Semana del  15 al 22 de Agosto de 2006

J Cross Cult Gerontol. 2005 Jun;20(2):127-40

Sievert LL, Goode-Null SK.

Department of Anthropology, University of Massachusetts, Amherst, Amherst, MA, 01003-9278, USA.

Worldwide, complaints of musculoskeletal pain are more frequent than complaints of hot flashes amongst women of menopausal age. The purpose of this study was to examine musculoskeletal pain among women of menopausal age in the city of Puebla, Mexico. An opportunity sample was recruited from public parks and markets, with representation from all social classes (n=755). Mean age was 50.1~years, and the majority were employed as saleswomen in small businesses. Symptom frequencies were collected by open-ended interviews and with a structured symptom list that queried symptom experience during the two weeks prior to interview. In response to open-ended questions, 'dolores de huesos' (bone pain) was volunteered by 47% of respondents as a symptom associated with menopause, second only to hot flashes (53%). From the structured symptom list, 55.8% and 55.6% reported back pain and joint stiffness during the two weeks prior to interview. Women with back pain and joint stiffness were less likely to report being active during their leisure time (p<.01). The results of backwards stepwise logistic regressions indicate that women with back pain were more likely to be older, with less education, a higher BMI, and ate less meat. Women with joint pain were more likely to be post-menopausal, with less education, more children, a higher BMI, and were likely to drink milk and coffee more than once/week but less than once/day. While menopause is not necessarily a risk factor for musculoskeletal pain, it is important to recognize the pervasiveness of this complaint among women of menopausal age.

Breast Dis. 2005-2006;24:3-15

Hankinson SE.

Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.

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, prolactin and insulin-like growth factors (IGF) with subsequent risk of breast cancer in postmenopausal women is summarized and evaluated. Overall, a strong positive association between breast cancer risk and circulating levels of both estrogens and androgens has now been well confirmed; women with hormone levels in the top 20% of the distribution (versus bottom 20% have a 2- to 3-fold higher risk of breast cancer. Accumulating data also indicate a significant positive association with prolactin levels, although additional confirmation is needed. In contrast, no important link has been found between circulating levels of IGF-I (and its binding protein, IGFBP-3) and breast cancer risk in postmenopausal women.

J Cross Cult Gerontol. 2005 Jun;20(2):109-25

Quandt SA, Spangler JG, Case LD, Bell RA, Belflower AE.

Department of Public Health Sciences, Wake Forest University, School of Medicine, Medical Center

Cigarette smoking is a recognized risk factor for low bone mineral density (BMD) and osteoporosis. Despite the prevalence of smokeless tobacco (ST) use by women in some areas of the United States, minority groups in the United Kingdom, and populations in South Asia and Africa, no data exist to evaluate its effect on bone health. The objective of the study is to identify risk factors for low BMD among older women in a multi-ethnic population, with particular attention to smoking and ST use. Data were collected in Robeson County, North Carolina. ST use from childhood is common among women in this community. Two hundred-forty women aged 60 years and older (approximately equal numbers of African Americans, Native Americans and whites) were recruited at a variety of community events to obtain a cross-section of the demographic composition of the county. The main outcome was BMD measured in the heel using a portable dual energy x-ray absorptiometry. Twenty-nine percent of women were current or former smokers, and 26% current or former ST users. Increased BMD was predicted by greater body mass index, estrogen use in the past year, and African American and Native American ethnicity. There was a significant interaction between ST use and age, and between smoking and nutritional supplement use. BMD declined with age; the decline with age was greater for women who were current or former ST users than for those who never used ST. Women who formerly smoked and did not use supplements had a decreased BMD. ST should be considered as an additional risk factor for osteoporosis in populations where its use is prevalent.

Alzheimer Dis Assoc Disord. 2006 July/September;20(3):141-146.

Roberts RO, Cha RH, Knopman DS, Petersen RC, Rocca WA.

Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN.

