Selección de Resúmenes de Menopausia

Semana del 21 al 27 de Mayo 2008

Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

 

 

Oncol Rep. 2008 Jun;19(6):1627-34.

Progestins regulate genes that can elicit both proliferative and antiproliferative effects in breast cancer cells.

Purmonen S, Manninen T, Pennanen P, Ylikomi T.

University of Tampere, Medical School, Department of Cell Biology, FIN-33014, University of Tampere, Finland.

Sex steroid hormone progesterone is known to have profound effects on the growth and differentiation of the normal mammary gland and malignant breast epithelial cells. In vitro progesterone and synthetic progesterone-like compounds (progestins) inhibit breast cancer cell growth. Medroxyprogesterone acetate (MPA) is a synthetic hormone widely used in the adjuvant treatment of advanced breast cancer, hormone replacement therapy and in oral contraceptives. It is a paradoxical hormone, since it inhibits breast cancer cell proliferation, but has also been implicated in increased breast cancer risk. To better understand the molecular mechanism by which cell proliferation and differentiation are regulated by progesterone and MPA in human breast cancer, we utilized cDNA microarray and quantitative real-time RT-PCR methods to identify their target genes. This study describes novel progestin/progesterone target genes in breast cancer cells and, notably, novel target genes that elucidate the underlying molecular mechanism of the dual role progestins play in the breast. A cDNA microarray containing 3000 genes showed notable regulation in 30 and 27 genes by MPA and progesterone, respectively. Only 6 out of the 30 genes regulated by MPA are down-regulated, but no progesterone down-regulation was observed. Overlapping in gene regulation by progesterone and MPA occurred, but the majority of genes regulated by these hormones were distinct. Given that progestins both stimulate and inhibit cancer cell growth, we report our findings on novel progestin and progesterone targets, which could explain the paradoxical actions of progestins in the breast.

 

 

Adv Exp Med Biol. 2008;617:151-60.

Women's health initiative studies of postmenopausal breast cancer.

Prentice RL.

Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

The WHI has provided randomized controlled trial data on interventions that are among the most important in relation to the health benefits and risks among postmenopausal women in the USA. Postmenopausal hormone therapy did not yield the anticipated major reduction in coronary heart disease, and was responsible for both stroke elevations and fracture reductions over average 5.6 (E + P) and 7.1 (E-alone) years intervention periods. BC hazard ratios for both E + P and E-alone were about as anticipated, based on preceding observational studies, among women who had used postmenopausal hormones prior to WHI enrollment, but were lower than expected among women without such prior exposures. Whether these lower hazard ratios reflect upward bias in the observational studies or detection lags among women who tended to be quite a few years from menopause when randomized in the WHI trials remains to be fully clarified. At any rate, E + P is associated with an elevated BC risk, while the effects of E-alone remain somewhat uncertain. The WHI DM trial is taking place among women having baseline % energy from fat around 35, in contrast to the 38-39% projected. This has led to a smaller than anticipated intervention vs. control group difference in dietary habits, and to projected and realized BC incidence rates that were about 9% lower in the intervention vs. the control group. The likelihood that this lower rate reflects a meaningful reduction in BC risk is enhanced by a lower BC hazard ratio among the 50% of women who started relatively higher in percent energy from fat, and by cohort studies, including that among women in the DM control group, showing clear positive trends between food record percent energy from fat and BC incidence.

 

 

Calcif Tissue Int. 2008 May 22. [Epub ahead of print]

Echogenic Carotid Artery Plaques are Associated with Vertebral Fractures in Postmenopausal Women with Low Bone Mass.

Kim SH, Kim YM, Cho MA, Rhee Y, Hur KY, Kang ES, Cha BS, Lee EJ, Lee HC, Lim SK.

Division of Endocrinology, Department of Internal Medicine, Kwandong University College of Medicine, Myongji Hospital, Goyang, South Korea, bonesh@naver.com.

Although low bone mass has been associated with atherosclerosis even after adjustment for age, little is known about the association between vertebral fractures and calcified atherosclerotic plaques. Our objective was to investigate whether osteoporotic vertebral fractures are independently related to the prevalence of atherosclerotic carotid plaques in postmenopausal women with low bone mass. We enrolled 195 postmenopausal women with osteopenia or osteoporosis. Bone mineral density and the presence of vertebral fractures were assessed. Intima media thickness and atherosclerotic plaques of the carotid artery were assessed using ultrasonography. Of the 195 subjects in the study, 84 had no plaques and 111 had at least one. The percentage of women with vertebral fractures was significantly higher in subjects with echogenic carotid plaques than in those without (27% vs. 11%, respectively; P < 0.05). However, there was no difference in the prevalence of vertebral fractures between women with echolucent plaques and those without (10.9% vs. 10.7%, respectively; P = nonsignificant). By logistic regression analysis with multivariate adjustment, age (P < 0.01), dyslipidemia (P < 0.05), and the presence of vertebral fracture (P < 0.05) were independent risk factors for echogenic carotid plaques. Osteoporotic vertebral fractures are associated with an increased risk of echogenic atherosclerotic plaques in postmenopausal women with low bone mass. It appears that the high association of echogenic atherosclerotic plaques and vertebral fractures could partially explain why osteoporotic vertebral fractures are linked to increased mortality.

 

 

Kidney Int. 2008 May 21. [Epub ahead of print]

Oral estrogen therapy in postmenopausal women is associated with loss of kidney function.

Ahmed SB, Culleton BF, Tonelli M, Klarenbach SW, Macrae JM, Zhang J, Hemmelgarn BR.

Department of Medicine, University of Calgary, Calgary, Alberta, Canada.

Women are generally protected against progressive loss of kidney function; however, this advantage seems to diminish with menopause. Because of conflicting reports on the association between use of hormone therapy and kidney function we studied 5845 women (1459 on hormone therapy and 4386 non-users) who were over 66 years of age and had at least 2 serum creatinine measurements during the 2 year study period. After adjustment for covariates, hormone use (estrogen-only, progestin-only, or both) was associated with a significant loss of estimated GFR as the primary outcome along with an increased risk of rapid loss of kidney function as the secondary outcome compared to non-users. This increased rate of loss was associated with oral but not transvaginal estrogen use. An increased cumulative dose of estrogen was also associated with a greater decline in estimated GFR. Our study shows an independent association in a dose-dependent manner of estrogen use and loss of kidney function in this elderly population.

 

 

BMJ. 2008 May 20. [Epub ahead of print]

Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis.

Canonico M, Plu-Bureau G, Lowe GD, Scarabin PY.

Inserm Unit 780, Cardiovascular Epidemiology Section, Villejuif Cedex, France.

OBJECTIVE: To assess the risk of venous thromboembolism in women using hormone replacement therapy by study design, characteristics of the therapy and venous thromboembolism, and clinical background. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline. Studies reviewed Eight observational studies and nine randomised controlled trials. Inclusion criteria Studies on hormone replacement therapy that reported venous thromboembolism. Review measures Homogeneity between studies was analysed using chi(2) and I(2) statistics. Overall risk of venous thromboembolism was assessed from a fixed effects or random effects model. RESULTS: Meta-analysis of observational studies showed that oral oestrogen but not transdermal oestrogen increased the risk of venous thromboembolism. Compared with non-users of oestrogen, the odds ratio of first time venous thromboembolism in current users of oral oestrogen was 2.5 (95% confidence interval 1.9 to 3.4) and in current users of transdermal oestrogen was 1.2 (0.9 to 1.7). Past users of oral oestrogen had a similar risk of venous thromboembolism to never users. The risk of venous thromboembolism in women using oral oestrogen was higher in the first year of treatment (4.0, 2.9 to 5.7) compared with treatment for more than one year (2.1, 1.3 to 3.8; P<0.05). No noticeable difference in the risk of venous thromboembolism was observed between unopposed oral oestrogen (2.2, 1.6 to 3.0) and opposed oral oestrogen (2.6, 2.0 to 3.2). Results from nine randomised controlled trials confirmed the increased risk of venous thromboembolism among women using oral oestrogen (2.1, 1.4 to 3.1). The combination of oral oestrogen and thrombogenic mutations or obesity further enhanced the risk of venous thromboembolism, whereas transdermal oestrogen did not seem to confer additional risk in women at high risk of venous thromboembolism. CONCLUSION: Oral oestrogen increases the risk of venous thromboembolism, especially during the first year of treatment. Transdermal oestrogen may be safer with respect to thrombotic risk. More data are required to investigate differences in risk across the wide variety of hormone regimens, especially the different types of progestogens.

