Index In Postmenopausal Women Research Articles

Bioavailable testosterone is independently associated with Fatty Liver Index in postmenopausal women.

IntroductionPrevious studies have examined the correlation between hyperandrogenemia and non-alcoholic fatty liver disease (NAFLD) in women and showed contradictory results. Therefore, we aimed to evaluate the relationship between testosterone level and Fatty Liver Index (FLI), as a surrogate marker for NAFLD, in a cohort of postmenopausal women.Material and methodsA total of 150 postmenopausal women were included in this cross-sectional study. Anthropometric and biochemical parameters, as well as blood pressure, were obtained. Non-alcoholic fatty liver disease is assessed by FLI, an algorithm based on body mass index, waist circumference, triglycerides and γ-glutamyl transferase, as a simple and accurate predictor of hepatic steatosis. Women were divided into three groups (FLI < 30, n = 80; 30 ≤ FLI < 60, n = 44; FLI ≥ 60, n = 26). Homeostasis model assessment of insulin resistance (HOMA-IR) as a surrogate marker of insulin resistance was calculated.ResultsMultiple linear regression analysis revealed that the best model consisted of 4 parameters (e.g., bioavailable testosterone (β = 0.288, p = 0.001), log HOMA-IR (β = 0.227, p = 0.005), log high-sensitivity C-reactive protein (β = 0.322, p < 0.001), and retinol-binding protein 4 (β = 0.226, p < 0.001)). Adjusted R2 for the best model was 0.550, which means that as much as 55.0% of variation in FLI could be explained with this model.ConclusionsBioavailable testosterone is independently associated with FLI in postmenopausal women.

Response and Rebuttal to Editorial Comment on TX-004HR Improves Sexual Function as Measured by the Female Sexual Function Index in Postmenopausal Women with Vulvar and Vaginal Atrophy: The REJOICE Trial

Response and Rebuttal to Editorial Comment on TX-004HR Improves Sexual Function as Measured by the Female Sexual Function Index in Postmenopausal Women with Vulvar and Vaginal Atrophy: The REJOICE Trial

Editorial Comment on “TX-004HR Improves Sexual Function as Measured by the Female Sexual Function Index in Postmenopausal Women With Vulvar and Vaginal Atrophy: The REJOICE Trial”

Editorial Comment on “TX-004HR Improves Sexual Function as Measured by the Female Sexual Function Index in Postmenopausal Women With Vulvar and Vaginal Atrophy: The REJOICE Trial”

TX-004HR Improves Sexual Function as Measured by the Female Sexual Function Index in Postmenopausal Women With Vulvar and Vaginal Atrophy: The REJOICE Trial

IntroductionTX-004HR is an investigational, applicator-free, vaginal soft gel capsule containing low-dose solubilized 17β-estradiol. The phase 3, randomized, double-blinded, placebo-controlled, multicenter REJOICE trial has shown TX-004HR to be safe and effective for the treatment of moderate to severe dyspareunia in postmenopausal women with vulvar and vaginal atrophy (VVA). AimTo evaluate the effect of TX-004HR on female sexual dysfunction in postmenopausal women with VVA. MethodsThe REJOICE study compared the effects of 12-week treatment with TX-004HR (4, 10, or 25 μg) with placebo in postmenopausal women (40–75 years old) with VVA and a most bothersome symptom of moderate to severe dyspareunia. Changes in the percentage of superficial and parabasal cells, vaginal pH, and dyspareunia were measured as co-primary end points. Female sexual dysfunction was evaluated as a secondary end point using the Female Sexual Function Index (FSFI) patient self-report inventory. Main Outcome MeasuresChanges from baseline to week 12 in total and individual domain FSFI scores for each TX-004HR dose were compared with those for placebo. ResultsAll three TX-004HR doses increased the baseline total FSFI score after 12 weeks, with 10 μg (P < .05) and 25 μg (P = .0019) having a significantly greater effect than placebo. A similar trend was observed for the individual FSFI domains, with 10 and 25 μg significantly improving baselines scores for pain and lubrication at 12 weeks (P ≤ .015 for all vs placebo). Changes from baseline to week 12 in arousal (P = .0085) and satisfaction (P = .0073) were significantly greater for TX-004HR 25 μg vs placebo. All three TX-004HR doses were comparable to placebo in their effect on desire and orgasm. ConclusionTX-004HR improved FSFI scores in a dose-dependent manner. The observed improvements in sexual function suggest that TX-004HR is a promising treatment option for postmenopausal VVA with a potential added beneficial effect on female sexual dysfunction.