An inverse association between estrogen therapy (ET) and Alzheimer disease (AD) has been reported in some, but not in all studies. We investigated the association between ET and AD in postmenopausal women using a population-based case-control design. Women who developed AD from 1985 through 1989 in Rochester, MN (cases, n=264) were individually matched by age (+/-1 y) to control women free of dementia from the same population (controls, n=264). ET exposure (>/=6 mo after menopause) was ascertained by abstracting the complete medical records archived in the records-linkage system of the Rochester Epidemiology Project. The frequency of ET use was similar in cases (11.4%) and controls [10.6%; odds ratio=1.10; 95% confidence interval (CI)=0.63-1.93]. However, cases who used ET had a suggestive trend for an earlier age at start of ET compared with controls (median, 49.0 vs. 50.5 y; P=0.06). Although smoking (ever vs. never) was not associated with AD overall, we observed an interaction between smoking and ET. The odds ratio of AD in ET users was 4.55 (95% CI=1.33-15.53) among smokers, but was 0.68 (95% CI=0.35-1.32) among never-smokers (P for interaction=0.01). Our findings do not confirm a significant association between ET and AD overall; however, the possible interaction with smoking deserves further study.

Breast Dis. 2005-2006;24:79-92

Geller BA, Vogel VG.

Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh, PA, USA.

In the United States, an estimated 211,240 new cases of breast cancer were diagnosed in 2005 and approximately 40,410 deaths occurred. In recent years, a number of randomized prospective trials have investigated the use of antiestrogens as a means to reduce the incidence of breast cancer. We aim to describe the results of these trials as they pertain to postmenopausal women. In the Breast Cancer Prevention Trial and the International Breast Cancer Intervention Study-I, tamoxifen reduced the risk of invasive breast cancer by 55% and 30%, respectively, among older participants. However, tamoxifen is associated with adverse events including thromboembolic disease and endometrial cancer. The Multiple Outcomes of Raloxifene Evaluation, aimed primarily at evaluating the use of raloxifene for the prevention of osteoporosis, demonstrated a 72% decreased breast cancer risk. Side effects of raloxifene include thromboembolic events, but not endometrial cancer. Results from the Study of Tamoxifen and Raloxifene trial comparing these two agents are expected in mid-2006. Ongoing chemoprevention trials are evaluating the use of the aromatase inhibitors. At present, tamoxifen is the only FDA-approved agent for breast cancer risk reduction. Decisions regarding its use must remain highly individualized, involving careful consideration of its risks versus benefits.

Breast Dis. 2005-2006;24:17-35

Lifetime reproductive and anthropometric risk factors for breast cancer in postmenopausal women.

Velie EM, Nechuta S, Osuch JR.

Michigan State University, Departments of Epidemiology and Surgery, B601 West Fee Hall, East Lansing,

Hormonally-linked adult reproductive and anthropometric risk factors have been well established in the etiology of postmenopausal breast cancer, though early life exposures have been evaluated only more recently. Here, we examine the evidence for associations between lifetime reproductive and anthropometric risk factors for postmenopausal breast cancer. The review finds some evidence for the hypothesis that breast cancer risk is determined by the number of susceptible stem cells, modified by the hormonal environment. The in utero experience of an infant may be associated with postmenopausal breast cancer; preeclampsia may decrease and greater birthweight increase risk, but more evidence is needed. Earlier and more rapid childhood growth appears to increase postmenopausal breast cancer risk and childhood obesity to decrease risk, but very few studies have yet examined these associations. Increased final height and earlier age at menarche are consistently associated with increased risk for postmenopausal breast cancer. Later age at first birth, decreased parity, later menopausal age, use of hormone replacement therapy (especially progestin containing), and increased postmenopausal adiposity are well-established risk factors for postmenopausal breast cancer. The effect of a woman's own pregnancy conditions and lactation are not established. Further investigation is needed to identify whether events occurring early in life modify later events or accumulate over the life course. Many aspects of this research can be conducted by examining the influence of early life events on intermediary events without the need for longitudinal data.

Expert Opin Investig Drugs. 2006 Sep;15(9):1091-103

Lasofoxifene: a third-generation selective estrogen receptor modulator for the prevention and treatment of osteoporosis.

Gennari L, Merlotti D, Martini G, Nuti R.

University of Siena, Department of Internal Medicine, Viale Bracci 1, 53100 Siena, Italy. gennari@unisi.it

This article reviews lasofoxifene, a new-generation selective estrogen receptor modulator (SERM) that is currently in Phase III development for the prevention and treatment of osteoporosis in postmenopausal women. This compound selectively binds to both of the estrogen receptors with a high affinity and a median inhibitory concentration that is similar to that seen with estradiol and > or = 10-fold higher than those reported for other SERMs (raloxifene and tamoxifen). Lasofoxifene has a remarkably improved oral bioavailability with respect to other SERMs due to increased resistance to intestinal wall glucuronidation. In both preclinical and short-term studies, the compound showed a favourable safety profile and demonstrated a proven efficacy in preventing bone loss and lowering cholesterol levels. Dose modelling from Phase II studies allowed the selection of lasofoxifene 0.25 mg/day as the lowest fully effective dose.

