Hormone replacement therapy increases levels of antibodies against heat shock protein 65 and certain species of oxidized low density lipoprotein

Hormone replacement therapy (HRT) reduces cardiovascular risks, although the initiation of therapy may be associated with transient adverse ischemic and thrombotic events. Antibodies against heat shock protein (Hsp) and oxidized low density lipoprotein (LDL) have been found in atherosclerotic lesions and plasma of patients with coronary artery disease and may play an important role in the pathogenesis of atherosclerosis. The aim of the present study was to assess the effects of HRT on the immune response by measuring plasma levels of antibodies against Hsp 65 and LDL with a low and high degree of copper-mediated oxidative modification of 20 postmenopausal women before and 90 days after receiving orally 0.625 mg equine conjugate estrogen plus 2.5 mg medroxyprogesterone acetate per day. HRT significantly increased antibodies against Hsp 65 (0.316 ± 0.03 vs 0.558 ± 0.11) and against LDL with a low degree of oxidative modification (0.100 ± 0.01 vs 0.217 ± 0.02) (P<0.05 and P<0.001, respectively, ANOVA). The hormone-mediated immune response may trigger an inflammatory response within the vessel wall and potentially increase plaque burden. Whether or not this immune response is temporary or sustained and deleterious requires further investigation.

Endothelial mediators of 17ß-estradiol-induced coronary vasodilation in the isolated rat heart

The present study was designed to determine relaxation in response to 17ß-estradiol by isolated perfused hearts from intact normotensive male and female rats as well as the contribution of endothelium and its relaxing factors to this action. Baseline coronary perfusion pressure was determined and the vasoactive effects of 17ß-estradiol (10 µM) were assessed by in bolus administration before and after endothelium denudation by infusion of 0.25 µM sodium deoxycholate or perfusion with 100 µM L-NAME, 2.8 µM indomethacin, 0.75 µM clotrimazole, 100 µM L-NAME plus 2.8 µM indomethacin, and 100 µM L-NAME plus 0.75 µM clotrimazole. Baseline coronary perfusion pressure differed significantly between males (84 ± 2 mmHg, N = 61) and females (102 ± 2 mmHg, N = 61). Bolus injection of 10 µM 17ß-estradiol elicited a transient relaxing response in all groups, which was greater in coronary beds from females. For both sexes, the relaxing response to 17ß-estradiol was at least in part endothelium-dependent. In the presence of the nitric oxide synthase inhibitor L-NAME, the relaxing response to 17ß-estradiol was reduced only in females. Nevertheless, in the presence of indomethacin, a cyclooxygenase inhibitor, or clotrimazole, a cytochrome P450 inhibitor, the 17ß-estradiol response was significantly reduced in both groups. In addition, combined treatment with L-NAME plus indomethacin or L-NAME plus clotrimazole also reduced the 17ß-estradiol response in both groups. These results indicate the importance of prostacyclin and endothelium-derived hyperpolarizing factor in the relaxing response to 17ß-estradiol. 17ß-estradiol-induced relaxation may play an important role in the regulation of coronary tone and this may be one of the reasons why estrogen replacement therapy reduces the risk of coronary heart disease in postmenopausal women.

Morphological changes induced by testosterone in the mammary glands of female Wistar rats

Increased levels of androgens in postmenopausal women are considered to be a risk factor for breast cancer. Testosterone, alone or in combination with estrogen, induces epithelial dysplasia and mammary tumors in Noble rats. Since this model of hormone-induced neoplasia has not been reported in other rat strains, we studied the effect of testosterone on the mammary gland morphology of female Wistar rats. Sixty adult, non-castrated, female Wistar rats were implanted in the dorsum midline with a silicone tube containing 50 mg testosterone (testosterone propionate in 30 animals and non-esterified testosterone in the remaining 30 animals) and 20 additional animals were implanted with empty tubes and used as control. Five animals per group were killed 30, 60, 90, 120, 150, and 180 days after implantation, and the mammary glands were dissected, fixed and embedded in paraffin. Histological sections were then stained with hematoxylin and eosin and picrosyrius red for collagen visualization. Morphological and morphometric analysis demonstrated ductal proliferation and acinotubular differentiation with secretory activity in all treated animals, peaking at 90 days of androgen exposure. After 90 days the proliferation of acinar epithelial cells was evident, but there was a progressive reduction of secretory differentiation and an increase in intralobular collagen fibers. There was no morphological evidence of dysplastic changes or other pre-neoplastic lesions. Testosterone treatment applied to adult, non-castrated female Wistar rats induced a mammary gland hyperplasia resembling the lactating differentiation, with progressive reduction in secretory differentiation.

