Drospirenone and levonorgestrel in combination with either 30 or 20 mcg ethinylestradiol reduce soluble adhesion molecules in Brazilian women; cross-sectional study

Background: The objective of this study was to evaluate the effect of three contraceptive pills containing ethinylestradiol (EE) (20 or 30 mcg) in combination with drospirenone (DRSP) and levonorgestrel (LNG) on plasma concentration of adhesion molecules vascular cell adhesion molecule -1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin. Study Design: A cross-sectional study was conducted with 72 participants (18-30 years old) distributed into three groups that used oral contraceptives containing EE 20 or 30 mcg combined with DRSP 3 mg or EE 30 mcg/LNG 150 mcg for at least 6 months. The control group was comprised of nonusers of contraceptives. Soluble VCAM-1, soluble ICAM-1 and soluble E-selectin were evaluated by enzyme-linked immunosorbent assay. Results: Compared to the control group, a significant decrease was found in VCAM-1 and ICAM-1 concentrations with use of DRSP/20 EE and LNG/30 EE. Conclusions: DRSP/20 EE and LNG/30 EE induce favorable changes in endothelial function. (C) 2012 Elsevier Inc. All rights reserved.

Effects of phytoestrogens derived from soy bean on expression of adhesion molecules on HUVEC

Background The risks of hormone replacement therapy have led to a search for new alternatives such as phytoestrogens, plant compounds with estrogen-like biological activity. Isoflavones are the phytoestrogens most extensively studied and can be found in soybean, red clover and other plants. Due to this estrogen-like activity, phytoestrogens can have some effect on atherosclerosis. Human umbilical vein endothelial cells (HUVEC) have been extensively used to study the biology and pathobiology of human endothelial cells and most of the knowledge acquired is due to experiments with cultures of these cells. Objective To evaluate the effects of the phytoestrogen extracts from Glycine max soy bean, genistein, formononetin, biochanin A and daidzein, as well as a mixture of these extracts (Mix), on expression of adhesion molecules, VCAM-1, ICAM-1 and E-selectin, by endothelial cell HUVEC, stimulated with lipopolysaccharide. Methods HUVEC were cultured in medium EBM2, pretreated with isoflavones for 24 and 48 h and then stimulated with lipopolysaccharide; in addition, isoflavones were added, after stimulation by lipopolysaccharide, to HUVEC. We evaluated the production of VCAM-1, ICAM-1 and E-selectin on cell surface, by cell-based enzyme immunoassay, and of sVCAM-1, sICAM-1 and sE-selectin in culture supernatant, by ELISA. Results Genistein, formononetin, biochanin A and daidzein, as well as the Mix were able to reduce VCAM-1, ICAM-1 and E-selectin on cell surface and in culture supernatant. Conclusion Isoflavones extracted from Glycine max soy bean, in vitro, presented antiatherogenic effects, reducing the expression of adhesion molecules and acting as preventive agents as well as therapeutic agents.

VIP expression in vessels of the vaginal wall: relationship with estrogen status

Objective Vasoactive intestinal peptide (VIP) is a neuropeptide with elevated expression in regions that control urogenital functions. Estrogen appears to modulate VIP expression in various organs, but this effect has not been demonstrated in the vaginal wall. The aim of this study was to evaluate the influence of estrogen status on VIP expression in vessels of the vaginal wall. Methods Surgical specimens were removed from the vaginal walls of 18 premenopausal women and 12 postmenopausal women who were given surgery for genital prolapse grade I or II. Vaginal specimens were stained with estrogen receptor-alpha (ER-alpha) and VIP antibodies. Levels of follicle stimulating hormone (FSH), estradiol, prolactin, fasting glucose and serum thyroxine stimulating hormone were also measured. Estrogen status was assessed on the basis of FSH and ER-alpha scores. Results The vaginal walls of premenopausal women had significantly higher ER-alpha scores than those of menopausal women (premenopausal group, 3.6 +/- 2.2; menopausal group, 1.4 +/- 1.8; p = 0.01). Premenopausal women also had significantly higher levels of VIP in the vaginal wall than menopausal women (p = 0.02). Increasing age was associated with lower level of VIP staining (odds ratio 0.88; 95% confidence interval 0.78-0.99). Conclusion Levels of ER-alpha and VIP expression in the posterior vaginal wall were higher in premenopausal than in menopausal women, but VIP expression was not associated with estrogen status. Age was an independent predictor of VIP staining in vaginal wall biopsies.