J Reprod Med. 2006 Jul;51(7):525-32

Obstetrician-gynecologists' patients' knowledge of and attitudes toward hormone therapy: a survey.

Power ML, Schulkin J.

Department of Research, American College of Obstetricians and Gynecologists, Washington, DC 20024,

OBJECTIVE: To investigate the opinions of obstetrician-gynecologists' patients toward hormone therapy (HT). STUDY DESIGN: Survey questionnaires for patients were mailed to obstetrician-gynecologists who belong to the Collaborative Ambulatory Research Network. RESULTS: Surveys were returned by 1,659 patients from 39 states and the District of Columbia. Women over 50 years old and postmenopausal women of all ages were more likely to report being well informed. Perimenopausal and postmenopausal women were significantly more likely than premenopausal women to have extensively considered the risks and benefits of HT (p<0.001). More highly educated women were more likely to be aware of the results of the recent clinical trials of HT and to have formed an opinion about the risks and benefits of HT. Women who had formed an opinion were essentially divided over whether HT use after menopause would be helpful or harmful. Less than half the women thought that physicians know enough about HT to give appropriate advice. CONCLUSION: There was little consensus regarding the risks and benefits of HT. Postmenopausal and more educated women considered themselves more informed and were more likely to have reached a decision regarding HT but were as evenly divided regarding the risks and benefits.

Salud Publica Mex. 2006 Jul-Aug;48(4):300-7

Reproductive and lifestyle factors associated with early menopause in Mexican women.

Ortega-Ceballos PA, Moran C, Blanco-Munoz J, Yunes-Diaz E, Castaneda-Iniguez MS, Salmeron J.

Instituto Nacional de Salud Publica, Cuernavaca, Morelos, Mexico. portega79@yahoo.com.mx

OBJECTIVE: The purpose of this study was to evaluate the relationship between certain reproductive and lifestyle factors and the occurrence of early natural menopause. MATERIAL AND METHODS: A case/control study was conducted on a basal population of 2510 women participating in the "Mexican Institute of Social Security health workers cohort study". Cases were defined as those women for whom natural menopause presented by age 47. Information was obtained through a self-administered questionnaire. RESULTS: The risk of early menopause is associated with short menstrual cycles [<26 days, OR = 3.79 (IC 95% 1.37-10.52)], a short period of oral contraceptives use [<1 year, OR = 2.63 (IC 95% 1.10-6.29)], a lower number of pregnancies [<2, OR = 1.63 (IC 95% 1.03-2.57)], low body mass index [< or =27 kg/m2, OR = 1.64 (IC 95% 1.10-2.43)], low schooling level [<6 years, OR = 3.02 (IC 95% 1.26-7.23)], smoking history [>15 cigarettes/day, OR = 2.7 (IC 95% 1.00-7.30)], and birth cohorts [> or =950, OR = 4.09 (IC 95% 2.62-6.39)]. CONCLUSIONS: The findings of this study suggest that both reproductive and lifestyle factors are significant elements in the occurrence of early menopause in Mexican women.

Menopause. 2006 Aug 11; [Epub ahead of print]

Effect of long-term treatment with raloxifene on mammary density in postmenopausal women.

Lasco A, Gaudio A, Morini E, Morabito N, Nicita-Mauro C, Catalano A, Denuzzo G, Sansotta C, Xourafa A, Macri I, Frisina N.

