Selección de Resúmenes de Menopausia

Noviembre de 2008

Juan Enrique Blümel. Departamento Medicina Sur. Universidad de Chile

 

Semana del 12 al 18 de Noviembre 2008

 

 Climacteric. 2008 Nov 10:1-10. [Epub ahead of print]

Effect of endogenous estradiol levels on bone resorption and bone mineral density in healthy postmenopausal women: a prospective study.

Mastaglia SR, Bagur A, Royer M, Yankelevich D, Sayegh F, Oliveri B.

Seccion Osteopatias Medicas, Hospital de Clinicas, Universidad de Buenos Aires.

Objective To investigate the effect of endogenous estrogens on bone mineral density (BMD) and bone markers in postmenopausal women over 24 months. Methods Fifty out of 99 postmenopausal women seen previously were re-assessed after 24 months. Levels of BMD, bone markers, serum estradiol (E(2)) and total testosterone were determined. Results BMD decreased in the femoral neck ( approximately 2%) (p < 0.008), but remained stable in the other skeletal areas; E(2) and serum Crosslaps (sCTX) decreased by 34% (p < 0.001) and 21% (p < 0.003), respectively. Women aged </= 65 years exhibited decreased BMD only in the femoral neck (2%, p < 0.01), without changes in bone markers. Women aged > 65 years exhibited a decrease in sCTX levels and stable BMD values at all skeletal sites. E(2) levels decreased similarly in both groups ( approximately 35%). Women with baseline E(2) levels >/= 10 pg/ml showed stable BMD in spite of their E(2) levels decreasing by 42% (p < 0.001); sCTX decreased by 21% (p < 0.01). Women with baseline E(2) levels < 10 pg/ml showed a 2% decrease (p < 0.001) in femoral neck BMD and a 19% decrease (p < 0.002) in E(2) levels, without changes in bone markers. Conclusion Although endogenous E(2) decreased to around 7 pg/ml in these menopausal women, this level would seem to be sufficient to maintain BMD in almost all skeletal areas, and to be more effective in older women.

 

Menopause. 2008 Nov 7. [Epub ahead of print]

Frequency and severity of hot flashes and sleep disturbance in postmenopausal women with hot flashes.

Ensrud KE, Stone KL, Blackwell TL, Sawaya GF, Tagliaferri M, Diem SJ, Grady D.

Veterans Affairs Medical Center, Minneapolis, MN; USA.

OBJECTIVE:: To determine whether greater frequency and severity of hot flashes are independently associated with insomnia symptoms and objective measures of disrupted sleep among healthy postmenopausal women with hot flashes. DESIGN:: A baseline cross-sectional analysis of a multicenter, randomized trial in 217 healthy postmenopausal women aged 40 to 60 years with hot flashes was conducted. Hot flash frequency and severity were recorded in a daily diary; frequency of moderate to severe hot flashes was the primary measure. Insomnia symptoms were assessed with the Insomnia Severity Index (ISI). Hot flash frequency and severity and objective parameters of sleep-wake patterns (using a wrist actigraph) were concurrently measured over an average of seven consecutive 24-hour periods in a subcohort of 112 women. RESULTS:: The mean age of participants was 54 years, and 80% were white; 33% had an ISI score greater than 14, consistent with at least moderate insomnia. In multivariable analysis, the mean ISI score showed a stepwise increase in magnitude with higher frequency of moderate to severe hot flashes (adjusted mean ISI score, 9.5, 11.4, 11.9, and 13.0 for quartiles 1-4, respectively; P for trend = 0.002). Higher frequency of moderate to severe hot flashes was also independently associated in a graded manner with greater nighttime wakefulness (P for trend = 0.028) and a higher number of long wake episodes (P for trend = 0.008) but was not related to sleep efficiency, total sleep time, or sleep latency. CONCLUSIONS:: Among healthy postmenopausal women with hot flashes, frequency of moderate to severe hot flashes was independently associated in a graded manner with severity of insomnia symptoms and objective measures of nighttime wakefulness and sleep fragmentation.

 

J Natl Cancer Inst. 2008 Nov 11. [Epub ahead of print]

Calcium Plus Vitamin D Supplementation and the Risk of Breast Cancer.

Chlebowski RT, Johnson KC, Kooperberg C, Pettinger M, et al; the Women's Health Initiative Investigators.

Background Although some observational studies have associated higher calcium intake and especially higher vitamin D intake and 25-hydroxyvitamin D levels with lower breast cancer risk, no randomized trial has evaluated these relationships. Methods Postmenopausal women (N = 36 282) who were enrolled in a Women's Health Initiative clinical trial were randomly assigned to 1000 mg of elemental calcium with 400 IU of vitamin D(3) daily or placebo for a mean of 7.0 years to determine the effects of supplement use on incidence of hip fracture. Mammograms and breast exams were serially conducted. Invasive breast cancer was a secondary outcome. Baseline serum 25-hydroxyvitamin D levels were assessed in a nested case-control study of 1067 case patients and 1067 control subjects. A Cox proportional hazards model was used to estimate the risk of breast cancer associated with random assignment to calcium with vitamin D(3). Associations between 25-hydroxyvitamin D serum levels and total vitamin D intake, body mass index (BMI), recreational physical activity, and breast cancer risks were evaluated using logistic regression models. Statistical tests were two-sided. Results Invasive breast cancer incidence was similar in the two groups (528 supplement vs 546 placebo; hazard ratio = 0.96; 95% confidence interval = 0.85 to 1.09). In the nested case-control study, no effect of supplement group assignment on breast cancer risk was seen. Baseline 25-hydroxyvitamin D levels were modestly correlated with total vitamin D intake (diet and supplements) (r = 0.19, P < .001) and were higher among women with lower BMI and higher recreational physical activity (both P < .001). Baseline 25-hydroxyvitamin D levels were not associated with breast cancer risk in analyses that were adjusted for BMI and physical activity. Conclusions Calcium and vitamin D supplementation did not reduce invasive breast cancer incidence in postmenopausal women. In addition, 25-hydroxyvitamin D levels were not associated with subsequent breast cancer risk. These findings do not support a relationship between total vitamin D intake and 25-hydroxyvitamin D levels with breast cancer risk.

 

Arch Intern Med. 2008 Nov 10;168(20):2261-7

10-year probability of recurrent fractures following wrist and other osteoporotic fractures in a large clinical cohort: an analysis from the Manitoba Bone Density Program.

Hodsman AB, Leslie WD, Tsang JF, Gamble GD.

Osteoporosis Program, Department of Medicine, University of Western Ontario, London, Ontario, Canada.