Antiresorptive drugs (bisphosphonates), atypical fractures and rebound effect: new evidence of similitude

Background: Homeopathy is based on treatment by similitude ('like cures like') administering to sick individuals substances that cause similar symptoms in healthy individuals, employing the secondary and paradoxical action of the organism as therapeutic response. This vital or homeostatic reaction of the organism can be scientifically explained by the rebound effect of drugs, resulting in worsening of symptoms after suspension of treatment. Bisphosphonates (BPs) reduce 'typical' fractures in patients with osteoporosis, but recent studies report 'atypical' fractures of the femur after stopping the BPs, a rebound effect may be the causal mechanism. Method: Review of the literature concerning the relationship between atypical femoral fractures and antiresorptive drugs (bisphosphonates), identifying the pathogenesis of this adverse event. Results: Several studies have described multiple cases of 'atypical' low-impact subtrochanteric stress fractures or complete fractures of the femur. These fractures are often bilateral, preceded by pain in the affected thigh, may have a typical X-ray appearance, and may delayed healing. Rebound of osteoclastic activity after suspension of antiresorptive drugs is a plausible mechanism to explain this phenomenon. Conclusion: As for other classes of drugs, the rebound effect of antiresorptive drugs supports Hahnemann's similitude principle (primary action of the drugs followed by secondary and opposite action of the organism), and clarifies this 'unresolved' issue. Unfortunately, the rebound effect is little discussed among health professionals, depriving them of important knowledge ensure safe management of drugs. Homeopathy (2012) 101, 231-242.

Strength training improves plasma parameters, body composition and liver morphology in ovariectomized rats

Objective. - The aim of this study was to identify the effects of strength training on plasma parameters, body composition and the liver of ovariectomized rats. Methods. - Wistar sedentary (SHAM), ovariectomized (OVX), and ovariectomized trained rats (strength training [OVX-EXE]) of 85% of one maximal repetition (1 RM), three times per week, for 10 weeks, were used on this study. We monitored the body weight and visceral (uterine, mesenteric and retroperitoneal) and subcutaneous adiposity, total cholesterol, triglycerides, HDL, blood glucose and liver morphology to identify the presence of macrovesicular steotosis (haematoxylin and eosin staining). Results. - We observed that strength training changed body weight (SHAM 293.0 +/- 14.5 g; OVX 342.6 +/- 10.8 g; OVX-EXE 317.7 +/- 11.9 g, P < 0.05), visceral and subcutaneous adiposity, glucose (SHAM 111.2 +/- 10.0 mg/dL; OVX 147.4 +/- 18.8 mg/dL; OVX-EXE 118.5 +/- 2.2 mg/dL, P < 0.05), increased HDL (SHAM 82.7 +/- 1.4 mg/dL; OVX 64.6 +/- 2.8 mg/dL; OVX-EXE 91.4 +/- 2.6 mg/dL, P < 0.05) and reduced macrovesicular steatosis in liver tissue. Conclusions. - Considering the data obtained in this research, we emphasise the use of strength exercise training as a therapeutic means to combat or control the metabolic disturbances associated with menopause, including adiposity, and adverse changes in blood glucose, blood HDL and macrovesicular steatosis. (C) 2011 Elsevier Masson SAS. All rights reserved.

Low fatness, reduced fat intake and adequate plasmatic concentrations of LDL-cholesterol are associated with high bone mineral density in women: a cross-sectional study with control group

