Selección de Resúmenes de Menopausia

Diciembre de 2007

Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

 

Semana del 19 al 26 de Diciembre de 2007

 

Int J Gynaecol Obstet. 2007 Dec 19 [Epub ahead of print]

Brachial artery responses in menopausal women using tibolone.

Carranza-Lira S, Cuan-Martínez JR, Rosales-Ortíz S.

Hospital de Ginecobstetricia “Luis Castelazo Ayala”, Instituto Mexicano del Seguro Social, México DF.

OBJECTIVE: To determine the effect of tibolone treatment on brachial artery pulsatility index (PI), resistance index (RI), and flux-mediated dilation (FMD) in postmenopausal Mexican women. METHOD: The FMD, PI, and RI of the right brachial artery were measured in 19 postmenopausal women before and after they received a hyperemic stimulus, first at baseline and then following a 6-month treatment with 2.5 mg of tibolone per day. Statistical analysis was performed using the t test. RESULTS: The mean+/-SD age was 52.2+/-3.9 years; time since menopause was 24.6+/-16.7 months; and treatment duration was 5.7+/-2.0 months. Compared with prestimulus measurements, a significant poststimulus increase in arterial diameter and a significant decrease in PI were observed at baseline. Compared with prestimulus measurements, a significant poststimulus increase in arterial diameter and a significant decrease in both PI and RI were observed post-treatment. CONCLUSION: Tibolone treatment had a favorable effect on brachial artery responses to hyperemic stimuli.

 

Int J Gynecol Pathol. 2008 Jan;27(1):61-67.

Endometrial Microcalcifications Detected by Ultrasonography: Clinical Associations, Histopathology, and Potential Etiology.

Truskinovsky AM, Gerscovich EO, Duffield CR, Vogt PJ.

Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota (A.M.T.)

SUMMARY: Endometrial microcalcifications are uncommon, with alleged clinical implications ranging from innocuous to ominous. We reviewed the histopathologic slides from 29 patients who had endometrial echogenic foci on pelvic ultrasound and found many endometrial microcalcifications. The extent of microcalcifications in each specimen was graded on a semiquantitative scale from 0 to 3. The mean patient age was 54 years (range, 34-81 years). The specimens included endometrial biopsies, curettages, and hysterectomies. Most of the patients had presented with abnormal vaginal bleeding. Fifteen patients (51.7%) were postmenopausal, 10 (34.5%) were premenopausal, and the rest were perimenopausal. The most frequent endometrial types were atrophic (39.5%), inactive (23.3%), and proliferative (14%). Six specimens (14%) showed benign endometrial polyps. One patient had well-differentiated endometrioid carcinoma of the endometrium without myometrial invasion. Specimens from 16 patients (55.2%) had microcalcifications. The patients with calcifications were older than those without calcifications (mean age, 60 vs. 47 years, respectively; P = 0.017). The extent of microcalcifications positively correlated with the presence of endometrial polyps (P = 0.00076), postmenopausal state (P = 0.004), atrophic endometrium (P = 0.002), and hormone replacement therapy (P = 0.013). The microcalcifications were concentric or amorphous, intraglandular or stromal. They were focally associated with minute papillary epithelial projections or with degenerated endometrial glands. Follow-up was available on 26 patients (89.7%). Except for the patient with endometrioid carcinoma, none has developed uterine, adnexal, or peritoneal malignancy. In summary, endometrial microcalcifications are histologically heterogeneous and are associated with older patient age, postmenopausal state, atrophic endometrium, and endometrial polyps. Those found incidentally by means of pelvic ultrasonography, in our experience, did not portend malignancy.

 

Int J Gynecol Pathol. 2008 Jan;27(1):45-48.

Endometrial Hyperplasia and Carcinoma in Endometrial Polyps: Clinicopathologic and Follow-Up Findings.

Mittal K, Da Costa D.

From the Department of Pathology, New York University School of Medicine, New York, NY.

SUMMARY:: The objectives of this study were: 1) to evaluate findings in follow-up hysterectomy specimens after a diagnosis of complex atypical hyperplasia or carcinoma in endometrial polyps (EMPs) for possible significance in management strategies; and 2)to identify features in these polyps, that are predictive of the presence of endometrial hyperplasia or carcinoma in subsequent hysterectomy. Records of all cases of EMPs with endometrial hyperplasia were retrieved from the files of New York University Medical Center from 1993 to 2005. Those cases with follow-up hysterectomy were selected for the study. Of the 29 patients with complex atypical hyperplasia within the polyp, 19 out of 29 (66%) patients had hyperplasia of the non-polyp endometrium, and adenocarcinoma was observed in 9 out of 29 (31%) patients on follow-up hysterectomy. The percentage of polyp area involved by the hyperplasia was predictive of finding endometrial disorder in subsequent hysterectomy (P = 0.005). Of the 8 patients with adenocarcinoma in situ (AIS) within the polyp 3 (38%) had myoinvasive adenocarcinoma. In contrast, in cases without AIS, 4 out of 21 (19%) had myoinvasive adenocarcinoma in follow-up hysterectomy. Eight of the nine cases with carcinoma in endometrial polyp had endometrial pathology on hysterectomy. Approximately two thirds of the patients with hyperplasia and 90% of patients with adenocarcinoma in endometrial polyps show endometrial pathology on subsequent hysterectomy. The above findings reinforce the need for hysterectomy especially in postmenopausal women with atypical complex hyperplasia or carcinoma in endometrial polyps even if these changes appear confined to the polyp in initial sampling.

 

J Am Diet Assoc. 2008 Jan;108(1):125-130.

Predictors of Diet Quality among Overweight and Obese Postmenopausal Women.

Boynton A, Neuhouser ML, Sorensen B, McTiernan A, Ulrich CM.

Previous studies have shown that sociodemographic characteristics can be determinants of healthful eating. However, health characteristics such as smoking status have not been well studied. The objective of this research, therefore, was to determine predictors of diet quality in postmenopausal women. We included 164 overweight or obese postmenopausal women aged 50 to 75 years living in and around Seattle, WA, and intake, measured by food frequency questionnaire, was used to calculate scores for the Diet Quality Index and Healthy Eating Index. Information on sociodemographic factors and health behaviors was collected by self-administered questionnaire. Body mass index was computed using duplicate measures of height and weight. Percent body fat was measured by dual-energy x-ray absorptiometry. Following data collection, one-way analysis of variance, chi(2), and Pearson correlations were used to compare means of diet quality scores across participant characteristics. We found that predictors of better diet quality in this study population were higher education and former smoking history (compared to never-smokers); there was no evidence for a relationship with income level. Individuals with higher-quality diets were more likely to have lower body mass index or percent body fat. Based on the results of this study, education level and smoking history are predictors of diet quality among overweight and obese postmenopausal women. These findings add to the increasing evidence for targeting public health interventions to individuals with lower education because this group stands to benefit from improved dietary intake. In addition, these results suggest that the timing of smoking cessation is a possible teachable moment for food and nutrition professionals.

 

Med Sci Sports Exerc. 2007 Dec 4 [Epub ahead of print]

Effect of Physical Activity on Menopausal Symptoms among Urban Women.

Nelson DB, Sammel MD, Freeman EW, Lin H, Gracia CR, Schmitz KH.