 

 

Maturitas. 2008 May 19. [Epub ahead of print]

Effect of natural early menopause on bone mineral density.

Francucci CM, Romagni P, Camilletti A, Fiscaletti P, Amoroso L, Cenci G, Morbidelli C, Boscaro M.

Division of Endocrinology, Department of Internal Medicine, Polytechnic University of Marche, Ancona, Italy.

OBJECTIVES: Early menopause (EM) is included among the risk factors for osteoporosis. Several studies have shown that women with early menopause have lower bone mineral density (BMD) than those with normal expected age of menopause. The aim of our cross-sectional study was to investigate the effects of time of menopause on vertebral bone mass in healthy postmenopausal women and to evaluate if early menopause is a risk factor for lower vertebral BMD. METHOD: We studied 782 who had never received drugs acting on bone mass. The study population was divided into three groups: women with early, normal (NM), and late (LM) menopause. Our study population was further categorized in 5-year age segments between 45 and >75. RESULTS: The three groups examined did not differ for age, age at menarche, body mass index (BMI), and vertebral BMD, while there were significant differences in age at menopause and years since menopause. Our study showed that women with EM presented significantly lower vertebral BMD than NM and LM in 50-54 age segments. Beyond 55 years, EM, NM, and LM women had no differences in lumbar BMD values. CONCLUSIONS: In conclusion, controversial data demonstrated that the absolute amount of bone loss is greater after early menopause than after normal or late menopause, even if a slight effect of early menopause on bone mass cannot be excluded.

 

 

Oncology. 2008 May 21;73(5-6):305-310. [Epub ahead of print]

Hormone Replacement Therapy as a Risk Factor for Non-Small Cell Lung Cancer: Results of a Case-Control Study.

Ramnath N, Menezes RJ, Loewen G, Dua P, Eid F, Alkhaddo J, Paganelli G, Natarajan N, Reid ME.

Department of Medicine, Roswell Park Cancer Institute, Buffalo, N.Y., USA.

Purpose: It was the aim of this study to assess the risk of lung cancer in postmenopausal women who received hormone replacement therapy (HRT). Experimental Design: This case-control study involves women who received medical services at Roswell Park Cancer Institute (RPCI) in Buffalo, New York, between 1982 and 1998, and who agreed to complete an epidemiological questionnaire. Participants with missing smoking data were excluded. The case group consisted of 595 women with primary lung cancer. Controls included 1,195 women, randomly selected from a pool of 5,845 eligible individuals, who received medical services at RPCI for non-neoplastic conditions; they had come to RPCI with a suspicion of neoplastic disease, but were diagnosed with neither benign nor malignant conditions. Controls were frequency matched 2:1 to cases on 5-year age intervals and exposure to smoking (ever/never). Cases and controls were comparable for age (means 61.3 and 61.0 years) and ever smoking (90%). Results: There were more former smokers among the cases (67 vs. 59% in controls); cases were less likely to be high school educated, were thinner, and were less likely to report HRT use compared with controls. Overall, hormone use was associated with a significant reduction in risk of lung cancer (adjusted odds ratio = 0.67; 95% confidence interval 0.53-0.85). Stratified analyses showed significant reductions in lung cancer risk in former smokers and women with normal to low body mass index. Conclusion: This study supports the hypotheses that there is a protective effect of HRT use on lung cancer risk in women.

 

 

Am J Cardiol. 2008 Jun 1;101(11):1599-1605. Epub 2008 Apr 2.

Usefulness of baseline lipids and C-reactive protein in women receiving menopausal hormone therapy as predictors of treatment-related coronary events.

Bray PF, Larson JC, Lacroix AZ, Manson J, Limacher MC, Rossouw JE, Lasser NL, Lawson WE, Stefanick ML, Langer RD, Margolis KL; Women's Health Initiative Investigators.

Cardeza Foundation for Hematologic Research and Jefferson Medical College, Philadelphia, Pennsylvania.

Blood lipids and high-sensitivity C-reactive protein (hs-CRP) are altered by hormone therapy. The goal of the present study was to determine whether lipids and hs-CRP have predictive value for hormone therapy benefit or risk for coronary heart disease events in postmenopausal women without previous cardiovascular disease. A nested case-control study was performed in the Women's Health Initiative hormone trials. Baseline lipids and hs-CRP were obtained from 271 incident patients with coronary heart disease (cases) and 707 controls. In a combined trial analysis, favorable lipid status at baseline tended to predict better coronary heart disease outcomes when using conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate (MPA). Women with a low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol ratio <2.5 had no increase in risk of coronary heart disease when using CEE with or without MPA (odds ratio 0.60, 95% confidence interval 0.34 to 1.06), whereas women with an LDL/HDL cholesterol ratio >/=2.5 had increased risk of coronary heart disease (odds ratio 1.73, 95% confidence interval 1.18 to 2.53, p for interaction = 0.02). Low hs-CRP added marginally to the value of LDL/HDL ratio <2.5 when predicting coronary heart disease benefit on hormone therapy. In conclusion, postmenopausal women with undesirable lipid levels had excess coronary heart disease risk when using CEE with or without MPA. However, women with favorable lipid levels, especially LDL/HDL cholesterol ratio <2.5, did not have increased risk of coronary heart disease with CEE with or without MPA irrespective of hs-CRP.

 

 

Maturitas. 2008 May 14. [Epub ahead of print]

Insulin resistance, obesity and breast cancer risk.

Pichard C, Plu-Bureau G, Neves-E Castro M, Gompel A.

Unité de Gynécologie endocrinienne, Hôtel-Dieu, APHP, Université Paris-5, Paris, France.

Breast cancer (BC) is one of the most important problems of public health. Among the avoidable risk factors during a woman's life, overweight and obesity are very important ones. Furthermore they are increasing worldwide. The risk of breast cancer is traditionally linked to obesity in postmenopausal women; conversely, it is neutral or even protective in premenopausal women. Since the initiator and promoter factors for BC act over a long time, it seems unlikely that the menopausal transition may have too big an impact on the role of obesity in the magnitude of the risk. We reviewed the literature in an attempt to understand this paradox, with particular attention to the body fat distribution and its impact on insulin resistance. The association of insulin resistance and obesity with BC risk are biologically plausible and consistent. Estradiol (E2) and IGFs act as mitogens in breast cancer cells. They act together and reciprocally. However the clinical and biological methods to assess the impact of insulin resistance are not always accurate. Furthermore insulin resistance is far from being a constant feature in obesity, particularly in premenopausal women; this complicates the analysis and explains the discrepancies in large prospective trials. The most consistent clinical feature to assess risk across epidemiological studies seems to be weight gain during lifetime. Loss of weight is associated with a lower risk for postmenopausal BC compared with weight maintenance. This observation should be an encouragement for women since loss of weight may be an effective strategy for breast cancer risk reduction.

 

 

                  Selección de Resúmenes de Menopausia

         Semana del 14 al 20 de Mayo 2008

                           Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

 

 

Cancer Epidemiol Biomarkers Prev. 2008 May;17(5):1088-95.

Nonsteroidal Anti-inflammatory Drugs and Change in Mammographic Density: A Cohort Study Using Pharmacy Records on Over 29,000 Postmenopausal Women.

Terry MB, Buist DS, Trentham-Dietz A, James-Todd TM, Liao Y.

Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA.