Background: Several parameters are associated with high bone mineral density (BMD), such as overweight, black background, intense physical activity (PA), greater calcium intake and some medications. The objectives are to evaluate the prevalence and the main aspects associated with high BMD in healthy women. Methods: After reviewing the database of approximately 21,500 BMD scans performed in the metropolitan area of Sao Paulo, Brazil, from June 2005 to October 2010, high BMD (over 1400 g/cm(2) at lumbar spine and/or above 1200 g/cm2 at femoral neck) was found in 421 exams. Exclusion criteria were age below 30 or above 60 years, black ethnicity, pregnant or obese women, disease and/or medications known to interfere with bone metabolism. A total of 40 women with high BMD were included and matched with 40 healthy women with normal BMD, paired to weight, age, skin color and menopausal status. Medical history, food intake and PA were assessed through validated questionnaires. Body composition was evaluated through a GE-Lunar DPX MD + bone densitometer. Radiography of the thoracic and lumbar spine was carried out to exclude degenerative alterations or fractures. Biochemical parameters included both lipid and hormonal profiles, along with mineral and bone metabolism. Statistical analysis included parametric and nonparametric tests and linear regression models. P < 0.05 was considered significant. Results: The mean age was 50.9 (8.3) years. There was no significant difference between groups in relation to PA, smoking, intake of calcium and vitamin D, as well as laboratory tests, except serum C-telopeptide of type I collagen (s-CTX), which was lower in the high BMD group (p = 0.04). In the final model of multivariate regression, a lower fat intake and body fatness as well a better profile of LDL-cholesterol predicted almost 35% of high BMD in women. (adjusted R2 = 0.347; p < 0.001). In addition, greater amounts of lean mass and higher IGF-1 serum concentrations played a protective role, regardless age and weight. Conclusion: Our results demonstrate the potential deleterious effect of lipid metabolism-related components, including fat intake and body fatness and worse lipid profile, on bone mass and metabolism in healthy women.

Bioactive compounds with effects on inflammation markers in humans

Obesity and other chronic diseases are accompanied by adipose tissue, liver, pancreas, muscle and brain low-grade chronic inflammation. Indeed, the obese condition and metabolic syndrome are characterized by an increased expression of inflammatory cytokines and infiltration of immune cells in adipocytes. The inflammatory response promotes the activation of transcriptional factors and pro-inflammatory cytokines, which can lead to an unresolved inflammatory response associated with an inhibition of insulin signalling and high risk for cardiovascular events. Epidemiological and intervention studies have been carried out to find out dietary patterns, foods and bioactive compounds with protective anti-inflammatory actions. The most studied compounds are polyphenols, especially isoflavone and anthocyanin, but quercertin, catechin and resveratrol have also been investigated. Furthermore, some studies have reported the effects of milk peptides, plant sterol and stanol, L-carnitine and alpha-lipoic acid on inflammatory processes. This review aimed to collect and discuss those relevant studies reported in the scientific literature following a systematic scientific search about the effect of such bioactive compounds on inflammation in humans.

Exogenous Administration of 15d-PGJ(2)-Loaded Nanocapsules Inhibits Bone Resorption in a Mouse Periodontitis Model

The 15-deoxy-(Delta 12,14)-PG J(2) (15d-PGJ(2)) has demonstrated excellent anti-inflammatory results in different experimental models. It can be used with a polymeric nanostructure system for modified drug release, which can change the therapeutic properties of the active principle, leading to increased stability and slower/prolonged release. The aim of the current study was to test a nano-technological formulation as a carrier for 15d-PGJ(2), and to investigate the immunomodulatory effects of this formulation in a mouse periodontitis model. Poly (D, L-lactide-coglycolide) nanocapsules (NC) were used to encapsulate 15d-PGJ(2). BALB/c mice were infected on days 0, 2, and 4 with Aggregatibacter actinomycetemcomitans and divided into groups (n = 5) that were treated daily during 15 d with 1, 3, or 10 mu g/kg 15d-PGJ(2)-NC. The animals were sacrificed, the submandibular lymph nodes were removed for FACS analysis, and the jaws were analyzed for bone resorption by morphometry. Immunoinflammatory markers in the gingival tissue were analyzed by reverse transcriptase-quantitative PCR, Western blotting, or ELISA. Infected animals treated with the 15d-PGJ(2)-NC presented lower bone resorption than infected animals without treatment (p < 0.05). Furthermore, infected animals treated with 10 mu g/kg 15d-PGJ(2)-NC had a reduction of CD4(+)CD25(+)FOXP3(+) cells and CD4/CD8 ratio in the submandibular lymph node (p < 0.05). Moreover, CD55 was upregulated, whereas RANKL was downregulated in the gingival tissue of the 10 mu g/kg treated group (p < 0.05). Several proinflammatory cytokines were decreased in the group treated with 10 mu g/kg 15d-PGJ(2)-NC, and high amounts of 15d-PGJ(2) were observed in the gingiva. In conclusion, the 15d-PGJ(2)-NC formulation presented immunomodulatory effects, decreasing bone resorption and inflammatory responses in a periodontitis mouse model. The Journal of Immunology, 2012, 189: 1043-1052.