Department of Public Health and Obstetrics and Gynecology, Temple University, Philadelphia, PA.

PURPOSE:: To determine whether physical activity, measured by expended kilocalories per week (kcal.wk), decreases the risk of menopausal symptoms among African American and Caucasian women. METHODS:: Level of physical activity and menopausal symptoms, including hot flashes, depression, anxiety, stress, and vasomotor, physiological, and somatic symptom summaries were measured in 401 women during an 8-yr period. Tertiles of physical activity at each assessment were defined as kilocalories per week: top third (>/= 1450 kcal.wk), middle third (< 1450 to 644 kcal.wk), and bottom third (< 644 kcal.wk). Regression models were used to estimate the independent effect of physical activity at each time period on menopausal symptoms after adjusting for covariates and hormone levels. Results were also stratified by race, smoking status, and menopausal status. RESULTS:: Overall, only perceived stress was related to level of physical activity, with women in both the middle and top tertiles of physical activity reporting lower mean levels of stress compared with women in the lowest tertile of activity. In the analysis by menopausal stage, active postmenopausal women continued to report lower mean levels of anxiety, stress, and depressive symptoms compared with inactive postmenopausal women. We did not find an association between level of physical activity and reports of hot flashes, even after adjusting for the variability in the hormonal changes. CONCLUSIONS:: Among a cohort of community-dwelling women, high levels of physical activity were related to lower levels of stress during an 8-yr follow-up period. In addition, levels of anxiety, stress, and depression were lowest among physically active postmenopausal women compared with inactive women in the same menopausal grouping

 

Menopause. 2007 Oct 10 [Epub ahead of print]

Use of complementary and alternative medicine during the menopause transition: longitudinal results from the Study of Women's Health Across the Nation.

Bair YA, Gold EB, Zhang G, Rasor N, Utts J, Upchurch DM, Chyu L, Greendale GA, Sternfeld B, Adler SR.

Planned Parenthood Affiliates of California, Sacramento, CA.

OBJECTIVE:: This study examined whether use of complementary and alternative (CAM) therapies during the menopause transition varied by ethnicity. DESIGN:: The Study of Women's Health Across the Nation is a prospective cohort study following a group of 3,302 women from five racial/ethnic groups at seven clinical sites nationwide. Using longitudinal data encompassing 6 years of follow-up, we examined trends in use of five categories of CAM (nutritional, physical, psychological, herbal, and folk) by menopause status and ethnicity. To account for potential secular trends in CAM use or availability, we also evaluated the trends in CAM use over calendar time. RESULTS:: Approximately 80% of all participants had used some form of CAM at some time during the 6-year study period. White and Japanese women had the highest rates of use (60%), followed by Chinese (46%), African American (40%), and Hispanic (20%) women. Overall use of CAM therapy remained relatively stable over the study period. In general, CAM use did not seem to be strongly associated with change in menopause transition status. Use of CAM among white women did not change with transition status. Among Chinese and African American participants, we observed an increase in CAM use as women transitioned to perimenopause and a decrease in use of CAM with transition to postmenopause. Among Hispanic and Japanese women, we observed a decrease in use of CAM in early perimenopause, followed by an increase as women entered late perimenopause and a decrease as they progressed to postmenopause. Patterns of use for the five individual types of CAM varied. White women had relatively stable use of all CAM therapies through the transition. Japanese women decreased use of nutritional and psychological remedies and increased use of physical remedies as they transitioned into late perimenopause. Among African American women, use of psychological remedies increased as they progressed through menopause. CONCLUSIONS:: Although CAM use did vary in some ethnic groups in relation to advancing menopause status, there was no evidence of influence of calendar time on CAM use. Patterns of CAM use during menopause are likely to be driven by personal experience, menopausal health, and access to therapies. Women's personal preferences should be taken into consideration by healthcare providers for medical decision making during menopause and throughout the aging process.

 

Menopause. 2007 Oct 10 [Epub ahead of print]

Associations between mammographic density and body composition in Hispanic and non-Hispanic white women by menopause status.

Caire-Juvera G, Arendell LA, Maskarinec G, Thomson CA, Chen Z.

Nutrition Department, Centro de Investigación en Alimentación y Desarrollo, Sonora, México.

OBJECTIVE:: To evaluate the associations of body composition, including percentage of lean and fat mass, with the percentage of mammographic density and mammographic dense area among pre- and postmenopausal Hispanic and non-Hispanic white women. DESIGN:: In this cross-sectional study, a total of 238 women aged 41 to 50 or 56 to 70 years were recruited from local mammography clinics and community health centers. Postmenopausal status was defined as an absence of any menstrual cycle within the past 12 calendar months or having a follicle-stimulating hormone level between 22 and 138 mIU/mL. The participants' most recent mammograms were used for the mammographic density analysis. Body composition was measured by dual-energy x-ray absorptiometry. The associations between the percentage of mammographic density or mammographic dense area and body composition components were analyzed using logistic regression. RESULTS:: Mammographic dense areas were similar in Hispanic and non-Hispanic white women. The percentage of mammographic density varied by ethnicity in premenopausal (P = 0.023), but not in postmenopausal women. Body composition, both higher lean mass and lower fat mass, was associated with a higher percentage of mammographic density (P < 0.05). Interestingly, a higher percentage of total body fat mass and a lower percentage of total body lean mass were correlated with larger breast dense areas in premenopausal women but with lower breast dense areas in postmenopausal women. These relationships between body composition and mammographic density measurements were not significantly affected by factors such as age, ethnicity, and body weight. CONCLUSIONS:: Body composition is highly correlated with mammographic density and should be examined as a possible confounding factor in studies involving mammographic density measurements and breast cancer risk.

 

Evid Rep Technol Assess (Full Rep). 2007 Aug;(158):1-235.

Effectiveness and safety of vitamin d in relation to bone health.

Cranney A, Horsley T, O'Donnell S, Weiler HA, Puil L, Ooi DS, Atkinson SA, Ward LM, Moher D, Hanley DA, Fang M, Yazdi F, Garritty C, Sampson M, Barrowman N, Tsertsvadze A, Mamaladze V.