BACKGROUND: Use of nonsteroidal anti-inflammatory drugs (NSAID) has been associated with a decrease in breast cancer risk, but it is unknown if they also reduce mammographic density, a strong intermediate marker of breast cancer risk. METHODS: We investigated NSAID use and mammographic density in 29,284 postmenopausal women who had two screening mammograms at Group Health in Seattle. We used pharmacy records to classify women as NSAID nonusers, continuers, initiators, or discontinuers based on use between the two mammograms and nine separate prescription and nonprescription NSAID classes. Using unordered polytomous logistic regression methods, we modeled the odds ratio (OR) of staying not dense, decreasing density, or increasing density relative to remaining dense based on Breast Imaging Reporting Data System classification of density. RESULTS: There was no association with density change from initiation or continuation of NSAIDs. However, both initiators and continuers of any NSAIDs were more likely to stay not dense than stay dense [OR, 1.12; 95% confidence interval (95% CI), 1.04-1.20; OR, 1.25; 95% CI, 1.05-1.49, respectively]. This association with staying not dense for initiators and continuers of any NSAID use was observed primarily among women ages <65 years at first mammogram (OR, 1.24; 95% CI, 1.12-1.36; OR, 1.48; 95% CI, 1.14-1.93, respectively). CONCLUSIONS: Initiation of NSAID use did not reduce mammographic density over the short term. Continuers of NSAID use were more likely to stay not dense compared with nonusers, suggesting that it is plausible that longer-term use of NSAIDs may be needed to reduce density.

 

 

Infect Disord Drug Targets. 2008 Mar;8(1):65-7.

Neuroprotective effects of estrogens: cross-talk between estrogen and intracellular insulin signalling.

González C, Díaz F, Alonso A.

Department of Functional Biology. Physiology Area, Oviedo University, Oviedo University, Oviedo. Spain.

The incidence of neurodegenerative diseases is higher in postmenopausal women that young women. In this sense, Alzheimer's and Parkinson's diseases, ischemic brain injury and memory or cognitive dysfunction increase dramatically when the ovarian function declines. On the other hand, insulin resistance represents an independent factor in the etiology of age-associated coronary and cerebrovascular disease. Therefore, depression, neurodegenerative diseases such as Alzheimer's and Parkinson's diseases and memory or cognitive dysfunction should be considered, in some cases, a result of metabolic syndrome, and that postmenopausal women are more vulnerable that young women to these diseases Several studies have suggested that the molecular mechanism by which estradiol exerts its neuroprotective effects involves activation of the PI3-k signalling pathway, which is activated by insulin and IGF-1. Therefore, it seems possible that ERalpha can interact with these signalling pathways, mainly with PI3-k and IRS-1, to promote neuroprotective effects in the brain. In particular, IGF-I seems to be particularly important in the process of neuroprotection; it can reverse age-related effects and attenuate the age-related decrease in cerebral glucose utilization. Moreover, gonadal hormones have been found to regulate IGF-I receptor. Therefore, it seems clear that the interaction of both systems plays a role in the prevention of neuronal age-related effects. These findings suggest that by interacting with some components of the IGF-I signalling pathway, ERalpha affects the actions of IGF-I in the brain and suggest future avenues of research. The relationship between insulin resistance states associated with aging in females, and the cross-talk between estradiol and proteins includes in the IRS-1/PI3-k/Akt and IGF-1-IR signalling pathways, will lead to a more complete understanding of the precise mechanism underlying estradiol-mediated neuroprotection. Numerous clinical studies have demonstrated that the incidence of neurodegenerative diseases in higher in postmenopausal women that young women. In this sense, Alzheimer's and Parkinson's disease, ischemic brain injury and memory or cognitive dysfunction increase dramatically when the ovarian function declines. Moreover, estrogen replacement therapy seems to be a good element in order to decrease the risk and/or severity of neurodegenerative conditions, and it would be able to improve some aspects related to memory and learning process.

 

 

Am J Clin Nutr. 2008 May;87(5):1384-91.

Carbohydrate intake, glycemic index, glycemic load, and risk of postmenopausal breast cancer in a prospective study of French women.

Lajous M, Boutron-Ruault MC, Fabre A, Clavel-Chapelon F, Romieu I.

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

BACKGROUND: Diets high in carbohydrates may result in chronically elevated insulin concentrations and may affect breast cancer risk by stimulation of insulin receptors or through insulin-like growth factor I (IGF-I)-mediated mitogenesis. Insulin response to carbohydrate intake is increased in insulin-resistant states such as obesity. OBJECTIVE: We sought to evaluate carbohydrate intake, glycemic index (GI), and glycemic load (GL) and subsequent overall and hormone-receptor-defined breast cancer risk among postmenopausal women. DESIGN: A prospective cohort analysis of dietary carbohydrate and fiber intakes was conducted among 62 739 postmenopausal women from the E3N French study who had completed a validated dietary history questionnaire in 1993. During a 9-y period, 1812 cases of pathology-confirmed breast cancer were documented through follow-up questionnaires. Nutrients were categorized into quartiles and energy-adjusted with the regression-residual method. Cox model-derived relative risks (RRs) were adjusted for known determinants in breast cancer. RESULTS: Dietary carbohydrate and fiber intakes were not associated with overall breast cancer risk. Among overweight women, we observed an association between GI and breast cancer (RR(Q1-Q4): 1.35; 95% CI: 1.00, 1.82; P for trend = 0.04). For women in the highest category of waist circumference, the RR(Q1-Q4) was 1.28 (95% CI: 0.98, 1.67; P for trend = 0.10) for carbohydrates, 1.35 (95% CI: 1.04, 1.75; P for trend = 0.01) for GI, and 1.37 (95% CI: 1.05, 1.77; P for trend = 0.003) for GL. We also observed a direct association between carbohydrate intake, GL, and estrogen receptor-negative breast cancer risk. CONCLUSIONS: Rapidly absorbed carbohydrates are associated with postmenopausal breast cancer risk among overweight women and women with large waist circumference. Carbohydrate intake may also be associated with estrogen receptor-negative breast cancer.

 

 

Am J Clin Nutr. 2008 May;87(5):1567S-1570S.

Amount and type of protein influences bone health.

Heaney RP, Layman DK.

Creighton University, Omaha, NE, USA.

Many factors influence bone mass. Protein has been identified as being both detrimental and beneficial to bone health, depending on a variety of factors, including the level of protein in the diet, the protein source, calcium intake, weight loss, and the acid/base balance of the diet. This review aims to briefly describe these factors and their relation to bone health. Loss of bone mass (osteopenia) and loss of muscle mass (sarcopenia) that occur with age are closely related. Factors that affect muscle anabolism, including protein intake, also affect bone mass. Changes in bone mass, muscle mass, and strength track together over the life span. Bone health is a multifactorial musculoskeletal issue. Calcium and protein intake interact constructively to affect bone health. Intakes of both calcium and protein must be adequate to fully realize the benefit of each nutrient on bone. Optimal protein intake for bone health is likely higher than current recommended intakes, particularly in the elderly. Concerns about dietary protein increasing urinary calcium appear to be offset by increases in absorption. Likewise, concerns about the impact of protein on acid production appear to be minor compared with the alkalinizing effects of fruits and vegetables. Perhaps more concern should be focused on increasing fruit and vegetable intake rather than reducing protein sources. The issue for public health professionals is whether recommended protein intakes should be increased, given the prevalence of osteoporosis and sarcopenia.

 

 

Am J Clin Nutr. 2008 May;87(5):1400-4.

Multivitamin-multimineral supplement use and mammographic breast density.

Bérubé S, Diorio C, Brisson J.

Unité de Recherche en Santé des Populations, Centre Hospitalier Affilié Universitaire de Québec, Québec, Canada.

BACKGROUND: The effect of multivitamin-multimineral supplements on the occurrence of chronic diseases, such as breast cancer, is unclear. Breast density is increasingly used as a biomarker of breast cancer risk. OBJECTIVE: The present study evaluated the association of multivitamin-multimineral supplement use with breast density. DESIGN: Premenopausal (n = 777) and postmenopausal (n = 783) women were recruited at the time of screening mammography. Anthropometric measurements were taken at recruitment. Demographic characteristics, behavioral factors, and health conditions were documented by telephone interview. Diet and multivitamin-multimineral and individual vitamin and mineral supplement use were assessed with a self-administered food-frequency questionnaire. Breast density from screening mammograms was measured using a computer-assisted method. Crude and adjusted means in breast density were evaluated according to multivitamin-multimineral supplement use using generalized linear models. RESULTS: Current multivitamin-multimineral supplement use was reported by 21.7% of women (20.7% and 22.6% of premenopausal and postmenopausal women, respectively). Premenopausal women who were currently using multivitamin-multimineral supplements had higher adjusted mean breast density (45.5%) than past (42.9%) or never (40.2%) users (P for heterogeneity = 0.03, P for trend = 0.009). Of the current users, breast density was not related to duration of multivitamin-multimineral supplement use. In postmenopausal women, multivitamin-multimineral supplement use was not associated with breast density (P for heterogeneity = 0.53, P for trend = 0.40). CONCLUSION: Regular use of multivitamin-multimineral supplements may be associated with higher mean breast density among premenopausal women. The relations of multivitamin-multimineral supplement use to breast density and breast cancer risk need to be clarified.

