian diet on risk of wrist fracture over 25 years in a cohort of peri- and postmenopausal women.

Thorpe DL, Knutsen SF, Lawrence Beeson W, Rajaram S, Fraser GE.

Department of Physical Therapy, School of Allied Health Professions, Loma Linda University, CA 92350, USA.

BACKGROUND: Evidence suggesting that a diet high in fruits and vegetables may be beneficial to bone health has sparked interest in the potential benefit of a vegetarian diet. However, other studies have raised a question regarding the adequacy of protein in such a diet. OBJECTIVE: The aim of the present study was to take a whole foods approach in examining the effects of foods high in protein on the risk of wrist fracture (WF) in a cohort with a significant proportion consuming a meat-free diet. DESIGN: A cohort study of women who completed two lifestyle surveys 25 years apart. SUBJECTS: One thousand eight hundred and sixty-five peri- and postmenopausal women at the time of the first survey. RESULTS: There was a significant interaction between meat consumption and foods high in vegetable protein. Among vegetarians, those who consumed the least vegetable protein intake were at highest risk for fracture. However, increasing levels of plant-based high-protein foods decreased WF risk, with a 68% reduction in risk (hazard ratio (HR) = 0.32, 95% confidence interval (CI) 0.13-0.79) in the highest intake group. Among those with lowest vegetable protein consumption, increasing meat intake decreased the risk of WF, with the highest consumption decreasing risk by 80% (HR = 0.20, 95% CI 0.06-0.66). CONCLUSIONS: The finding that higher consumption frequencies of foods rich in protein were associated with reduced WF supports the importance of adequate protein for bone health. The similarity in risk reduction by vegetable protein foods compared with meat intake suggests that adequate protein intake is attainable in a vegetarian diet.

 

Forum Nutr. 2007;60:25-30.

Nutrigenetics.

El-Sohemy A.

Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ont., Canada.

Nutrients interact with the human genome to modulate molecular pathways that may become disrupted, resulting in an increased risk of developing various chronic diseases. Genetic polymorphisms affect the metabolism of dietary factors, which in turn affects the expression of genes involved in a number of important metabolic processes. Genetic polymorphisms affecting nutrient metabolism may explain some of the inconsistencies among epidemiological studies relating diet to chronic diseases such as cancer, diabetes, rheumatoid arthritis, osteoporosis and cardiovascular disease. Understanding how genetic variations influence nutrient digestion, absorption, transport, biotransformation, uptake and elimination will provide a more accurate measure of exposure to the bioactive food ingredients ingested. Furthermore, genetic polymorphisms in the targets of nutrient action such as receptors, enzymes or transporters could alter molecular pathways that influence the physiological response to dietary interventions. Among the candidate genes with functional variants that affect nutrient metabolism are those that code for xenobiotic-metabolizing enzymes (also called drug-metabolizing enzymes). These enzymes are involved in the phase I and II biotransformation reactions that produce metabolites with either increased or decreased biological activity compared to the parent compound. A number of dietary factors are known to alter the expression of these genes that, in turn, metabolize a vast array of foreign chemicals including dietary factors such as antioxidants, vitamins, phytochemicals, caffeine, sterols, fatty acids and alcohol. Knowledge of the genetic basis for the variability in response to these dietary factors should result in a more accurate measure of exposure of target tissues of interest to these compounds and their metabolites. Examples of how 'slow' and 'fast' metabolizers respond differently to the same dietary exposures will be discussed. Identifying relevant diet-gene interactions will benefit individuals seeking personalized dietary advice as well as improve public health recommendations by providing sound scientific evidence linking diet and health.

 

Am J Clin Nutr. 2007 Aug;86(2):434-43.

High folate intake is associated with lower breast cancer incidence in postmenopausal women in the Malmo Diet and Cancer cohort.

Ericson U, Sonestedt E, Gullberg B, Olsson H, Wirfält E.

Department of Clinical Sciences, Lund University, Malmö, Sweden, and the Department of Clinical Sciences, Lund University, Lund, Sweden.