BACKGROUND: Wrist fractures are the most prevalent type of fracture occurring in postmenopausal women. We sought to contrast the probability of recurrent osteoporotic fractures after a primary wrist fracture with other important primary fracture sites. METHODS: A historical cohort study comprising 21,432 women 45 years or older referred for bone mineral density (BMD) testing. Longitudinal health service records were assessed for the presence of fracture codes before and after BMD testing (359,737 person-years of observation). RESULTS: A total of 2652 women (12.4%) experienced a primary fracture (wrist, vertebra, humerus, hip) prior to BMD testing, of which wrist fractures were the largest single group (1225 [46.2%]). The adjusted hazard ratio (HR) for recurrent osteoporotic fracture following a primary wrist fracture (HR, 1.58; 95% confidence interval [CI], 1.29-1.93) was lower than for other primary fractures (HR, 2.66; 95% CI, 2.30-3.08). Primary wrist fractures were not significantly associated with subsequent hip fractures (adjusted HR, 1.29; 95% CI, 0.88-1.89), whereas other primary fracture sites were individually and collectively significant predictors of future hip fractures (HR, 1.72; 95% CI, 1.31-2.26). The 10-year probability of any recurrent fracture after a primary wrist fracture was 14.2% (95% CI, 11.9%-16.5%), which was significantly less than for other primary fractures (spine, 25.7%; hip, 24.9%; humerus, 23.7%; P < .001 for all comparisons vs wrist) but greater than in those without prior fractures (10.8%; P < .001). The relationship between BMD and fracture risk was much stronger after a primary wrist fracture (HR, 2.20 per standard deviation; 95% CI, 1.70-2.80) than after other primary osteoporotic fractures (HR, 1.21; 95% CI, 1.05-1.40), reflecting the dominance of the other fracture information over BMD. CONCLUSIONS: Wrist fractures are the most common of the clinical osteoporotic fractures in patients referred for BMD testing. However, the risk of recurrent fractures in the 10 years following a wrist fracture is substantially lower than that following other osteoporotic fractures, although it remains significantly higher than for those who have yet to experience a fracture.

 

Arch Intern Med. 2008 Nov 10;168(20):2245-53

Inflammatory, lipid, thrombotic, and genetic markers of coronary heart disease risk in the women's health initiative trials of hormone therapy.

Rossouw JE, Cushman M, Greenland P, Lloyd-Jones DM, Bray P, et al. Women's Health Initiative Branch.

BACKGROUND: Clinical trials of postmenopausal hormone therapy (HT) have shown increased risk of coronary heart disease (CHD) in the first few years after initiation of therapy and no overall benefit. METHODS: This nested case-control study evaluates a range of inflammatory, lipid, thrombotic, and genetic markers for their association with CHD in the 4 years after randomization and assesses whether any of these markers modified or mediated the initially increased risk associated with HT in postmenopausal women aged 50 to 79 years at baseline. Conjugated equine estrogens, 0.625 mg/d, or placebo was given to 10 739 hysterectomized women, and the same estrogen plus medroxyprogesterone acetate, 2.5 mg/d, was given to 16 608 women with an intact uterus. RESULTS: In multivariate-adjusted analyses of 359 cases and 820 controls in the combined trials, baseline levels of 12 of the 23 biomarkers studied were associated with CHD events: interleukin 6, matrix metalloproteinase 9, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, triglycerides, D-dimer, factor VIII, von Willebrand factor, leukocyte count, homocysteine, and fasting insulin. Biomarkers tended to be more strongly associated with CHD in the initial 2 years after randomization. The genetic polymorphism glycoprotein IIIa leu33pro was significantly associated with CHD. Baseline low-density lipoprotein cholesterol interacted significantly with HT so that women with higher levels were at higher risk for CHD when given HT (P = .03 for interaction). The levels of several biomarkers were changed by HT, but these changes did not seem to be associated with future CHD events. CONCLUSIONS: Several thrombotic, inflammatory, and lipid biomarkers were associated with CHD events in postmenopausal women, but only low-density lipoprotein cholesterol modified the effect of HT. Further research is needed to identify the mechanisms by which HT increases the risk of CHD.

 

Am J Clin Nutr. 2008 Nov;88(5):1304-12

Dietary fat and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition.

Sieri S, Krogh V, Ferrari P, Berrino F, Pala V, Thiébaut AC, Tjřnneland A, Olsen A, Overvad K, et al

Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

BACKGROUND: Epidemiologic studies have produced conflicting results with respect to an association of dietary fat with breast cancer. OBJECTIVE: We aimed to investigate the association between fat consumption and breast cancer. DESIGN: We prospectively investigated fat consumption in a large (n = 319,826), geographically and culturally heterogeneous cohort of European women enrolled in the European Prospective Investigation into Cancer and Nutrition who completed a dietary questionnaire. After a mean of 8.8 y of follow-up, 7119 women developed breast cancer. Cox proportional hazard models, stratified by age and center and adjusted for energy intake and confounders, were used to estimate hazard ratios (HRs) for breast cancer. RESULTS: An association between high saturated fat intake and greater breast cancer risk was found [HR = 1.13 (95% CI: 1.00, 1.27; P for trend = 0.038) for the highest quintile of saturated fat intake compared with the lowest quintile: 1.02 (1.00, 1.04) for a 20% increase in saturated fat consumption (continuous variable)]. No significant association of breast cancer with total, monounsaturated, or polyunsaturated fat was found, although trends were for a direct association of risk with monounsaturated fat and an inverse association with polyunsaturated fat. In menopausal women, the positive association with saturated fat was confined to nonusers of hormone therapy at baseline [1.21 (0.99, 1.48) for the highest quintile compared with the lowest quintile; P for trend = 0.044; and 1.03 (1.00, 1.07) for a 20% increase in saturated fat as a continuous variable]. CONCLUSIONS: Evidence indicates a weak positive association between saturated fat intake and breast cancer risk. This association was more pronounced for postmenopausal women who never used hormone therapy.

 

Maturitas. 2008 Nov 7. [Epub ahead of print]

Hormone replacement therapy use and the risk of stroke.

Renoux C, Dell'aniello S, Garbe E, Suissa S.

McGill Pharmacoepidemiology Research Unit, Jewish General Hospital, McGill University, Montreal. Ca

OBJECTIVES: Randomised trials reported an increase risk of stroke with an estrogen plus progestogen formulation of hormone replacement therapy (HRT). A recent trial also reported an increased risk with tibolone, a selective tissue estrogenic activity regulator. METHODS: We used the General Practice Research Database to conduct a case-control study within a cohort of women aged 50-79 between January 1987 and October 2006, without history of stroke prior to cohort entry. We identified all cases of stroke occurring during the study period and selected up to four controls matched to each case on age, general practice and year of start in the practice. Information on HRT use during the year preceding the index date was obtained. Conditional logistic regression was used to estimate the rate ratios of stroke associated with current use of the different HRTs. RESULTS: The cohort included 870,286 women, of whom 15,710 experienced a stroke during follow-up and were matched to 59,958 controls. The adjusted rate ratio of stroke associated with current use of tibolone relative to non-use of HRT was 1.08 (95% CI: 0.82-1.44). The rate ratios with current use of estrogens alone and estrogen plus progestogen were 1.26 (95% CI: 1.10-1.45) and 1.19 (95% CI: 1.05-1.36) respectively. CONCLUSIONS: We found no evidence of an elevated risk of stroke associated with the use of tibolone, although the low number of subjects using tibolone does not permit to rule out a small risk. The small elevated risk of stroke with estrogens or estrogens plus progestogen is consistent with that reported in randomised trials.