Sleep disorders in climacteric women

Introduction: This paper examines the various factors that contribute to the occurrence of sleep alterations during peri and post climacteric and thus produce significant imperil to women's quality of life. Among the probable causes of insomnia or sleep disorders associated to climacteric stand out the occurrence of vasomotor symptoms, depressive state and respiratory distress during sleep, such as sleep apnea, along with chronic pain, although psychosocial factors related to the climacteric bear major influence on such clinical status. Method: The bibliographic analysis was carried out using several electronic data base namely: Cochrane, Medline, Embase, Bni Plus, Biological Abstracts, Psycinfo, Web Of Science, Sigle, Dissertation Abstracts and ZETOC published in English, Spanish and Poruguese. The key terms used were: sleep, REM sleep, slow wave sleep polysomnography; electroencephalogram; sleep disturbances; disturbances of sleep onset and maintenance; excessive somnolence disturbances; climacteric; menopause; depression; neurobiology; biologic models; circadian rhythm; mental health and epidemiology. Case studies and letters to the editor were excluded. The summaries of the identified studies found in the data base were analyzed and assessed, and the data analyzed separately according to the subjective or objective criteria for data collection. Results: The climacteric transition constitutes a period of major risk for the development of depressive, vasomotor and insomnia symptoms although not caused solely by hypoestrogenism. The diagnostic methods used in the study of sleep disorders range from subjective assessment by means of response to specific questionnaires to the objective analysis of actigraphic or polissonographic daytime and nocturnal reports. Polissonographic studies of the whole night, performed at the laboratory, are the golden method of choice for diagnostic of sleep disorders. Studies point to the high prevalence of sleep disorders in the climacteric, especially insomnia, apnea and periodic movement of legs and also to the fact that this phase of life presents decrease in the quality of sleep. Women in peri and post climacteric show higher sleep latency and difficulty in its maintenance and refer being less satisfied with its quality even when compared to those who are not climacteric. Exception made to the vasomotor symptomatology, the other climacteric complaints such as mood disturbances, libido alterations, cognitive deficit, articular pain and sleep disorders are markedly associated to psychosocial factors, lifestyle and especially to women's perception of what the climacteric means to their lives. Conclusion: The analysis of the available studies revealed a proneness to deterioration of quality of life of climacteric women markedly in the sleep disturbances, depressed mood and anxiety domains and should not to be basically attributed to the climacteric. It is necessary that the professionals consider the need of assessment of such pathologies as complex phenomena and the literature lacks studies contemplating such dimensions.

Study of the osteoconductive capacity of hydroxyapatite implanted into the femur of ovariectomized rats

Osteoporosis is a global public health that affects postmenopausal women due to the deficiency of estrogen, a hormone that plays an important role in the microarchitecture of bone tissue. Osteoporosis predisposes to pathological bone fracture that can be repaired by conventional methods. However, depending on the severity and quantity of bone loss, the use of autogenous grafts or biomaterials such as hydroxyapatite might be necessary. The latter has received increasing attention in the medical field because of its good biological properties such as osteoconductivity and biocompatibility with bone tissue. The objective of this study was to evaluate using histologic and radiographic analyses, the osteogenic capacity of hydroxyapatite implanted into the femur of rats with ovariectomy-induced osteoporosis. Eighteen rats were divided into three groups with six animals in each: group nonovariectomized, bilaterally ovariectomized not receiving estrogen replacement therapy, and bilaterally ovariectomized submitted to estrogen replacement therapy. Defects were created experimentally in the distal epiphysis of the femur with a surgical drill and filled with porous hydroxyapatite granules. The animals were sacrificed 8 weeks after surgery. The volume of newly formed bone in the implant area was quantified by morphometrical methods. The results were analyzed by ANOVA followed by the Tukey test (P < 0.05). The hydroxyapatite granules showed good radiopacity. Histological analysis revealed less quantity of newly formed bone in the ovariectomized group not submitted to hormone replacement therapy. In conclusion, bone neoformation can be expected even in bones compromised by estrogen deficiency, but the quantity and velocity of bone formation are lower. Microsc. Res. Tech., 2011. (c) 2011 Wiley Periodicals, Inc.