OBJECTIVES: To review and synthesize the literature in the following areas: the association of specific circulating 25(OH)D concentrations with bone health outcomes in children, women of reproductive age, postmenopausal women and elderly men; the effect of dietary intakes (foods fortified with vitamin D and/or vitamin D supplementation) and sun exposure on serum 25(OH)D; the effect of vitamin D on bone mineral density (BMD) and fracture or fall risk; and the identification of potential harms of vitamin D above current reference intakes. DATA SOURCES: MEDLINE(R) (1966-June Week 3 2006); Embase (2002-2006 Week 25); CINAHL (1982-June Week 4, 2006); AMED (1985 to June 2006); Biological Abstracts (1990-February 2005); and the Cochrane Central Register of Controlled Trials (2nd Quarter 2006). REVIEW METHODS: Two independent reviewers completed a multi-level process of screening the literature to identify eligible studies (title and abstract, followed by full text review, and categorization of study design per key question). To minimize bias, study design was limited to randomized controlled trials (RCTs) wherever possible. Study criteria for question one were broadened to include observational studies due to a paucity of available RCTs, and question four was restricted to systematic reviews to limit scope. Data were abstracted in duplicate and study quality assessed. Differences in opinion were resolved through consensus or adjudication. If clinically relevant and statistically feasible, meta-analyses of RCTs on vitamin D supplementation and bone health outcomes were conducted, with exploration of heterogeneity. When meta-analysis was not feasible, a qualitative systematic review of eligible studies was conducted. RESULTS: 167 studies met our eligibility criteria (112 RCTs, 19 prospective cohorts, 30 case-controls and six before-after studies). The largest body of evidence on vitamin D status and bone health was in older adults with a lack of studies in premenopausal women and infants, children and adolescents. The quality of RCTs was highest in the vitamin D efficacy trials for prevention of falls and/or fractures in older adults. There was fair evidence of an association between low circulating 25(OH)D concentrations and established rickets. However, the specific 25(OH)D concentrations associated with rickets is uncertain, given the lack of studies in populations with dietary calcium intakes similar to North American diets and the different methods used to determine 25(OH)D concentrations. There was inconsistent evidence of an association of circulating 25(OH)D with bone mineral content in infants, and fair evidence that serum 25(OH)D is inversely associated with serum PTH. In adolescents, there was fair evidence for an association between 25(OH)D levels and changes in BMD. There were very few studies in pregnant and lactating women, and insufficient evidence for an association between serum 25(OH)D and changes in BMD during lactation, and fair evidence of an inverse correlation with PTH. In older adults, there was fair evidence that serum 25(OH)D is inversely associated with falls, fair evidence for a positive association with BMD, and inconsistent evidence for an association with fractures. The imprecision of 25(OH)D assays may have contributed to the variable thresholds of 25(OH)D below which the risk of fractures, falls or bone loss was increased. There was good evidence that intakes from vitamin D-fortified foods (11 RCTs) consistently increased serum 25(OH)D in both young and older adults. Eight randomized trials of ultraviolet (UV)-B radiation (artificial and solar exposure) were small and heterogeneous with respect to determination of the exact UV-B dose and 25(OH)D assay but there was a positive effect on serum 25(OH)D concentrations. It was not possible to determine how 25(OH)D levels varied by ethnicity, sunscreen use or latitude. Seventy-four trials examined the effect of vitamin D(3) or D(2) on 25(OH)D concentrations. Most trials used vitamin D(3), and the majority enrolled older adults. In three trials, there was a greater response of serum 25(OH)D concentrations to vitamin D(3) compared to vitamin D(2), which may have been due to more rapid clearance of vitamin D(2) in addition to other mechanisms. Meta-analysis of 16 trials of vitamin D(3) was consistent with a dose-response effect on serum 25(OH)D when comparing daily doses of <400 IU to doses >/= 400 IU. An exploratory analysis of the heterogeneity demonstrated a significant positive association comparable to an increase of 1 - 2 nmol/L in serum 25(OH)D for every 100 additional units of vitamin D although heterogeneity remained after adjusting for dose. Vitamin D(3) in combination with calcium results in small increases in BMD compared to placebo in older adults although quantitative synthesis was limited due to variable treatment durations and BMD sites. The evidence for fracture reduction with vitamin D supplementation was inconsistent across 15 trials. The combined results of trials using vitamin D(3) (700 - 800 IU daily) with calcium (500 - 1,200 mg) was consistent with a benefit on fractures although in a subgroup analysis by setting, benefit was primarily in elderly institutionalized women (fair evidence from two trials). There was inconsistent evidence across 14 RCTs of a benefit on fall risk. However, a subgroup analysis showed a benefit of vitamin D in postmenopausal women, and in trials that used vitamin D(3) plus calcium. In addition, there was a reduction in fall risk with vitamin D when six trials that adequately ascertained falls were combined. Limitations of the fall and fracture trials included poor compliance with vitamin D supplementation, incomplete assessment of vitamin D status and large losses to follow-up. We did not find any systematic reviews that addressed the question on the level of sunlight exposure that is sufficient to maintain serum 25(OH)D concentrations but minimizes risk of melanoma and non-melanoma skin cancer. There is little evidence from existing trials that vitamin D above current reference intakes is harmful. In most trials, reports of hypercalcemia and hypercalciuria were not associated with clinically relevant events. The Women's Health Initiative study did report a small increase in kidney stones in postmenopausal women aged 50 to 79 years whose daily vitamin D(3) intake was 400 IU (the reference intake for 50 to 70 years, and below the reference intake for > 70 years) combined with 1000 mg calcium. The increase in renal stones corresponded to 5.7 events per 10,000 person-years of exposure. The women in this trial had higher calcium intakes than is seen in most post-menopausal women. CONCLUSIONS: The results highlight the need for additional high quality studies in infants, children, premenopausal women, and diverse racial or ethnic groups. There was fair evidence from studies of an association between circulating 25(OH)D concentrations with some bone health outcomes (established rickets, PTH, falls, BMD). However, the evidence for an association was inconsistent for other outcomes (e.g., BMC in infants and fractures in adults). It was difficult to define specific thresholds of circulating 25(OH)D for optimal bone health due to the imprecision of different 25(OH)D assays. Standard reference preparations are needed so that serum 25(OH)D can be accurately and reliably measured, and validated. In most trials, the effects of vitamin D and calcium could not be separated. Vitamin D(3) (>700 IU/day) with calcium supplementation compared to placebo has a small beneficial effect on BMD, and reduces the risk of fractures and falls although benefit may be confined to specific subgroups. Vitamin D intake above current dietary reference intakes was not reported to be associated with an increased risk of adverse events. However, most trials of higher doses of vitamin D were not adequately designed to assess long-term harms.

 

Horm Metab Res. 2007 Dec 18 [Epub ahead of print]

Treatment of Subclinical Hypothyroidism Reduces Atherogenic Lipid Levels in a Placebo-controlled Double-blind Clinical Trial.

Teixeira PF, Reuters VS, Ferreira MM, Almeida CP, Reis FA, Melo BA, Buescu A, Costa AJ, Vaisman M.

Endocrinology Service of Clementino Fraga Filho University Hospital,  Federal University of Rio de Janeiro, Brazil.

Many studies have found clinical and metabolic alterations in subclinical hypothyroidism, however, there are disagreements about the benefits of levothyroxine therapy. The objective of the present study was to analyze the effects of 6 months of treatment on the lipid profile of patients with subclinical hypothyroidism. A randomized double blind, placebo-controlled clinical assay was conducted. Sixty patients were enrolled in stratified random allocation by TSH levels that generated similar groups in average: free thyroxine levels, lipid levels, age, clinical score, and sedentary. At 6 months, 18 patients in the levothyroxine and 20 in the placebo group were reevaluated and a fall in all atherogenic lipid variables was observed with treatment. The TC and LDL-c variations (-22.6+/-37.2 and -18.5+/-34.6 mg/dl, respectively) in the group that received LT4 were statistically different (p=0.023 and p=0.012) from those occurring in the placebo group (+7.3+/-37.1 and +14.7+/-40.6 mg/dl). Baseline characteristics associated with better improvement in the levels of TC and LDL-c were the presence of TPO-Ab, TSH levels >8.0 muUI/ml, Body Mass Index >/=25 kg/m (2), and the presence of menopause. We concluded that treatment with dose-adjusted levothyroxine reduced atherogenic lipid levels in some patients. Further studies to determine the effects of LT4 replacement in specific subgroups of SH patients are still necessary, especially in patients with TSH <8.0 muUI/ml.