Association between Bone Mineral Density and Platelet Indices in Postmenopausal Women

Objective: It was shown that low bone mass is associated with increased cardiovascular mortality in early and late menopausal period. The aim of this study was to investigate the relationship between bone mineral density (BMD) and platelet indices (mean platelet volume [MPV], platelet distribution width [PDW] and platelet count [PC]) in postmenopausal women. Materials and Methods: We retrospectively investigated BMD and platelet parameters of the women aged between 55-75 years between January 2012-December 2015 and 311 women meeting study criteria were included in the study. Participants were divided into 3 groups (control, osteopenia, osteoporosis groups) according to BMD parameters. The average values of age, BMD and platelet indices of groups were compared. Potential correlations between platelet indices with age and BMD levels were investigated and the correlation level and direction were investigated when age variable was controlled. Results: Participants in osteopenia and osteoporosis groups had significantly higher OPH values than those in the control group (p=0.002). When age variable controlled, there was a weak and negative correlation between OPH and with lumbar, femoral neck and femur total BMD (r=-0.177, p=0.002; r=-0.160, p=0.005; r=-0.151, p=0.008 respectively). On the other hand, there was no significant relationship between BMD with PC or PDW. Conclusion: The results of this study showed that there is a weak and negative correlation between the BMD the MPV. Further studies on osteoporosis and platelet indices, may contribute to better understanding of increased thrombotic risk in postmenopausal period.

The influence of bone mineral density and bisphosphonate therapy on the determinants of oral health and changes on dental panoramic radiographs in postmenopausal women.

The aim of this study was to assess the determinants of oral health including the number of decayed, missing, and filled teeth (DMFT) and periodontal indices in postmenopausal women with osteoporosis, osteoporosis treated with bisphosphonate therapy, and control group and to examine the correlation between dental panoramic indices (Mental Index-MI, Mandibular Cortical Index-MCI) and bone mineral density in these three groups of patients. The presented non-interventional study involved 120 postmenopausal women: women with osteoporosis (O) (n=45), women with osteoporosis treated with bisphosphonates (OBP) (n=45), and control group (C) (n=30). DMFT, plaque, gingival and papilla bleeding index, pocket depth, clinical attachment loss, and the presence of periodontitis were evaluated for each patient. MI and MCI of all participants were measured on a dental panoramic radiograph. Group OBP showed significantly higher gingival, bleeding index and deeper pocket depth than C and/or O group. No significant differences were found in MI (p=.303) or MCI (p=.06) in all the examined groups. Also, there were no significant differences between the three groups in the presence of periodontitis as well as in the DMFT index. BP therapy could have a negative influence on periodontal health. Further, MI and MCI are not precise diagnostic tools for diagnosing low BMD in postmenopausal women. BP therapy could have a negative influence on the determinants of oral health in postmenopausal women with osteoporosis.

Risk-Benefit Index of Tamoxifen and Raloxifene for Chemoprevention of Korean Breast Cancer

