Selección de Resúmenes de Menopausia

Abril de 2008

Dr. Juan Enrique Blümel, Universidad de Chile

 

Semana del 26 al 1 de Abril de 2008

 

Maturitas. 2008 Mar 26 [Epub ahead of print]

Obesity, estrone, and coronary artery disease in postmenopausal women.

Silva TC, Barrett-Connor E, Ramires JA, Mansur AP.

Heart Institute (InCor), University of São Paulo Medical School, 05468-000 São Paulo, Brazil.

OBJECTIVES: The link between obesity and endogenous estrogen with coronary artery disease (CAD) in postmenopausal women is uncertain. In this prospective study we analyzed the association of body mass index (BMI) and blood levels of estrone in postmenopausal women with known CAD or with a high risk factor score for CAD. METHODS: Participants were 251 female clinic patients aged 50-90 years who were postmenopausal and not using estrogen therapy. Clinical and behavioral characteristics and fasting blood for estrone and heart disease risk factors were collected at baseline, and again at 1 and 2 years. Women were grouped according to their BMI (kg/m(2)) as normal (18.5</=BMI<25), overweight (25</=BMI<30) or obese (BMI >/=30), and by low and high estrone levels (<15 and >/=15pg/mL, respectively). Fatal and nonfatal events were recorded for 2 years after baseline. RESULTS: Women with a low estrone level were older, thinner, and had less hypertension, diabetes, and lower triglyceride and glucose levels. BMI was positively associated with estrone levels, hypertension, and diabetes and inversely associated with HDL cholesterol. There were 14 deaths, 8 attributed to CAD. The Kaplan-Meier survival curve showed a nonsignificant trend (p=0.074) of greater all cause mortality in women with low estrone levels (<15mL). In this model, adjusted for BMI, age [OR=1.08; p=0.03], C-reactive protein [OR=1.24; p=0.024] and hypertension [OR=6.22; p=0.003] were independent predictors of all cause mortality. CONCLUSIONS: Postmenopausal women with low estrone levels (<15pg/mL) had a trend for increased mortality over the next 2 years. Larger, longer studies are needed.

 

Lancet Oncol. 2008 Apr;9(4):385-91.

Oestrogen and the colon: potential mechanisms for cancer prevention.

Kennelly R, Kavanagh DO, Hogan AM, Winter DC.

Department of Surgery, St Vincent's University Hospital, Dublin, Ireland.

The role of oestrogen in oncogenesis has been examined extensively, especially in the context of breast cancer, and receptor modulators are an integral part of targeted treatment in this disease. The role of oestrogen signalling in colonic carcinoma is poorly understood. Men are more susceptible than women to colon cancer. Furthermore, hormone-replacement therapy affords an additive protective effect for postmenopausal women, and when these women do develop cancer, they typically have less aggressive disease. The discovery of a second oestrogen receptor (ERbeta) and its over expression in healthy human colon coupled with reduced expression in colon cancer suggests that this receptor might be involved. The underlying mechanism, however, remains largely unknown. In this Review, we discuss the various hypotheses presented in the published literature. We examine the cellular and molecular mechanisms through which oestrogen is purported to exert its protective influence, and we review the evidence available to support these claims.

 

Osteoporos Int. 2008 Mar 29 [Epub ahead of print]

Bone mineral density at menopause does not predict breast cancer incidence.

Trémollieres FA, Pouillès JM, Laparra J, Ribot C.

Unité Ménopause et Maladies Osseuses et Métaboliques, Hôpital Paule de Viguier, Toulous,e France.

INTRODUCTION: This study aimed to investigate the relationship between BMD and the risk of breast cancer (BC) in young postmenopausal women. METHODS: As part of a clinical research program, 2,137 women who were perimenopausal or within their 5 first postmenopausal years were scanned between 1988-1990 and reviewed on average 13.1 years after their initial examination. Ninety-eight incident BC cases were recorded throughout the follow-up. RESULTS: Women with incident BC significantly differed from those who had never had BC with regard to age at menarche, age of birth of 1st child, familial history of BC and postmenopausal hormone therapy (PHT) use. There was no significant difference between the two groups for baseline DXA of the spine. There was a trend for BC cases for having lower femoral neck BMD compared to women without BC. However, women with low BMD were more likely to have taken PHT by the end of the study. In Cox multivariate analyses the relationship between BC risk and femoral neck BMD no longer existed. CONCLUSIONS: There was no relationship between BMD measured within the first postmenopausal years and the risk of BC, which makes unlikely the possibility of using BMD as a predictor factor for BC in early postmenopausal women.

 

Salud Publica Mex. 2008 Mar-Apr;50(2):126-35.

Physical activity and breast cancer risk in Mexican women.

Ortiz-Rodríguez SP, Torres-Mejía G, Mainero-Ratchelous F, Angeles-Llerenas A, López-Caudana AE, et al.

Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México.

Objetive: To evaluate the effect of moderate physical activity (hours per week and METs hours per week) on the risk of breast cancer (BC) in Mexican women. Material and methods: This is the initial stage of a case control multicentric study based in the Federal District, Monterrey and Veracruz, Mexico, during 2004. Fifty eight cases paired to 58 control cases on quinquennium of age, and belonging to the health system were analyzed: three hospitals from the IMSS, three from ISSSTE and three from SS participated. Results: In postmenopausal women, there was a reduction of the risk in BC by every additional hour per week of moderate physical activity (RM= 0.91; IC95% 0.85-0.97); in premenopausal women, the reduction of the risk was not statistically significant (RM= 0.99; IC95% 0.94-1.05) (p= 0.048, effect modification). Conclusion: Moderate physical activity reduces the risk of BC in postmenopausal Mexican women.

 

Am J Epidemiol. 2008 Mar 27 [Epub ahead of print]

Estrogen Plus Progestin Therapy and Breast Cancer in Recently Postmenopausal Women.