OBJECTIVE:: To evaluate in a group of postmenopausal women the effects of long-term raloxifene treatment on breast density using a digitized analysis of mammograms and on insulinlike growth factor-1 (IGF-1), insulinlike growth factor binding protein-3 (IGFBP-3), and sex hormone-binding globulin (SHBG) plasma levels. DESIGN:: Seventy healthy postmenopausal women with normal body weight were enrolled in this study and were divided into two groups based on their bone status, evaluated by dual-energy x-ray at the lumbar spine (L2-4). Fifty women (chronological age 52.4 +/- 4.1 y, menopausal age 42.1 +/- 3.9 y), in whom the L2-4 T score was less than -2.5 SD, were treated with raloxifene HCl 60 mg/day orally for 2 years. The other 20 women (chronological age 53.6 +/- 3.5 y, age at menopause 43.1 +/- 3.6 y), in whom the L2-4 T score ranged between -1 and -2.5 SD, were enrolled as controls. All 70 women received calcium (1 g/d orally) and cholecalciferol (880 UI/d orally) supplementation. Moreover, all women followed a normocaloric and personalized diet. All women had mammography at baseline and after 2 years of therapy. The mammographic images on traditional support were acquired by using a film scanner and were then elaborated by means of ad hoc software. Moreover, assessments of IGF-1, IGFBP-3, and SHBG plasma levels were obtained at baseline and after 24 months. RESULTS:: After 24 months of therapy, there was a significant variation in the raloxifene-treated group with respect to baseline in the distribution of gray classes of radiographic images. In particular an attenuation of graphic trace with a reduction of the areas with the lowest and most elevated gray classes was observed. In the control group, no significant variations of graphic traces were observed. Moreover, raloxifene treatment significantly reduced IGF-1 and increased IGFBP-3 and SHBG plasma levels at 24 months. During follow-up, IGF-1, IGFPB-3, and SHBG levels did not change significantly in the control group. CONCLUSIONS:: Long-term treatment with raloxifene in a population of postmenopausal women is able to reduce breast density. Such an effect could perhaps explain the reduction in the incidence of mammary carcinoma observed in the Multiple Outcomes of Raloxifene Evaluation study probably due to the direct antiestrogenic activity of raloxifene on mammalian tissue and/or its indirect activity increasing SHBG levels or modifying the IGF-1/IGFBP-3 ratio.

Arch Intern Med. 2006 Aug 14;166(15):1578-1584

Association of New-Onset Breast Discomfort With an Increase in Mammographic Density During Hormone Therapy.

Crandall CJ, Karlamangla A, Huang MH, Ursin G, Guan M, Greendale GA.

Department of Biostatistics, University of California, Los Angeles; University of Southern California. LA BACKGROUND: Postmenopausal use of estrogen and progestin therapy increases breast density and breast discomfort. Whether this increase in breast density is heralded by new-onset breast discomfort is unknown. METHODS: We used data from the Postmenopausal Estrogen/Progestin Interventions Mammographic Density Study, which retrieved and examined baseline and 12-month mammograms for 594 (67.9%) of 875 women aged 45 to 64 years enrolled in the randomized controlled trial. Treatments included placebo, 0.625 mg/d of conjugated equine estrogens, 0.625 mg/d of conjugated equine estrogens and medroxyprogesterone acetate (10 mg/d for 12 d/mo or 2.5 mg/d continuously), or 0.625 mg/d of conjugated equine estrogens and 200 mg/d of micronized progestin for 12 d/mo. Breast density (the percent of the breast composed of dense tissue) was calculated from digitized mammograms obtained at baseline and at 12-month follow-up. Breast discomfort was ascertained at baseline and at follow-up using standardized self-report questionnaires. In bivariate analysis, and then in multivariable linear regression models, we assessed the association between change in percent breast density from baseline to 12-month follow-up and new-onset breast discomfort in participants who had no breast discomfort at baseline (N = 533). RESULTS: After adjustment for age, treatment assignment (placebo, conjugated equine estrogens, or progestin-containing regimen), and other potential confounders, women with new-onset breast discomfort had a 3.9% increase in percent breast density compared with a 0.6% increase in percent breast density among women without new-onset breast discomfort (beta = .033, P<.001). The association between incident breast discomfort and increased percent breast density was similar in all active treatment arms. CONCLUSION: In postmenopausal women randomly assigned to menopausal hormone therapy vs placebo, new-onset breast discomfort is associated with increased mammographic density.

J Womens Health (Larchmt). 2006 Jul-Aug;15(6):734-46

Recent Changes in Cardiovascular Risk Factors among Women and Men.

Kim JK, Alley D, Seeman T, Karlamangla A, Crimmins E.

Andrus Gerontology Center, University of Southern California, Los Angeles, California.