ABSTRACT Aim: According to the NSABP-P1 and P2 studies, tamoxifen and raloxifene can protect breast cancer and hip fracture, but they can induce endometrial cancer, stroke, and pulmonary embolism. We estimated the risks and benefits of tamoxifen and raloxifene using a Korean database in order to evaluate the feasibility of using tamoxifen and raloxifene for breast cancer chemoprevention in Korean women. Methods: Data were reviewed on the incidences of breast cancer, hip fracture, endometrial cancer and stroke in the absence of tamoxifen and raloxifene treatment in Korean women. We also reviewed NSABP-P1 and P2 data on the effects of tamoxifen and raloxifene on these outcomes. A risk-benefit index was calculated according to age and specific risk of breast cancer. Sensitivity analyses were performed of assumptions regarding the effects of tamoxifen and raloxifene. Results: Compared to U.S. women, the numbers of hip fractures and endometrial cancers were lower, but the number of strokes was much higher. The net benefit of tamoxifen and raloxifene were reduced with increasing age because of a high risk of stroke in older women. Older Korean women had more risk than benefit from tamoxifen and raloxifene chemoprevention. Only women younger than age 40 had a positive risk-benefit index of tamoxifen with an average 5-year risk of breast cancer in Korea. Sensitivity analysis showed that this result was robust. Raloxifene has more favorable index in postmenopausal women with a uterus. Conclusions: Women under the age 40 had more benefit than risk from tamoxifen chemoprevention. In the postmenopausal women with a uterus, raloxifene has more favorable risk-benefit index than tamoxifen. Disclosure: All authors have declared no conflicts of interest.

Combined estrogen replacement therapy on metabolic control in postmenopausal women with diabetes mellitus

Previous studies have shown that the incidence of diabetes is higher when women come to menopause. This study was carried out to examine the effects of combined estrogen replacement therapy (ERT) on diabetes in postmenopausal women. PubMed/MEDLINE was searched for English-language articles published between January 1997 and June 2011. Studies that examined ERT on the incidence of diabetes and randomized clinical trials that evaluated combined ERT (estrogen plus progesterone) on diabetic indices in postmenopausal women were included. Pooled relative risks were calculated using a random- or a fixed-effects model. Sixteen studies comprising 17,971 cases were included. Based on the pooled data, ERT significantly reduced the incidence of diabetes [odds ratio (OR), 0.61; 95% confidence interval (CI), 0.55–0.68, ERT past/current/continuous use vs. never use; OR, 0.57; 95% CI, 0.51–0.65, ERT current/continuous use vs. past/never use]. Women with combined ERT have significantly lower levels of fasting plasma glucose (mean difference, –1.41 mM/L; 95% CI, –2.49 to −0.33 mM/L) and HbA1c (mean difference, –0.73%; 95% CI, from −1.28 to −0.18%) compared with placebo. Furthermore, combined ERT dramatically reduced plasma total cholesterol (mean difference, –0.34 mM/L; 95% CI, from −0.53 to −0.15 mM/L) and low-density lipoprotein (mean difference, –0.43 mM/L; 95% CI, from −0.71 to −0.14 mM/L) but slightly increased high-density lipoprotein (mean difference, 0.02 mM/L; 95% CI, from −0.07 to 0.12 mM/L) levels as compared with placebo control. This systemic review and meta-analysis provides evidence that postmenopausal women taking low-dose combined ERT have a decreased risk of developing diabetes and have better diabetic control.

Sex hormones and breast cancer risk and prognosis

The study of large prospective collections of plasma samples from women prior to the development of breast cancer has firmly established certain sex steroids as being significantly associated with risk. The strongest associations have been found in postmenopausal women in whom the within person variability of most hormones is markedly reduced but some positive associations have also been seen in premenopausal women. Plasma estrogens show the strongest correlations with risk and these are strengthened by measurement or calculation of the proportion of estradiol that circulates free of sex hormone binding globulin (SHBG), consistent with this being the most active fraction. The relationships have been reported to potentially explain virtually all of the association of breast cancer with body mass index in postmenopausal women; this is likely to be due to non-ovarian estrogen synthesis being prominent in subcutaneous fat. These strong relationships have led to plasma and urine estrogen levels being used as intermediate end-points in the search for genes that affect breast cancer risk via their role in steroid disposition. Plasma androgen levels also show a relationship with breast cancer risk that is weakened but not eliminated by ‘correction’ for estrogen levels. This has been argued to be evidence of the local production of estrogens being important in the etiology of breast cancer. Given that plasma steroid levels do not correlate closely with mammographic density, which is strongly associated with risk, the opportunity exists to combine the two factors in assessing breast cancer risk but the low availability of suitable estrogen assays is a major impediment to this. In established breast cancer, plasma estrogens have been found to correlate with gene expression of estrogen dependent genes and the expression of these varies across the menstrual cycle of premenopausal women.There is infrequently a need for routine measurement of plasma estrogen levels but it has been important in the comparative pharmacology and dose-related effectiveness of aromatase inhibitors. Measurement may be needed to identify residual ovarian function in women who have amenorrhea subsequent to cytotoxic chemotherapy indicating their unsuitability for aromatase inhibitor treatment. Use of highly sensitive assays has also revealed that the association between BMI and plasma estrogen levels persists in patients on 3rd generation aromatase inhibitors and that measurable increments in plasma estrogen levels occur with some vaginal estrogen preparations that are of concern in relation to treatment efficacy.