 

 

BioDrugs. 2008;22(3):137-44.

Calcitonin - A Drug of the Past or for the Future? : Physiologic Inhibition of Bone Resorption while Sustaining Osteoclast Numbers Improves Bone Quality.

Karsdal MA, Henriksen K, Arnold M, Christiansen C.

Pharmacology Department, Nordic Bioscience A/S, Herlev, Denmark.

Postmenopausal osteoporosis results from a continuous imbalance between bone resorption and bone formation, favoring bone resorption. An increasing number of treatments for osteoporosis are in development and on the market. A range of differences and similarities are found between these treatment options, and these need to be carefully evaluated before the initiation of treatment. This article summarizes data from in vitro and animal studies, as well as clinical trials, on the effect of calcitonin on bone turnover.Calcitonin was found to exert its antiresorptive effects via directly reducing osteoclastic resorption, and thus leads to an increase in bone mineral density and bone strength. Furthermore, calcitonin appears to mainly target the most active osteoclasts, and in contrast to most other antiresorptive agents it does not reduce the number of osteoclasts. Finally, in humans, while attenuating resorption, calcitonin treatment does not interfere markedly with bone formation, in contrast to other currently available antiresorptive agents. Thus, we speculate that calcitonin treatment will lead to a continuously positive bone balance in contrast with other antiresorptive agents currently on the market and thereby, in a physiologic manner, result in improved bone quality.Calcitonin is currently only available in injectable and nasal formulations. An oral formulation may, however, improve patient acceptance and compliance. Currently, several different routes are being pursued to identify an optimal oral formulation, of which the technology based on 5-CNAC is the most advanced. There are promising clinical data available for this formulation from both osteoarthritis and osteoporosis clinical trials, although the antifracture efficacy is not yet known.

 

 

Menopause. 2008 May 13. [Epub ahead of print]

Aromatase inhibitors and mammographic breast density in postmenopausal women receiving hormone therapy.

Mousa NA, Crystal P, Wolfman WL, Bedaiwy MA, Casper RF.

OBJECTIVE:: One of the main concerns regarding long-term use of hormone therapy (HT) in symptomatic menopausal women is the perceived increased risk of breast cancer. A method to reduce breast cancer risk in this population of women is urgently needed. We hypothesized that adding aromatase inhibitors (AIs) to HT would reduce local breast estrogen exposure and breast cancer risk without altering the beneficial systemic effects of HT on menopausal symptoms or bone density. The aim of this study was to investigate the effect of AIs and HT on mammographic breast density (MBD) as a surrogate marker of breast cancer risk in postmenopausal women receiving low-dose HT. DESIGN:: This was a retrospective cohort study conducted at private clinics affiliated with a university hospital. One group of postmenopausal women (n = 28) received low-dose HT daily plus letrozole 2.5 mg three times weekly. Postmenopausal women receiving HT alone (n = 28) served as controls. MBD, the primary outcome, was measured using quantitative image analysis software as well as by visual analysis by a radiologist. Hypoestrogenic effects, adverse reactions, and bone mineral densities were secondary outcome measures. RESULTS:: The mammograms of 18 women in the study group and 22 women in the control group were suitable for comparison. A statistically significant reduction in MBD occurred in the women who received HT plus an AI, whereas no significant change was observed in the women receiving HT alone. There was no significant increase in hypoestrogenic symptoms during the use of AIs, and bone mineral densities were not significantly reduced. CONCLUSIONS:: Adding an AI to HT may lower MBD in postmenopausal women. AIs could be good candidates for primary chemoprevention of breast cancer in postmenopausal women using HT.

 

 

Ann Fr Anesth Reanim. 2008 May 7. [Epub ahead of print]

Oral contraception and hormone replacement therapy: Management of their thromboembolic risk in the perioperative period

Chalhoub V, Edelman P, Staiti G, Benhamou D.

Département d’anesthésie-réanimation, hôpital de Bicêtre, 78, Le Kremlin-Bicêtre cedex, France.

OBJECTIVES: Many women scheduled for surgery are using either oral contraception (OC) or hormone replacement therapy (HRT). These two treatments are associated with a significant albeit moderately increased risk of venous thromboembolic events which might increase the risk associated with surgery. DATA SOURCE: Record of French and English references from Medline((R)) database. DATA EXTRACTION: Data were selected including prospective and retrospective studies, reviews, and case reports. DATA SYNTHESIS: Thromboembolism induced by these two pharmacologic classes is similar and close to that produced by pregnancy. The increased risk is usually small, especially after the first year of administration of either class of drug, for progestogen-only contraception drugs and for transdermal HRT. The increased risk should be compared with the occurrence of undesired pregnancy after discontinuation of OC or the occurrence of climateric symptoms after discontinuation of HRT. Maintaining OC during the perioperative period is legitimate and strengthening prophylaxis is justified during the first year of combined OC administration. Stressful climateric symptoms can lead to maintain HRT and strengthening prophylaxis is justified during the first year of oral HRT. Transdermal HRT may not need to be stopped and probably does not require any additional antithrombotic measure. CONCLUSION: The increased thromboembolic risk is to be compared with the risks of stopping either treatment. In most cases, these two treatments can be maintained and antithrombotic prophylaxis is moderately strengthened in particular cases.

 

 

J Clin Epidemiol. 2008 May 9. [Epub ahead of print]

Self-reported data on reproductive variables were reliable among postmenopausal women.

Lucas R, Azevedo A, Barros H.

Department of Hygiene and Epidemiology, University of Porto Medical School, Alameda Prof. Hernâni Monteiro, 4200 319 Porto, Portugal.

OBJECTIVE: We aimed to assess the reliability of self-reported reproductive variables in postmenopausal women. STUDY DESIGN AND SETTING: We evaluated 535 women in two interviews, as part of the recruitment and first follow-up of a cohort of Portuguese adults. Median time between evaluations was 5 years. Women were inquired about sociodemographic characteristics, cognitive status, and reproductive history: gravidity, parity, lifetime use of oral contraceptives, menopausal status, age at menopause, hysterectomy, oophorectomy, and lifetime use of hormone replacement therapy (HRT). RESULTS: Age at menopause was consistent within 1 year for 66% of women and agreement was higher in women reporting surgical menopause. Reliability regarding age at menopause decreased with time since menopause. Gravidity was consistent for 81% of women, whereas parity was consistent for 94%. The proportion of different answers regarding number of pregnancies and number of live births was higher in women with high gravidity and parity, respectively. Agreement was 96% for hysterectomy and 92% for oophorectomy. The proportion of consistent reports was 90% for oral contraceptives and 93% for HRT. Women with higher education reported parity and HRT more reliably. CONCLUSION: Agreement was over 90% for self-reported parity, hysterectomy, oophorectomy, and HRT, which supports their use in analytical studies.

 

                  Selección de Resúmenes de Menopausia

         Semana del 7 al 13 de Mayo de 2008

                           Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

 

 

Menopause. 2008 May 2 [Epub ahead of print]

Oophorectomy, hormone therapy, and subclinical coronary artery disease in women with hysterectomy: the Women's Health Initiative coronary artery calcium study.

Allison MA, Manson JE, Langer RD, for the Women's Health Initiative and Women's Health Initiative Coronary Artery Calcium Study Investigators.