Background: The purpose of this study was to examine change over the 1990s in the proportion of men and women with measured high-risk values of cardiovascular risk factors. Methods: Change in the prevalence of high-risk conditions based on clinical cutoffs for 10 cardiovascular risk factors was assessed in respondents aged >/=40 from the nationally representative, cross-sectional National Health and Nutrition Examination Surveys (NHANES) III (1988-1994) and IV (1999-2002). Results: Both sexes experienced a reduction in the prevalence of high-risk levels of cholesterol (total, high-density lipoprotein [HDL], and low-density lipoprotein [LDL]) and high homocysteine and an increase in obesity and high C-reactive protein (CRP). Changes in the prevalence of high total cholesterol and high CRP were more pronounced among women. The percentage of women with high diastolic and systolic blood pressure increased, whereas this percentage decreased among men. During the same time, there was an increase in undiagnosed high blood pressure and in the use of antihypertensive medications without achieving adequate blood pressure control among women. Both sexes increased their use of cholesterollowering medication. These changes in diagnosis rates and medication usage did not explain the trends in the prevalence of high-risk blood pressure or high-risk cholesterol, although the larger increase in high CRP among women is related to increased use of postmenopausal hormone therapy over the 1990s. Conclusions: We found mixed trends in cardiovascular risk factors for both women and men; some improved and some deteriorated. Changes in medication use and obesity did not explain these trends.

Am J Med Sci. 2006 Aug;332(2):55-60

Statins, fracture risk, and bone remodeling: what is true?

Rizzo M, Rini GB.

From the Department of Clinical Medicine and Emerging Diseases, University of Palermo, Palermo, Italy.

Besides the action on plasma lipid levels, statins show a series of ancillary effects defined as all of their vascular and nonvascular effects independent from the cholesterol reduction. It has been recently hypothesized that one of these ancillary effects could be the improvement of bone health, due to the interference with bone metabolism. This may potentially represent the rationale for statins' use in the treatment of osteoporosis, the most common disease of the bone. Both experimental observations and clinical studies on this topic generated a number of conflicting results; however, the largest randomized clinical trials, the Scandinavian Simvastatin Survival Study (4S), Long Term Intervention with Pravastatin in Ischemic Disease (LIPID), and Heart Protection Study (HPS), indicate that statins do not prevent or reduce fracture risk.

Curr Osteoporos Rep. 2006 Sep;4(3):96-102

The Role of Vitamin D forBone Health and Fracture Prevention.

Holick MF.

Boston University School of Medicine, 715 Albany Street,M-1013, Boston, MA 02118, USA. Vitamin D inadequacy is pandemic in adults. Vitamin D deficiency causes osteopenia, precipitates and exacerbates osteoporosis, causes the painful bone disease osteomalacia, and increases muscle weakness, which worsens the risk of falls and fractures. Vitamin D deficiency can be prevented by sensible sun exposure and adequate supplementation. Monitoring serum 25-hydroxyvitamin D is the only way to determine vitamin D status. Recent recommendations suggest that in the absence of sun exposure, adults should ingest 1000 IU of vitamin D3 per day. The ideal healthy blood level of 25-hydroxyvitamin D should be 30 to 60 ng/mL. Vitamin D intoxication occurs when 25-hydroxyvitamin D levels are greater than 150 ng/mL. Three recent reports suggesting that vitamin D and calcium supplementation does not decrease the risk of fracture will be put into perspective in light of the vast literature supporting increasing vitamin D and calcium intake as an effective method for decreasing risk of vertebral and nonvertebral fractures.

Semana del  8 al 14 de Agosto de 2006

Dr. Juan Enrique Blümel

Climacteric. 2006 Sep;9(5):6-12

Cardiovascular health and the menopause: the gynecologist as the patients' interface.

Arias RD.

Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, USA.

The large decrease in estrogen following menopause appears to explain the dramatic increase in cardiovascular disease (CVD) in postmenopausal women. Gynecologists are well placed to play a primary role in the diagnosis, prevention and management of CVD in these patients; this role may include advice on lifestyle changes, and, if appropriate, prescribing preventative treatments such as hormone replacement therapy (HRT) and lipid-lowering drugs. The use of estrogen replacement therapy (ERT) to prevent CVD is supported by a number of observational studies. However, recently, large, randomized trials gave unexpected, conflicting data on the cardiovascular benefits of HRT, leading to confusion, and influencing both patient and clinical perceptions regarding the role of HRT postmenopause. These different outcomes may be due to differences in the HRT regimens, mean age and mean time from menopause at enrollment, duration of therapy, and patient selection bias in observational studies. A 'unified hypothesis' consistent with findings from all studies has now been developed: HRT initiated at the time of the menopause prevents CVD, whereas HRT initiated years after the menopause seems to increase CHD events. This knowledge is essential for gynecologists making clinical decisions regarding HRT use.