17 beta-Estradiol replacement in young, adult and middle-aged female ovariectomized rats promotes improvement of spatial reference memory and an antidepressant effect and alters monoamines and BDNF levels in memory- and depression-related brain areas

Clinical and experimental evidence suggest that estrogens have a major impact on cognition, presenting neurotrophic and neuroprotective actions in regions involved in such function. In opposite, some studies indicate that certain hormone therapy regimens may provoke detrimental effects over female cognitive and neurological function. Therefore, we decided to investigate how estrogen treatment would influence cognition and depression in different ages. For that matter, this study assessed the effects of chronic 17 beta-estradiol treatment over cognition and depressive-like behaviors of young (3 months old), adult (7 months old) and middle-aged (12 months old) reproductive female Wistar rats. These functions were also correlated with alterations in the serotonergic system, as well as hippocampal BDNF. 17 beta-Estradiol treatment did not influence animals' locomotor activity and exploratory behavior, but it was able to improve the performance of adult and middle-aged rats in the Morris water maze, the latter being more responsive to the treatment. Young and adult rats displayed decreased immobility time in the forced swimming test, suggesting an effect of 17 beta-estradiol also over such depressive-like behavior. This same test revealed increased swimming behavior, triggered by serotonergic pathway, in adult rats. Neurochemical evaluations indicated that 17 beta-estradiol treatment was able to increase serotonin turnover rate in the hippocampus of adult rats. Interestingly, estrogen treatment increased BDNF levels from animals of all ages. These findings support the notion that the beneficial effects of 17 beta-estradiol over spatial reference memory and depressive-like behavior are evident only when hormone therapy occurs at early ages and early stages of hormonal decline. (C) 2011 Elsevier B.V. All rights reserved.

The impact of asymptomatic vertebral fractures on quality of life in older community-dwelling women: the Sao Paulo Ageing & Health Study

OBJECTIVES: The aim of this study was to investigate the impact of asymptomatic vertebral fractures on the quality of life in older women as part of the Sao Paulo Ageing & Health Study. METHODS: This study was a cross-sectional study with a random sample of 180 women 65 years of age or older with or without vertebral fractures. The Quality of Life Questionnaire of the European Foundation for Osteoporosis was administered to all subjects. Anthropometric data were obtained by physical examination, and the body mass index was calculated. Lateral thoracic and lumbar spine X-ray scans were obtained to identify asymptomatic vertebral fractures using a semi-quantitative method. RESULTS: Women with asymptomatic vertebral fractures had lower total scores [61.4(15.3) vs. 67.1(14.2), p = 0.03] and worse physical function domain scores [69.5(20.1) vs. 77.3(17.1), p = 0.02] for the Quality of Life Questionnaire of the European Foundation for Osteoporosis compared with women without fractures. The total score of this questionnaire was also worse in women classified as obese than in women classified as overweight or normal. High physical activity was related to a better total score for this questionnaire (p = 0.01). Likewise, lower physical function scores were observed in women with higher body mass index values (p < 0.05) and lower physical activity levels (p < 0.05). Generalized linear models with gamma distributions and logarithmic link functions, adjusted for age, showed that lower total scores and physical function domain scores for the Quality of Life Questionnaire of the European Foundation for Osteoporosis were related to a high body mass index, lower physical activity, and the presence of vertebral fractures (p < 0.05). CONCLUSION: Vertebral fractures are associated with decreased quality of life mainly physical functioning in older community-dwelling women regardless of age, body mass index, and physical activity. Therefore, the results highlight the importance of preventing and controlling asymptomatic vertebral fractures to reduce their impact on quality of life among older women.