Prentice RL, Chlebowski RT, Stefanick ML, Manson JE, Pettinger M, Hendrix SL, Hubbell FA, et al

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

The Women's Health Initiative trial found a modestly increased risk of invasive breast cancer with daily 0.625-mg conjugated equine estrogens plus 2.5-mg medroxyprogesterone acetate, with most evidence among women who had previously received postmenopausal hormone therapy. In comparison, observational studies mostly report a larger risk increase. To explain these patterns, the authors examined the effects of this regimen in relation to both prior hormone therapy and time from menopause to first use of postmenopausal hormone therapy ("gap time") in the Women's Health Initiative trial and in a corresponding subset of the Women's Health Initiative observational study. Postmenopausal women with a uterus enrolled at 40 US clinical centers during 1993-1998. The authors found that hazard ratios agreed between the two cohorts at a specified gap time and time from hormone therapy initiation. Combined trial and observational study data support an adverse effect on breast cancer risk. Women who initiate use soon after menopause, and continue for many years, appear to be at particularly high risk. For example, for a woman who starts soon after menopause and adheres to this regimen, estimated hazard ratios are 1.64 (95% confidence interval: 1.00, 2.68) over a 5-year period of use and 2.19 (95% CI: 1.56, 3.08) over a 10-year period of use.

 

Metab Syndr Relat Disord. 2006 Spring;4(1):17-27.

The WHO and NCEP/ATPIII Definitions of the Metabolic Syndrome in Postmenopausal Women: Are They So Different?

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

Institute of Nutraceuticals and Functional Foods, Laval University, Québec (Québec), Canada., Lipid Research Center, CHUL Research Center, Québec (Québec), Canada.

Background: The aim of this study was to examine the metabolic risk profile in postmenopausal women characterized by either the metabolic syndrome (MS) as defined by the World Health Organization (WHO) or the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATPIII). Methods: One hundred and eight postmenopausal women (56.9 +/- 4.2 years; 28.5 +/- 5.9 kg/m(2)) were examined. Each underwent an oral glucose tolerance test, an euglycemic-hyperinsulinemic clamp, an assessment of body fat distribution by computed tomography, a complete plasma lipid-lipoprotein profile, and standard measurements of inflammatory markers. Results: The prevalence of the MS-WHO was 29.6% in our women. Type 2 diabetes was found in 28.1% of women with the MS-WHO. Thirty-one percent of women had the MS-ATP, from which 36.4% had type 2 diabetes. Among the 32 women identified as having MS-WHO, 25 (78.1 %) were also identified as having the MS-ATP. On the other hand, among the 34 women identified as having MS-ATP, 24 (70.0 %) also had MS-WHO (kappa = 0.60). When we subdivided our sample of women as having either isolated MS-WHO, isolated MS-ATP, or combined MS-WHO and MS-ATP, we observed a more deteriorated metabolic risk profile (higher values for visceral adipose tissue, 2-h plasma glucose, and lower HDL-cholesterol concentrations) in women characterized by isolated MS-ATP compared to women with isolated MS-WHO. Conclusions: These results suggest that, in postmenopausal women, the concordance in the identification of subjects with the MS using each of the proposed definitions is only moderate.

 

Aust N Z J Obstet Gynaecol. 2008 Apr;48(2):207-13.

Prevalence of endometrial cancer and hyperplasia in non-symptomatic overweight and obese women.

Viola AS, Gouveia D, Andrade L, Aldrighi JM, Viola CF, Bahamondes L.

Obstetrics and Gynaecology, Faculty of Medical Sciences, Universidade Estadual de Campinas, Campinas, Brazil.

Background: Obesity is a public health problem and it is necessary to identify if non-symptomatic obese women must be submitted to endometrial evaluation. Aims: To determine the prevalence of endometrial hyperplasia and cancer in non-symptomatic overweight or obese women. Methods: A cross-sectional study was carried out in 193 women submitted to an endometrial biopsy using a Pipelle de Cornier. The findings were classified as normal, hyperplasia or cancer, and the results were compared to body mass index (BMI; kg/m(2)). For the purpose of statistical analysis, women were divided into two groups: women of reproductive age and postmenopausal women, and according to BMI as overweight or obese. Results: The prevalence of endometrial cancer and hyperplasia was 1.0% and 5.8% in women of reproductive age and 3.0% and 12.1% in postmenopausal women, respectively. According to logistic regression, being in the postmenopause increased the risk of endometrial hyperplasia and cancer to 1.19 (95% confidence interval (CI): 0.36-3.90), while being postmenopausal and severely obese increased the odds ratio (OR) to 1.58 (95%CI: 0.30-8.23) and being postmenopausal and morbidly obese increased the OR to 2.72 (95%CI: 0.65-11.5). No increase in risk was found in women of reproductive age who were either overweight or obese. Discussion: Our results show that non-symptomatic, severe or morbidly obese postmenopausal women have a high risk of developing endometrial hyperplasia or cancer; however, no such risk was found for women of reproductive age.

 

J Natl Cancer Inst. 2008 Mar 25 [Epub ahead of print]

Increased Risk of Recurrence After Hormone Replacement Therapy in Breast Cancer Survivors.

Holmberg L, Iversen OE, Rudenstam CM, Hammar M, Kumpulainen E, Jaskiewicz J, Jassem J, et al

Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

Background Hormone replacement therapy (HT) is known to increase the risk of breast cancer in healthy women, but its effect on breast cancer risk in breast cancer survivors is less clear. The randomized HABITS study, which compared HT for menopausal symptoms with best management without hormones among women with previously treated breast cancer, was stopped early due to suspicions of an increased risk of new breast cancer events following HT. We present results after extended follow-up. Methods HABITS was a randomized, non-placebo-controlled noninferiority trial that aimed to be at a power of 80% to detect a 36% increase in the hazard ratio (HR) for a new breast cancer event following HT. Cox models were used to estimate relative risks of a breast cancer event, the maximum likelihood method was used to calculate 95% confidence intervals (CIs), and chi(2) tests were used to assess statistical significance, with all P values based on two-sided tests. The absolute risk of a new breast cancer event was estimated with the cumulative incidence function. Most patients who received HT were prescribed continuous combined or sequential estradiol hemihydrate and norethisterone. Results Of the 447 women randomly assigned, 442 could be followed for a median of 4 years. Thirty-nine of the 221 women in the HT arm and 17 of the 221 women in the control arm experienced a new breast cancer event (HR = 2.4, 95% CI = 1.3 to 4.2). Cumulative incidences at 5 years were 22.2% in the HT arm and 8.0% in the control arm. By the end of follow-up, six women in the HT arm had died of breast cancer and six were alive with distant metastases. In the control arm, five women had died of breast cancer and four had metastatic breast cancer (P = .51, log-rank test). Conclusion After extended follow-up, there was a clinically and statistically significant increased risk of a new breast cancer event in survivors who took HT.