Endocr Pract. 2006 Jul;12(4):436-45

Secondary osteoporosis: a review of the recent evidence.

Painter SE, Kleerekoper M, Camacho PM.

Division of Endocrinology, Loyola University Medical Center, Maywood, Illinois.

Objective: To review several causes of secondary osteoporosis as well as screening recommendations for underlying disorders. Methods: We conducted a review of the literature on many of the causes of osteoporosis that have been published during the past 15 years, focusing on those sources available from 2000 through the present. Indeed, more than two-thirds of the articles that we reviewed were printed during the past 6 years. These reports examined secondary osteoporosis in general, as well as many of the specific causes. Results: Secondary osteoporosis occurs in almost two-thirds of men, more than half of premenopausal and perimenopausal women, and about one-fifth of postmenopausal women. Its causes are vast, and they include hypogonadism, medications, hyperthyroidism, vitamin D deficiency, primary hyperparathyroidism, solid organ transplantation, gastrointestinal diseases, hematologic diseases, Cushing's syndrome, and idiopathic hypercalciuria. These causes have their own pathogenesis, epidemiologic features, and effect on the skeleton. Conclusion: The causes of secondary osteoporosis are numerous, and an understanding of their characteristics with respect to bone density and potential fracture risk is essential in the management of osteoporosis. A heightened awareness of the possibility of their existence is necessary to provide optimal care.

Bone. 2006 Aug 7; [Epub ahead of print]

Bone tissue compositional differences in women with and without osteoporotic fracture.

McCreadie BR, Morris MD, Chen TC, Sudhaker Rao D, Finney WF, Widjaja E, Goldstein SA.

Orthopaedic Research Laboratories, Department of Orthopaedic Surgery, University of Michigan, 2015 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.

It is generally accepted that the hallmark of osteoporosis is a reduction in bone mass. There is significant overlap, however, in bone mineral density between osteoporotic and normal individuals. This study examined the chemical composition of bone tissue obtained from women who had sustained a fracture and women without fracture to determine if there are differences between the two groups. Nineteen fractured and eleven non-fractured proximal femurs were obtained, matched for age and bone volume fraction obtained from micro-computed tomography. Trabecular bone specimens were examined by Raman spectroscopy to determine measures of chemical composition. A subset of the specimens was utilized to compare locations at the fracture and regions at least 2 mm away from apparent tissue damage using Raman spectroscopy. In addition, fifteen iliac crest biopsies each were obtained from women who had sustained a fracture and from normal controls. Raman spectroscopy was used to determine measures of chemical composition of trabecular and cortical bone. The results demonstrated that femoral bone tissue in the region of visible damage had a trend towards differences compared to regions at least 2 mm from visible damage. Femoral trabecular bone in fractured women had a higher carbonate/amide I area ratio than in unfractured women. Iliac crest biopsies revealed a higher carbonate/phosphate ratio in cortical bone from women who had sustained a fracture. Results suggest that the chemical composition of bone tissue may be an additional risk factor for osteoporotic fracture.

Mayo Clin Proc. 2006 Aug;81(8):1013-22.

Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US claims databases.

Siris ES, Harris ST, Rosen CJ, Barr CE, Arvesen JN, Abbott TA, Silverman S.

Toni Stabile Osteoporosis Center, Department of Medicine, Columbia University Medical Center, Harkness Pavilion 9-964, 180 Fort Washington Ave, New York, NY 10032, USA. es27@columbia.edu