 

 

Semana del 5 al 11 de Diciembre de 2007

 

Life Sci. 2007 Nov 7 [Epub ahead of print]

Mental stress induces sustained elevation of blood pressure and lipid peroxidation in postmenopausal women.

Morimoto K, Morikawa M, Kimura H, Ishii N, Takamata A, Hara Y, Uji M, Yoshida KI.

Department of Environmental Health, Faculty of Life Science and Human Technology, Nara Women's University, Kita-Uoya Nishi-machi, Nara 630-8506, Japan.

Mental stress is thought to underlie cardiovascular events, but there is information on oxidative stress induced by mental stress in association with cardiovascular responses in women. Using a sensitive assay for plasma 4-hydroxy-2-nonenal (HNE), as a marker for oxidative stress, we addressed the relation between pressor responses and oxidative stress induced by mental or physical stress in premenopausal and postmenopausal women. Healthy subjects (7 postmenopausal and 8 premenopausal women, in early and late follicular phases) were subjected to mental and physical stress evoked by a Color Word Test (CWT) and isometric handgrip, respectively. The CWT induced a rapid elevation of diastolic blood pressure (DBP), at a higher level in the postmenopausal than in the premenopausal women (p<0.01), and this higher DBP was sustained during the CWT and recovery (p<0.01). The CWT induced a significant elevation in plasma noradrenaline in premenopausal women in the early follicular phase and in postmenopausal women (p<0.05). Plasma nitric oxide metabolites were higher in postmenopausal than in the premenopausal women in the late follicular phase (p<0.05), but did not change during exposure to the two types of stress in either group. Plasma HNE was increased during recovery from the CWT, but not the handgrip, in postmenopausal women (2.4 times, p<0.05). There was a significant difference in the time course of the CWT-induced HNE response between the postmenopausal and premenopausal women (p<0.05). These findings suggest that mental, but not physical, stress causes sustained diastolic blood pressure elevation in postmenopausal women, accompanied by heightened oxidative stress.

 

Arterioscler Thromb Vasc Biol. 2007 Dec 6 [Epub ahead of print]

Time Since Menopause Influences the Acute and Chronic Effect of Estrogens on Endothelial Function.

Vitale C, Mercuro G, Cerquetani E, Marazzi G, Patrizi R, Volterrani M, Fini M, Collins P, Rosano GM.

Department of Internal Medicine, IRCCS San Raffaele, Roma, Italy.

Objetive: We evaluated whether time since menopause influences the acute and chronic effect of Estradiol (E) on vascular endothelial function. Methods and Results: We studied flow-mediated dilatation (FMD) in 134 postmenopausal women (PMW) before and after acute and chronic E administration. At baseline FMD was inversely associated to time from menopause (r=-0.67, P<0.001) and age (r=-0.43, P<0.05), in exogenous estrogen naïve but not in previous users. Acute and chronic E improved endothelial function in all women. E administration improved FMD more in women within 5 years since menopause than in those with more than 5 years since menopause (76% and 74% versus 45% and 48%, acute and chronic E, respectively; P<0.05). Among women with more than 5 years since menopause acute and chronic E increased FMD more in previous E users than in nonusers (59% and 63% versus 31% and 38%, acute and chronic E, respectively; P<0.01). Multivariate analysis showed that time from menopause was a predictor of impaired FMD and of its improvement after acute and chronic E. CONCLUSIONS: Time from menopause influences FMD in PMW. The acute and chronic effect of E on FMD is time dependent and is reduced by a longer time since menopause.

 

Maturitas. 2007 Dec 1 [Epub ahead of print]

Ultra low-dose hormone replacement therapy and bone protection in postmenopausal women.

Gambacciani M, Cappagli B, Ciaponi M, Pepe A, Vacca F, Genazzani AR.

Department of Obstetrics and Gynecology, Pisa University Hospital, Pisa, Italy.

OBJECTIVES: The aim of the present study was to evaluate the effects of low doses of hormone replacement therapy (HRT) in normal young postmenopausal women. METHODS: In an open trial healthy, non-obese postmenopausal women received for 2 years a low-dose continuous combined HRT (LD-HRT) containing 1mg estradiol+0.5mg norethisterone acetate each pill for 28 days, or 0.5mg of 17beta-estradiol and 0.25mg of norethisterone acetate (Ultra low dose, Ultra-LD-HRT) along with 1000mg of calcium per day. Control group consisted of women receiving only 1000mg of calcium per day, for 2 years. Menopausal symptoms were evaluated by the Green climacteric scale for the first 12 weeks of the study while bleeding profiles, bone mineral density (BMD) and bone turnover were assessed for 24 months. RESULTS: LD-HRT and Ultra-LD-HRT were effective in reducing menopausal clinical symptoms. In the control group, BMD significantly (P<0.05) decreased at the spine (-2.8+/-0.2%), and femoral neck (-2.8+/-0.7%). In LD-HRT treated group BMD showed a significant (P<0.05) increase at the spine (5.2+/-0.7%), and femoral neck (2.8+/-0.4%) after 24 months. In the Ultra-LD-HRT treated women spine and femoral neck BMD showed a significant (P<0.05) increase (2.0+/-0.3 and 1.8+/-0.3%, respectively) after 24 months. In these women treated with LD-HRT and Ultra-LD-HRT the BMD values were significantly (P<0.05) different from those measured in calcium-treated women. CONCLUSIONS: LD-HRT and Ultra-LD-HRT can alleviate subjective symptoms providing an effective protection against the postmenopausal decrease of BMD.

 

Int J Cardiol. 2007 Dec 4 [Epub ahead of print]

No added value of age at menopause and the lifetime cumulative number of menstrual cycles for cardiovascular risk prediction in postmenopausal women.

Atsma F, van der Schouw YT, Grobbee DE, Hoes AW, Bartelink ML.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.

BACKGROUND: The aim of the present study was to investigate the added value of age at menopause and the lifetime cumulative number of menstrual cycles in cardiovascular risk prediction in postmenopausal women. METHODS: This study included 971 women. The ankle-arm index was used as a proxy for cardiovascular morbidity and mortality. The ankle-arm index was calculated for each leg by dividing the highest ankle systolic blood pressure by the highest brachial systolic blood pressure. A cut-off value of 0.95 was used to differentiate between low and high risk women. Three cardiovascular risk models were constructed. In the initial model all classical predictors for cardiovascular disease were investigated. This model was then extended by age at menopause or the lifetime cumulative number of menstrual cycles to test their added value for cardiovascular risk prediction. Differences in discriminative power between the models were investigated by comparing the area under the receiver operating characteristic (ROC) curves. RESULTS: The mean age was 66.0 (+/-5.6) years. The 6 independent predictors for cardiovascular disease were age, systolic blood pressure, total to HDL cholesterol ratio, current smoking, glucose level, and body mass index >/=30 kg/m(2). The ROC area was 0.69 (0.64-0.73) and did not change when age at menopause or the lifetime cumulative number of menstrual cycles was added. CONCLUSIONS: The findings in this study among postmenopausal women did not support the view that age at menopause or a refined estimation of lifetime endogenous estrogen exposure would improve cardiovascular risk prediction as approximated by the ankle-arm index.

 

Appl Physiol Nutr Metab. 2007 Dec;32(6):1210-1.