From the 1University of California San Diego, La Jolla, CA; USA

OBJECTIVE:: Surgical menopause has been associated with an increased risk of coronary heart disease events. In this study, we aimed to determine the associations between coronary artery calcium (CAC) and hysterectomy, oophorectomy, and hormone therapy use with a focus on the duration of menopause for which there was no hormone therapy use. DESIGN:: In a substudy of the Women's Health Initiative placebo-controlled trial of conjugated equine estrogens (0.625 mg/d), we measured CAC by computed tomography 1.3 years after the trial was stopped. Participants included 1,064 women with previous hysterectomy, aged 50 to 59 years at baseline. The mean trial period was 7.4 years. Imaging was performed at a mean of 1.3 years after the trial was stopped. RESULTS:: Mean age was 55.1 years at randomization and 64.8 years at CAC measurement. In the overall cohort, there were no significant associations between bilateral oophorectomy, years since hysterectomy, years since hysterectomy without taking hormone therapy (HT), years since bilateral oophorectomy, and years of HT use before Women's Health Initiative enrollment and the presence of CAC. However, there was a significant interaction between bilateral oophorectomy and prerandomization HT use for the presence of any CAC (P = 0.05). When multivariable analyses were restricted to women who reported no previous HT use, those with bilateral oophorectomy had an odds ratio of 2.0 (95% CI: 1.2-3.4) for any CAC compared with women with no history of oophorectomy, whereas among women with unilateral or partial oophorectomy, the odds of any CAC was 1.7 (95% CI: 1.0-2.8). Among women with bilateral oophorectomy, HT use within 5 years of oophorectomy was associated with a lower prevalence of CAC. CONCLUSIONS:: Among women with previous hysterectomy, subclinical coronary artery disease was more prevalent among those with oophorectomy and no prerandomization HT use, independent of traditional cardiovascular disease risk factors. The results suggest that factors related to oophorectomy and the absence of estrogen treatment in oophorectomized women may be related to coronary heart disease.

 

 

Menopause. 2008 May 8 [Epub ahead of print

Understanding how personality factors may influence quality of life: development and validation of the Cervantes Personality Scale.

Castelo-Branco C, Palacios S, Ferrer-Barriendos J, Parrilla JJ, Manubens M, Alberich X, Martí A; The Cervantes Study Group.

OBJECTIVE:: To develop and validate a simple personality scale to be used as a complementary tool for menopause-specific quality-of-life instruments. DESIGN:: A population-based random sample of 2,274 Spanish women stratified by age groups and education level was used in the validation phase. The initial 94-item questionnaire was reduced to 20 items by examining the frequency and variability with which women were responding to each of the items. The measurement properties were tested by conducting reliability (internal consistency and test-retest) and validation analyses (correlations, and factor analysis). RESULTS:: The final 20-item scale consisted of three domains: introversion (seven items), emotional instability (seven items), and insincerity (control subscale, six items). Cronbach's alpha coefficients for the subscales of emotional instability, introversion, and insincerity were 0.7966, 0.7135, and 0.7042, respectively. The test-retest correlation was r = 0.763 for introversion, r = 0.720 for emotional instability, and r = 0.680 for insincerity (P < 0.001). The Cervantes Personality Scale is short and easy to administer. Scores range from 0 (the most extraverted personality) to 35 (the most introverted personality) for the introversion domain, from 0 (the most emotionally stable personality) to 35 (the most emotionally unstable personality) for the emotional instability domain, and from 0 (the most sincere response) to 30 (the most insincere response) for the insincerity domain. CONCLUSIONS:: A novel self-report 20-item scale for assessing three stable personality traits (introversion, emotional instability, and insincerity) in peri- and postmenopausal women is presented. We provide preliminary evidence that the Cervantes Personality Scale is a useful psychometric tool for studying personality in women going through the menopausal transition.

 

 

Menopause. 2008 May-Jun;15(3):524-9

Postmenopausal status according to years since menopause as an independent risk factor for the metabolic syndrome.

Joon Cho G, Hyun Lee J, Tae Park H, Ho Shin J, Cheol Hong S, Kim T, Young Hur J, et al.

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

OBJECTIVE:: Features of the metabolic syndrome such as abdominal adiposity, insulin resistance, and dyslipidemia develop with the transition from pre- to postmenopausal status in women. We investigated the effects of postmenopausal status on the prevalence of the metabolic syndrome according to years since menopause. DESIGN:: We studied 1,002 women, 618 premenopausal and 384 postmenopausal, who participated in annual health examinations at Anam Hospital in Seoul, Korea. RESULTS:: Using multivariate logistic regression analysis, we determined that postmenopausal status was an independent risk factor for the metabolic syndrome. Moreover, after controlling for age and body mass index, postmenopausal women had an increased risk of the metabolic syndrome (odds ratio, 2.93; 95% CI, 1.62-5.33) and the abnormalities of its individual components. The risk for the metabolic syndrome increased up to 14 years since menopause, then decreased. For its individual components, postmenopausal women with 5 to 9 years since menopause had the highest risk of high blood pressure; postmenopausal women with less than 5 years since menopause had an increased risk of abdominal obesity and high glucose. With 10 to 14 years since menopause, postmenopausal women had an increased risk of high triglycerides. CONCLUSIONS:: Postmenopausal status is an independent risk factor for the metabolic syndrome and all of its individual components. The risk for the metabolic syndrome increased up to 14 years since menopause. In addition, postmenopausal status has effects during different periods since menopause for each of these components.

 

 

Acta Oncol. 2008;47(4):747-54.

Adverse bone effects during pharmacological breast cancer therapy.

Bjarnason NH, Hitz M, Jorgensen NR, Vestergaard P.

Institute for Rational Pharmacotherapy, Danish Medicines Agency, Denmark.

The improved survival and cure rate of breast cancer patients leads to increased diagnosis of later occurring side effects to therapy such as osteoporosis. Conventional chemotherapies such as CMF and CEF are known to induce premature menopause, which increases bone loss but these therapies have additional detrimental effects on bone. The loss in bone mass during chemotherapy is substantial and may lead to increased fracture risk. The influence of taxanes on bone is less well known. Whereas tamoxifen has a slight protective effect on bone loss the opposite is true for aromatase inhibitors. Adverse effect reportings show, that adjuvant treatment with aromatase inhibitors in postmenopausal women increases the risk of clinical fractures as compared to tamoxifen. The Danish Bone Society suggests that all women with operable breast cancer have their fracture risk evaluated including a BMD measurement prior to initiation of adjuvant aromatase inhibitor therapy as a part of the standard examination program. If osteoporosis is diagnosed, anti-osteoporosis therapies should be considered. Moreover, all women undergoing adjuvant chemotherapy and endocrine therapy should be informed of the risk of bone loss and should receive life style advice of how to preserve bone. Adjuvant regimens in breast cancer patients improve survival and cure rates. Therefore it is preferable to use such therapies although they increase risk of side effects such as osteoporosis.

 

 

Endocr Pract. 2008 Apr;14(3):293-7.

Increase in bone mass after correction of vitamin d insufficiency in bisphosphonate-treated patients.

Geller JL, Hu B, Reed S, Mirocha J, Adams JS.

Cedars-Sinai Medical Center, University of California Los Angeles, Los Angeles, California.

Objective: To assess the relative contribution of vitamin D insufficiency to loss of bone mineral density (BMD) in patients taking bisphosphonates.Methods: Patients were eligible for inclusion if they had osteoporosis or osteopenia and demonstrated a decline in BMD during the preceding year while taking stable doses of alendronate or risedronate, plus supplemental calcium and vitamin D. Patients with previously known secondary causes of osteoporosis were excluded from the study. Eligible patients underwent prospective measurement of bilateral hip and lumbar spine BMD by dual-energy x-ray absorptiometry, serum 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D, intact parathyroid hormone, osteocalcin, and thyroid-stimulating hormone (thyrotropin), and urinary calcium:creatinine ratio.Results: Annual BMD was assessed in 175 previously bisphosphonate-responsive patients with low BMD. Of the 175 patients, 136 (78%) had either a significant interval increase or no change in BMD, whereas 39 (22%) had a significant decrease. Of the 39 patients who lost BMD, 20 (51%) had vitamin D insufficiency (25-OHD <30 ng/mL). After a single course of orally administered vitamin D2 (500,000 IU during a 5-week period), the 25-OHD level returned to normal in 17 of the 20 vitamin D-insufficient patients and was associated with significant (P<.02) 3.0% and 2.7% increases in BMD at the lumbar spine and the femoral neck, respectively. Failure to normalize the serum 25-OHD level was associated with further loss of BMD.Conclusion: Vitamin D insufficiency was the most frequently identified cause of bone loss in patients with declining BMD during bisphosphonate therapy. Correction of vitamin D insufficiency in these patients led to a significant rebound in BMD.