OBJECTIVE: To characterize the relationships between adherence (complance and persistence) to bisphosphonate therapy and risk of specific fracture types in postmenopausal women. PATIENTS AND METHODS: Data were collected from 45 employers and 100 health plans in the continental United States from 2 claims databases during a 5-year period (January 1, 1999, through December 31, 2003). Claims from patients receiving a bisphosphonate prescription (alendronate or risedronate) were evaluated for 6 months before the Index prescription and during 24 months of follow-up to determine total, vertebral, and nonvertebral osteoporotic fractures, persistence (no gap in refills for >30 days during 24 months), and refill compliance (medication possession ratio > or = 0.80). RESULTS: The eligible cohort included 35,537 women (age, > or = 45 years) who received a bisphosphonate prescription. A subgroup with a specified diagnosis of postmenopausal osteoporosis was also evaluated. Forty-three percent were refill compliant, and 20% persisted with bisphosphonate therapy during the 24-month study period. Total, vertebral, nonvertebral, and hip fractures were significantly lower in refill-compliant and persistent patients, with relative risk reductions of 20% to 45%. The relationship between adherence and fracture risk remained significant after adjustment for baseline age, concomitant medications, and fracture history. There was a progressive relationship between refill compliance and fracture risk reduction, commencing at refill compliance rates of approximately 50% and becoming more pronounced at compliance rates of 75% and higher. CONCLUSIONS: Adherence to bisphosphonate therapy was associated with significantly fewer fractures at 24 months. Increasing refill compliance levels were associated with progressively lower fracture rates. These findings suggest that incremental changes in medication-taking habits could improve clinical outcomes of osteoporosis treatment.

Menopause. 2006 Aug 7; [Epub ahead of print]

Menopause, insulin resistance, and risk factors for cardiovascular disease.

Manco M, Nolfe G, Calvani M, Natali A, Nolan J, Ferrannini E, Mingrone G; on behalf of the European Group for the Study of Insulin Resistance.

From the 1Institute of Internal Medicine, Catholic University, Rome; 2CNR Institute of Cybernetics "E. Caianiello," Pozzuoli; 3CNR Institute of Internal Medicine, Pisa, Italy; and 4Department of Endocrinology, St. James's Hospital, Dublin, Ireland.

OBJECTIVE:: In this retrospective analysis of the European Group for the Study of Insulin Resistance database, a clamp data pooling project, a cardiovascular risk score (CVS) was assessed to verify whether hyperinsulinemia and/or insulin resistance were independent cardiovascular risk factors and to investigate how menopause affected CVS and insulin resistance. DESIGN:: Information was obtained on whole-body glucose uptake (M), determined by the euglycemic hyperinsulinemic clamp technique, normalized by fat-free mass (FFM), and insulin concentration (I) at a steady state. Body composition was estimated using a labeled water technique or bioimpedance. Other parameters measured included blood pressure, lipid levels, and waist-to-hip ratio. CVS was computed using a structural equation model that included age, body mass index, blood lipids, and blood pressure. The study population included 523 normal and overweight patients. Women were grouped according to fertility status, and men, according to age (cutoff 50 y). RESULTS:: M/kgFFM/I significantly decreased after menopause (12.41 +/- 3.40 vs 10.96 +/- 3.68; P < 0.01) and in men 50 years and older (11.39 +/- 3.47 vs 10.32 +/- 3.77 mumol.min.kg.muUI/mL; P < 0.02). CVS was lowest in fertile women (-0.414 +/- 0.57 vs 0.107 +/- 0.43; P < 0.0001) and highest in men 50 years and older (0.045 +/- 0.455 vs 0.257 +/- 0.51; P < 0.001). CVS significantly correlated with M/kgFFM/I in men 49 years and younger (ro = -0.27, P < 0.0001) and 50 years and older (ro = -0.38, P < 0.0001) and with fasting insulin in fertile women (ro = -0.29, P < 0.01) and in the other groups (ro ranging from 0.37 to 0.45, P < 0.0001). CONCLUSIONS:: Menopause does not seem to strictly relate to a decrease in insulin sensitivity as postmenopausal women had the same insulin sensitivity as age-matched men. In the population studied, the best predictor of CVS was fasting insulin rather than insulin sensitivity.

Eur Heart J. 2006 Aug 9; [Epub ahead of print]

Randomized trial of effects of continuous combined HRT on markers of lipids and coagulation in women with acute coronary syndromes: WHISP Pilot Study.

Collins P, Flather M, Lees B, Mister R, Proudler AJ, Stevenson JC.

Cardiac Medicine, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK; Department of Cardiology, Royal Brompton & Harefield NHS Trust, Sydney Street, London SW3 6NP, UK.