Effect of estrogen receptor-alpha (ESR1) gene polymorphism on high density lipoprotein levels in response to hormone replacement therapy

Studies have shown that estrogen replacement therapy and estrogen plus progestin replacement therapy alter serum levels of total, LDL and HDL cholesterol levels. However, HDL cholesterol levels in women vary considerably in response to hormone replacement therapy (HRT). A significant portion of the variability of these levels has been attributed to genetic factors. Therefore, we investigated the influence of estrogen receptor-alpha (ESR1) gene polymorphisms on HDL levels in response to postmenopausal HRT. We performed a prospective cohort study on 54 postmenopausal women who had not used HRT before the study and had no significant general medical illness. HRT consisted of conjugated equine estrogen and medroxyprogesterone acetate continuously for 1 year. The lipoprotein levels were measured from blood samples taken before the start of therapy and after 1 year of HRT. ESR1 polymorphism (MspI C>T, HaeIII C>T, PvuII C>T, and XbaI A>G) frequencies were assayed by restriction fragment length polymorphism. A general linear model was used to describe the relationships between HDL levels and genotypes after adjusting for age. A significant increase in HDL levels was observed after HRT (P = 0.029). Women with the ESR1 PvuII TT genotype showed a statistically significant increase in HDL levels after HRT (P = 0.032). No association was found between other ESR1 polymorphisms and HDL levels. According to our results, the ESR1 PvuII TT genotype was associated with increased levels of HDL after 1 year of HRT.

Is liver transplantation associated with decreased bone mass in climacteric women?

PURPOSE: To evaluate whether climacteric women undergoing liver transplantation had higher prevalence of decreased bone mass than those without any liver disease. METHODS: A cross-sectional study with 48 women receiving follow-up care at a university hospital in Southeastern Brazil, from February 4th 2009 to January 5th 2011, was conducted. Of these women, 24 were 35 years or older and had undergone liver transplantation at least one year before study entry. The remaining 24 women had no liver disease and their ages and menstrual patterns were similar to those of transplanted patients. Laboratorial tests (follicle-stimulating hormone and estradiol) and bone density measurements of the lumbar spine and femur (equipment Hologic, Discovery WI) were performed. Statistical analysis was carried out by Fisher's exact test, simple Odds Ratio (OR), and multiple logistic regression. RESULTS: Mean age of the women included in the study was 52.8 (±10.7) years-old, 27.1% were premenopausal and 72.9% were peri/postmenopausal. Approximately 14.6% of these women exhibited osteoporosis and 35.4% had low bone mass. The following items were associated with decreased bone mass: being postmenopausal (OR=71.4; 95%CI 3.8 - 1,339.7; p<0.0001), current age over 49 years-old (OR=11.4; 95%CI 2.9 - 44.0; p=0.0002), and serum estradiol levels lower than 44.5 pg/mL (OR=18.3; 95%CI 3.4 - 97.0; p<0.0001). Having a history of liver transplantation was not associated with decreased bone mass (OR=1.4; 95%CI 0.4 - 4.3; p=0.56). CONCLUSION: Liver transplantation was not associated with decreased bone mass in this group of climacteric women.

Self-perception of sexual life and associated factors: a population study conducted in women aged 50 or more years

PURPOSE: To evaluate the prevalence of women aged 50 years or more who are sexually active and their self-perception with respect to their sexual lives. Associated factors were also assessed. METHODS: A cross-sectional, population-based, self-reported household survey involving 622 Brazilian women aged 50 years or more. Sociodemographic, clinical, and behavioral factors were evaluated. The sexual life self-perception was classified as very good, good, fair, poor, or very poor. Data were analyzed using the χ² test, Fisher's exact test, and Poisson multiple regression analysis. Prevalence ratios and their 95% confidence intervals were also calculated. RESULTS: Of the women in this sample, 228 (36.7%) reported having a sexual life and, of these, 53.5% classified it as very good or good, while 46.5% considered it fair, poor, or very poor. The bivariate analysis indicated that being postmenopausal (p=0.025) and using natural remedies to treat the menopause (p=0.035) were factors associated with the woman classifying their sexual lives as fair, poor, or very poor. Multiple regression analysis showed that more women who had used or were currently using natural remedies for the menopause scored their sexual lives as fair, poor, or very poor. CONCLUSIONS: More than half the women aged 50 years or more in this study were not sexually active. A poorer sexual life self-perception was associated with the use of natural remedies to treat menopausal symptoms. This may indicate a need to improve the way in which these women are evaluated and treated. Women's assessment of their own sexual lives may prove a useful tool in clinical practice.