 

 

Expert Opin Drug Saf. 2008 May;7(3):259-70

Raloxifene in breast cancer prevention.

Gennari L, Merlotti D, Paola VD, Nuti R.

University of Siena, Department of Internal Medicine, Viale Bracci 1, 53100 Siena, Italy

BACKGROUND: Raloxifene is a benzothiophene, selective estrogen receptor modulator with estrogen-agonist effects in the skeleton and the cardiovascular system but estrogen-antagonist effects in the uterus and the mammary gland. This compound was first approved in different countries for the prevention and treatment of osteoporosis. OBJECTIVE/METHODS: We performed a literature search to review available preclinical and clinical data that has led to the recent FDA approval of raloxifene as a chemopreventive agent for breast cancer in postmenopausal women. RESULTS/CONCLUSIONS: Different placebo-controlled trials indicated that raloxifene is effective in reducing invasive breast cancer risk in postmenopausal women. In a recent comparative study, a similar efficacy between raloxifene and tamoxifen for breast cancer prevention was demonstrated, but raloxifene showed a more favorable safety profile.

 

 

J Neuroendocrinol. 2008 May;20 Suppl 1:69-74

Endocannabinoids and the regulation of bone metabolism.

Bab I, Ofek O, Tam J, Rehnelt J, Zimmer A.

Bone Laboratory, The Hebrew University of Jerusalem, Jerusalem, Israel. babi@cc.huji.ac.il

In mammals, including humans, bone metabolism is manifested as an ongoing modelling/remodelling process whereby the bone mineralised matrix is being continuously renewed. Recently, the main components of the endocannabinoid system have been reported in the skeleton. Osteoblasts, the bone forming cells, and other cells of the osteoblastic lineage, as well as osteoclasts, the bone resorbing cells, and their precursors, synthesise the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG). CB(1) cannabinoid receptors are present in sympathetic nerve terminals in close proximity to osteoblasts. Activation of these CB(1) receptors by elevated bone 2-AG levels communicates brain-to-bone signals as exemplified by traumatic brain injury-induced stimulation of bone formation. In this process, the retrograde CB(1) signalling inhibits noradrenaline release and alleviates the tonic sympathetic restrain of bone formation. CB(2) receptors are expressed by osteoblasts and osteoclasts. Their activation stimulates bone formation and suppresses bone resorption. CB(2)-deficient mice display a markedly accelerated age-related bone loss. Ovariectomy-induced bone loss can be both prevented and rescued by a CB(2) specific agonist. Hence, synthetic CB(2) ligands, which are stable and orally available, provide a basis for developing novel anti-osteoporotic therapies, free of psychotropic effects. The CNR2 gene (encoding CB(2)) in women is associated with low bone mineral density, offering an assay for identifying females at risk of developing osteoporosis.

 

 

J Clin Endocrinol Metab. 2008 May 6 [Epub ahead of print

Serial assessment of serum bone metabolism markers identifies women with the highest rate of bone loss and osteoporosis risk.

Ivaska KK, Lenora J, Gerdhem P, Akesson K, Väänänen HK, Obrant KJ.

Clinical and Molecular Osteoporosis Research Unit, Lund University, Department of Orthopaedics, Malmö University Hospital, SE-20502 Malmö, Sweden; University of Turku, Institute of Biomedicine, Department of Anatomy, FI-20520 Turku, Finland; Karolinska Institute, Department of Orthopaedics, Karolinska University Hospital, SE-14186 Stockholm, Sweden.

Context: One of the important challenges in the management of osteoporosis is to identify women who are at high risk of developing osteoporosis and fragility fractures. Objective: To evaluate if assessment of bone metabolism at multiple occasions can identify women with the highest risk for bone loss. Design: The Malmö OPRA study is an ongoing longitudinal study. Participants have been evaluated at baseline and after 1, 3 and 5 years. Setting: Population-based study. Participants: 1044 women, all 75 years old at baseline. Main outcome measures: Seven bone turnover markers were assessed at baseline, 1, 3 and 5 years (n=573). Five year change in areal bone mineral density (aBMD) was also determined. Results: Baseline markers correlated weakly to change in total body aBMD. The associations were more pronounced when the average of the baseline and 1-year measurements was used (standardized regression coefficients -0.12 to -0.23, p<0.01). Adding the 3-year and 5-year measurement further strengthened the correlation (regression coefficients up to -0.30 (p<0.001)). Women with constantly high turnover lost significantly more bone at total body (-2.6%) than women with intermediate (-1.6%) or low turnover (-0.2%, p for trend <0.001). They also had a greater decrease in hip BMD (-8.3%, -6.0% and -5.1%, respectively, p=0.010). Results were similar also in the subgroup of women with osteopenia. Conclusions: Our results suggest that serial assessment of bone turnover improves the identification of women with the highest rate of bone loss and osteoporosis risk.

 

 

Ann Intern Med. 2008 May 6;148(9):637-46

Relative effectiveness of osteoporosis drugs for preventing nonvertebral fracture.

Cadarette SM, Katz JN, Brookhart MA, Stürmer T, Stedman MR, Solomon DH.

Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, and Boston University, Boston, Massachusetts 02120, USA.

BACKGROUND: Little information is available on the comparative effectiveness of osteoporosis pharmacotherapies. OBJECTIVE: To compare the relative effectiveness of osteoporosis treatments to reduce nonvertebral fracture risk among older adults. DESIGN: Cohort study. SETTING: Enrollees in 2 statewide pharmaceutical benefit programs for persons age 65 years or older. PATIENTS: 43,135 new recipients of oral bisphosphonates, nasal calcitonin, and raloxifene who began treatment from 2000 to 2005. The mean age was 79 years (SD, 6.9), and 96% were women. MEASUREMENTS: The primary outcome was nonvertebral fracture (hip, humerus, or radius or ulna) within 12 months of treatment initiation. Cox proportional hazard models stratified by state and adjusted for risk factors for fracture were used to compare fracture rates. Alendronate was the reference category in all analyses. RESULTS: A total of 1051 nonvertebral fractures were observed within 12 months (2.62 fractures per 100 person-years). No large differences in fracture risk were found between risedronate (hazard ratio [HR], 1.01 [95% CI, 0.85 to 1.21]) or raloxifene (HR, 1.18 [CI, 0.96 to 1.46]) and alendronate. However, among those with a fracture history, raloxifene recipients experienced more nonvertebral fractures within 12 months (HR, 1.78 [CI, 1.20 to 2.63]) compared with alendronate recipients. Patients who received calcitonin experienced more nonvertebral fractures than those who received alendronate (HR, 1.40, [CI, 1.20 to 1.63]). Results were similar in sensitivity analyses that examined different lengths of follow-up (6 months and 24 months), were restricted to hip fracture as the outcome, and were completed in various subgroups. LIMITATION: Confounder adjustment was limited to health care utilization data, and the confidence bounds of some comparisons were too wide to rule out potential clinically important differences between agents. CONCLUSION: Differences in fracture risk between risedronate or raloxifene and alendronate were small. Nasal calcitonin recipients may have a higher risk for nonvertebral fractures compared with alendronate recipients. Future studies that can better adjust for possible confounding may further clarify these relationships.

 

                  Selección de Resúmenes de Menopausia

         Semana del 30 de Abril al 6 de Mayo de 2008

                           Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

 

 

Arch Intern Med. 2008 Apr 28;168(8):861-6

Postmenopausal hormone therapy and stroke: role of time since menopause and age at initiation of hormone therapy.

Grodstein F, Manson JE, Stampfer MJ, Rexrode K.

Channing Laboratory, Brigham and Women's Hospital, 181 Longwood Ave, Boston, MA 02115. fgrodstein@partners.org.