BACKGROUND: Epidemiologic studies of associations between folate intake and breast cancer are inconclusive, but folate and other plant food nutrients appear protective in women at elevated risk. OBJECTIVE: The objective was to examine the association between folate intake and the incidence of postmenopausal breast cancer. DESIGN: This prospective study included all women aged >/=50 y (n = 11699) from the Malmö Diet and Cancer cohort. The mean follow-up time was 9.5 y. We used a modified diet-history method to collect nutrient intake data. At the end of follow-up, 392 incident invasive breast cancer cases were verified. We used proportional hazard regression to calculate hazard ratios (HRs). RESULTS: Compared with the lowest quintile, the incidence of invasive breast cancer was reduced in the highest quintile of dietary folate intake (HR: 0.56; 95% CI: 0.35, 0.90; P for trend = 0.02); total folate intake, including supplements (HR: 0.56; 95% CI: 0.34, 0.91; P for trend = 0.006); and dietary folate equivalents (HR: 0.59; 95% CI: 0.36, 0.97; P for trend = 0.01). CONCLUSION: A high folate intake was associated with a lower incidence of postmenopausal breast cancer in this cohort.

 

Eur J Vasc Endovasc Surg. 2007 Aug 1; [Epub ahead of print]

The Impact of Hormone Replacement Therapy on the Pathophysiology of Peripheral Arterial Disease.

Davies RS, Vohra RK, Bradbury AW, Adam DJ.

University Department of Vascular Surgery, Heart of England NHS Foundation Trust, Birmingham, UK; Department of Vascular Surgery, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK.

BACKGROUND: Hormone replacement therapy (HRT) is recommended to post-menopausal women to control menopausal symptoms and prevent osteoporosis. The management of women with peripheral arterial disease (PAD) and who are taking HRT is controversial. AIM: To summarise what is known about HRT and its effect on the natural progression of PAD and its subsequent treatment. METHODS: A MEDLINE (1966-2004) and Cochrane library search for articles relating to HRT and PAD was undertaken. RESULTS: The potential benefits of unopposed estrogen therapy on atherosclerotic progression and limb microcirculation are outweighed by the increased risk of endometrial dysplasia and thrombotic complications. Only one major study (Rotterdam) specifically assessed the impact of HRT on the clinical course of PAD. The findings suggested a decreased risk of PAD among healthy post-menopausal women taking HRT which contrasts with the sub-group analyses of other major studies (HERS/HERS II). HRT appears to reduce the primary success rates of both endovascular and open surgical revascularisation in patients with PAD. CONCLUSIONS: Further studies are required to investigate the effects of HRT on the progression of PAD and its management.

 

Fertil Steril. 2007 Aug 4; [Epub ahead of print]

The ReSTAGE Collaboration: defining optimal bleeding criteria for onset of early menopausal transition.

Harlow SD, Mitchell ES, Crawford S, Nan B, Little R, Taffe J; for the ReSTAGE Collaboration.

Epidemiology.

OBJECTIVE: Criteria for staging the menopausal transition are not established. This article evaluates five bleeding criteria for defining early transition and provides empirically based guidance regarding optimal criteria. DESIGN/SETTING: Prospective menstrual calendar data from four population-based cohorts: TREMIN, Melbourne Women's Midlife Health Project (MWMHP), Seattle Midlife Women's Health Study (SMWHS), and Study of Women's Health Across the Nation (SWAN) with annual serum FSH from MWMHP and SWAN. PARTICIPANTS: 735 TREMIN, 279 SMWHS, 216 MWMHP, and 2270 SWAN women aged 35-57 at baseline who maintained menstrual calendars. MAIN OUTCOME MEASURE(S): Age at and time to menopause for: standard deviation >6 and >8 days, persistent difference in consecutive segments >6 days, irregularity, and >/=45 day segment. Serum FSH concentration. RESULT(S): Most women experienced each of the bleeding criteria. Except for a persistent >6 day difference that occurs earlier, the criteria occur at a similar age and at approximately the same age as late transition in a large proportion of women. FSH was associated with all proposed markers. CONCLUSION(S): The early transition may be best described by ovarian activity consistent with the persistent >6 day difference, but further study is needed, as other proposed criterion are consistent with later menstrual changes.