Short-term effects of low-dose estrogen/drospirenone vs low-dose estrogen/dydrogesterone on glycemic fluctuations in postmenopausal women with metabolic syndrome

This study aims to compare the effects of low-dose emidrate estradiol/drospirenone (E2/DRSP) vs low-dose emidrate estradiol/dydrogesterone (E2/DG) combination on the mean amplitude of glycemic excursions (MAGE) value in postmenopausal women affected by metabolic syndrome (MS). One hundred sixty postmenopausal women were recruited to receive a treatment with oral doses of E2/1 mg plus drospirenone/2 mg (E2/DRSP group) or oral dose of E2/1 mg plus dydrogesterone/5 mg (E2/DG group) for 6 months. At enrollment and after 6 months, anthropometric, metabolic, and inflammatory parameters have been assessed. MAGE, evaluated during 48-h continuous subcutaneous glucose monitoring (CSGM), allowed us to assess daily glucose fluctuations at baseline and after 6 months. After hormone therapy, both groups showed a significant decline in fasting plasma glucose levels (p < 0.05), while only E2/DRSP group showed a statistically significant decline in waist circumferences, post-prandial glycemia, LDL, plasma triglycerides, MAGE, HOMA index, and plasma IL-6 (p < 0.05) levels. In the whole population (n = 160), after 6 months of indicated therapy, changes in fasting plasma glucose and PAI-1 levels correlated with the changes in MAGE values, while only in E2/DRSP group that MAGE reduction was positively associated with a stronger decrease in waist circumferences, triglycerides, and TNF-α plasma levels. The independent effect of hormone therapy (HT) on reduction in MAGE value has been tested in three different multiple linear regression models. HT resulted to be associated with MAGE, independent of other confounding variables. Although both groups had a decline in fasting plasma glucose, only drospirenone treatment revealed positive effects on glycemic excursions and insulin sensitivity, induced favorable changes in lipid profile, and showed an improvement of inflammatory indices in postmenopausal women with MS.

Bone mineral density, vertebral fractures and body mass index in postmenopausal women with abdominal aortic calcification

Background: Evidence suggest that there are connections between osteoporosis and cardiovascular diseases. Objectives: The aim of the study was to analyze the relationship between radiological measurements of abdominal aorta calcifications (AAC) and bone mineral density (BMD) in postmenopausal women. Methods: In this cross-sectional study were included 125 postmenopausal women 50–84 years of age. BMD of the spine and hip was measured by dual energy X-ray absorptiometry (DXA). AAC were assessed by lateral radiographs of lumbar spine (L1–L4), using the antero-posterior severity score (0–24). Vertebral fractures were evaluated from T4 to L4 using Genant’s semiquantitative method. Results: Forty-one (32.8%) patients had osteoporosis and 61 (48.8%) had AAC with a mean score of 3.1. Postmenopausal women with AAC were older and had significantly lower femoral neck and trochanteric BMD than subjects without AAC (all p < 0.01). There were no significant differences in the frequency of fractures between subjects with AAC and those without AAC (p > 0.05). In univariate analysis, age, height, weight, femoral and trochanter BMD were significantly associated with the severity of AAC score. In multiple regression analysis, femoral neck BMD, but not lumbar spine, trochanter BMD or age, was an independent predictor of AAC. Conclusions: Reduced femoral neck BMD is negatively associated with the presence of AAC in postmenopausal women. The association between BMD and AAC seems to be age-independent, which suggests a common pathogenesis for bone loss and vascular calcifications.