Comparison of anaerobic threshold determined by visual and mathematical methods in healthy women

Several methods are used to estimate anaerobic threshold (AT) during exercise. The aim of the present study was to compare AT obtained by a graphic visual method for the estimate of ventilatory and metabolic variables (gold standard), to a bi-segmental linear regression mathematical model of Hinkley's algorithm applied to heart rate (HR) and carbon dioxide output (VCO2) data. Thirteen young (24 ± 2.63 years old) and 16 postmenopausal (57 ± 4.79 years old) healthy and sedentary women were submitted to a continuous ergospirometric incremental test on an electromagnetic braking cycloergometer with 10 to 20 W/min increases until physical exhaustion. The ventilatory variables were recorded breath-to-breath and HR was obtained beat-to-beat over real time. Data were analyzed by the nonparametric Friedman test and Spearman correlation test with the level of significance set at 5%. Power output (W), HR (bpm), oxygen uptake (VO2; mL kg-1 min-1), VO2 (mL/min), VCO2 (mL/min), and minute ventilation (VE; L/min) data observed at the AT level were similar for both methods and groups studied (P > 0.05). The VO2 (mL kg-1 min-1) data showed significant correlation (P < 0.05) between the gold standard method and the mathematical model when applied to HR (r s = 0.75) and VCO2 (r s = 0.78) data for the subjects as a whole (N = 29). The proposed mathematical method for the detection of changes in response patterns of VCO2 and HR was adequate and promising for AT detection in young and middle-aged women, representing a semi-automatic, non-invasive and objective AT measurement.

Poor sleep in middle-aged women is not associated with menopause per se

Whether sleep problems of menopausal women are associated with vasomotor symptoms and/or changes in estrogen levels associated with menopause or age-related changes in sleep architecture is unclear. This study aimed to determine if poor sleep in middle-aged women is correlated with menopause. This study recruited women seeking care for the first time at the menopause outpatient department of our hospital. Inclusion criteria were an age ≥40 years, not taking any medications for menopausal symptoms, and no sleeping problems or depression. Patients were assessed with the Pittsburgh Sleep Quality Index (PSQI), modified Kupperman Index (KI), and Menopause Rating Scale (MRS). A PSQI score of <7 indicated no sleep disorder and ≥7 indicated a sleep disorder. Blood specimens were analyzed for follicle-stimulating hormone and estradiol levels. A total of 244 women were included in the study; 103 (42.2%) were identified as having a sleep disorder and 141 as not having one. In addition, 156 (64%) women were postmenopausal and 88 (36%) were not menopausal. Follicle-stimulating hormone and estradiol levels were similar between the groups. Patients with a sleep disorder had a significantly higher total modified KI score and total MRS score (both, P<0.001) compared with those without a sleep disorder. Correlations of the PSQI total score with the KI and MRS were similar in menopausal and non-menopausal women. These results do not support that menopause per se specifically contributes to sleep problems.

Mid-upper arm circumference in pregnant women and its relation to birth weight

OBJECTIVE: In order to determine the relationship between some maternal anthropometric indicators and birth weight, crown-heel length and newborn's head circumference, 92 pregnant women were followed through at the prenatal service of hospital in S. Paulo, Brazil. MATERIAL AND METHOD: The following variables were established for the mother: weight, height, mid-upper arm circumference, pre-pregnancy weight, gestational weight gain and Quetelet's index. For the newborn the following variables were recorded: birth weight, crown-heel length, head circumference and gestational age by Dubowitz's method. RESULTS: Significant associations were noted between gestational age and newborn variables. In addition, maternal mid-arm circumference (MUAC) and pre-pregnancy weight were found to be positively correlated to birth weight (r=0.399; r=0.378, respectively). The multivariate linear regression shows that gestational age, mother's arm circumference and pre-pregnancy weight continue to be significant predictors of birth weight. On the other hand, only gestational age and mother's age was associated with crown-heel length. Similarly MUAC was significantly associated with crown-heel length (r= 0.306; P=0.0030). CONCLUSION: Maternal mid-upper arm circumference is a potential indicator of maternal nutritional status. It could be used in association with other anthropometric measurements, instead of pre-pregnancy weight, as an alternative indicator to assess women at risk of poor pregnancy outcome.