 

Ultrasound Obstet Gynecol. 2007 Aug 10; [Epub ahead of print]

Ultrasound assessment of endometrial morphology and vascularity to predict endometrial malignancy in women with postmenopausal bleeding and sonographic endometrial thickness >/= 4.5 mm.

Opolskiene G, Sladkevicius P, Valentin L.

Department of Obstetrics and Gynecology, Malmö University Hospital, Lund University, Malmö, Sweden.

OBJECTIVES: To determine which endometrial morphology characteristics as assessed by gray-scale ultrasound and which endometrial vessel characteristics as assessed by power Doppler ultrasound are useful for discriminating between benign and malignant endometrium in women with postmenopausal bleeding (PMB) and sonographic endometrial thickness >/= 4.5 mm and to develop logistic regression models to calculate the individual risk of endometrial malignancy in women with PMB, endometrial thickness >/= 4.5 mm, good visibility of the endometrium and detectable Doppler signals in the endometrium. METHODS: Of 223 consecutive patients with PMB and sonographic endometrial thickness >/= 4.5 mm, 120 fulfilled our inclusion criteria. They underwent transvaginal gray-scale and power Doppler ultrasound examination, which was videotaped for later analysis by two examiners with more than 15 years' experience in gynecological ultrasonography. They independently assessed endometrial morphology and vascularity using predetermined criteria. Their agreed-upon description was compared with the histological diagnosis. Univariate and multivariate logistic regression analyses were used. The best diagnostic test was defined as the one with the largest area under the receiver-operating characteristics curve (AUC). RESULTS: Thirty (25%) endometria were malignant. Inter-observer agreement for the description of endometrial morphology and vascularity was moderate to good (Kappa 0.49-0.78). The best ultrasound variables to predict malignancy were heterogeneous endometrial echogenicity (AUC 0.83), endometrial thickness (AUC 0.80), and irregular branching of endometrial blood vessels (AUC 0.77). A logistic regression model including endometrial thickness and heterogeneous endometrial echogenicity had an AUC of 0.91. Its mathematically best risk cut-off yielded a positive likelihood ratio of 4.4, and a negative likelihood ratio of 0.1. Adding Doppler information to the model improved diagnostic performance marginally (AUC 0.92). CONCLUSIONS: In selected high-risk women with PMB and an endometrial thickness of >/= 4.5 mm, calculation of the individual risk of endometrial malignancy using regression models including gray-scale and Doppler characteristics can be used to tailor management. These models would need to be tested prospectively before introduction into clinical practice.

 

 

Semana del 1 al 7 de Agosto 2007

Menopause. 2007 Jul 18;Publish Ahead of Print [Epub ahead of print]

Past oral contraceptive and hormone therapy use and endogenous hormone concentrations in postmenopausal women.

Chan MF, Dowsett M, Folkerd E, Wareham N, Luben R, Welch A, Bingham S, Khaw KT.

Public Health and Primary Care, University of Cambridge School of Clinical Medicine,Cambridge, UK.

Objective: Exogenous sex hormone use is associated with many health effects. Current exogenous hormone use influences endogenous sex hormone levels, but little is known about longer term effects on endogenous hormones after cessation of use. The aim of this study was to examine the relationship between past hormone use and current endogenous hormone status. DESIGN:: This was a cross-sectional study of 1,983 postmenopausal women aged 55 to 81 years from the general community. The women were not currently using exogenous hormones. Past use of oral contraceptives (OCs) and hormone therapy (HT) as well as circulating endogenous sex hormones and sex hormone-binding globulin concentrations were evaluated. Results: Past OC users had significantly lower endogenous estradiol, estrone, androstenedione, testosterone, and sex hormone-binding globulin concentrations compared with never users independent of age, body mass index, smoking, physical activity, and reproductive factors. Past HT users had significantly lower testosterone and 17alpha-hydroxyprogesterone concentrations. Past OC use and HT use were both independently associated with lower testosterone concentrations: -9% (95% CI: -16% to -2%) for ever OC use compared with never OC use and -7% (95% CI: -17% to -2%) for ever HT use compared with never HT use. The magnitude of 5% to 10% differences in endogenous hormone concentrations was similar or greater for past OC use compared with past HT use, although OC use occurred earlier in the past. Conclusions: Past OC use and HT use seem to be related to long-term differences in endogenous sex hormones and sex hormone-binding globulin concentrations in postmenopausal women many years after cessation of use. These findings have implications for understanding the longer term effects of exogenous hormone exposures earlier in life with health and disease risk in later life.