 

Maturitas. 2008 Nov 7. [Epub ahead of print]

Postmenopausal hormone drugs and breast and colon cancer: Nordic countries 1995-2005.

Hemminki E, Kyyrönen P, Pukkala E.

National Research and Development Centre for Welfare and Health (STAKES), Helsinki, Finland.

OBJECTIVES: The purpose of this study was to utilize the variation in the level and timing of the change in postmenopausal hormone therapy (HT) use between the Nordic countries to assess the population-level impact of decline in HT use on the breast and colon cancer incidences. METHODS: Nationwide HT-sales data in defined daily doses (DDDs) per 1000 inhabitant in 1995-2005 in Finland, Iceland, Norway and Sweden were obtained from drug control authorities. Breast and colon cancer incidence data by 5-year age-groups were obtained from the National Cancer Registers. By time series analysis we estimated in each age-group and country how much a change in HT-sales changes cancer incidence. RESULTS: The decline of HT-sales varied; the decline from the highest sales was 61% in Sweden, 51% in Norway, 43% in Iceland and 25% in Finland. With the exception of Finland, the breast cancer incidence increased from 1995 to the year following the year with maximum HT-sales and decreased after that year. In the model combining countries and years, changes in HT-sales predicted the change in breast cancer incidence, an average 7% for each 10 DDD units of HT-sales. No clear association between HT-sales and colon cancer incidence was found. CONCLUSIONS: The time and country specific data suggest, that on the population level, a notable drop from high level of HT use somewhat decreases breast cancer incidence or breaks its increasing trends. The suggested protective effect of HT for colon cancer was not seen.

 

Climacteric. 2008;11(6):498-508.

Low- and standard-estrogen dosage in oral therapy: dose-dependent effects on insulin and lipid metabolism in healthy postmenopausal women.

Villa P, Sagnella F, Perri C, Suriano R, Costantini B, Macrí F, Ricciardi L, Lanzone A.

Department of Obstetrics and Gynecology, Universitŕ Cattolica del Sacro Cuore, Rome, Italy.

OBJECTIVE: To evaluate the influences of different doses of daily oral unopposed 17beta-estradiol compared with placebo, both on glucose tolerance and lipid metabolism in healthy postmenopausal women. PATIENTS AND METHODS: Forty-eight normoinsulinemic postmenopausal women were enrolled in the study. Patients were assigned to receive randomly 1 mg (group A) or 2 mg (group B) of oral micronized estradiol therapy daily or to the placebo (group C), for 12 weeks. RESULTS: The low-dose estradiol treatment determined an improvement of the peripheral insulin sensitivity, made evident by a significant increase both in the metabolic index and oral glucose insulin sensitivity index (p < 0.01 and p < 0.05, respectively) as well as a decrease in the homeostasis model assessment-estimated insulin resistance (p < 0.01). Conversely, in the standard-dose group, the metabolic index significantly decreased (p < 0.05), showing a slight deterioration in insulin sensitivity. For lipid metabolism, the 1 mg dose showed a neutral effect, while 2 mg had a beneficial effect on low density lipoprotein cholesterol, but caused an increase in triglycerides (p < 0.01 and p < 0.05, respectively). CONCLUSIONS: The oral low dose of unopposed estradiol therapy had a favorable effect on glycoinsulinemic metabolism in healthy postmenopausal women; however, the standard dose caused a slight but significant deterioration in insulin sensitivity.

 

Climacteric. 2008;11(6):509-17

Androgens in relationship to cardiovascular risk factors in the menopausal transition.

Mesch VR, Siseles NO, Maidana PN, Boero LE, Sayegh F, Prada M, Royer M, Schreier L, et al.

Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.

OBJECTIVE: To establish the relationship between androgens and cardiovascular disease (CVD) risk factors in the menopausal transition. METHODS: A total of 124 women were divided into four groups: 29 premenopausal (PreM), 35 women in the menopausal transition still menstruating (MTM), 29 women in the menopausal transition with 3-6 months amenorrhea (MTA), and 31 postmenopausal women (PostM). Levels of triglycerides, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, glucose and insulin were assayed in all samples and waist circumference was measured. In a subgroup of 83 women (19 PreM, 21 MTM, 28 MTA and 15 PostM), levels of total testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS) and estradiol were determined. The free androgen index, Homeostasis Model Assessment (HOMA) index, Quantitative Insulin Sensitivity Check Index (QUICKI) and McAuley index, estradiol/total testosterone and triglyceride/HDL cholesterol ratios were calculated. RESULTS: Androstenedione was higher in MTA vs. PostM women (p < 0.05); DHEAS was higher in PreM women vs. the other three groups (p < 0.05). Sex hormone binding globulin (SHBG) in MTM women was higher than in MTA women (p < 0.05); the free androgen index was lower in MTM women than in MTA and PostM women. SHBG and the free androgen index showed negative and positive correlations, respectively with waist circumference, insulin resistance and lipids. In a multiple regression analysis, considering waist circumference, neither free androgen index nor SHBG showed significant differences between groups. The waist circumference correlated only with SHBG (p = 0.022) and correlations between SHBG and insulin resistance markers continued to be significant, but relationships between SHBG and lipoproteins and all correlations found with free androgen index were lost. CONCLUSIONS: An increment in the androgenic milieu that correlates with abdominal fat, insulin resistance and atherogenic lipoproteins becomes evident after the menopausal transition and suggests that evaluation of cardiovascular disease risk in these women should include androgens, considering that abdominal obesity is one of the main determinants of the relationship between androgenic parameters and cardiovascular risk factors.

 

Climacteric. 2008;11(6):489-97

The effect of continuous combined conjugated equine estrogen plus medroxyprogesterone acetate and tibolone on cardiovascular metabolic risk factors.

Skouby SO, Sidelmann JJ, Nilas L, Gram J, Jespersen J.

Department of Obstetrics and Gynecology, Herlev Hospital, University of Copenhagen, Denmark.