Breast cancer in Mexican women: an epidemiological study with cervical cancer control

INTRODUCTION: In Mexico, breast cancer (BC) is one of the main causes of cancer deaths in women, with increasing incidence and mortality in recent years. Therefore, the aim of the study is identify possible risk factors related to BC. METHODS: An epidemiological study of hospital cases of BC and controls with cervical uterine cancer (CUCA) was carried out at eight third level concentration hospitals in Mexico City. The total of 353 incident cases of BC and 630 controls with CUCA were identified among women younger than 75 years who had been residents of the metropolitan area of Mexico City for at least one year. Diagnosis was confirmed histologically in both groups. Variables were analyzed according to biological and statistical plausibility criteria. Univariate, bivariate and multivariate analyses were carried out. Cases and controls were stratified according to the menopausal hormonal status (pre and post menopause). RESULTS: The factors associated with BC were: higher socioeconomic level (OR= 2.77; 95%CI = 1.77 - 4.35); early menarche (OR= 1.32; 95%CI= 0.88 - 2.00); old age at first pregnancy (>31 years: OR= 5.49; 95%CI= 2.16 - 13.98) and a family history of BC (OR= 4.76; 95% CI= 2.10 - 10.79). In contrast, an increase in the duration of the breastfeeding period was a protective factor (>25 months: OR= 0.38; 95%CI= 0.20 - 0.70). CONCLUSIONS: This study contributes to the identification of risk factors for BC described in the international literature, in the population of Mexican women. Breastfeeding appears to play an important role in protecting women from BC. Because of changes in women`s lifestyles, lactation is decreasing in Mexico, and young women tend not to breastfeed or to shorten the duration of lactation.

Nutritional status of pregnant women: prevalence and associated pregnancy outcomes

INTRODUCTION: Although obesity is well recognized as a current public health problem, its prevalence and impact among pregnant women have been less investigated in Brazil. The objective of the study was to evaluate the impact of pre-obesity and obesity among pregnant women, describing its prevalence and risk factors, and their association with adverse pregnancy outcomes. METHODS: A cohort of 5,564 pregnant women, aged 20 years or more, enrolled at aproximately 20 to 28 weeks of pregnancy, seen in prenatal public clinics of six state capitals in Brazil were followed up, between 1991 and 1995. Prepregnancy weight, age, educational level and parity were obtained from a standard questionnaire. Height was measured in duplicate and the interviewer assigned the skin color. Nutritional status was defined using body mass index (BMI), according to World Health Organization (WHO) criteria. Odds ratios and 95% confidence interval were calculated using logistic regression. RESULTS: Age-adjusted prevalences (and 95% CI) based on prepregnancy weight were: underweight 5.7% (5.1%-6.3%), overweight 19.2% (18.1%-20.3%), and obesity 5.5% (4.9%-6.2%). Obesity was more frequently observed in older black women, with a lower educational level and multiparous. Obese women had higher frequencies of gestational diabetes, macrosomia, hypertensive disorders, and lower risk of microsomia. CONCLUSIONS: Overweight nutritional status (obesity and pre-obesity) was seen in 25% of adult pregnant women and it was associated with increased risk for several adverse pregnancy outcomes, such as gestational diabetes and pre-eclampsia.

Climacteric symptoms and quality of life: validity of women's health questionnaire

OBJECTIVE: To evaluate the reliability and validity of the Portuguese version of the Women's Health Questionnaire. METHODS: In order to evaluate the Women's Health Questionnaire (WHQ), an analytical cross-sectional study was carried out at the women's menopause outpatient clinic of a university hospital in São Paulo, Brazil. There were studied 87 women in perimenopause or menopause, defined as experiencing at least one year's absence of menstrual flow. The following variables were collected: demographic data, clinical variables (Kupperman index and correlate numeric scale) and quality of life indexes (SF-36 and utility). RESULTS: The WHQ proved to be a questionnaire easily translated into Portuguese and well-adjusted to Brazilian women. The internal consistency of the overall WHQ was excellent (Cronbach alpha =0.83; 95% CI: 0.71-0.91). Test-retest reliability was also excellent (intraclass correlation coefficient [ICC]=0.92; 95% IC: 0.86-0.96) and had good absolute agreement (0.84; 95% CI: 0.71-0.92). A satisfactory clinical validity was observed. The construct validity was corroborated by clear associations with others scales. A good index of responsiveness after the intervention was reached. CONCLUSIONS: The Portuguese version of the WHQ is of easy and fast administration and understanding. Its measuring properties were related, allowing its use in the evaluation of Brazilian climacteric women's quality of life for various purposes.