 

Menopause. 2007 Jul 6;Publish Ahead of Print [Epub ahead of print]

Vaginal, endometrial, and reproductive hormone findings: randomized, placebo-controlled trial of black cohosh, multibotanical herbs, and dietary soy for vasomotor symptoms: the Herbal Alternatives for Menopause (HALT) Study.

Reed SD, Newton KM, Lacroix AZ, Grothaus LC, Grieco VS, Ehrlich K.

Group Health Center for Health Studies, Seattle, WA.

Objective: To evaluate vaginal, endometrial, and reproductive hormone effects of three herbal regimens compared with placebo and hormone therapy (HT). Design: This was a 1-year, randomized, double-blind, placebo-controlled trial of 351 women, ages 45 to 55, with two or more vasomotor symptoms per day. Women were randomly assigned to (1) black cohosh, (2) a multibotanical containing black cohosh, (3) the same multibotanical plus dietary soy counseling, (4) HT, or (5) placebo. Women were ineligible if they had used HT in the previous 3 months or menopausal herbal therapies in the previous month. Data on vaginal cytology and dryness were collected (at baseline and 3 and 12 mo). Daily menstrual diaries were maintained by 313 women with a uterus, and abnormal bleeding was evaluated. Serum estradiol, follicle-stimulating hormone, luteinizing hormone, and steroid hormone-binding globulin were assessed (baseline and 12 mo) among 133 postmenopausal women. Gynecologic outcomes of the five groups were compared. Results: The five groups did not vary in baseline vaginal cytology profiles, vaginal dryness, menstrual cyclicity, or hormone profiles. The HT group had a lower percentage of parabasal cells and vaginal dryness than the placebo group at 3 and 12 months (P< 0.05). Abnormal bleeding occurred in 53 of 313 (16.9%) women. There were no differences in frequency of abnormal bleeding between any of the herbal and placebo groups, whereas women in the HT group had a greater risk than those in the placebo group (P<0.001). Among postmenopausal women, HT significantly decreased FSH hormone and increased estradiol; none of the herbal interventions showed significant effects on any outcomes at any time point. Conclusions: Black cohosh, used alone or as part of a multibotanical product with or without soy dietary changes, had no effects on vaginal epithelium, endometrium, or reproductive hormones.

 

Menopause. 2007 May 21;Publish Ahead of Print [Epub ahead of print

Raloxifene slows down the progression of intima-media thickness in postmenopausal women.

Colacurci N, Fornaro F, Cobellis L, De Franciscis P, Torella M, Sepe E, Arciello A, Cacciapuoti F, Paolisso G, Manzella D.

Department of Obstetrics, Gynecology, and Neonatology, School of Medicine, Naples, Italy.

Objective: To investigate the effect of raloxifene on atherosclerosis progression in healthy postmenopausal women. DESIGN: In a prospective fashion, a total of 155 healthy postmenopausal women were randomly assigned to receive raloxifene 60 mg/day or a matching placebo for 18 months. Atherosclerosis progression was evaluated by B-mode ultrasonography measuring the intima-media thickness (IMT) of the carotid arteries. Plasma levels of triglycerides, low-density lipoprotein cholesterol, soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, E-selectin, interleukin-6, tumor necrosis factor alpha, adiponectin, and the degree of insulin resistance by the homeostatic model assessment method were also determined. Results: The progression slope of carotid IMT was 0.0112 mm/18 months in the raloxifene group and 0.0857mm/18 months in the placebo group (P < 0.004). Raloxifene treatment compared with placebo produced a significant decrease in plasma triglycerides (P < 0.02), low-density lipoprotein cholesterol (P < 0.02), soluble forms of intercellular adhesion molecule-1 (P < 0.005) and vascular cell adhesion molecule-1 (P < 0.04), E-selectin (P < 0.02), interleukin-6 (P < 0.005), tumor necrosis factor alpha (P < 0.005) levels, and homeostatic model assessment index (P < 0.005) and a significant increase in plasma adiponectin levels (P < 0.001). Logistic regression analysis indicated that women receiving raloxifene had a lower risk of IMT progression (odds ratio = 0.41; 95% CI: 0.32-0.70). Conclusions: Raloxifene treatment, possibly through an increase in plasma adiponectin levels, may slow the progression of IMT in postmenopausal women.