AIMS: Randomized trials have not demonstrated coronary heart disease benefit from hormone replacement therapy (HRT). We hypothesized that low-dose HRT may avoid harm. METHODS AND RESULTS: We studied the effects of HRT on lipids and coagulation in women with acute coronary syndromes. A total of 100 post-menopausal women >55 years were enrolled between 2 and 28 days after an acute coronary syndrome and randomized to oral oestradiol-17beta 1 mg plus norethisterone acetate 0.5 mg daily, or matching placebo, and followed for up to 12 months. Levels of lipids, lipoproteins, and haemostasis markers were measured at baseline, 3, and 6 months. There were no significant differences in lipid levels between the two groups, probably due to concomitant statin use. Antithrombin and factor VII levels were significantly lower in the HRT group, whereas fibrinogen was significantly decreased in the placebo group. No evidence of increased coagulation activation was observed, nor of adverse cardiovascular outcomes [odds ratio (OR) 0.63 (95% confidence intervals 0.31-1.31)]. CONCLUSION: Low-dose HRT may give cardiovascular benefit. These findings require confirmation in a full clinical trial with evaluation of cardiovascular outcomes as the primary objective.

Climacteric. 2006 Sep;9(5):19-27

Managing cardiovascular risk in menopausal women.

Rosano GM, Vitale C, Tulli A.

Centre for Clinical and Basic Research, Department of Medical Sciences, IRCCS San Raffaele, Rome, Italy.

Blood pressure control and prevention of glucose intolerance are primary factors in overcoming the increased cardiovascular risks in menopausal women. This heightened risk may partially be explained by the metabolic syndrome - a precursor of type 2 diabetes - in which the renin-angiotensin-aldosterone system may play a pivotal role. Once diabetes occurs, the cardiovascular risk is considerably greater in postmenopausal women than in men - especially if hypertension is also present. An additional risk factor, weight gain, is common in postmenopausal women not treated with hormone replacement therapy. Rigorous control of blood pressure has been shown to be particularly beneficial in women with metabolic syndrome; a reduction in blood pressure can reduce the mortality rate of ischemic stroke. The administration of hormone replacement therapy can also reduce the likelihood of coronary heart disease in postmenopausal women; therefore therapy should be started early in the menopausal transition to maximize cardiovascular protection. As such, an ideal hormone replacement therapy that can overcome hypertension, prevent body weight gain and control serum triglycerides offers an important advance in cardiovascular risk management during the menopause.

Menopause. 2006 Aug 4; [Epub ahead of print]

Escitalopram versus ethinyl estradiol and norethindrone acetate for symptomatic peri- and postmenopausal women: impact on depression, vasomotor symptoms, sleep, and quality of life.

Soares CN, Arsenio H, Joffe H, Bankier B, Cassano P, Petrillo LF, Cohen LS.

From the 1Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario; 2Perinatal and Reproductive Psychiatry Clinical Research Program, Massachusetts General Hospital, Boston, MA; and 3Department of Psychiatry, Harvard Medical School, Boston, MA.

OBJECTIVE:: To examine the efficacy and tolerability of escitalopram (ESCIT) compared to estrogen and progestogen therapy (EPT) for the treatment of symptomatic peri- and postmenopausal women. DESIGN:: Forty women (aged 40-60 years) with depressive disorders and menopause-related symptoms were randomly assigned to an 8-week open trial with ESCIT (flexible dose, 10-20 mg/day; fixed dose, 10 mg/day for the first 4 weeks) or estrogen plus progestogen therapy (ethinyl estradiol 5 mug/day plus norethindrone acetate 1 mg/day). Primary outcome measures included Montgomery-Asberg Depression Rating Scale and the Greene Climacteric Scale at week 8. Secondary outcome measures included the Clinical Global Impressions as well as sleep and quality of life assessments. RESULTS:: Thirty-two women (16 on EPT, 16 on ESCIT) were included in the analyses. Full remission of depression (score of <10 on the Montgomery-Asberg Depression Rating Scale) was observed in 75% (12/16) of subjects treated with ESCIT, compared to 25% (4/16) treated with EPT (P = 0.01, Fisher's exact tests). Remission of menopause-related symptoms (>50% decrease in Greene Climacteric Scale scores) was noted in 56% (9/16) of women treated with ESCIT compared to 31.2% (5/16) on EPT (P = 0.03, Pearson's chi tests). Improvement in sleep, hot flashes, and quality of life was observed with both treatments. CONCLUSIONS:: ESCIT is more efficacious than EPT for the treatment of depression and has a positive impact on other menopause-related symptoms. ESCIT may constitute a treatment option for symptomatic menopausal women who are unable or unwilling to use hormone therapy.