OBJECTIVES: Hormone treatment (HT) after the menopause affects lipid and carbohydrate metabolism and inflammation and may modify risk factors relevant for the clinical expression of the metabolic syndrome and cardiovascular disease. Tibolone has pharmacodynamic properties different from other hormone preparations. Here, we compare the effect of combined HT and tibolone on metabolic risk markers for the development of cardiovascular disease. METHODS: Postmenopausal women were randomly assigned to 1.25 or 2.5 mg/day of tibolone or oral continuous combined conjugated equine estrogen plus medroxyprogesterone acetate (CEE/MPA). Cardiovascular risk factors were determined at baseline and after 12 months of treatment. RESULTS: Body mass index and blood pressure were unaffected by the HT. HOMA-IR decreased in the CEE/MPA group (3.69 vs. 3.38; p = 0.02). Treatment with tibolone increased tissue-type plasminogen activator activity (0.87 IU/ml vs. 1.21 IU/ml; p = 0.005) and C-reactive protein (0.83 mg/l vs. 1.88 mg/l; p < 0.001), and decreased plasminogen activator inhibitor activity (6.9 IU/ml vs. 2.0 IU/ml; p < 0.001) and triglycerides (0.99 vs. 0.87 mmol/l; p = 0.004). Both treatments decreased total cholesterol significantly. CONCLUSIONS: CEE/MPA and tibolone have comparable effects on most metabolic risk factors investigated. The effect of tibolone on fibrinolysis and triglycerides suggests that tibolone has a favorable pharmacological profile on these risk factors when compared to CEE/MPA.

 

 

Semana del 4 al 11 de Noviembre de 2008

 

N Engl J Med. 2008 Nov 6;359(19):2005-17

Testosterone for low libido in postmenopausal women not taking estrogen.

Davis SR, Moreau M, Kroll R, Bouchard C, Panay N, Gass M, Braunstein GD, Hirschberg AL, et al. APHRODITE Study Team.

BACKGROUND: The efficacy and safety of testosterone treatment for hypoactive sexual desire disorder in postmenopausal women not receiving estrogen therapy are unknown. METHODS: We conducted a double-blind, placebo-controlled, 52-week trial in which 814 women with hypoactive sexual desire disorder were randomly assigned to receive a patch delivering 150 or 300 microg of testosterone per day or placebo. Efficacy was measured to week 24; safety was evaluated over a period of 52 weeks, with a subgroup of participants followed for an additional year. The primary end point was the change from baseline to week 24 in the 4-week frequency of satisfying sexual episodes. RESULTS: At 24 weeks, the increase in the 4-week frequency of satisfying sexual episodes was significantly greater in the group receiving 300 microg of testosterone per day than in the placebo group (an increase of 2.1 episodes vs. 0.7, P<0.001) but not in the group receiving 150 microg per day (1.2 episodes, P=0.11). As compared with placebo, both doses of testosterone were associated with significant increases in desire (300 microg per day, P<0.001; 150 microg per day, P=0.04) and decreases in distress (300 microg per day, P<0.001; 150 microg per day, P=0.04). The rate of androgenic adverse events - primarily unwanted hair growth - was higher in the group receiving 300 microg of testosterone per day than in the placebo group (30.0% vs. 23.1%). Breast cancer was diagnosed in four women who received testosterone (as compared with none who received placebo); one of the four received the diagnosis in the first 4 months of the study period, and one, in retrospect, had symptoms before undergoing randomization. CONCLUSIONS: In postmenopausal women not receiving estrogen therapy, treatment with a patch delivering 300 microg of testosterone per day resulted in a modest but meaningful improvement in sexual function. The long-term effects of testosterone, including effects on the breast, remain uncertain.

 

Climacteric. 2008 Oct 31:1-8. [Epub ahead of print

Effects of drospirenone on cardiovascular markers in human aortic endothelial cells.

Seeger H, Wallwiener D, Mueck AO.

University Women's Hospital, Section of Endocrinology and Menopause, Tuebingen, Germany.

Objectives The effect of the new progestogen drospirenone on biochemical markers in terms of cardiovascular effects was investigated in the presence and absence of aldosterone and compared to progesterone and the progestogens medroxyprogesterone acetate (MPA) and promegestone (R5020), and the antimineralocorticoid spironolactone. Methods Human female aortic endothelial cells were used for the experiments. The progestogens were tested alone at 0.1 and 10 mumol/l and in combination with aldosterone at a concentration of 10 mumol/l. The adhesion molecule E-selectin, the chemokine monocyte attracting protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1) were chosen as markers. Results In combination with aldosterone, spironolactone, drospirenone, progesterone and R5020 were able to inhibit the aldosterone-induced increase in MCP-1 concentration, the effect being greatest for spironolactone. In contrast, MPA did not show any significant effect. For E-selectin, similar results were found; however, R5020 and MPA were not able to act antagonistically. Spironolactone, drospirenone and progesterone were able to significantly reduce the aldosterone-induced stimulation of PAI-1. For MPA and R5020, no significant effect was found. Conclusions The new progestogen drospirenone seems to have favorable effects on the cardiovascular system due to its antimineralocorticoid property. Clinical studies must prove the results of this in vitro experiment.

 

Cancer Epidemiol Biomarkers Prev. 2008 Nov;17(11):3116-22.

Migraine in postmenopausal women and the risk of invasive breast cancer.

Mathes RW, Malone KE, Daling JR, Davis S, Lucas SM, Porter PL, Li CI.

Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, P. O. Box 19024, Seattle, WA

BACKGROUND: The frequency of migraine headache changes at various times of a woman's reproductive cycle. Menarche, menses, pregnancy, and perimenopause may carry a different migraine risk conceivably because of fluctuating estrogen levels, and in general, migraine frequency is associated with falling estrogen levels. Given the strong relationship between endogenous estrogen levels and breast cancer risk, migraine sufferers may experience a reduced risk of breast cancer. METHODS: We combined data from two population-based case-control studies to examine the relationship between migraine and risk of postmenopausal invasive breast cancer among 1,199 ductal carcinoma cases, 739 lobular carcinoma cases, and 1,474 controls 55 to 79 years of age. Polytomous logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Women who reported a clinical diagnosis of migraine had reduced risks of ductal carcinoma (OR, 0.67; 95% CI, 0.54-0.82) and lobular carcinoma (OR, 0.68; 95% CI, 0.52-0.90). These associations were primarily limited to hormone receptor-positive tumors as migraine was associated with a 0.65-fold (95% CI, 0.51-0.83) reduced risk of estrogen receptor-positive (ER(+))/progesterone receptor-positive (PR(+)) ductal carcinoma. The reductions in risk observed were seen among migraine sufferers who did and did not use prescription medications for their migraines. CONCLUSIONS: These data suggest that a history of migraine is associated with a decreased risk of breast cancer, particularly among ER(+)/PR(+) ductal and lobular carcinomas. Because this is the first study to address an association between migraine history and breast cancer risk, additional studies are needed to confirm this finding.

 

Arch Gerontol Geriatr. 2008 Nov 4. [Epub ahead of print

Response of oxidative stress markers and antioxidant parameters to an 8-week aerobic physical activity program in healthy, postmenopausal women.

Karolkiewicz J, Michalak E, Pospieszna B, Deskur-Śmielecka E, Nowak A, Pilaczyńska-Szcześniak L.

University School of Physical Education, Królowej Jadwigi str. 27/39, 61-871 Poznań, Poland.