 

Menopause. 2007 Mar 7;Publish Ahead of Print [Epub ahead of print]

Correlation between estrogens and serum adipocytokines in premenopausal and postmenopausal women.

Hong SC, Yoo SW, Cho GJ, Kim T, Hur JY, Park YK, Lee KW, Kim SH.

Department of Obstetrics and Gynecology, College of Medicine, Korea University, Seoul, Korea.

Objective: The purpose of this study was to investigate the association between serum adipocytokines (adiponectin, resistin, leptin, and tumor necrosis factor alpha [TNF-alpha]) and endogenous estrogen (estrone and estradiol) levels in healthy premenopausal and postmenopausal women. DESIGN:: This study included 53 healthy premenopausal women, 45 healthy postmenopausal women, and 10 postmenopausal women with the metabolic syndrome who were participating in general health examinations. A secondary analysis was performed on levels of adiponectin, resistin, leptin, TNF-alpha, estrone (E1), and estradiol (E2). Results: After accounting for body mass index, TNF-alpha was significantly increased (1.5 +/- 0.1 vs 2.0 +/- 0.1 pg/mL, P < 0.05) in healthy postmenopausal women as compared with healthy premenopausal women, whereas leptin was decreased (5.6 ± 1.1 vs 4.0 ± 1.1 ng/mL). Estrogen (E1 and E2) was positively correlated with leptin in only healthy premenopausal women, whereas estrogen did not correlate with any adipocytokine in healthy postmenopausal women. In the multiple regression analysis, only leptin significantly contributed to insulin resistance. Combining healthy premenopausal and postmenopausal women, E1 correlated negatively with TNF-alpha (r = -0.23, p< 0.05) and positively with leptin (r = 0.35, p< 0.01) and did not correlate with resistin. E2 correlated negatively with TNF-alpha (r = -0.24, p< 0.05) and positively with leptin (r = 0.34, p< 0.01); it did not correlate with adiponectin or resistin. Leptin might stimulate the increase of plasma gonadotropin-releasing hormone levels, which could result in a positive correlation with estrogen in premenopausal women but not in postmenopausal women. Conclusions: Estrogen deficiency resulted in increased TNF-a levels. Serum leptin levels correlated positively with estrogen levels in premenopausal women. However, the increase in obesity in postmenopausal women increased leptin, which increases insulin resistance.

 

Obstet Gynecol. 2007 Aug;110(2):230-240

Symptoms Associated With Menopausal Transition and Reproductive Hormones in Midlife Women.

Freeman EW, Sammel MD, Lin H, Gracia CR, Pien GW, Nelson DB, Sheng L.

Department of Medicine, University of Pennsylvania; Philadelphia, PA.