Association of estrogen with glucocorticoid levels in visceral fat in postmenopausal women

The aim of this study is to clarify the association between estrogen and glucocorticoid levels in adipose tissues of premenopausal and postmenopausal women. Forty (15 premenopausal and 25 postmenopausal) women aged 22 to 79 years were recruited through elective gynecological surgical operation, and both subcutaneous and visceral fat were collected during the surgical operation. Messenger RNA (mRNA) expressions of 11β hydroxysteroid dehydrogenase type 1 (HSD1), which catalyzes cortisone to cortisol, and 17β-HSD1 and 17β hydroxysteroid dehydrogenase type 2 (HSD2), which catalyze the interconversion of estrone (E1) and estradiol (E2), were measured by real-time reverse transcription polymerase chain reaction. The levels of E1, E2, cortisol, and cortisone in adipose tissues were measured by liquid chromatography tandem mass spectrometry. The visceral fat area was significantly increased (P < 0.01) in postmenopausal women compared with that in premenopausal women. The cortisol/cortisone ratio (P < 0.01) and the expression of 11β-HSD1 mRNA (P < 0.001) in visceral fat, but not in subcutaneous fat, in postmenopausal women were significantly higher than those in premenopausal women. There was a significant correlation (r = 0.69, P < 0.05) between the E1/E2 ratio of visceral fat and body mass index in postmenopausal women. A significant correlation (r = 0.54, P < 0.05) between the cortisol/cortisone ratio and the E1/E2 ratio of visceral fat was observed in postmenopausal women. The expression of 11β-HSD1 mRNA in visceral fat increases in postmenopausal women, and the E1/E2 ratio in visceral fat may be associated with local glucocorticoid levels after menopause.

Short-term effect of pitavastatin on the reactive hyperemic index in post-menopausal women with high levels in serum LDL-cholesterol

Pre-procedural use of statins is suggested to improve clinical outcomes in both short- and long-terms for patients with acute coronary syndrome who underwent percutanous coronary intervention [1,2]. Recent experimental and clinical studies indicate that statins have pleiotropic vascular protective effects beyond cholesterol reduction [3,4]. Endothelial function is one of the earliest abnormalities that can be detected in the development of atherosclerosis and contributes to predict the outcome of coronary heart disease [5–7].

Abstract P4-09-02: Prognostic and Predictive Value of Centrally Reviewed Ki67 Labeling Index in Postmenopausal Women with Endocrine-Responsive Breast Cancer: Results from Austrian Breast and Colorectal Cancer Study Group Trial 8

Abstract Purpose: The aim of the present study was to assess the prognostic and predictive value of Ki67 labeling index in postmenopausal hormone receptor-positive early breast cancer patients who were treated with adjuvant tamoxifen or anastrozole after tamoxifen. Patients and Methods: We determined the expression of Ki67 by immunohistochemistry on whole tissue sections of breast carcinoma patients who had been enrolled in Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 8 and received tamoxifen for 5 years or tamoxifen for 2 years followed by anastrozole for 3 years. Ki67 labeling index was evaluated as continuous variable or dichotomized at 10%. Distant recurrence and death were analyzed using Cox models adjusted for clinical and pathological factors. Results: High Ki67 labeling index was observed in 394 of 1587 (23%) tumors and was associated with poor outcome. Patients with high Ki67 labeling index had a significantly shorter distant recurrence-free survival (adjusted hazard ratio [HR] for distant recurrence 2.16, 95% confidence interval [CI] 1.43-3.25, P &amp;lt; 0.001) and overall survival (adjusted HR for death 1.77, 95% CI 1.30-2.42, P &amp;lt; 0.001) as compared to patients with low Ki67 labeling index. No interaction between Ki67 labeling index and treatment was observed (P = 0.84). Conclusion: High Ki67 labeling index is an independent poor prognostic factor for distant recurrence and death in postmenopausal women with early-stage, hormone receptor-positive breast cancer but is not predictive for outcome of adjuvant treatment with either tamoxifen or tamoxifen followed by anastrozole. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-09-02.