 

Clin Endocrinol (Oxf). 2008 Mar 15 [Epub ahead of print]

The majority of Danish non-toxic goitre patients are ineligible for Levothyroxine suppressive therapy.

Fast S, Bonnema SJ, Hegedüs L.

Department of Endocrinology and Metabolism, Odense University Hospital, Denmark.

Objective: Levothyroxine suppressive therapy (LT4-therapy), aimed at shrinking thyroid nodules is controversial. Despite evidence of limited effect and long-term side effects, questionnaire surveys indicate widespread use. Our aim was to determine, in consecutive non-toxic goitre patients, the proportion ineligible for LT4-therapy. Exclusion criteria were set up in agreement with recent guidelines. Setting: Secondary/tertiary referral centre at University Clinic. Subjects and methods: During 1997-2001, 822 patients were referred to our endocrine unit on suspicion of non-toxic goitre. Patients were evaluated clinically including fine needle aspiration biopsy, thyroid scintigraphy and ultrasound. Seven-hundred and forty-five patients (627 women and 118 men; median age 47 years, range 11-90) were potential candidates for LT4-therapy. Based on guidelines we defined conditions where LT4-therapy is contraindicated. Exclusion criteria included: 1) Serum TSH <1.0 mIU/l, 2) Postmenopausal status, or males older than 60 years, 3) Thyroid volume above 100 ml, 4) Intrathoracic goitre, 5) Clinical suspicion of malignancy, 6) Dominant thyroid cyst, 7) Nondiagnostic FNA, 8) Previous ineffective LT4-therapy, 9) Elevated serum calcitonin, 10) Osteoporosis or cardiovascular disease. Results: 84% of patients were ineligible for LT4-therapy. In diffuse goitre (n=35) 63%, in uninodular goitre (n=320) 77% and in multinodular goitre (n=390) 91% were ineligible. Main ineligibility reasons were a low serum TSH, postmenopausal status, a large goitre or clinical suspicion of malignancy. Conclusion: The vast majority of consecutive Danish non-toxic goitre patients (84%) were ineligible for LT4-therapy. Due to low efficacy and potential long-term adverse effects on the skeleton and cardiovascular system we strongly advocate against LT4-therapy for non-toxic goitre.

 

Am J Epidemiol. 2008 Mar 21 [Epub ahead of print]

Predictors of the Timing of Natural Menopause in the Multiethnic Cohort Study.

Henderson KD, Bernstein L, Henderson B, Kolonel L, Pike MC.

Department of Cancer Etiology, City of Hope National Medical Center, Duarte, CA.

The timing of natural menopause has implications for several health endpoints; in particular, it is a risk factor for breast cancer. The authors investigated factors influencing the timing of natural menopause among 95,704 women with a mean age of 59.7 years (10th-90th percentile range, 47.0-71.0) in five racial/ethnic groups in the Multiethnic Cohort Study, including non-Latina Whites, Japanese Americans, African Americans, Native Hawai'ians, and Latinas. The authors investigated whether race/ethnicity and several lifestyle and reproductive characteristics were associated with the timing of natural menopause. Race/ethnicity was a significant independent predictor of the timing of natural menopause. Other factors, including smoking, age at menarche, parity, and body mass index, did not significantly alter the race/ethnicity-specific hazard ratios. Relative to non-Latina Whites, natural menopause occurred earlier among Latinas (US-born Latinas: hazard ratio (HR) = 1.10, 95% confidence interval (CI): 1.07, 1.14; non-US-born Latinas: HR = 1.25, 95% CI: 1.21, 1.30) and later among Japanese Americans (HR = 0.93, 95% CI: 0.90, 0.95). These results support the hypothesis that the timing of natural menopause is driven by a combination of genetic, reproductive, and lifestyle factors.

 

Maturitas. 2008 Mar 20 [Epub ahead of print]

Effects of estradiol and norethisterone on lipids, insulin resistance and carotid flow.

Fernandes CE, Pompei LM, Machado RB, Ferreira JA, Melo NR, Peixoto S.

ABC School of Medicine, São Paulo, Brazil.

OBJECTIVES: To evaluate the lipid profile, insulin resistance and vasomotricity, and the interaction between these factors, in postmenopausal women receiving hormone therapy. METHODS: A prospective, randomized, double-blind study was carried out in which 77 postmenopausal women received one of the three treatment regimens: (A) 2mg oral micronized estradiol (E(2)) (n=25); (B) 2mg oral E(2)+1mg oral norethisterone acetate (NETA) (n=28); or C) placebo (n=24), daily for 6 months. Evaluations were carried out at baseline and at the end of treatment on lipid and lipoprotein profiles, homeostasis model assessment of insulin resistance (HOMA-IR) and pulsatility index (PI) of the internal carotid artery by Doppler ultrasonography. RESULTS: Mean increases of 15.6% and 2.4% and a reduction of 6.4% in high-density lipoprotein (HDL) levels were found for the E(2), E(2)+NETA and placebo groups, respectively. Reductions of 9.5% and 3.7% and an increase of 12.1% in low-density lipoprotein (LDL), and reductions of 20.0% and 3.8% and an increase of 28.8% in the LDL:HDL ratio were found for the E(2), E(2)+NETA and placebo groups, respectively (p<0.001 in all cases). Insulin levels and HOMA-IR decreased 12.8% and 12.3% in the E(2) group and increased 12.9% and 16.0% in the E(2)+NETA group (p<0.05), respectively. Carotid PI following treatment was 1.18+/-0.23, 1.38+/-0.20 and 1.41+/-0.21 for the E(2), E(2)+NETA and placebo groups, respectively (p=0.0006). CONCLUSIONS: Oral estrogen therapy led to an improvement in lipid profile, insulin resistance and carotid blood flow, which was cancelled when NETA was associated.