Associations between abdominal adiposity, exercise, morbidity, and mortality.

Kuk JL.

School of Kinesiology and Health Studies, York University, Toronto, ON M3J 1P3

The increasing prevalence of abdominal obesity worldwide poses a serious public health problem and thus presents a target for research designed to improve the assessment or treatment of abdominal obesity. Specifically, the first study in this thesis investigated the influence of age and gender on visceral (VAT) and abdominal (ASAT) subcutaneous adipose tissue for a given waist circumference (WC) in 481 men and women varying widely in age and body mass index (BMI). Significant gender differences in VAT and ASAT for a given WC were observed; however, only the relationship between WC and VAT was substantially influenced by age. The second study examined whether the associations between VAT, ASAT, and the metabolic syndrome (MetS) were altered depending on the measurement methodology used to assess VAT and ASAT. The odds ratio (OR) for MetS was higher for total VAT volume (OR = 7.26), and for partial volumes at T12-L1 (OR = 7.46) and L1-L2 (OR = 8.77) compared with the classic L4-L5 (OR = 3.94) measurement. The OR for MetS was not substantially different among the ASAT measures (OR~2.6). Measurement site for VAT, but not ASAT, has a substantial influence on the magnitude of the association with MetS. The third study examined the independent associations between VAT, ASAT, liver fat, and all-cause mortality in 291 men (97 decedents and 194 controls, mortality follow-up of 2.2 +/- 1.3 y). In a model including VAT, ASAT, liver fat, age, and length of follow-up, only VAT (1.93 (1.15-3.23)) remained a significant predictor of mortality. We concluded that VAT is a strong, independent predictor of all-cause mortality in men. The purpose of the final study was to determine the effect of aerobic exercise dose (energy expenditure) on WC in sedentary, overweight or obese postmenopausal women (n = 424). The women were randomly assigned to a control group or one of three aerobic exercise groups that exercised at energy expenditures of 4, 8, or 12 kcal.kg body mass-1.week-1. On comparison with controls, there were significant reductions in WC in the exercise groups (~3 cm, p < 0.05), which were independent of weight loss. However, the amount of exercise performed was not associated with reductions in WC in a dose-dependent manner.

 

J Thromb Thrombolysis. 2007 Dec 4 [Epub ahead of print]

Assessment of hypercoagulability markers and lipid levels in postmenopausal women undergoing either oral or transdermal hormone replacement therapy.

Guimarães DA, das Graças Carvalho M, Cardoso J, de Oliveira Sousa M, Franco RM, de Almeida Franco H, Alvim TC, da Silva Teixeira G, Dusse LM, Fernandes AP.

Faculty of Pharmacy, Federal University of Minas Gerais, Av. Antonio Carlos, 6627, Belo Horizonte, Minas Gerais, CEP: 31270-901, Brazil, daniamgb@yahoo.com.br.

Background This study investigated the effect of either oral or transdermal hormone replacement therapy (HRT) on haemostatic, fibrinolytic and lipid profiles in a group of Brazilian women 3 months after beginning treatment by comparing these results with those obtained immediately before HRT. Methods Plasma levels of TAT, DDi, F1+2, PC, PS, AT, PAI-1 and serum lipids were determined in blood samples collected from 24 women undergoing oral HRT and from 11 women undergoing transdermal HRT. Results Significant increases in DDi and F1+2 plasma levels were observed after 3 months of oral HRT, while PS levels decreased. After transdermal HRT, a significant decrease was observed only for AT levels. Conclusion After 3 months of oral HRT and in the absence of major genetic and acquired risk factors, women displayed a predisposition for activation of blood coagulation, and an increased activity of the fibrinolytic system. Oral HRT seemed to be more effective in predisposing haemostatic changes as compared to transdermal.

 

Fertil Steril. 2007 Dec 3 [Epub ahead of print]

Increased insulin-like growth factor-1 after oophorectomy in postmenopausal women.

Fogle RH, Chang L, Patel SK, Stanczyk FZ, Paulson RJ.

University of Southern California Keck School of Medicine, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Los Angeles, California.

IGF-1 levels increased, and IGF-2 and IGFBP-3 levels remained unchanged, in postmenopausal women following oophorectomy. The increase in IGF-1 likely results from decreased ovarian steroidogenic precursors resulting from removal of the hormonally active ovary. This finding raises concerns, given the association between increased IGF-1 and elevated colon cancer risk, and adds to the literature suggesting a potential benefit from ovarian preservation.

 

Appl Physiol Nutr Metab. 2007 Dec;32(6):1089-1096.

Relationship between insulin sensitivity and the triglyceride-HDL-C ratio in overweight and obese postmenopausal women: a MONET study.

Karelis AD, Pasternyk SM, Messier L, St-Pierre DH, Lavoie JM, Garrel D, Rabasa-Lhoret R.

Department of Kinanthropology, Université du Québec à Montréal, Montreal, QC H2X 3R9, Canada.

The objective of this cross-sectional study was to examine the relationship between the triglyceride-HDL-cholesterol ratio (TG:HDL-C) and insulin sensitivity in overweight and obese sedentary postmenopausal women. The study population consisted of 131 non-diabetic overweight and obese sedentary postmenopausal women (age; 57.7 +/- 5.0 y; body mass index (BMI), 32.2 +/- 4.3 kg/m2). Subjects were characterized by dividing the entire cohort into tertiles based on the TG:HDL-C (T1 < 0.86 vs. T2= 0.86 to 1.35 vs. T3 > 1.35, respectively). We measured (i) insulin sensitivity (using the hyperinsulinenic-euglycemic clamp and homeostasis model assessment (HOMA)), (ii) body composition (using dual-energy X-ray absorptiometry), (iii) visceral fat (using computed tomography), (iv) plasma lipids, C-reactive protein, 2 h glucose concentration during an oral glucose tolerance test (2 h glucose), as well as fasting glucose and insulin, (v) peak oxygen consumption, and (vi) lower-body muscle strength (using weight training equipment). Significant correlations were observed between the TG:HDL-C and the hyperinsulinemic-euglycemic clamp (r = -0.45; p < 0.0001), as well as with HOMA (r = 0.42; p < 0.0001). Moreover, the TG:HDL-C significantly correlated with lean body mass, visceral fat, 2 h glucose, C-reactive protein, and muscle strength. Stepwise regression analysis showed that the TG:HDL-C explained 16.4% of the variation in glucose disposal in our cohort, which accounted for the greatest source of unique variance. Other independent predictors of glucose disposal were 2 h glucose (10.1%), C-reactive protein (CRP; 7.6%), and peak oxygen consumption (5.8%), collectively (including the TG:HDL-C) explaining 39.9% of the unique variance. In addition, the TG:HDL-C was the second predictor for HOMA, accounting for 11.7% of the variation. High levels of insulin sensitivity were associated with low levels of the TG:HDL-C. In addition, the TG:HDL-C was a predictor for glucose disposal rates and HOMA values in our cohort of overweight and obese postmenopausal women.

 

Osteoporos Int. 2007 Dec 6 [Epub ahead of print]

Wrist fracture as a predictor of future fractures in younger versus older postmenopausal women: results from the National Osteoporosis Risk Assessment (NORA).

Barrett-Connor E, Sajjan SG, Siris ES, Miller PD, Chen YT, Markson LE.