Objective: To test the hypothesis that prevalence of women with menopausal symptoms of hot flushes; aches, joint pain, and stiffness; depressed mood; poor sleep; decreased libido; or vaginal dryness increases with progression through the menopausal transition. Methods: Women in the Penn Ovarian Aging Study were assessed longitudinally for 9 years. Data were obtained from structured interviews, a validated symptom questionnaire, menstrual bleeding dates and early follicular hormone measures (estradiol [E2], follicle-stimulating hormone [FSH], and inhibin b). Menopausal stages were based on menstrual bleeding patterns. Other risk factors included age, race, history of depression, current smoking, body mass index, and perceived stress. Generalized linear regression models for repeated measures were used to estimate associations among the variables with each symptom. Results: The prevalence of hot flushes; aches, joint pain, and stiffness; and depressed mood increased in the menopausal transition. Menopausal stage was associated with hot flushes (P<.001); aches joint pain, and stiffness (P<.001); and depressed mood (P=.002). Within-woman fluctuations of E2 were associated with hot flushes and aches. Poor sleep, decreased libido, and vaginal dryness were not associated with menopausal stages. There was 80% power to detect an absolute difference of 11% for libido and vaginal dryness and 17% for poor sleep in the prevalence of these symptoms in the late menopausal transition compared with premenopausal status. Conclusion: The study highlights the role of menopausal stages for some symptoms of midlife women and indicates that stages in the transition to menopause are associated with hot flushes; aches, joint pain, and stiffness; and depressed mood. Fluctuations of E2, decreased levels of inhibin b, and increased FSH levels were associated with these symptoms. EVIDENCE: II.

 

Cancer Causes Control. 2007 Jul 31; [Epub ahead of print

Protection of mammography screening against death from breast cancer in women aged 40-64 years.

Norman SA, Russell Localio A, Weber AL, Coates RJ, Zhou L, Bernstein L, Malone KE, Marchbanks PA, Weiss LK, Lee NC, Nadel MR.

Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, USA.

Objective: This study assessed the efficacy of community-based screening mammography in protecting against breast cancer death, asking whether age differences in efficacy persisted in the 1990s. Methods: In a case-control study with follow-up, odds ratios (OR) were used to estimate the relative mortality rates from invasive breast cancer among women with at least one screening mammogram in the two years prior to a baseline reference date compared to non-screened women, adjusting for potential confounding. The multicenter population-based study included 553 black and white women diagnosed during 1994-1998 who died in the following five years, and 4016 controls without breast cancer. Results: Efficacy for reducing the rate of breast cancer death within five years after diagnosis was greater at ages 50-64 years (OR = 0.47, 95% confidence interval (CI) 0.35-0.63) than at ages 40-49 (OR = 0.89, 95% CI 0.65-1.23), and greater among postmenopausal (OR = 0.45, 95% CI 0.33-0.62) than premenopausal women (OR = 0.74, 95% CI 0.53-1.04). Estimates of efficacy were conservative, as shown by sensitivity analyses addressing whether cancer was discovered by a screening mammogram, age at which screening was received, the length of the screening observation window, and years of follow-up after diagnosis. Conclusions: Despite the persistence of age differences in efficacy of mammography screening, with greater observed benefit for women aged 50-64 years, these findings support current screening recommendations for women 40-64 years old.

 

Rev Assoc Med Bras. 2007 May-Jun;53(3):229-33

Quantitative calcaneal ultrasound evaluation allows distinguishing women with and without fractures.

Velho LA, Bellangero W, Bahamondes L.

Faculade de Ciências Médicas, Universidade Estadual de Campinas.

Objective: International studies have pointed out quantitative ultrasound as an important method to assess bone fragility and risk of fracture. This study was performed to compare quantitative ultrasound (QUS) in two groups of Brazilian women, those with a fracture and those with no previous history of fracture. The aim was to assess whether there was any difference between the right and the left foot s and whether two sequential measurements in each foot were statistically equivalent. METHODS: A total of 52 women, 26 with and 26 with no fractures, matched by age (+/- 2 years), years since menopause (+/- 2 years), and body mass index (kg/m(2)) (+/- 2) were evaluated. Results: Results were compared by the Student's t test for matched samples. Values (mean +/- SD) for the stiffness index (SI) were 54.9 (+/- 16.6) and 80.4 (+/- 17.3), and for the T Score were -2.9 (+/- 0.94) and -1.3 (+/- 0.95) for the groups with and with no fractures, respectively. The first and second measurements of the SI for the right foot and the mean measurement of each foot were found similar when compared. There was a statistical significance (p<0.01). Conclusions: The QUS was shown to distinguish between women with and with no fractures. Also, no differences were observed in the QUS of the left or right foot as well as in the first or second measurements of each foot in the women under study.