 

 

Semana del 19 al 25 de Marzo de 2008

 

Obesity (Silver Spring). 2008 Feb 28 [Epub ahead of print

Contribution of the Lean Body Mass to Insulin Resistance in Postmenopausal Women With Visceral Obesity: A Monet Study.

Brochu M, Mathieu ME, Karelis AD, Doucet E, Lavoie ME, Garrel D, Rabasa-Lhoret R.

1Faculty of Physical Education and Sports, University of Sherbrooke, Sherbrooke, Quebec, Canada.

Some insulin-resistant obese postmenopausal (PM) women are characterized by an android body fat distribution type and higher levels of lean body mass (LBM) compared to insulin-sensitive obese PM women. This study investigates the independent contribution of LBM to the detrimental effect of visceral fat (VF) levels on the metabolic profile. One hundred and three PM women (age: 58.0 +/- 4.9 years) were studied and categorized in four groups on the basis of their VF (higher vs. lower) and lean BMI (LBMI = LBM (kg)/height (m (2)); higher vs. lower). Measures included: fasting lipids, glucose homeostasis (by euglycemic/hyperinsulinemic clamp technique and 2-h oral glucose tolerance test (OGTT)), C-reactive protein (CRP) levels, fat distribution (by computed tomography (CT) scan), and body composition (by dual-energy X-ray absorptiometry). Women in the higher VF/higher LBMI group had lower glucose disposal and higher plasma insulin levels compared to the other groups. They also had higher plasma CRP levels than the women in the lower VF/lower LBMI group. VF was independently associated with insulin levels, measures of glucose disposal, and CRP levels (P < 0.05). LBMI was also independently associated with insulin levels, glucose disposal, and CRP levels (P < 0.05). Finally, significant interactions were observed between LBMI and VF levels for insulin levels during the OGTT and measures of glucose disposal (P < 0.05). In conclusion, VF and LBMI are both independently associated with alterations in glucose homeostasis and CRP levels. The contribution of VF to insulin resistance seems to be exacerbated by increased LBM in PM women.

 

J Womens Health (Larchmt). 2008 Mar 17 [Epub ahead of print]

Coronary Heart Disease Risk and Bone Mineral Density among U.S. Women and Men.

Broussard DL, Magnus JH.

Tulane University Health Sciences Center, School of Public Health and Tropical Medicine, New Orleans, Louisiana.

ABSTRACT Aims: Low bone mineral density (BMD) has been shown to predict cardiovascular disease (CVD) and coronary heart disease (CHD) mortality in both women and men. The purpose of the current study was to determine whether a CHD risk assessment tool might be useful for identifying persons likely to have low BMD in a multiethnic population of women and men. Methods: Cross-sectional data for 3881 women and men aged 50-74 years without overt CHD or stroke from the Third National Health and Nutrition Examination Survey (NHANES III) were used to explore the relationship between BMD and 10-year CHD risk, as estimated using the Framingham CHD risk prediction algorithm, in gender-stratified multiple logistic regression models. Results: When compared with women who had a <10% CHD risk, women with a 10%-19% CHD risk were 45% more likely and those with a >/=20% CHD risk were 73% more likely to have low BMD. Similar increases in low BMD risk were not detected in men. Conclusions: In the United States, 10-year Framingham CHD risk assessment may be useful for identifying older women who should be evaluated for osteoporosis and referred for BMD measurement. The impact of such a screening strategy on fracture prevention needs further elucidation.

 

BJOG. 2008 Mar 19 [Epub ahead of print

Differential impact of conventional and low-dose oral hormone therapy, tibolone and raloxifene on mammographic breast density, assessed by an automated quantitative method.

Eilertsen AL, Karssemeijer N, Skaane P, Qvigstad E, Sandset PM.

Department of Haematology and Faculty Division, Ullevål University Hospital Trust, Oslo, Norway.

Objective To evaluate impact of different postmenopausal hormone therapy (HT) regimens and raloxifene on mammographic breast density. Design Open, randomised, comparative clinical trial. Setting Women were recruited through local newspapers and posters. They were examined at the Departments of Haematology, Gynaecology, and Radiology in a University Hospital. Population A total of 202 healthy postmenopausal women between the age of 45 and 65 years. Methods Women were randomly assigned to receive daily treatment for 12 weeks with tablets containing low-dose HT containing 1 mg 17 beta-estradiol + 0.5 mg norethisterone acetate (NETA) (n= 50), conventional-dose HT containing 2 mg 17 beta-estradiol and 1 mg NETA (n= 50), 2.5 mg tibolone (n= 51), or 60 mg raloxifene (n= 51). Mammographic density was determined at baseline and after 12 weeks by an automated technique in full-field digital mammograms. Main outcome measures Mammographic density was expressed as volumetric breast density estimations. Results Mammographic breast density increased significantly and to a similar degree in both the conventional- and low-dose HT groups. A small reduction in mammographic breast density was seen in the raloxifene group, whereas those allocated to tibolone treatment only showed minor changes. Conclusions Our findings demonstrated a significant difference in impact on mammographic breast density between the regimens. Although these results indicate a differential effect of these regimens on breast tissue, the relation to breast cancer risk remains unresolved.

 

Cancer Epidemiol Biomarkers Prev. 2008 Mar;17(3):655-60

Postmenopausal Hormone Therapy and Lung Cancer Risk in the Cancer Prevention Study II Nutrition Cohort.

Rodriguez C, Spencer Feigelson H, Deka A, Patel AV, Jacobs EJ, Thun MJ, Calle EE.