Department of Family and Preventive Medicine, University of California, San Diego, Stein Clinical Research Building, Room 349, 9500 Gilman Drive, Mail Code: 0607, La Jolla, CA, 92093-0607, USA, ebarrettconnor@ucsd.edu.

The short-term association between wrist-fracture history and future fracture has not been simultaneously compared between younger and older postmenopausal women. This 3-year follow-up study of 158,940 women showed a similar future fracture risk in younger and older women with wrist-fracture history. INTRODUCTION: We examined the association between prior wrist fracture and future osteoporosis-related fractures within 3 years in younger and older postmenopausal women. METHODS: In the National Osteoporosis Risk Assessment (NORA) study, 158,940 postmenopausal women, aged 50-98 (median 63) years, provided information on fracture history since age 45, and responded to follow-up surveys 1 or 3 years later when new fractures were queried. Cox regression models were used to obtain relative risk (RR) and 95% confidence interval (CI) estimates. RESULTS: Of the 158,940 participants, 8,665 reported a history of wrist fracture at baseline; 4,316 women reported at least one new fracture within three years. The RR for any subsequent clinical fracture, adjusted for covariates and baseline BMD T-score, was 2.4 (2.0, 2.9) for younger and 2.1 (1.9, 2.3) for older women. A prior wrist fracture increased the risk of a future wrist fracture about 3-fold and doubled the risk of any osteoporotic fracture. CONCLUSIONS: Prior wrist fracture strongly predicts three-year risk of any future osteoporotic fracture for older and younger postmenopausal women, independent of baseline BMD and common osteoporosis risk factors. More consideration should be given to evaluating and managing osteoporosis in younger and older women with a history of wrist fracture, independent of their BMD.

 

Gynecol Endocrinol. 2007 Oct;23 Suppl 1:32-41.

Progestins and breast cancer.

Pasqualini JR.

Hormones and Cancer Research Unit, Institut de Puériculture et de Périnatalogie, Paris, France.

Progestins exert their progestational activity by binding to the progesterone receptor (form A, the most active and form B, the less active) and may also interact with other steroid receptors (androgen, glucocorticoid, mineralocorticoid, estrogen). They can have important effects in other tissues besides the endometrium, including the breast, liver, bone and brain. The biological responses of progestins cover a very large domain: lipids, carbohydrates, proteins, water and electrolyte regulation, hemostasis, fibrinolysis, and cardiovascular and immmunological systems. At present, more than 200 progestin compounds have been synthesized, but the biological response could be different from one to another depending on their structure, metabolism, receptor affinity, experimental conditions, target tissue or cell line, as well as the biological response considered. There is substantial evidence that mammary cancer tissue contains all the enzymes responsible for the local biosynthesis of estradiol (E(2)) from circulating precursors. Two principal pathways are implicated in the final steps of E(2) formation in breast cancer tissue: the 'aromatase pathway', which transforms androgens into estrogens, and the 'sulfatase pathway', which converts estrone sulfate (E(1)S) into estrone (E(1)) via estrone sulfatase. The final step is the conversion of weak E(1) to the potent biologically active E(2) via reductive 17beta-hydroxysteroid dehydrogenase type 1 activity. It is also well established that steroid sulfotransferases, which convert estrogens into their sulfates, are present in breast cancer tissues. It has been demonstrated that various progestins (e.g. nomegestrol acetate, medrogestone, promegestone) as well as tibolone and their metabolites can block the enzymes involved in E(2) bioformation (sulfatase, 17beta-hydroxysteroid dehydrogenase) in breast cancer cells. These substances can also stimulate the sulfotransferase activity which converts estrogens into the biologically inactive sulfates. The action of progestins in breast cancer is very controversial; some studies indicate an increase in breast cancer incidence, others show no difference and still others a significant decrease. Progestin action can also be a function of combination with other molecules (e.g. estrogens). In order to clarify and better understand the response of progestins in breast cancer (incidence, mortality), as well as in hormone replacement therapy or endocrine dysfunction, new clinical trials are needed studying other progestins as a function of the dose and period of treatment.

 

Obstet Gynecol. 2007 Dec;110(6):1290-6.

Physical functioning and menopause States.

Sowers M, Tomey K, Jannausch M, Eyvazzadeh A, Nan B, Randolph J Jr.

Departments of Epidemiology, School of Public Health, Obstetrics/Gynecology, and Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan.

OBJECTIVE: To assess whether losses in physical functioning are related to the natural menopause, hysterectomy, or calendar time during midlife, after adjustment for body size and smoking. METHODS: A longitudinal assessment of physical functioning was conducted from 2000/01 through 2005/06 in a population-based sample of 544 women at midlife enrolled in the Michigan Bone Health and Metabolism Study. Longitudinal mixed models were used to relate menopausal status to measures of physical functioning. Perception of physical functioning was assessed with the Medical Outcomes Study Short-Form 36 questionnaire. Eight performance-based measures of physical functioning were also included. RESULTS: Women with hysterectomy (with or without estrogen from ovarian conservation or exogenous replacement) had reduced levels of functioning and greater rates of change in the 2-lb lift (P<.005), sit-to-stand (P<.01), timed stair climb (P<.01), timed walk (P<.01), velocity (P<.05), and perception of physical functioning (P<.01) compared with premenopausal and perimenopausal women after adjustment for time since baseline, body size, and smoking. Diminished functioning in postmenopausal women was observed in hand grip (P<.005), 2-lb lift (P<.05), sit-to-stand (P<.05), velocity (P<.05), and perceived physical functioning (P<.05). Based on regression analyses, there was greater loss in women with hysterectomy compared with natural menopause. Level of functioning among postmenopausal women with exogenous hormone replacement was similar to premenopausal women on eight of nine physical functioning measures. CONCLUSION: Hysterectomy, even with availability of an estrogen source, seems to be a "risk" state for diminishing physical function at midlife, and this may initiate a vulnerable stage for future compromised quality of life.

 

Fertil Steril. 2007 Nov 28 [Epub ahead of print]

Randomized, multicenter, double-blind, placebo-controlled trial to evaluate the efficacy and safety of synthetic conjugated estrogens B for the treatment of vulvovaginal atrophy in healthy postmenopausal women.

Simon JA, Reape KZ, Wininger S, Hait H.

Obstetrics and Gynecology, George Washington University School of Medicine and Health Sciences, Washington.

OBJECTIVE: To evaluate the safety and efficacy of synthetic conjugated estrogens B (SCE-B; 0.3 mg/d) for 12 weeks in the treatment of vulvovaginal atrophy in symptomatic, postmenopausal women. DESIGN: Prospective, randomized, multicenter, double-blind, placebo-controlled trial. SETTING: Forty-two participating sites in the United States. PATIENT(S): Postmenopausal women with at least one moderate to severe symptom of vaginal atrophy. INTERVENTION(S): Daily oral administration, in a randomized, placebo-controlled setting, of SCE-B (0.3 mg) or of placebo for 12 weeks. MAIN OUTCOME MEASURE(S): Mean changes in vaginal maturation index, percentage of parabasal and superficial cells, vaginal pH, and severity of the most bothersome symptom (MBS) between baseline and predetermined time points were assessed. Safety and tolerability were evaluated. RESULT(S): A total of 310 women (mean age, 58.6 y) were enrolled. Synthetic conjugated estrogens B yielded statistically significantly greater differences in vaginal maturation index and vaginal pH from baseline to the end of treatment. Vaginal dryness (44.4%) and pain during intercourse (30.2%) were the symptoms most commonly identified as the MBS. A statistically significant mean reduction in the severity of the MBS was noted for SCE-B. There were no clinically significant differences observed between the two groups for findings related to safety. CONCLUSION(S): Synthetic conjugated estrogens B (0.3 mg/d) was effective in treating vulvovaginal atrophy in symptomatic postmenopausal women. Significant improvement was seen in vaginal maturation index, vaginal pH, and severity of MBS from baseline to the end of treatment.