BACKGROUND: We evaluated stroke risk associated with hormone therapy (HT) in younger women, in recently menopausal women, and in older women. METHODS: Prospective, observational analyses were performed in postmenopausal participants of the Nurses' Health Study, from 1976 to 2004, with biennial mailed questionnaires. Proportional hazards models were used to calculate multivariable-adjusted relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: We found a significantly increased risk of stroke for women currently taking HT (estrogen alone: RR, 1.39; 95% CI, 1.18-1.63; and estrogen with progestin: RR, 1.27; 95% CI, 1.04-1.56), a finding that is nearly identical to that of the Women's Health Initiative. This increased risk was observed for women initiating HT at young ages or near menopause and at older ages or more than 10 years after menopause. Short-term (<5 years) HT initiated at younger ages was not associated with a clear increase in stroke; however, this apparently null result was based on a small number of cases. The incidence of stroke was relatively low in younger women, and the attributable risk in women aged 50 through 54 years indicated approximately an additional 2 cases of stroke per 10 000 women per year taking hormones. We found a strong relationship between dose of oral conjugated estrogen and stroke, with RRs of 0.93, 1.54, and 1.62 for doses of 0.3, 0.625, and 1.25 mg, respectively (P for trend, <.001). CONCLUSIONS: Hormone therapy is associated with an increased risk of stroke, and this increased risk does not appear to be related to the timing of the initiation of HT. In younger women, with lower stroke risk, the attributable risk of stroke owing to hormone use is modest and might be minimized by lower doses and shorter treatment duration.

 

 

P R Health Sci J. 2008 Mar;27(1):85-91.

Relationship between loss of libido and signs and symptoms of depression in a sample of Puerto Rican middle-aged women.

Avellanet YR, Ortiz AP, Pando JR, Romaguera J.

Department of Obstetrics and Gynecology, Medical Sciences Campus, University of Puerto Rico, PO Box 355067, San Juan, Puerto Rico 00936-5067.

Female sexual dysfunction is a multi-causal and multidimensional problem combining sexual, physiological, physical, psychological, and interpersonal determinants. Loss of libido or loss of sexual desire, as a symptom of one of the primary sexual dysfunctions described in females, is highly prevalent in the general female population. Research on the psychological aspect associated with loss of libido among Hispanic female populations is limited. The objective of this study was to determine how the loss of libido is affected by signs and symptoms of depression, once potential confounders are controlled. Nine-hundred and nineteen Puerto Rican women ages 40 to 59 years living in Puerto Rico participated in health-fairs conducted in twenty-two municipalities between May 2000 and November 2001. Contingency tables and chi-square statistics were used to evaluate the bivariate associations of loss of libido with demographic and lifestyle characteristics, symptom experience and obstetric and gynecologic histories. A logistic regression model was used to estimate the magnitude of the association between loss of libido and signs and symptoms of depression, after controlling for confounders. The overall prevalence of loss of libido in this population was 40.8%. Loss of libido was significantly associated with depressive symptoms (p < 0.05) after adjusting for age, educational attainment, employment status, physical activity, menopausal status/ hormone therapy use and genitourinary symptoms. Women reporting 1-2 depressive symptoms were 67% (95% CI = 1.08-2.60) more likely than women reporting no symptomatology to report loss of libido. The odds of loss of libido increased as the number of depressive symptoms increased [(3-4 symptoms: POR = 3.67, 95% CI = 2.16-5.56); (5-6 symptoms: POR = 5.52, 95% CI = 3.16-9.66)]. Consistent with previous studies, signs and symptoms of depression were significantly associated with loss of libido. Future longitudinal studies should further elucidate the temporal sequence between depression and sexual dysfunctions in this population.

 

 

Arch Intern Med. 2008 Apr 28;168(8):840-6

Persistent hot flushes in older postmenopausal women.

Huang AJ, Grady D, Jacoby VL, Blackwell TL, Bauer DC, Sawaya GF.

MPhil, 1635 Divisadero St, Ste 600, San Francisco, CA 94115. ahuang@ucsfmed.org.

OBJECTIVE: To examine the prevalence, natural history, and predictors of hot flushes in older postmenopausal women. METHODS: Prevalence, severity, and 3-year change in severity of hot flushes were assessed by questionnaire in 3167 older postmenopausal women with osteoporosis. Logistic regression was used to identify characteristics associated with symptoms at baseline and after 3 years of follow-up. RESULTS: At baseline, 375 women (11.8%) reported bothersome hot flushes. Women were more likely to have baseline symptoms if they were less educated (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.06-1.53 per 4-year decrease), more recently menopausal (OR, 1.44; 95% CI, 1.34-1.56 per 5-year decrease), had previously used estrogen (OR, 1.57; 95% CI, 1.23-2.00), or had undergone hysterectomy (OR, 1.51; 95% CI, 1.14-1.99). Hot flushes were also associated with higher body mass index (OR, 1.22; 95% CI, 1.08-1.38 per 1 SD), higher follicle-stimulating hormone levels (OR, 1.34; 95% CI, 1.20-1.51 per 1 SD), lower high-density lipoprotein levels (OR, 1.17; 95% CI, 1.03-1.34 per 1 SD decrease), vaginal dryness (OR, 1.52; 95% CI, 1.19-1.93), and trouble sleeping (OR, 2.48; 95% CI, 1.94-3.16), but not estradiol levels. Of the 375 women with baseline symptoms, 278 contributed 3-year data, and 157 (56.5%) of these women reported persistent symptoms after 3 years. Fewer years since menopause (OR, 1.15; 95% CI, 1.01-1.32 per 5-year decrease) and trouble sleeping (OR, 1.97; 95% CI, 1.19-3.26) were associated with symptom persistence. CONCLUSIONS: For a substantial minority of women, hot flushes are a persistent source of discomfort into the late postmenopausal years. Identification of risk factors for hot flushes may help guide evaluation and treatment in this population.

 

 

Am J Epidemiol. 2008 Apr 29 [Epub ahead of print

Conjugated Equine Estrogens and Breast Cancer Risk in the Women's Health Initiative Clinical Trial and Observational Study.

Prentice RL, Chlebowski RT, Stefanick ML, Manson JE, Langer RD, Pettinger M, Hendrix SL, Hubbell FA, Kooperberg C, Kuller LH, Lane DS, McTiernan A, O'Sullivan MJ, Rossouw JE, Anderson GL.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.

The Women's Health Initiative randomized controlled trial found a trend (p = 0.09) toward a lower breast cancer risk among women assigned to daily 0.625-mg conjugated equine estrogens (CEEs) compared with placebo, in contrast to an observational literature that mostly reports a moderate increase in risk with estrogen-alone preparations. In 1993-2004 at 40 US clinical centers, breast cancer hazard ratio estimates for this CEE regimen were compared between the Women's Health Initiative clinical trial and observational study toward understanding this apparent discrepancy and refining hazard ratio estimates. After control for prior use of postmenopausal hormone therapy and for confounding factors, CEE hazard ratio estimates were higher from the observational study compared with the clinical trial by 43% (p = 0.12). However, after additional control for time from menopause to first use of postmenopausal hormone therapy, the hazard ratios agreed closely between the two cohorts (p = 0.82). For women who begin use soon after menopause, combined analyses of clinical trial and observational study data do not provide clear evidence of either an overall reduction or an increase in breast cancer risk with CEEs, although hazard ratios appeared to be relatively higher among women having certain breast cancer risk factors or a low body mass index.

 

 

J Bone Joint Surg Am. 2008 May;90(5):953-61

Improving evaluation and treatment for osteoporosis following distal radial fractures. A prospective randomized intervention.

Rozental TD, Makhni EC, Day CS, Bouxsein ML.

Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Stoneman 10, Boston, MA 02215, USA. trozenta@bidmc.harvard.edu

BACKGROUND: Fragility fractures are associated with a significant increase in the risk of future fracture, but the rates of evaluation to identify osteoporosis after such injuries are low. The purpose of this study was to determine the rates of evaluation and treatment of osteoporosis following distal radial fractures and to test two interventions in the outpatient clinic to improve evaluation and treatment rates. METHODS: In the first part of the study, the medical records of 298 consecutive patients treated for a fragility fracture of the distal part of the radius were reviewed. Primary outcome measures were a bone mineral density examination and treatment with osteoporosis medication within six months after the fracture. In the second part of the study, fifty patients with a fragility fracture of the distal part of the radius were prospectively randomized to receive one of two interventions. These consisted of (1) the orthopaedic surgeon ordering a bone mineral density examination and forwarding the results to the primary care physician or (2) the orthopaedic surgeon sending a letter to the primary care physician outlining guidelines for osteoporosis screening. Patients were contacted at six months after the fracture to determine the rates of evaluation and treatment for osteoporosis. RESULTS: The first part of the study revealed that, following a distal radial fracture, 21.3% of 240 patients had a bone mineral density examination and 78.7% were never screened. Osteopenia was the most common diagnosis among those screened (57%). Most (72.5%) of the 240 patients received no medication, whereas 6.7% received calcium and vitamin D; 11.3%, bisphosphonates; 2.5%, hormone replacement therapy; and 7.1%, a combination regimen. The treatment rate for the patients who had undergone a bone mineral density examination was 2.5-fold higher than the rate for those who had not had bone mineral density testing (53% compared with 21%, p < 0.001). In the second part of the study, the patients randomized to Intervention 1 had two to threefold greater rates of bone mineral density testing (93% compared with 30%, p < 0.001), discussion of osteoporosis with their primary care physician (89% compared with 35%, p < 0.001), and initiation of osteoporosis therapy (74% compared with 26%, p < 0.001) compared with patients randomized to Intervention 2. CONCLUSIONS: Rates of evaluation and treatment for osteoporosis after fragility fractures remain low (21.3% and 27.5%, respectively). Patients who undergo a bone mineral density examination are more likely to receive treatment. Ordering a bone mineral density examination in the orthopaedic clinic can dramatically improve osteoporosis evaluation and treatment rates following fragility fractures of the distal part of the radius.

 

 

Maturitas. 2008 Apr 28 [Epub ahead of print

Does a short cessation of HRT decrease mammographic density?

Weaver K, Kataoka M, Murray J, Muir B, Anderson E, Warren R, Warsi I, Highnam R, Glasier A.

Reproductive Healthcare, Dean Terrace Family Planning Clinic, 18 Dean Terrace, Edinburgh EH4 1NL, United Kingdom.

BACKGROUND: Hormone replacement therapy (HRT) is known to increase breast density, thus decreasing the sensitivity of cancer screening by mammography. Some authors recommend short cessation of HRT before mammography, but evidence showing the effect of such short cessation is limited. The purpose of this study is to examine whether a short cessation of HRT changes mammographic density. METHODS: Forty-eight women taking HRT agreed to have mammograms taken before and after stopping HRT for 4 weeks. Mammographic density was measured by Wolfe's four-point classification, six-categorical visual scale and two different computer methods (interactive-thresholding and SMF). Density values of mammography before and after the cessation of HRT were compared using Wilcoxon signed-rank test for categorical variables and paired t-test for continuous variables. Changes in breast pain and tenderness during mammography, radiation dose, compression force, and breast thickness were also recorded. RESULTS: No significant changes in mammographic density were observed by either visual or computer methods. There were no significant changes in breast pain or in tenderness on mammograms before and after the month's cessation of HRT. Radiographic measurements were not significantly altered by the 4-week cessation of HRT. CONCLUSION: In this screening population, a 4-week cessation of HRT before mammograms did not significantly alter mammographic density.

 

 

Clin Rheumatol. 2008 Apr 29 [Epub ahead of print

Effects of physical training on bone mineral density in fertile women with idiopathic osteoporosis.

Bergström I, Brinck J, Sääf M.

Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Huddinge, M52, Stockholm, 141 86, Sweden, ingrid.b.bergstrom@karolinska.se.

The aim of this study was to investigate whether moderate physical training can improve the bone mineral density (BMD) in women with idiopathic osteoporosis. Ten pre-menopausal women aged 24-44 years diagnosed with idiopathic osteoporosis were included in the study. The physical training program consisted of three fast 30-min walks plus one or two sessions of 1-h training per week during 1 year at a training centre separate from the hospital. All patients were given supplements of vitamin D and calcium. Bone mineral density was measured in the femoral neck area and the lumbar spine by dual energy X-ray absorptiometry. The measurements were performed at baseline and after 12 months of training and compared with the measurements at the time of diagnosis, 1-3 years before the study. Eight women fulfilled the 12-month training period, and their mean (SD) BMD at start was 0.88 (0.08) g/cm(2) in the spine and 0.76 (0.13) g/cm(2) in the femoral neck. The mean spine BMD increase was 0.031 g/cm(2) (3.5%) after 1 year of training, which was significant (Wilcoxon's non-parametric test, p = 0.018). The mean increment in BMD in the femoral neck was insignificant, 0.007 g/cm(2) (0.9%) after the intervention (p = 0.74). However, the bone loss during the 1- to 3-year period from diagnosis to study start was, on average, 0.045 g/cm(2) or 5.0% in the femoral neck (p = 0.042), thus indicating a positive indirect effect of the intervention. There is no evidence-based therapy for women with idiopathic osteoporosis. It is therefore of importance to elucidate the impact of moderate physical activity in this group of patients. A 1-year training program was sufficient to induce a small but significant change in the spine BMD.

 

 

Chem Res Toxicol. 2008 May 1 [Epub ahead of print

Oxidative DNA Damage in XPC-Knockout and Its Wild Mice Treated with Equine Estrogen.

Okamoto Y, Chou PH, Kim SY, Suzuki N, Laxmi YR, Okamoto K, Liu X, Matsuda T, Shibutani S.

Long-term hormone replacement therapy with equine estrogens is associated with a higher risk of breast, ovarian, and endometrial cancers. Reactive oxygen species generated through redox cycling of equine estrogen metabolites may damage cellular DNA. Such oxidative stress may be linked to the development of cancers in reproductive organs. Xeroderma pigmentosa complementation group C-knockout ( Xpc-KO) and wild-type mice were treated with equilenin (EN), and the formation of 7,8-dihydro-8-oxodeoxyguanosine (8-oxodG) was determined as a marker of typical oxidative DNA damage, using liquid chromatography electrospray tandem mass spectrometry. The level of hepatic 8-oxodG in wild-type mice treated with EN (5 or 50 mg/kg/day) was significantly increased by approximately 220% after 1 week, as compared with mice treated with vehicle. In the uterus also, the level of 8-oxodG was significantly increased by more than 150% after 2 weeks. Similar results were observed with Xpc-KO mice, indicating that Xpc does not significantly contribute to the repair of oxidative damage. Oxidative DNA damage generated by equine estrogens may be involved in equine estrogen carcinogenesis.

 

 

Aesthetic Plast Surg. 2008 Apr 30 [Epub ahead of print

Do Cosmetic Surgeons Consider Estrogen-Containing Drugs to Be of Significant Risk in the Development of Thromboembolism?

Johnson RL, Hemington-Gorse SJ, Dhital SK.

Department of Plastic Surgery, The Countess of Chester Hospital, Liverpool Road, Chester, UK.

BACKGROUND: Well-documented evidence shows that estrogen increases the risk of deep vein thrombosis (DVT), and that the effects of DVT are compounded by the stress of surgery and an anesthetic. METHODS: This study sought to determine the current views and practice of plastic surgeons regarding combined oral contraceptive and surgery. In the United Kingdom, 285 consultant plastic surgeons were identified, and postal questionnaires were distributed to each surgeon. RESULTS: Of 286 postal questionnaires distributed to consultant plastic surgeons, 53% were returned and analyzed. Most of the surgeons considered combined oral contraceptive and surgery to be a risk factor for DVT, although only 54% discontinued it before surgery. Approximately 50% believed hormone-replacement therapy (HRT) is a risk, but fewer than a one-fourth of surgeons stopped its use before surgery. There was a range of distribution for the length of time HRT was discontinued for surgery. The majority of consultants discontinue HRT use for 5 to 6 weeks before surgery and until full ambulation after surgery. Data retrieved were used to compare documented evidence relating to combined oral contraceptive and surgery and its association with DVT. CONCLUSION: This survey shows that the management of patients taking estrogen-containing medication before plastic surgery varies, and guidelines regarding this should be sought.