Calcium and vitamin D supplementation through fortified dairy products counterbalances seasonal variations of bone metabolism indices: the Postmenopausal Health Study

To assess the effectiveness of a dietary intervention combined with fortified dairy products on bone metabolism and bone mass indices in postmenopausal women. Forty postmenopausal women (55-65 years old) were equally randomized into a dietary group (DG), receiving daily and for 30 months, 1,200 mg of calcium and 7.5 μg of vitamin D(3) for the first 12 months that increased to 22.5 μg for the remaining 18 months of intervention through fortified dairy products; and a control group (CG). Differences in the changes of bone metabolism and bone mass indices were examined with repeated measures ANOVA. A significant increase was observed for PTH levels only in the CG during the first six winter months of intervention (p = 0.049). After 30 months of intervention, during winter, serum 25(OH)D significantly decreased in the CG while remained in the same high levels as in the summer period in the DG. Serum RANKL levels decreased significantly in the DG compared with the increase in the CG during the 30-month intervention period (p = 0.005). Serum CTx decreased significantly in the DG after six (-0.08; -0.12 to -0.03) and 12 (-0.03; -0.08 to -0.02) months of intervention. Finally, the DG had more favorable changes in total body BMD than the CG (p < 0.001). Increasing dietary intake of calcium and vitamin D in osteopenic postmenopausal women appears to be effective in producing favorable changes in several bone metabolism and bone mass indices and in counterbalancing seasonal variations in hormonal and biochemical molecules.

Serum Sclerostin Levels Negatively Correlate with Parathyroid Hormone Levels and Free Estrogen Index in Postmenopausal Women

Sclerostin is a negative regulator of bone formation. The aim of the study was to compare serum sclerostin levels in premenopausal and postmenopausal women and evaluate its relationship to estrogen, TH, bone turnover, and bone mass. We conducted a cross-sectional observational study of healthy community-dwelling pre- and postmenopausal women. There were no interventions. We compared serum sclerostin levels in pre- and postmenopausal women and correlated sclerostin levels with female sex hormones, calciotropic hormones, bone turnover markers, and bone mineral density. Premenopausal women were 26.8 yr old, and postmenopausal women were 56.8 yr old. Postmenopausal women had lower values for estradiol (30 +/- 23 vs. 10 +/- 4 pg/ml; P < 0.001), estrone (61 +/- 24 vs. 29 +/- 10 pg/ml; P <0.001), and free estrogen index (FEI) (6 +/- 4 vs. 3 +/- 2 pmol/nmol; P = 0.008) and significantly lower bone mineral density at all sites compared to premenopausal women, with no significant differences in levels of PTH, 25-hydroxy or 1,25-dihydroxy vitamin D levels. Postmenopausal women had significantly higher serum sclerostin levels (1.16 +/- 0.38 ng/ml vs. 0.48 +/- 0.15 ng/ml; P < 0.001). Because most of the premenopausal women were on oral contraceptives, subsequent analyses were limited to postmenopausal women. There were significant negative correlations between sclerostin and FEI and sclerostin and PTH in this group. Using multiple regression analysis, both FEI (beta = -0.629; P = 0.002) and PTH (beta = -0.554; P = 0.004) were found to be independent predictors of sclerostin levels in postmenopausal women. Our findings suggest that serum sclerostin levels are regulated by both estrogens and PTH in postmenopausal women. These findings need to be explored further in larger prospective studies.

Effect of Total Dietary Fat and Omega 3 Fatty Acid Intake on Plasma Estrogen and Androgen Indices in Postmenopausal Women: Risk Reduction for Breast Cancer

Effect of Total Dietary Fat and Omega 3 Fatty Acid Intake on Plasma Estrogen and Androgen Indices in Postmenopausal Women: Risk Reduction for Breast Cancer

Bone mineral density and its relationship with body mass index in postmenopausal women with type 2 diabetes mellitus in mainland China