 

 

Semana del 28 de Noviembre al 4 de Diciembre de 2007

 

Neurology. 2007 Nov 13;69(20):1921-30.

Dietary patterns and risk of dementia: the Three-City cohort study.

Barberger-Gateau P, Raffaitin C, Letenneur L, Berr C, Tzourio C, Dartigues JF, Alpérovitch A.

INSERM, U593, University Victor Segalen Bordeaux , France. Pascale.Barberger-Gateau@isped.u-bordeaux2.fr

Dietary fatty acids and antioxidants may contribute to decrease dementia risk, but epidemiologic data remain controversial. The aim of our study was to analyze the relationship between dietary patterns and risk of dementia or Alzheimer disease (AD), adjusting for sociodemographic and vascular risk factors, and taking into account the ApoE genotype. Methods: A total of 8,085 nondemented participants aged 65 and over were included in the Three-City cohort study in Bordeaux, Dijon, and Montpellier (France) in 1999-2000 and had at least one re-examination over 4 years (rate of follow-up 89.1%). An independent committee of neurologists validated 281 incident cases of dementia (including 183 AD). RESULTS: Daily consumption of fruits and vegetables was associated with a decreased risk of all cause dementia [HR] 0.72, 95% CI 0.53 to 0.97) in fully adjusted models. Weekly consumption of fish was associated with a reduced risk of AD (HR 0.65, 95% CI 0.43 to 0.994) and all cause dementia but only among ApoE epsilon 4 noncarriers (HR 0.60, 95% CI 0.40 to 0.90). Regular use of omega-3 rich oils was associated with a decreased risk of borderline significance for all cause dementia (HR 0.46, 95% CI 0.19 to 1.11). Regular consumption of omega-6 rich oils not compensated by consumption of omega-3 rich oils or fish was associated with an increased risk of dementia (HR 2.12, 95% CI 1.30 to 3.46) among ApoE epsilon 4 noncarriers. Conclusion: Frequent consumption of fruits and vegetables, fish, and omega-3 rich oils may decrease the risk of dementia and AD, especially among ApoE epsilon 4 noncarriers.

 

Climacteric. 2007 Dec;10(6):508-26.

Management of cardiovascular risk in the perimenopausal women: a consensus statement of European cardiologists and gynecologists.

Collins P, Rosano G, Casey C, Daly C, Gambacciani M, Hadji P, Kaaja R, Mikkola T, Palacios S, Preston R, Simon T, Stevenson J, Stramba-Badiale M.

Cardiovascular risk is poorly managed in women, especially during the menopausal transition when susceptibility to cardiovascular events increases. Clear gender differences exist in the epidemiology, symptoms, diagnosis, progression, prognosis and management of cardiovascular risk. Key risk factors that need to be controlled in the perimenopausal woman are hypertension, dyslipidemia, obesity and other components of the metabolic syndrome, with the avoidance and careful control of diabetes. Hypertension is a particularly powerful risk factor and lowering of blood pressure is pivotal. Hormone replacement therapy is acknowledged as the gold standard for the alleviation of the distressing vasomotor symptoms of the menopause, but the findings of the Women's Health Initiative study generated concern for the detrimental effect on cardiovascular events. Thus, hormone replacement therapy cannot be recommended for the prevention of cardiovascular disease. Whether the findings of WHI in older postmenopausal women can be applied to younger perimenopausal women is unknown. It is increasingly recognized that hormone therapy is inappropriate for older postmenopausal women no longer displaying menopausal symptoms. Both gynecologists and cardiovascular physicians have an important role to play in identifying perimenopausal women at risk of cardiovascular morbidity and mortality, and should work as a team to identify and manage risk factors, such as hypertension.

 

Climacteric. 2007 Dec;10(6):480-90.

The influence of smoking on uterine bleeding during continuous and interrupted oral hormone therapy.

Bjarnason NH, Jorgensen HL, Byrjalsen I, Alexandersen P, Christiansen C.

To study the influence of smoking on uterine bleeding patterns during continuous and interrupted oral hormone therapy (HT). Methods Using a post-hoc strategy, we included five oral HT groups from three studies. The therapies consisted of continuous estrogen (estradiol, estradiol valerate or piperazine estrone sulfate) in combination with continuous progestogen (cyproterone acetate, gestodene or norethisterone acetate) or in combination with interrupted progestogen (norethisterone) given on days 4-6, 10-12, 16-18, 22-24 and 28-30. A total of 145 healthy postmenopausal women (54 smokers and 91 non-smokers), who had been followed for 2 years, were included in the analyses. Uterine bleeding data were collected from bleeding calendars. Results In general, smoking women experienced significantly less days with uterine bleeding per cycle than non-smoking women during continuous and interrupted HT (0.53 +/- 0.1 vs. 1.6 +/- 0.1; p < 0.001). Smoking women were also more likely than non-smoking women to be amenorrheic during these therapies (48.2% vs. 29.7%; p < 0.05). Finally, more smoking than non-smoking women attained amenorrhea during HT (94.4% vs. 76.9%p < 0.01). Conclusions In healthy postmenopausal women, smoking may reduce uterine bleeding during interrupted and continuous HT regimens containing a broad selection of estrogens and progestogens. Further study with appropriate stratification for smoking status is warranted.

 

Climacteric. 2007 Dec;10(6):466-70.

False alarm: postmenopausal hormone therapy and ovarian cancer.

Shapiro S.

Dpt of Family Medicine and Public Health, University of Cape Town Medical School, Cape Town, South Africa.

Background In a follow-up study of 948 576 women, based on respective relative risk (RR) estimates of 1.23 and 1.20 for incident and fatal ovarian cancer among current users of postmenopausal hormone therapy (HT), the Million Women Study investigators have estimated that, since 1991, HT has resulted in 1300 additional cases and 1000 deaths. Critique The association was almost entirely confined to hysterectomized women, some of whom would not have been at risk because their ovaries had been removed; the findings in that group were uninterpretable. Among non-hysterectomized women, the RR was 1.12 and compatible with chance.The response rate to a follow-up questionnaire was only 64%, and HT-exposed women who developed ovarian cancer may selectively have responded. The risk of ovarian cancer was no longer increased once women stopped using HT, an effect that was pathologically and clinically incompatible with causation. Symptoms of as yet undiagnosed ovarian cancer may have caused HT use, rather than the reverse. The histological classification of the tumors was not centrally adjudicated. A meta-analysis of nine studies of current HT use, for which the aggregated RR was 1.28, was acknowledged by the investigators to be defective. Only the findings among non-hysterectomized women were to some limited extent interpretable and, among them, there was virtually no evidence to suggest that current HT use increases the risk of ovarian cancer. It follows that the estimated numbers of additional cases of incident and fatal ovarian cancer that were attributed to HT use were spurious, and arbitrary extrapolation back to 1991, which was many years before the Million Women Study, had no scientific rationale.