Construction and validation of an instrument that breaks the silence: the impact of domestic and/or sexual violence on women's health, as shown during climacterium

Objective: The aim of this study was to construct and to validate a measure of the consequences of domestic violence on women's health during climacterium. Methods: A questionnaire was administered at the Outpatient Climacterium Clinic to 124 women aged 40 to 65 years who were the victims of domestic and/or sexual violence (experimental group). They were divided into three groups: (1) those who were victims of violence exclusively during childhood/adolescence, (2) those who were victims of violence exclusively during adulthood, and (3) those who were victims of violence throughout their lives. The instrument included 34 items evaluating the beginning, frequency, and type of violence; the search for health assistance and reporting of the violence; the violence and the number of comorbidities; and violence and the Kupperman Menopausal Index. We also included a control group composed of perimenopausal and postmenopausal women who did not experience any violence (n = 120). Results: The instrument presented a Cronbach alpha = 0.82, good reliability among the examiners (+0.80), and a good possibility of reproducibility. The mean age of menopause was 45.4 years, and the mean age in the control group was 48.1 years. Group 1 showed a mean of 5.1 comorbidities, Group 2 had 4.6, and Group 3 had 4.4. Sexual violence (43.5%) and other types of violence both presented average comorbidities (4.60) but represented a significant impairment in the victim's sexual life. There were significant associations in group 3 and a high Kupperman Menopausal Index score. In the experimental group, 80.6% did not seek health services for the violence they experienced. Conclusions: The questionnaire presented good internal consistency and a validated construction. It can be easily reproduced and is indicated to evaluate the consequences of domestic and/or sexual violence on women's health during climacterium.

Low Bone Mineral Density in Middle-Aged Breast Cancer Survivors: Prevalence and Associated Factors

Background: The aim of this study was to investigate the prevalence of low bone mineral density (BMD) and associated factors in middle-aged breast cancer survivors (BCS). Patients and Methods: A cross-sectional study was conducted with 70 BCS of 45-65 years of age undergoing complete oncology treatment. Logistic regression models were used to identify factors associated with low BMD (osteopenia and osteoporosis taken together as a single group). Results: The mean age of participants was 53.2 +/- 5.9 years. BMD was low at the femoral neck in 28.6% of patients and at the lumbar spine in 45.7%. Body mass index <= 30 kg/m(2) (adjusted odds ratio (OR) 3.43; 95% confidence interval (CI) 1.0-11.3) and postmenopausal status (OR adjusted 20.42; 95% CI 2.0-201.2) were associated with low BMD at the lumbar spine. Femoral neck measurements, age > 50 years (OR 3.41; 95% CI 1.0-11.6), and time since diagnosis > 50 months (OR adjusted 3.34; 95% CI 1.0-11.3) increased the likelihood of low BMD. Conclusion: These findings show that low BMD is common in middle-aged BCS. Factors were identified that may affect BMD in BCS and should be considered when implementing strategies to minimize bone loss in middle-aged women with breast cancer.

The renin–angiotensin system plays a major role in voiding dysfunction of ovariectomized rats

Aims: The renin–angiotensin system (RAS) plays a major role in cardiovascular diseases in postmenopausal women, but little is known about its importance to lower urinary tract symptoms. In this study we have used the model of ovariectomized (OVX) estrogen-deficient rats to investigate the role of RAS in functional and molecular alterations in the urethra and bladder. Main methods: Responses to contractile and relaxant agents in isolated urethra and bladder, as well as cystometry were evaluated in 4-month OVX Sprague–Dawley rats. Angiotensin-converting enzyme activity and Western blotting for AT1/AT2 receptors were examined. Key findings: Cystometric evaluations in OVX rats showed increases in basal pressure, capacity and micturition frequency, as well as decreased voiding pressure. Angiotensin II and phenylephrine produced greater urethral contractions in OVX compared with Sham group. Carbachol-induced bladder contractions were significantly reduced in OVX group. Relaxations of urethra and bladder to sodium nitroprusside and BAY 41-2272 were unaffected by OVX. Angiotensin-converting enzyme activity was 2.6-fold greater (p < 0.05) in urethral tissue of OVX group,whereas enzyme activity in plasma and bladder remained unchanged. Expressions of AT1 and AT2 receptors in the urethra were markedly higher in OVX group. In bladder, AT1 receptors were not detected, whereas AT2 receptor expression was unchanged between groups. 17β-Estradiol replacement (0.1 mg/kg, weekly) or losartan (30 mg/kg/day) largely attenuated most of the alterations seen in OVX group. Significance: Prolonged estrogen deprivation leads to voiding dysfunction and urethral hypercontractility that are associated with increased ACE activity and up-regulation of angiotensin AT1/AT2 receptor in the urethral tissue.