Bone mineral density (BMD) and its association with body mass index (BMI) are uncertain in postmenopausal women with type 2 diabetes mellitus (T2DM) in mainland China. This study was performed to assess this association including 1,042 postmenopausal women with T2DM and 919 non-diabetic control subjects. Bone mineral density of the posteroanterior spine and of the left hip was measured by use of dual-energy X-ray absorptiometry. Diabetic participants were divided into three groups according to BMI, i.e. low BMI (DML < 18.5 kg/m(2)), intermediate BMI (DMM 18.5-24.9 kg/m(2)), and high BMI (DMH >or= 25 kg/m(2)). The BMD values of diabetic subjects between groups exhibited a significant gradient difference, with DML < DMM < DMH. On the fitting curves, where BMD in various skeletal regions varied with age, BMDs of DML were approximately 15% lower than those of DMM, and those of DMM were approximately 10% lower than those of DMH. For prevalence and risks of osteoporosis a gradient difference was observed among diabetic groups, DML > DMM approximately control > DMH. The osteoporosis risk was higher for the hip than for the lumbar spine, especially in DML. This study indicated that postmenopausal women with T2DM had higher BMD and lower osteoporosis risk in the lumbar spine, and that lower BMI was an indicator of osteoporosis in mainland China.

Prognostic and Predictive Value of Centrally Reviewed Ki-67 Labeling Index in Postmenopausal Women With Endocrine-Responsive Breast Cancer: Results From Breast International Group Trial 1-98 Comparing Adjuvant Tamoxifen With Letrozole

To evaluate the prognostic and predictive value of Ki-67 labeling index (LI) in a trial comparing letrozole (Let) with tamoxifen (Tam) as adjuvant therapy in postmenopausal women with early breast cancer. Breast International Group (BIG) trial 1-98 randomly assigned 8,010 patients to four treatment arms comparing Let and Tam with sequences of each agent. Of 4,922 patients randomly assigned to receive 5 years of monotherapy with either agent, 2,685 had primary tumor material available for central pathology assessment of Ki-67 LI by immunohistochemistry and had tumors confirmed to express estrogen receptors after central review. The prognostic and predictive value of centrally measured Ki-67 LI on disease-free survival (DFS) were assessed among these patients using proportional hazards modeling, with Ki-67 LI values dichotomized at the median value of 11%. Higher values of Ki-67 LI were associated with adverse prognostic factors and with worse DFS (hazard ratio [HR; high:low] = 1.8; 95% CI, 1.4 to 2.3). The magnitude of the treatment benefit for Let versus Tam was greater among patients with high tumor Ki-67 LI (HR [Let:Tam] = 0.53; 95% CI, 0.39 to 0.72) than among patients with low tumor Ki-67 LI (HR [Let:Tam] = 0.81; 95% CI, 0.57 to 1.15; interaction P = .09). Ki-67 LI is confirmed as a prognostic factor in this study. High Ki-67 LI levels may identify a patient group that particularly benefits from initial Let adjuvant therapy.

Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women.

SummaryVitamin K mediates the synthesis of proteins regulating bone metabolism. We have tested whether high vitamin K2 intake promotes bone mineral density and bone strength. Results showed that K2 improved BMC and femoral neck width, but not DXA-BMD. Hence high vitamin K2 intake may contribute to preventing postmenopausal bone loss.IntroductionVitamin K is involved in the synthesis of several proteins in bone. The importance of K vitamins for optimal bone health has been suggested by population-based studies, but intervention studies with DXA-BMD as a clinical endpoint have shown contradicting results. Unlike BMC, DXA-BMD does not take into account the geometry (size, thickness) of bone, which has an independent contribution to bone strength and fracture risk. Here we have tested whether BMC and femoral neck width are affected by high vitamin K intake.MethodsA randomized clinical intervention study among 325 postmenopausal women receiving either placebo or 45 mg/day of vitamin K2 (MK-4, menatetrenone) during three years. BMC and hip geometry were assessed by DXA. Bone strength indices were calculated from DXA-BMD, femoral neck width (FNW) and hip axis length (HAL).ResultsK2 did not affect the DXA-BMD, but BMC and the FNW had increased relative to placebo. In the K2-treated group hip bone strength remained unchanged during the 3-year intervention period, whereas in the placebo group bone strength decreased significantly.ConclusionsVitamin K2 helps maintaining bone strength at the site of the femoral neck in postmenopausal women by improving BMC and FNW, whereas it has little effect on DXA-BMD.