 

Int J Equity Health. 2007 Nov 23;6(1):19 [Epub ahead of print]

The Oslo Health Study: Is bone mineral density higher in affluent areas?

Alver K, Sogaard AJ, Falch JA, Meyer HE.

Based on previously reported differences in fracture incidence in the socioeconomic less affluent Oslo East compared to the more privileged West, our aim was to study bone mineral density (BMD) in the same socioeconomic areas in Oslo. We also wanted to study whether possible associations were explained by socio-demographic factors, level of education or lifestyle factors. Methods: Distal forearm BMD was measured in random samples of the participants in The Oslo Health Study by single energy x-ray absorptiometry (SXA). 578 men and 702 women born in Norway in the age-groups 40/45, 60 and 75 years were included in the analyses. Socioeconomic regions, based on a social index dividing Oslo in two regions - East and West, were used. Results: Age-adjusted mean BMD in women living in the less affluent Eastern region was 0.405 g/cm2 and significantly lower than in West where BMD was 0.419 g/cm2. Similarly, the odds ratio of low BMD (Z-score<=-1) was 1.87 (95% CI: 1.22-2.87) in women in Oslo East compared to West. The same tendency, although not statistically significant, was also present in men. Multivariate analysis adjusted for education, marital status, body mass index, physical inactivity, use of alcohol and smoking, and in women also use of post menopausal hormone therapy and early onset of menopause, did hardly change the association. Additional adjustments for employment status, disability pension and physical activity at work for those below the age of retirement, gave similar results. Conclusion: We found differences in BMD in women between different socioeconomic regions in Oslo that correspond to previously found differences in fracture rates. The association in men was not statistically significant. The differences were not explained by socio-demographic factors, level of education or lifestyle factors.

 

Arch Intern Med. 2007 Nov 26;167(21):2329-36.

Low bone mass in premenopausal women with depression.

Eskandari F, Martinez PE, Torvik S, Phillips TM, Sternberg EM, Mistry S, Ronsaville D, Wesley R, et al

MHSc, Building 10, Clinical Research Center, Room 6-3940, Bethesda. cizzag@intra.niddk.nih.gov.

An increased prevalence of low bone mineral density (BMD) has been reported in patients with major depressive disorder (MDD), mostly women. Methods: Study recruitment was conducted from July 1, 2001, to February 29, 2003. We report baseline BMD measurements in 89 premenopausal women with MDD and 44 healthy control women enrolled in a prospective study of bone turnover. The BMD was measured by dual-energy x-ray absorptiometry at the spine, hip, and forearm. Mean hourly levels of plasma 24-hour cytokines, 24-hour urinary free cortisol, and catecholamine excretion were measured in a subset of women. We defined MDD according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). Results: The prevalence of low BMD, defined as a T score of less than -1, was greater in women with MDD vs controls at the femoral neck (17% vs 2%; P = .02) and total hip (15% vs 2%; P = .03) and tended to be greater at the lumbar spine (20% vs 9%; P = .14). The mean +/- SD BMD, expressed as grams per square centimeters, was lower in women with MDD at the femoral neck (0.849 +/- 0.121 vs 0.866 +/- 0.094; P = .05) and at the lumbar spine (1.024 +/- 0.117 vs 1.043 +/- 0.092; P = .05) and tended to be lower at the radius (0.696 +/- 0.049 vs 0.710 +/- 0.055; P = .07). Women with MDD had increased mean levels of 24-hour proinflammatory cytokines and decreased levels of anti-inflammatory cytokines. Conclusions: Low BMD is more prevalent in premenopausal women with MDD. The BMD deficits are of clinical significance and comparable in magnitude to those resulting from established risk factors for osteoporosis, such as smoking and reduced calcium intake. The possible contribution of immune or inflammatory imbalance to low BMD in premenopausal women with MDD remains to be clarified.

 

Climacteric. 2007 Dec;10(6):448-65.

Influence of menopause on mood: a systematic review of cohort studies.

Vesco KK, Haney EM, Humphrey L, Fu R, Nelson HD.

Oregon Evidence-based Practice Center, Oregon Health & Science University, Portland.

Objective This systematic evidence review evaluates the independent influence of the menopausal transition on mood including depression, anxiety, and other psychological symptoms. Methods Community-based, prospective cohort studies of mid-life women transitioning through menopause that assessed at least one mood symptom on two or more occasions were identified by searches of MEDLINE (1966-2007) and PsycINFO (1974-2007) databases. Articles were selected based on predetermined inclusion and exclusion criteria. Each study was quality-rated by three authors; poor quality studies were excluded. Results Nine studies met inclusion criteria. They varied broadly in design, outcome measures, statistical methodology, and in consideration of and adjustment for important confounders. Five found no association between the menopausal transition and depression, negative mood, major depressive disorder, other psychological symptoms, and general mental health. Three found that women entering or completing the menopausal transition were more likely than premenopausal women to be depressed. One found that well-being increased from the early to late menopausal transition. Conclusion There is no demonstrated pattern of an adverse independent influence of the menopausal transition on mood symptoms in mid-life women. However, the available studies are too methodologically diverse to be definitive.

 

Curr Med Res Opin. 2007 Nov 28 [Epub ahead of print]

Ibandronate and the risk of non-vertebral and clinical fractures in women with postmenopausal osteoporosis: results of a meta-analysis of phase III studies.

Harris ST, Blumentals WA, Miller PD.

The marketed doses of ibandronate, 150 mg once-monthly oral and 3 mg quarterly intravenous (IV) injection, produce greater increases in lumbar spine bone mineral density than treatment with the 2.5 mg oral daily dose. This meta-analysis assessed whether these doses also reduce fracture risk relative to placebo.Study design and methods: Individual patient data from the intent-to-treat populations of the BONE, IV fracture prevention, MOBILE, and DIVA studies were grouped into three dose levels based on annual cumulative exposure (ACE), defined as the annual dose (mg) x bioavailability (0.6%, oral; 100%, IV) or placebo. Six key non-vertebral fractures (NVFs) (clavicle, humerus, wrist, pelvis, hip, and leg), all NVFs, and all clinical fractures were examined. Results: This meta-analysis included 8710 patients. Cox proportional-hazards models estimated the adjusted relative risk (RR) for fracture with ibandronate versus placebo, and time to fracture was compared using log-rank tests. The high-dose group (ACE >/= 10.8 mg) showed significant reductions in the adjusted RR of key NVFs (34.4%, p=0.032), all NVFs (29.9%, p = 0.041), and clinical fractures (28.8%, p=0.010) relative to placebo. The high-dose group also had significantly longer time to fracture versus placebo for key NVFs (p = 0.031), all NVFs (p=0.025), and clinical fractures (p = 0.002). Study limitations included: not all studies were placebo-controlled; a limited number of baseline characteristics were available for multivariate analyses. Conclusion: Ibandronate at dose levels of ACE >/= 10.8 mg, which includes the marketed 150 mg once-monthly oral and 3 mg quarterly IV injection regimens, may provide significant non-vertebral and clinical fracture efficacy.