The aim of the study was to assess the influence of an 8-week aerobic physical activity program on oxidative stress markers, antioxidant parameters, and selected metabolic parameters in healthy, postmenopausal women. The study was carried out in a group of 41 healthy women (mean age 65 years) participating in an 8-week cycle ergometer physical workout of moderate intensity. Before and after completing the training program, the following parameters were assessed: total antioxidant status (TAS) and concentrations of thiobarbituric acid reactive substances (TBARS) in plasma, serum levels of antibodies against oxidatively modified low-density lipoproteins (LDL) (oLAB), serum concentrations of glucose, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), insulin, and reduced glutathione (GSH) concentrations in red blood cells (RBC). Atherogenic index of plasma (AIP) and insulin resistance index (HOMA(IR)) were calculated. The 8-week aerobic physical activity program resulted in significant decrease (p<0.01) in serum glucose and LDL-cholesterol (LDL-C) levels, plasma TBARS concentrations (p<0.05), and in significant decrease of HOMA(IR) (p<0.01). TAS of plasma and GSH concentrations in RBC increased significantly (p<0.01) over the study period. The results show that an 8-week aerobic training enhanced insulin sensitivity, and improved the balance between oxidants and antioxidants in healthy, postmenopausal women.

 

Menopause. 2008 Nov 5. [Epub ahead of print

Association of oral but not transdermal estrogen therapy with enhanced platelet reactivity in a subset of postmenopausal women.

Flaumenhaft R, Nachtigall M, Lowenstein J, Nachtigall L, Nachtigall R, Nachtigall L.

Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.

OBJECTIVE:: We sought to determine the effects of oral versus transdermal estrogen therapy on platelet function in postmenopausal women. DESIGN:: Blood obtained from 84 postmenopausal women was tested for closure times using the Platelet Function Analyzer-100 before and after administration of oral or transdermal estrogen for 8 weeks. RESULTS:: Women with normal closure times at baseline (n = 71) demonstrated no significant change after receiving estrogen therapy with oral (n = 29) or transdermal (n = 42) estrogen. Women with borderline closure times of 61 to 66 seconds (n = 13) showed a significant acceleration of closure times (P = 0.0008) after oral estrogen therapy (-6.8 +/- 0.7 seconds, n = 5) but no significant change from baseline after transdermal estrogen therapy (1.1 +/- 0.5 seconds, n = 8). CONCLUSIONS:: An acceleration of closure times as measured by the Platelet Function Analyzer-100 in women with borderline baseline closure times is associated with the use of oral, but not transdermal, estrogen therapy. These results suggest that oral estrogen therapy increases platelet reactivity in a subset of women.

 

Clin Interv Aging. 2008;3(3):483-9.

Hip fracture protection by alendronate treatment in postmenopausal women with osteoporosis: a review of the literature.

Iwamoto J, Sato Y, Takeda T, Matsumoto H.

Department of Sports Medicine, Keio University School of Medicine, Tokyo, Japan.

Osteoporosis most commonly affects postmenopausal women, placing them at a significant risk of fractures. In particular, hip fractures are an important cause of mortality and morbidity among postmenopausal women. Anti-resorptive therapies that produce greater decreases in bone turnover markers together with greater increases in bone mineral density (BMD) are associated with greater reductions in fracture risk, especially at sites primarily composed of cortical bone such as the hip. Thus, treatment with potent anti-resorptive drugs like alendronate is a strategy for preventing hip fractures in postmenopausal women with osteoporosis. The purpose of this paper is to discuss the efficacy of alendronate against hip fractures and the mechanism for this anti-fracture efficacy in postmenopausal women with osteoporosis. A meta-analysis of randomized controlled trials has shown that alendronate reduces the risk of hip fractures by 55% in postmenopausal women with osteoporosis. According to the analyses of the Fracture Intervention Trial, each 1 standard deviation reduction in a 1-year change in bone-specific alkaline phosphatase (BSAP) is associated with 39% fewer hip fractures in alendronate-treated postmenopausal women, and those with at least 30% reduction in BSAP have a 74% lower risk of hip fractures relative to those with less than 30%. Alendronate is effective in reducing the risk of hip fractures across a spectrum of ages. The mechanism for this anti-fracture efficacy has been clarified; alendronate strongly suppresses bone turnover and subsequently increases hip BMD, decreases cortical porosity, improves parameters of hip structure geometry (cortical thickness, cross-sectional area, section modulus, and buckling ratio), and produces more uniform mineralization (increases the mean degree of mineralization of bone) in cortical bone. A once-weekly regimen of alendronate administration provides better patient compliance and persistence with the treatment than the once-daily dosing regimen, leading to greater efficacy against hip fractures. Thus, the efficacy of alendronate against hip fractures has been confirmed in postmenopausal women with osteoporosis, especially with a once-weekly dosing regimen.

 

Clin Interv Aging. 2008;3(3):445-51.

Once-yearly zoledronic acid in the prevention of osteoporotic bone fractures in postmenopausal women.

Lambrinoudaki I, Vlachou S, Galapi F, Papadimitriou D, Papadias K.

Department of Obstetrics and Gynecology, University of Athens, Aretaieion Hospital, Greece.

Zoledronic acid is a nitrogen-containing, third-generation bisphosphonate that has recently been approved for the treatment of postmenopausal osteoporosis as an annual intravenous infusion. Zoledronic acid is an antiresorptive agent which has a high affinity for mineralized bone and especially for sites of high bone turnover. Zoledronic acid is excreted by the kidney without further metabolism. Zoledronic acid administered as a 5 mg intravenous infusion annually increases bone mineral density in the lumbar spine and femoral neck by 6.7% and 5.1% respectively and reduces the incidence of new vertebral and hip fractures by 70% and 41% respectively in postmenopausal women with osteoporosis. Most common side effects are post-dose fever, flu-like symptoms, myalgia, arthralgia, and headache which usually occur in the first 3 days after infusion and are self-limited. Rare adverse effects include renal dysfunction, hypocalcemia, atrial fibrillation, and osteonecrosis of the jaw.

 

Breast Cancer Res Treat. 2008 Nov 4. [Epub ahead of print

Acupuncture for treating hot flashes in breast cancer patients: a systematic review.

Lee MS, Kim KH, Choi SM, Ernst E.

Department of Medical Research, Korea Institute of Oriental Medicine, Daejeon, 305-811, South Korea,

The objective of this review was to assess the effectiveness of acupuncture as a treatment option for hot flashes in patients with breast cancer. We searched the literature using 14 databases from their inceptions to August 2008, without language restrictions. We included randomised clinical trials (RCTs) comparing real with sham acupuncture or another active treatment or no treatment. Their methodological quality was assessed using the modified Jadad score. Three RCTs compared the effects of manual acupuncture with sham acupuncture. One RCT showed favourable effects of acupuncture in reducing hot flash frequency, while other two RCTs failed to do so. The meta-analysis show significant effects of acupuncture compared with sham acupuncture (n = 189, weight mean difference, 3.09, 95% confidence intervals -0.04 to 6.23, P = 0.05) but marked heterogeneity was observed in this model (chi (2) = 8.32, P = 0.02, I (2) = 76%). One RCT compared the effects of electroacupuncture (EA) with hormone replacement therapy. Hormone therapy was more effective than EA. Another RCT compared acupuncture with venlafaxine and reported no significant intergroup difference. A further RCT compared acupuncture with applied relaxation and failed to show a significant intergroup difference. In conclusion, the evidence is not convincing to suggest acupuncture is an effective treatment of hot flash in patients with breast cancer. Further research is required to investigate whether there are specific effects of acupuncture for treating hot flash in patients with breast cancer.