 

QJM. 2007 Jul 30; [Epub ahead of print

The effect of hormone replacement therapy on cognitive function in post-menopausal women.

Lavi R, Doniger GM, Simon E, Hochner-Celnikier D, Zimran A, Elstein D.

Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel.

Background: Despite interest in causes of dementia in older persons, particularly in post-menopausal women, it is unclear whether hormone replacement therapy (HRT) is a risk factor. AIM: To assess cognitive function in post-menopausal women with high educational status receiving HRT, compared to non-users. Design: Cognitive functioning was assessed with in women aged 55-60 years with at least university-level education, using the Mindstreams system, a computerized cognitive battery with multiple domains. Results: 0f 165 women meeting the inclusion/exclusion criteria, 82 women (49.7%) declined participation. Of the remaining 83, 40 (48.2%) had never received HRT; the remainder was divided into women receiving 5-9 years HRT (n = 29)versus those with >/=10 years HRT (n = 11). There were no statistically significant differences between HRT users and non-users in global scores or sub-domains of cognitive functioning, and no difference between those women receiving HRT for 5-9 years vs. >/=10 years. Discussions: Long-term HRT does not appear to impair cognitive functioning in highly-educated women. Recommendations regarding post-menopausal HRT should be made on an individual basis.

 

Future Microbiol. 2006 Jun;1:33-51.

Viruses and human breast cancer.

Lawson JS, Günzburg WH, Whitaker NJ.

School of Public Health, University of New South Wales, Sydney, Australia

There are well-established risk factors for breast cancer, most of which relate to estrogens and growth hormones in females. These include early-age menarche, late-age menopause, postmenopausal obesity and use of hormone therapy. However, these factors do not account for the sixfold difference in breast cancer incidence and mortality between countries and the fact that these differences dramatically lessen after migration; nor do they account for male breast cancer. Accordingly, hormone-responsive viruses have become major suspects as etiological agents for human breast cancer. Human papillomaviruses, mouse mammary tumor virus and Epstein-Barr virus are the prime candidate viruses as causes of human breast cancer. Human papillomaviruses and the mouse mammary tumor virus have hormone responsive elements that appear to be associated with enhanced replication of these viruses in the presence of corticosteroid and other hormones. This biological phenomenon is particularly relevant because of the hormone dependence of breast cancer. Viral genetic material for each of these candidate viruses has been identified by polymerase chain reaction in breast tumors but rarely in normal breast tissue controls. Pooled data from controlled studies show substantial odds ratios for the presence of viral genetic material in breast tumors compared with normal controls. These and additional data provide substantial, but not conclusive, evidence that human papillomavirus, the mouse mammary tumor virus and Epstein-Barr virus may have a role in the etiology of human breast cancer. If conclusive evidence for a role of these viruses in breast carcinogenesis can be developed, there is a practical possibility of primary prevention.

 

Int J Epidemiol. 2007 Jul 26; [Epub ahead of print

Experience of famine and bone health in post-menopausal women.

Kin CF, Shan WS, Shun LJ, Chung LP, Jean W.

Department of Community and Family Medicine, School of Public Health, Hong Kong SAR.

Background: Famines have occurred in all areas of the world in every period of history. Many studies have shown that poor growth and development and adverse environmental conditions in childhood are associated with osteoporosis in later life. However, little information is available on the relation between famine and bone health. METHODS: This study examines the hypothesis that past experience of famine has an adverse impact on bone health, using data from Ms Os (Hong Kong), a large cohort study on osteoporosis in Asian women. There were 1826 Hong Kong women aged 65 years or older recruited from the community. A standardized, structured interview and DXA were performed. Subjects who had experienced famine tended to have lower levels of education, social status and current daily calcium intake. They also have higher rates of cigarette consumption, depression and coronary heart disease. Results: After adjustment for confounders, we found that subjects who had experienced famine have a significantly higher rate of developing osteoporosis than those who had not. Conclusions: We conclude that past exposure to famine, especially in childhood, is associated with osteoporosis.