Epidemiology and Surveillance Research, American Cancer Society, National Home Office, Northwest, Atlanta, GA

BACKGROUND: Studies of postmenopausal hormone therapy and lung cancer incidence have reported positive, negative, and null associations. Most of these studies, however, have had limited ability to control rigorously for cigarette smoking or to examine risk separately by smoking status. METHODS: We examined the association between postmenopausal hormone therapy and lung cancer incidence by smoking status among 72,772 women in the Cancer Prevention Study II Nutrition Cohort. Proportional hazards modeling was used to calculate rate ratios (RR). RESULTS: During follow-up from 1992 to 2003, we identified 659 cases of incident lung cancer. Current use of any postmenopausal hormone therapy was significantly associated with decreased risk of incident lung cancer [multivariate RR, 0.76; 95% confidence interval (95% CI), 0.62-0.92]. Similar risk estimates were observed for unopposed estrogen use (RR, 0.76; 95% CI, 0.60-0.94) and for estrogen plus progestin (RR, 0.76; 95% CI, 0.57-1.01). Risk associated with current use of postmenopausal hormone therapy was decreased among never smokers (RR, 0.56; 95% CI, 0.33-0.95) as well as current smokers (RR, 0.76; 95% CI, 0.55-1.05) and former smokers (RR, 0.76; 95% CI, 0.58-0.99). Former hormone use was not associated with lung cancer. No trend with duration of hormone use was detected. CONCLUSION: These results support the hypothesis that postmenopausal hormone therapy is associated with reduced risk of lung cancer, although the absence of a dose-response relationship weakens the evidence for causality.

 

J Clin Endocrinol Metab. 2008 Mar 18 [Epub ahead of print

Randomized Trial of Once-Weekly PTH(1-84) on Bone Mineral Density and Remodeling.

Black DM, Bouxsein ML, Palermo L, McGowan JA, Newitt D, Rosen E, Majumdar S, Rosen CJ; for the PTH Once-Weekly Research (POWR) group.

San Francisco Coordinating Center, San Francisco, CA, USA.

Context: Daily parathyroid hormone (PTH) administration increases bone mineral density (BMD) and reduces fracture risk. However, cost and compliance significantly limit clinical use. Objective: To determine whether less frequent PTH administration increases lumbar spine BMD Design: Double-blind, randomized placebo-controlled trial Participants: 50 postmenopausal women ages 45-70 with femoral neck BMD T-score between -1.0 and -2.0 Setting: St. Joseph Hospital, Bangor, Maine Intervention: Subcutaneous injections of daily PTH(1-84) (100 microg) or placebo for one month, followed by weekly injections (PTH or placebo) for 11 months Outcomes: Change in lumbar spine DXA areal BMD (aBMD, Primary). Secondary outcomes included volumetric BMD (vBMD) at spine and hip by QCT, trabecular bone microarchitecture by MRI of distal radius, and biochemical bone turnover markers. Results: At 12 months, lumbar spine aBMD increased 2.1% in PTH-treated women compared to placebo (p=0.03). Vertebral trabecular vBMD increased 3.8% in PTH-treated women compared to placebo group (p=0.08). PTH-treated women also had higher distal radial trabecular bone volume, number, and thickness compared to placebo-treated women (p<0.04). After one month of daily PTH, PINP was markedly increased compared to placebo (p<0.0001) and a difference persisted, although lessened, throughout the study. Bone resorption indices were unchanged in PTH-treated women and were reduced in placebo group. Conclusion: Once-weekly PTH after one month of daily treatment increases spine BMD, radial trabecular bone and bone formation markers in postmenopausal women. These results suggest that less frequent alternatives to daily PTH dosing for two years could be effective. Further studies are required to define the optimal frequency of PTH administration.

 

Appl Physiol Nutr Metab. 2008 Apr;33(2):309-14.

Relationship between the metabolic syndrome and physical activity energy expenditure: a MONET study.

Karelis AD, Lavoie ME, Messier V, Mignault D, Garrel D, Prud'homme D, Rabasa-Lhoret R.

The purpose of this cross-sectional study was to examine the association between the metabolic syndrome (MetS) and physical activity energy expenditure (PAEE) in overweight and obese sedentary postmenopausal women. The study population consisted of 137 overweight and obese sedentary postmenopausal women (age, 57.7 +/- 4.8 years; BMI, 32.4 +/- 4.6 kg.m-2). Subjects had the MetS if 3 out of the following 5 criteria were met: visceral fat > 130 cm2, high-density lipoprotein (HDL) cholesterol < 1.29 mmol.L-1, fasting triglycerides >= 1.7 mmol.L-1, blood pressure >= 130/85 mmHg, and fasting glucose >=5.6 mmol.L-1. We measured (i) body composition (by dual-energy X-ray absorptiometry); (ii) visceral fat (by computed tomography); (iii) insulin sensitivity (using the hyperinsulinemic-euglycemic clamp); (iv) plasma lipids, fasting glucose, and insulin, as well as 2 h glucose during an oral glucose tolerance test; (v) resting blood pressure; (vi) peak oxygen consumption (VO2 peak); (vii) PAEE (using doubly labeled water); and (viii) lower-body muscle strength (using weight-training equipment). Forty-two women (30.7%) had the MetS in our cohort. Individuals without the MetS had significantly higher levels of PAEE (962 +/- 296 vs. 837 +/- 271 kcal.d-1; p < 0.05), VO2 peak (18.2 +/- 3.0 vs. 16.7 +/- 3.2 mL.min-1.kg-1; p < 0.05), and insulin sensitivity, as well as significantly lower levels of 2 h glucose and central lean body mass. No differences in total energy expenditure, resting metabolic rate, and muscle strength between groups were observed. Logistic regression analysis showed that 2 h glucose (odds ratio (OR): 1.50 (95% CI 1.17-1.92)), central lean body mass (OR: 1.17 (95% CI 1.05-1.31)), and PAEE (OR: 0.998 (95% CI 0.997-1.000)), but not VO2 peak and (or) muscle strength, were independent predictors of the MetS. Lower levels of PAEE and higher levels of 2 h glucose, as well as central lean body mass, are independent determinants of the MetS in our cohort of overweight and obese postmenopausal women.

 

Menopause. 2008 Mar 14 [Epub ahead of print]

Associations of circulating adiponectin with estradiol and monocyte chemotactic protein-1 in postmenopausal women.

Miyatani Y, Yasui T, Uemura H, Yamada M, Matsuzaki T, Kuwahara A, Tsuchiya N, Yuzurihara M, Kase Y, Irahara M.