 

Minerva Ginecol. 2008 Dec;60(6):475-84.

L-thyroxin treatment and post-menopausal osteoporosis: relevance of the risk profile present in clinical history.

La Vignera S, Vicari E, Tumino S, Ciotta L, Condorelli R, Vicari LO, Calogero AE.

Department of Biomedical Sciences, University of Catania, Catania, Italy

AIM: Nodular thyroid disease and osteoporosis share some common factors such as: 1) elevated frequency in the general population; 2) major prevalence in the female sex; 2) incidence proportional to the age. There is a wide debate in literature regarding the real impact of chronic treatment with L-thyroxin (LT4) on the bone mineral density (BMD), especially in post-menopausal women. The aim of this study was to undertake to evaluate the effects of LT4 administration for the treatment of normo-functioning nodular thyroid disease on the BMD in post-menopausal women after one year of continuative treatment. Particular attention was paid in examining the role of some anamnestic risk factors for osteoporosis on the clinical response. METHODS: Ninety nine postmenopausal women of age comprised between 50 and 56 years were examined before and after 1 year of therapy with a fixed dose of LT4 for the treatment of nodular thyroid disease by monitoring the following laboratory parameters: thyroid stimulating hormone (TSH), FT4, FT3, antithyroglobulin antibodies [AbTG], hyroid peroxidase antibodies [AbTPO], serum calcium and alkaline phosphatase levels and 24-urinary excretion of calcium and hydroxyproline. Bone mineral density (BMD) was measured by dual X-ray absorptiometry of the lumbar vertebrae. RESULTS: The results of this study showed that the patients on treatment with LT4 have a slight, but significant reduction of the BMD after 1 year of treatment, associated with increased serum levels of alkaline phosphatase and urinary excretion of hydroxyproline. Comparison between patients with unsuppressed (group A) or suppressed (group B) TSH following LT4 treatment showed that group B patients had significantly lower BMD. The following risk factors influenced, in a statistically significant manner, the BMD: 1) Body Mass Index <19 kg/m(2); 2) the onset of menarche after the age of 15 years; 3) history positive for period of amenorrhoea; 4) nulliparity; 5) surgical menopause; 6) lack of hormonal replacement therapy; and 7) presence of auto-antibodies against thyroid antigens. CONCLUSION: LT4 treatment in postmenopausal women reduced significantly the BMD. This treatment should be therefore prescribed with caution in this condition and particularly when the following risk factors are present: surgically driven menopause, constitutional thinness, history of nulliparity, absence of hormonal treatment, positive history of secondary amenorrhoea during the reproductive age, autoimmune thyroid disease and delayed menarche.

 

 

Semana del 29 de Octubre al 4 de Noviembre de 2008

 

Menopause. 2008 Oct 24. [Epub ahead of print]

Transdermal estradiol gel 0.1% for the treatment of vasomotor symptoms in postmenopausal women.

Hedrick RE, Ackerman RT, Koltun WD, Halvorsen MB, Lambrecht LJ.

Hawthorne OB/GYN Associates, Winston-Salem, NC.

OBJECTIVE:: The objective of this study was to evaluate the efficacy and safety of three doses of estradiol gel 0.1% (Divigel, a novel formulation consisting of 1 mg estradiol per 1 g transdermal gel) to reduce the frequency and severity of vasomotor symptoms and signs of vulvar and vaginal atrophy associated with menopause. DESIGN:: A total of 488 postmenopausal women were evaluated in a 12-week study comparing placebo with estradiol gel 0.1% at doses of 1.0, 0.5, and 0.25 mg/day, with estimated daily deliveries of 0.027, 0.009, and 0.003 mg of estradiol, respectively. Primary endpoints were the change from baseline in daily frequency and severity of moderate to severe vasomotor symptoms. Change from baseline in the signs of vulvar and vaginal atrophy (vaginal pH and percentage of superficial cells) was also assessed. RESULTS:: Treatment with estradiol gel 0.1% showed statistically significant reductions in frequency and severity of vasomotor symptoms from baseline compared with placebo as early as Week 2 that were maintained throughout treatment. Signs of vulvar and vaginal atrophy were also significantly improved from baseline with all three doses of estradiol gel 0.1% compared with placebo. CONCLUSIONS:: Low-dose transdermal estradiol gel 0.1% is an effective treatment for relief of vasomotor symptoms, as well as signs of vulvar and vaginal atrophy, associated with menopause. Estradiol gel 0.1% offers multiple dosing options to individualize patient therapy, including the lowest available effective dose (0.25 mg estradiol, delivering 0.003 mg/d estradiol) to treat the vasomotor symptoms of menopause.

 

Maturitas. 2008 Oct 23. [Epub ahead of print]

The relationship between depression and sexual function in menopause period.

Yangın HB, Sözer GA, Sengün N, Kukulu K.

Akdeniz University, Antalya Healt School, Antalya, Turkey.

OBJECTIVES: Menopause is a physiological process that is lived universally by every middle age woman. This study has been made with the aim of determining the relation between depression situation and sexual function of women in menopause period. METHODS: This study was made with 300 women in menopause who applied to Akdeniz University Research and Application Hospital on January 2007. Study used socio-demographic data descriptive survey form, Beck Depression Inventory and sexual function scale as data collection tool. Data were collected by researchers in face-to-face interviews. RESULTS: In the study it was found that age and marriage duration of women could reduce sexual function. Depression was determined in 29.3% of women and sexual dysfunction in 65% of women. Significant negative relation was found between sub-dimension of sexual function scale of women vaginal slickness, orgasm, pain, total sexual dysfunction and depression point. CONCLUSION: In the study it was determined that while depression points increased with menopause, sexual function reduced and with the increase of depression point, sexual dysfunction increased too. Qualitative studies must be made that will examine emotional situations and sexual life of women.

 

Menopause. 2008 Oct 27. [Epub ahead of print]

Relative androgen excess during the menopausal transition predicts incident metabolic syndrome in midlife women: Study of Women's Health Across the Nation.

Torréns JI, Sutton-Tyrrell K, Zhao X, Matthews K, Brockwell S, Sowers M, Santoro N.

From the 1Department of Obstetrics/Gynecology and Women's Health, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ.