Suspected acute toxoplasmosis in pregnant women

OBJECTIVE: To determine the prevalence of reagent serology for suspected acute toxoplasmosis in pregnant women and to describe clinical, laboratory and therapeutic profiles of mothers and their children. METHODS: A retrospective study was conducted with IgM-anti-Toxoplasma gondii-reagent pregnant women and their children who attended the public health system in the state of Paraná, Southern Brazil, from January 2001 to December 2003. Information were obtained from clinical, laboratory (ELISA IgM/IgG) and ultrasonographic data and from interviews with the mothers. To test the homogeneity of the IgM indices in relation to the treatment used, the Pearson's Chi-square test was applied. Comparisons were considered significant at a 5% level. RESULTS: Two hundred and ninety (1.0%) cases of suspected IgM-reagent infection were documented, with a prevalence of 10.7 IgM-reagent women per 1,000 births. Prenatal care started within the first 12 weeks for 214/290; 146/204 were asymptomatic. Frequent complaints included headaches, visual disturbance and myalgia. Ultrasonography revealed abnormalities in 13 of 204 pregnancies. Chemoprophylaxis was administered to 112/227; a single ELISA test supported most decisions to begin treatment. Pregnant women with IgM indices =2.000 tended to be treated more often. Among exposed children, 44/208 were serologically followed up and all were IgG-reagent, and three IgM-reagent cases showed clinical symptoms. CONCLUSIONS: The existence of pregnant women with laboratorially suspected acute toxoplasmosis who were not properly followed up, and of fetuses that were not adequately monitored, shows that basic aspects of the prenatal care are not being systematically observed. There is need of implementing a surveillance system of pregnant women and their children exposed to T. gondii.

Relationship between the iron status of pregnant women and their newborns

OBJECTIVE: To determine the relationship between iron nutritional status of pregnant women and their newborns using a combination of hematological and biochemical parameters for the diagnosis of iron deficiency. METHODS: A cross-sectional study was conducted in Jundiaí, Southeastern Brazil, in 2000. Venous blood samples collected from 95 pregnant women and from their umbilical cord and used for the determination of complete blood count, serum iron, total iron-binding capacity, serum ferritin, zinc protoporphyrin, and transferrin saturation. Women were classified into three groups: anemic, iron deficient and non-iron deficient. Statistical analysis included the Tukey-HSD test, Pearson's correlation coefficient and multiple linear regression analysis. RESULTS: Among pregnant women, 19% were anemic (97.9% mildly anemic and 2.1% moderately anemic) and 30.5% were iron deficient. No significant difference was seen in mean values of any parameter studied between newborns in the three groups (p>0.05). Multiple linear regression analysis showed weak association between neonatal and maternal parameters. CONCLUSIONS: The iron nutritional status of pregnant women with iron deficiency or mild anemia does not seem to have a significant impact on the iron levels of their children.

Knowledge, attitude and practice of mammography among women users of public health services

OBJECTIVE: To evaluate knowledge, attitude and practice related to mammography among women users of local health services, identifying barriers to its performance. METHODS: A total of 663 women were interviewed at 13 local health centers in a city of Southeastern Brazil, in 2001. Interviewees were randomly selected at each center and they were representative from different socioeconomic conditions. The number of interviewees at each center was proportional to monthly mean appointments. For data analysis, answers were described as knowledge, attitude, practice and their respective adequacies and then they were correlated with control variables through the chi-square test. RESULTS: Only 7.4% of the interviewees had adequate knowledge on mammography, while 97.1% of women had an adequate attitude. The same was seen for the practice of mammography that was adequate in 35.7% of the cases. The main barrier to mammography was lack of referral by physicians working at the health center (81.8%). There was an association between adequacy of attitude and five years or more of education and being married. There was also an association between adequacy of mammography practice and being employed and family income up to four minimum wages. CONCLUSIONS: Women users of local health services had no adequate knowledge and practice related to mammography despite having an adequate attitude about this exam.