Departments of Obstetrics and Gynecology, Tsumura Central Research Institute, Ibaraki-ken, Japan.

OBJECTIVE:: The aim of the present study was to clarify the association of serum adiponectin concentrations with serum 17beta-estradiol concentrations in pre-, peri-, and postmenopausal women. In addition, the associations of serum adiponectin with serum concentrations of proinflammatory and anti-inflammatory cytokines were examined in women during the menopausal transition. DESIGN:: A total of 197 women were enrolled in this study: 33 premenopausal women, 80 perimenopausal women, and 84 postmenopausal women. Serum adiponectin concentration was measured by an enzyme-linked immunosorbent assay. Serum concentrations of the proinflammatory cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor alpha, anti-inflammatory cytokine IL-10, and the chemokines IL-8, macrophage inflammatory protein-1beta and monocyte chemotactic protein-1 were measured by using a multiplexed human cytokine assay. RESULTS:: Serum adiponectin concentration showed a significant negative correlation with serum estradiol concentration (r = -0.400, P = 0.001) in postmenopausal women but not in pre- and perimenopausal women, and this correlation was significant after adjustment for age and body mass index. Serum adiponectin concentration also showed a significant negative correlation with serum monocyte chemotactic protein-1 concentration (r = -0.244, P= 0.05) in postmenopausal women. CONCLUSION:: An increase in adiponectin level due to a decrease in estradiol results in a reduction in monocyte chemotactic protein-1 level in postmenopausal women, suggesting that adiponectin may be associated with a protective role against insulin resistance and atherosclerosis, which occur in the postmenopausal stage.

 

 

Semana del 5 al 11 de Marzo de 2008

 

Acta Cytol. 2008 Jan-Feb;52(1):8-13.Links

Osteopenia and osteoporosis can be Predicted from Pap test.

Repse-Fokter A, Fokter SK.

Department of Pathomorphology and Cytology, Celje General Hospital, Celje, Slovenia. alenka.repse-

OBJECTIVE: To determine sensitivity and specificity of Pap tests for osteopenia and osteoporosis using bone

mineral density (BMD) with dual x-ray absorptiometry (DXA) as the reference standard. STUDY DESIGN: DXA measurement was performed on 136 routine Pap smears. Results of DXA measurement were expressed in T-scores, indicating degree of deviation compared to a young adult population of same age and gender. Smears were grouped into atrophic and mature cell patterns. Using a stereologic analysis, mean areas of squamous cells, their nuclei and their cytoplasm were estimated. RESULTS: There was significant positive correlation between cell area and T-score (p < 0.001), as well as between cytoplasm area and T-score (p < 0.001). There was no significant relationship between nucleus area and T-score (p > 0.05). Mean T-scores of patients with atrophic cells were significantly lower than mean T-scores of patients with mature cell patterns (p < 0.001). The group including patients with atrophic or mature cells had a sensitivity of 61.4% and specificity of 86.4%, with positive predictive value of 95.9% in detecting patients with osteopenia or osteoporosis. CONCLUSION: Women with atrophic smear pattern are susceptible to osteopenia or osteoporosis; many cases could be detected with routine Pap test without additional costs.

 

Neurodegener Dis. 2008;5(3-4):257-60. Epub 2008 Mar 6.

The long-term effects of oophorectomy on cognitive and motor aging are age dependent.

Rocca WA, Grossardt BR, Maraganore DM.

Division of Epidemiology, Mayo Clinic College of Medicine, Rochester, Minn., USA.

Background: The evidence for a neuroprotective effect of estrogen in women remains controversial. Objective: We studied the long-term risk of parkinsonism and of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Methods: We conducted a historical cohort study among all women residing in Olmsted County, Minn., USA, who underwent unilateral or bilateral oophorectomy before the onset of menopause for a noncancer indication from 1950 through 1987. Each member of the oophorectomy cohort was matched by age to a referent woman from the same population who had not undergone oophorectomy. In total, we studied 1,252 women with unilateral oophorectomy, 1,075 women with bilateral oophorectomy, and 2,368 referent women.

Women were followed for a median of 25-30 years. Parkinsonism was assessed using screening and examination, through a medical records- linkage system, and through death certificates. Cognitive status was assessed using a structured questionnaire via a direct or proxy telephone interview. Results: The risk of parkinsonism and of cognitive impairment or dementia increased following oophorectomy. In particular, we observed significant linear trends of increasing risk for either outcome with younger age at oophorectomy. Conclusion: Our findings, combined with previous laboratory and epidemiologic findings, suggest that estrogen may have an age-dependent neuroprotective effect.

 

Int J Fertil Womens Med. 2007 Mar-Jun;52(2-3):93-6.

Climacteric symptom control after the addition of low-dose esterified conjugated estrogens to raloxifene standard doses.

Carranza-Lira S, Gooch AL, Saldivar N, Osterwalder MS.

Gynecologic Endocrinology Department Hospital de Ginecología y Obstetricia Luis Castelazo Ayala, DF México.

INTRODUCTION: Hormone therapy (HT) is one the best options for climacteric symptom control; however when women are switched to raloxifene, after several years of HT, they restart with symptoms. OBJECTIVE: To evaluate the effect of the addition of low-dose esterified conjugated estrogens to the conventional dose of raloxifene in the control of climacteric symptoms. MATERIALS AND METHODS: 14 healthy postmenopausal patients were studied.

Climacteric symptoms were evaluated at baseline and 3 months after the beginning of treatment by the Kupperman's index (KI) and by the sum of the symptom evaluations carried out with an analog visual scale called SUMEVA. In all the anthropometric variables were documented, as well as time since menopause and endometrial thickness. At random they were distributed in some of the following groups: I) Raloxifene 60 mg/day (n=7) and II) Raloxifene 60 mg/day plus esterified conjugated estrogens 0.312 mg/day (n=7). STATISTICAL ANALYSIS: Differences among the groups, as well as those among baseline and those at the end of treatment, were determined by student's t test for independent samples and paired samples respectively. RESULTS: There were no differences in anthropometric variables, nor in the time since menopause. After three months of treatment the libido alterations vertigo and vaginal dryness were significantly greater in group I. In group II a significant decrease in hot flushes, insomnia, nervousness, vaginal dryness, KI, and SUMEVA were found, as was a significant increase in endometrial thickness. CONCLUSION: The treatment that is proposed in this study can constitute a temporary alternative during the period

of transition from HT to raloxifene.