OBJECTIVE:: During the menopausal transition, total testosterone (T) remains unchanged, whereas estrogen decreases markedly, creating a state of relative androgen excess. We hypothesized that change in the T-to-estradiol (T/E2) ratio during the menopausal transition would be associated with incident metabolic syndrome. DESIGN:: The association between incident metabolic syndrome and total E2, total T, sex hormone-binding globulin, the free androgen index, baseline total T/E2 ratio, and the change of this ratio over time was evaluated in a multiethnic cohort of 1,862 premenopausal and perimenopausal women without diabetes enrolled in the Study of Women's Health Across the Nation. RESULTS:: New cases (n = 257) of metabolic syndrome were identified in the cohort during 6,296 woman-years of follow-up. The age-adjusted total T/E2 ratio increased by 10.1% per year during the 5 years of follow-up. Neither baseline nor change in E2 was associated with incident metabolic syndrome. Low sex hormone-biding globulin, free androgen index, and high total T at baseline all increased the risk of metabolic syndrome, but their change over time did not. Both baseline total T/E2 ratio (1.41; 95% CI = 1.17-1.69; P < 0.001) and its rate of change (1.24; 95% CI = 1.01-1.52; P < 0.04) were associated with increased incident metabolic syndrome independent of ethnicity. CONCLUSIONS:: The interaction between T and E2 during the menopausal transition, rather than the individual change of each over time, is a factor in the determination of risk of developing metabolic syndrome during the menopausal transition. This relationship was independent of ethnicity and other factors associated with prevalent metabolic syndrome before the onset of the menopausal transition.

 

Eur J Pharmacol. 2008 Oct 21. [Epub ahead of print]

Opposing effects of bisphosphonates and advanced glycation end-products on osteoblastic cells.

Gangoiti MV, Cortizo AM, Arnol V, Felice JI, McCarthy AD.

Bioquímica Patológica, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Argentina.

Patients with long-standing Diabetes mellitus can develop osteopenia and osteoporosis. We have previously shown that advanced glycation endproducts reduce the bone-forming activity of osteoblasts. Bisphosphonates are used for the treatment of various bone disorders, since they reduce osteoclastic function and survival, and stimulate osteoblastic bone-forming capacity. In this work we have investigated whether bisphosphonates are able to revert advanced glycation endproducts-induced deleterious effects in osteoblasts. MC3T3E1 and UMR106 osteoblastic cells were incubated with control or advanced glycation endproducts-modified bovine serum albumin, in the presence or absence of different doses of the bisphosphonates Alendronate, Pamidronate or Zoledronate. After 24-72 h of culture, we evaluated their effects on cell proliferation and apoptosis, type-1 collagen production, alkaline and neutral phosphatase activity, and intracellular reactive oxygen species production. Advanced glycation endproducts significantly decreased osteoblast proliferation, alkaline phosphatase activity and type 1 collagen production, while increasing osteoblastic apoptosis and reactive oxygen species production. These effects were completely reverted by low doses (10(-8) M) of bisphosphonates. High doses of bisphosphonates (10(-4)-10(-5) M) were toxic for osteoblasts. Nifedipine (L-type calcium channel blocker) did not affect the advanced glycation endproducts-induced decrease in osteoblastic proliferation, although it blocked the reversion of this effect by 10(-8) M Alendronate. Both advanced glycation endproducts and Alendronate inhibited the activity of intracellular neutral phosphatases. In conclusion, we show that bisphosphonates revert the deleterious actions of advanced glycation endproducts on osteoblastic cells, and that these effects of bisphosphonates depend on: (a) Ca(2+) influx through L-type voltage-sensitive channels, and (b) blockage of advanced glycation endproducts-induced reactive oxygen species generation.

 

COPD. 2008 Oct;5(5):291-7.

African Americans and men with severe COPD have a high prevalence of osteoporosis.

Li L, Brennan KJ, Gaughan JP, Ciccolella DE, Kuzma AM, Criner GJ.

Division of Pulmonary and Critical Care, Temple University School of Medicine, Philadelphia, Pennsylvania

Osteoporosis is a non-pulmonary manifestation whose true prevalence is uncertain in severe chronic obstructive pulmonary disease (COPD). We describe the prevalence and risk factors for osteoporosis in a large, well characterized COPD cohort. Dual energy x-ray absorptiometry of the lumbar spine and hip, full pulmonary function testing, cardiopulmonary exercise test, 6 minute walk distance and demographics were performed in 179 non-selected COPD patients. Patients were 59 +/- 7 years old, smoked 53 +/- 32 pack years, FEV(1) 26% +/- 9.8, and 45% were currently taking prednisone. Bone mineral density measurements were abnormal in 97%; 66% had dual energy X-ray absorptiometry defined osteoporosis, while 31% had osteopenia. The prevalence of osteoporosis in males versus females was 70% versus 62% (p = 0.33); both groups had similar fracture rates. The prevalence of osteoporosis in African Americans versus Caucasians was 69% versus 65% (p = 0.78). Caucasians had a significantly lower Ward's Triangle T score than African Americans (-2.52 +/- -0.96 vs. -2.16 +/- -0.91, p = 0.04). Those with bone fractures took higher doses of prednisone than those without fractures. Univariate analysis identified BMI and FVC% as predictors for osteoporosis (p = 0.03 OR 0.934 p = 0.006 OR 0.974). Multivariate analysis revealed only FVC% as a significant predictor (p = 0.006, OR 0.974). Osteoporosis is highly prevalent in severe COPD, and affects males and African Americans to a similar degree as females and Whites. Osteoporosis should be considered in severe COPD regardless of race or gender.

 

Menopause. 2008 Oct 27. [Epub ahead of print]

Hysterectomy and weight gain.

Fitzgerald DM, Berecki-Gisolf J, Hockey RL, Dobson AJ.

Faculty of Health Sciences, University of Queensland, Herston, Queensland, Australia.

OBJECTIVE:: To investigate whether overweight women are more likely to have a hysterectomy and whether hysterectomy leads to increased weight gain. DESIGN:: Survey data of middle-aged women participating in the Australian Longitudinal Study on Women's health in 1996 (ages 45-50 y; n = 13,125), 1998 (n = 10,612), 2001 (n = 10,293), and 2004 (n = 9309) included self-reported height, weight, and hysterectomy. First, we conducted a cohort analysis, comparing body mass index (BMI) of women categorized according to hysterectomy status. Second, we used a nested case-control analysis to compare weight gain between women who underwent hysterectomy and women who did not have a hysterectomy, matched for prehysterectomy weight, height, menopause status, and educational level. RESULTS:: At survey 1, the mean BMI of women who subsequently had a hysterectomy was greater than that of women without a hysterectomy by survey 2 (difference, 1.1 kg/m; 95% CI, 0.5-1.6). Results were similar for surveys 2 to 3 (BMI difference, 0.8 kg/m; 95% CI, 0.3-1.3) and surveys 3 to 4 (BMI difference, 0.8 kg/m; 95% CI, 0.1-1.4).Having a hysterectomy between surveys 1 and 2 was not associated with percentage of weight gain over the 3 or 6 years after survey 2 (odds ratio, 0.98 [95% CI, 0.96-1.01] and 0.99 [95% CI, 0.97-1.01], respectively). Having a hysterectomy between surveys 2 and 3 was weakly associated with percentage of weight gain over 3 years (odds ratio, 1.03 [95% CI, 1.00-1.05]). CONCLUSIONS:: Among women older than 45 to 50 years, hysterectomy did not lead to greater weight gain but was more likely to be performed in heavier women.