 

Steroids. 2008 Jan 18 [Epub ahead of print]

Vascular cell signaling by membrane estrogen receptors.

Kim KH, Moriarty K, Bender JR.

Division of Cardiovascular Medicine and Departments of Internal Medicine and Immunobiology, the Raymond and Beverly Sackler Foundation Cardiovascular Laboratory, Yale University School of Medicine, New Haven, USA.

The definition of estrogen's actions has expanded from transcriptional regulation to the rapid, membrane-initiated activation of numerous signal transduction cascades. Multiple biological effects of estrogen have been shown in numerous animals, cellular and molecular studies, which support the favorable effects of estrogen on vascular structure, function, and cell signaling. Work from several laboratories has shown that these effects are mediated by distinct forms of estrogen receptor (ER) alpha. This includes estrogen-stimulated rapid activation of endothelial nitric oxide synthase (eNOS), resulting in the elaboration of the athero-protective, angiogenesis-promoting product nitric oxide (NO). We have described the expression of ER46, an N-terminus truncated isoform of the ERalpha, in human endothelial cells (EC), and its critical role in membrane-initiated, rapid responses to 17beta-estradiol (E2). We have

proposed an ER46-centered, eNOS activating molecular complex in human EC caveolar membranes, containing c-Src, phosphatidylinositol 3-kinase (PI3K), Akt and eNOS. Our previous studies support estrogen-induced rapid eNOS activation via a sequential c-Src/PI3K/Akt cascade in EC. In this review, we describe estrogen-induced, rapid, non-genomic actions in endothelium, driven by c-Src-ER46-caveolin-1 interactions, with consequent activation of eNOS. Amidst ongoing controversies in hormone replacement therapy, these molecular and cellular data, defining favorable estrogenic effects on the endothelium, provide a strong impetus to resolve these clinical questions.

 

Fertil Steril. 2008 Mar 4 [Epub ahead of print]

Effect of ovarian hormones on serum adiponectin and resistin concentrations.

Chalvatzas N, Dafopoulos K, Kosmas G, Kallitsaris A, Pournaras S, Messinis IE.

Departments of Obstetrics and Gynecology, University of Thessalia, Larissa, Greece.

OBJECTIVE: To investigate the effect of ovarian hormones on adiponectin and resistin levels in women. DESIGN:

Experimental study. SETTING: University hospital. PATIENT(S): Thirteen normally cycling women (7 in group 1and 6 in group 2) and 8 postmenopausal women (group 3). INTERVENTION(S): Women of group 1 wereinvestigated in a control cycle and in a subsequent cycle in which total abdominal hysterectomy plus bilateralsalpingooophorectomy (TAH+BSO) was performed on day 3. In both cycles, the women received increasing doses of E (2) from days 3 to 5. Women of group 2 underwent TAH+BSO on day 3 without receiving any hormonaltreatment. Women of group 3 received increasing doses of E (2) for 15 days. MAIN OUTCOME MEASURE(S): Adiponectin, resistin, and E (2) concentrations. RESULT(S): In group 1, serum adiponectin and resistin levels did notshow any significant changes for the week following day 3 and were similar in the two cycles. In group 2,adiponectin and resistin levels were similar before and after TAH+BSO and remained stable during the firstpostoperative week. In group 3, no significant changes in adiponectin and resistin levels were seen during the 15 daysof E (2) administration. CONCLUSION(S): Adiponectin and resistin values were not affected either by estrogentreatment or after ovariectomy in women. It is suggested that ovarian hormones are not involved in the regulation of adiponectin and resistin secretion in women.

 

J Clin Oncol. 2008 Mar 10;26(8):1260-8.

Use of different postmenopausal hormone therapies and risk of histology- and hormone receptor-defined invasive breast cancer.

Fournier A, Fabre A, Mesrine S, Boutron-Ruault MC, Berrino F, Clavel-Chapelon F.

Institut National de la Santé et de la Recherche Médicale, Cedex, France.

PURPOSE: We previously found that the risk of invasive breast cancer varied according to the progestagen

component of combined postmenopausal hormone therapy (CHT): progesterone, dydrogesterone, or other

progestagens. We conducted the present study to assess how these CHTs were associated with histology- and

hormone receptor-defined breast cancer. PATIENTS AND METHODS: We used data from the French E3N cohort study, with 80,391 postmenopausal women followed for a mean duration of 8.1 years; 2,265 histologically confirmed invasive breast cancers were identified through biennial self-administered questionnaires completed from 1990 to2002. The relative risks (RRs) were estimated using Cox proportional hazards models. RESULTS: Compared withpostmenopausal hormone therapy (HT) never-use, ever-use of estrogen+progesterone was not significantlyassociated with the risk of any breast cancer subtype, but increasing duration of estrogen+progesterone wasassociated with increasing risks of lobular (P = .06) and estrogen receptor-positive/progesterone receptor-negative(ER+/PR-; P = .02). Estrogen+dydrogesterone was associated with a significant increase in risk of lobular carcinoma(RR, 1.7; 95% CI, 1.1 to 2.6). Estrogen+other progestagens was associated with significant increases in risk of ductal and lobular carcinomas (RR, 1.6; 95% CI, 1.3 to 1.8; and 2.0; 95% CI, 1.5 to 2.7, respectively), of ER+/PR+ and ER

+/PR- carcinomas (RR, 1.8; 95% CI, 1.5 to 2.1; and 2.6; 95% CI, 1.9 to 3.5, respectively), but not of ER-/PR+ or ER-/PR- carcinomas (RR, 1.0; 95% CI, 0.5 to 2.1; and 1.4; 95% CI, 0.9 to 2.0, respectively). CONCLUSION: The increase in risk of breast cancer observed with the use of CHTs other than estrogen+progesterone and estrogen+dydrogesterone seems to apply preferentially to ER+ carcinomas, especially those ER+/PR-, and to affect both

ductal and lobular carcinomas.