 

Curr Opin Endocrinol Diabetes Obes. 2008 Dec;15(6):502-7.

Osteoporosis: how long should we treat?

Sebba A.

University of South Florida, Tampa, Florida 34684, USA. asebba@tampabay.rr.com

PURPOSE OF REVIEW: Bisphosphonates are the most commonly used treatment for osteoporosis. The pharmacology of bisphosphonates suggests the possibility of discontinuing treatment for a period, and patients frequently ask about this. In an attempt to help answer these questions, this review will consider recent data relevant to continuing and discontinuing long-term bisphoshonate therapy and other osteoporosis therapy. RECENT FINDINGS: Morphometric vertebral fracture protection continues for 1 year after discontinuation of risedronate for 3 years and there are now similar bishosphonate data for hip fractures. Nonvertebral fractures -in high-risk women - and perhaps clinical vertebral fractures may be reduced in women treated for 10 years with alendronate compared with those who stopped treatment after 5 years. After discontinuing bisphosphonates, bone mineral density appears to deplete more rapidly in the spine than in the hip and biochemical markers appear to increase. These changes occur very rapidly after discontinuing denosumab. Fractures at unusual sites have been reported with long-term bisphosphonate use. SUMMARY: It appears that a drug holiday can be considered in many patients, although high-risk patients may benefit from continued bisphosphonate therapy. Recent unusual fracture cases need to be considered in making long-term treatment decisions.

 

Best Pract Res Clin Endocrinol Metab. 2008 Aug;22(4):615-23.

The endocrine prevention of breast cancer.

Howell A.

CRUK Department of Medical Oncology, Christie Hospital, Manchester, UK.

Breast cancer incidence is increasing in all parts of the world. Although in Western countries death rates are declining, there is a need to make attempts to prevent the disease in order to reduce the trauma of diagnosis and treatment. Endocrine approaches to breast cancer prevention have been the most successful approach to cancer prevention to date. Studies with tamoxifen were initiated when it was noted that, during adjuvant treatment after surgery to prevent relapse, the incidence of new contralateral cancers was reduced by half. Four trials of >/=5 years of tamoxifen compared with placebo in women at increased risk of breast cancer were initiated in the 1980s and showed a similar reduction in breast cancer, but only in oestrogen-receptor-positive disease. Recent follow-up indicated that there is a carry-over effect of tamoxifen after the completion of treatment at 5 years so that the preventive effect at 10 years is significantly great than at 5. The selective oestrogen receptor modulator (SERM) raloxifene has also been assessed as a preventive agent in two major international randomized trials compared with placebo and shows a protective effect similar to that of tamoxifen. An American study subsequently compared tamoxifen and raloxifene in a trial of nearly 20,000 women at increased risk (the STAR trial) and demonstrated that the two agents were equally effective but that the toxicity of raloxifene was less. Adjuvant trials comparing tamoxifen and the modern potent aromatase inhibitors (anastrozole, letrozole and exemestane) indicate that they are superior to tamoxifen and reduce contralateral breast cancer by approximately 70%. This observation has led to the initiation of two trials in postmenopausal women comparing anastrozole (the IBISII trial) or exemestane (the MAP-3 trial) with placebo. Currently it is recommended that tamoxifen is used to prevent breast cancer in premenopausal women and raloxifene for postmenopausal women (it is not effective in the premenopausal group),and we await the results of the aromatase inhibitor trials.

 

Diabetes Care. 2008 Oct 28. [Epub ahead of print]

Circulating Levels of Resistin and Risk of Type 2 Diabetes in Men and Women: Results from Two Prospective Cohorts.

Chen BH, Song Y, Ding EL, Roberts CK, Manson JE, Rifai N, Buring JE, Gaziano JM, Liu S.

Program on Genomics and Nutrition, Department of Epidemiology, UCLA School, Los Angeles, CA.

Objective: To investigate the role of circulating resistin levels in the development of type 2 diabetes using two prospective cohorts of well-characterized men and women. Research design and methods: We conducted two prospective case-control studies nested in the Women's Health Study (WHS) and Physicians' Health Study II (PHS II). In the WHS, during a median of 10-years follow-up, 359 postmenopausal women apparently healthy at baseline, who later developed type 2 diabetes, were prospectively matched with 359 healthy controls. In the PHS II, with 8 years total follow-up, 170 men apparently healthy at baseline, who later developed type 2 diabetes, were matched with 170 healthy controls. Controls were matched by age, race, and time of blood draw. Results: Resistin levels at baseline were significantly higher in women than in men (p<0.001) and in cases than controls in both women (p<0.001) and men (p=0.07). After adjustment for matching factors, physical activity, alcohol intake, smoking, and family history of diabetes, the RR of type 2 diabetes comparing the highest to the lowest quartile of resistin in women was 2.23 (95%CI=1.33-3.75; p(trend)=0.002). This association was attenuated after further adjusting for BMI (RR=1.51, 95%CI=0.86-2.65; p(trend)=0.21) or CRP (RR=1.19, 95%CI=0.68-2.09; p(trend)=0.59). A similar yet weaker pattern was observed in men. Conclusions: Elevated levels of circulating resistin were significantly related to increased risk of type 2 diabetes, which appears to be partially accounted for by adiposity and the inflammatory process.

 

Horm Metab Res. 2008 Oct 27. [Epub ahead of print]

Sex Hormone Binding Globulin and Aging.

Caldwell JD, Jirikowski GF.

Lake Erie College of Osteopathic Medicine, Erie, PA, USA.

New and more active concepts of steroid binding globulin action are emerging from recent research. As a result, examination of steroid levels in aging humans and the role of steroid binding globulins need to be re-visited. This review will discuss the possibility that sex hormone binding globulin (SHBG) plays an active role in the aging process. It will discuss the changes in blood levels of SHBG in aging humans in association with sexual activity, prostate hypertrophy and cancer, uterine leiomyoma, breast cancer, obesity and particularly the relationship between SHBG and HDL-cholesterol, Alzheimer's disease, osteoporosis, and cardiovascular disease. Starting with the idea that SHBG is an active participant in steroid action demands a re-evaluation of data demonstrating a primary change in blood SHBG levels in association with various pathologies. Here we discuss the postulate that SHBG may act at its own receptor at the plasma membrane level to influence other receptors such as scavenger receptors and HDL-cholesterol receptors. We will also suggest that SHBG is a critical marker for mating and thus may be an important physiological molecule in control of aging.