 

J Clin Endocrinol Metab. 2008 Mar 4 [Epub ahead of print]

Does Osteoprotegerin or RANKL Mediate the Association Between Bone and Coronary Artery Calcification?

Bakhireva LN, Laughlin GA, Bettencourt R, Barrett-Connor E.

Division of Pharmacy Practice, University of New Mexico, Albuquerque, NM; Department Family and Preventive Medicine, University of California, San Diego; La Jolla, CA. Context:Accumulating evidence indicates that vascular and bone mineralization may be related, though the exact mechanism remains unknown. Objective: To investigate whether an observed inverse association between bone mineral density (BMD) and coronary artery calcification (CAC) in postmenopausal women currently taking estrogen therapy (ET) is mediated by osteoprotegerin (OPG) or RANK ligand (RANKL). Design: Participants were 92

postmenopausal women (aged 58-81 years) taking ET who had hip and spine BMD assessed by dual-energy x-ray absorptiometry and CAC measured by electron-beam computed tomography in 1998-2002, and serum RANKL and OPG levels measured in samples collected in 1997-1999. Total CAC score was dichotomized as "none/minimal" (</=10) versus "some" (>10). Results: OPG serum levels were higher in women who had some CAC compared to those who had none/minimal (126.8+/-1.08 vs. 102.9+/-1.07 pg/ml, respectively, p=0.03); these differences became nonsignificant after adjustment for age and other risk factors (p=0.51). A one standard deviation increase in hip BMD was associated with significantly lower odds of having CAC > 10 (OR=0.52; 95% CI: 0.29-0.93) independent of age,fat-free mass, HDL cholesterol, current smoking, and use of cholesterol-lowering medications. Other skeletal sites demonstrated a similar pattern. Addition of RANKL and/or OPG to the model had minimal effect on the magnitudeor statistical significance of the BMD-CAC association. Additionally, a test of interaction indicated that RANKL andOPG are not significant effect modifiers. Conclusions: Serum OPG and RANKL do not account for the observe dassociation between bone and coronary artery calcification among postmenopausal women using hormone therapy.

 

J Clin Endocrinol Metab. 2008 Mar 4 [Epub ahead of print]

Effects in Postmenopausal Women of Estradiol and Medroxyprogesterone Alone and Combined on Resistance Artery Function and Endothelial Morphology and Movement.

Kublickiene K, Fu XD, Svedas E, Landgren BM, Genazzani AR, Simoncini T.

Department of Clinical Science, Intervention and Technology, Section for Obstetrics and Gynecology, KarolinskaInstitute, Karolinska University Hospital-Huddinge campus, 14186 Stockholm, Sweden; Molecular and Cellular Gynecological Endocrinology Laboratory (MCGEL), Department of Reproductive Medicine and Child Development, University of Pisa, 56100, Pisa, Italy.

Context: Endothelial dysfunction in resistance arteries after menopause is important for the development of highblood pressure and cardiovascular disease. Objective: To study the effects of different hormone replacement therapies (HRT) on the function and morphology of isolated resistance arteries, and to look for their mechanisticbasis. Design and setting: A randomized, placebo-controlled double-blind study in a University hospital, along with laboratory-based studies. Patients and interventions: We isolated resistance arteries in subcutaneous biopsies from 55 postmenopausal women before and after 3 months of therapy with estradiol (E2), medroxyprogesterone acetate(MPA), E2 + MPA or placebo. In addition, we studied isolated human endothelial cells. Main Outcome Measuresand Results: Artery flow-mediated dilatation was augmented after treatment with E2 or E2+MPA, whereas MPA orplacebo had no effect. Pressure-induced myogenic tone was reduced by E2 + MPA, while it was unchanged in theother groups. Scanning microscopy showed that E2 improved endothelial cell morphology and decreased signs ofendothelial apoptosis, but the addition of MPA impaired these events. E2, MPA or the combination all increased theexpression and phosphorylation of the actin-binding protein, moesin and of the focal adhesion complex controller, focal adhesion kinase and induced the rearrangement of cytoskeletal actin and vinculin fibers. All treatments promoted endothelial cell horizontal migration, with E2 inducing the strongest effect. Conclusions: This study file:///C|/Documents%20and%20Settings/HBLTJEFELABORATORIO/Mis%20documentos/080311.htm (4 of 5)13-03-2008 6:37:31 Selección de Resúmenes de Menopausia

suggests that HRT with estrogens or in combination with MPA may benefit the function of resistance arteries and may preserve the morphological integrity of endothelial cells by regulatory actions on the cytoskeleton.

 

Am J Obstet Gynecol. 2008 Mar;198(3):265.e1-7.

The effect of ultralow-dose transdermal estradiol on sexual function in

postmenopausal women.

Huang A, Yaffe K, Vittinghoff E, Kuppermann M, Addis I, Hanes V, Quan J, Grady D.

Department of Medicine, University of California San Francisco School of Medicine, San Francisco, CA, USA. OBJECTIVE: This study was undertaken to examine the effect of ultralow-dose transdermal estradiol on sexual function in postmenopausal women. STUDY DESIGN: Analysis of data from a multicenter, randomized, doubleblind,placebo-controlled trial of a 0.014 mg/day transdermal estradiol patch in 417 women aged 60 to 80 years.Sexual function was assessed by self-administered questionnaires at baseline and 4, 12, and 24 months. A lineareffects model was used to assess treatment effects using data from all on-study assessments. RESULTS: Womenrandomly assigned to estradiol had a 4.3 point greater improvement in the vaginal pain/dryness domain relative toplacebo (95% CI = 0.3-8.4, P = .04). No significant differences in frequency of sexual activity or other sexualfunction domains (desire, satisfaction, problems, or orgasm) were observed between treatment groups (P > or = .10(or all). CONCLUSIONS: Ultralow-dose estradiol resulted in modest improvement in sexual function related tovaginal pain and dryness, but not in other domains of sexual function.file:///C|/Documents%20and%20Settings/HBLTJEFELABORATORIO/Mis%20documentos/080311.htm (5 of 5)13-03-2008 6:37:31