Paraoxonase 1 serum activity in women: the effects of menopause, the C(-107)T polymorphism and food intake

ABSTRACT Objective The aims of this study were to investigate changes in serum paraoxonase 1 (PON1) activity in women at the pre and postmenopausal stages and its association with the PON1 C(-107)T polymorphism and food intake profile. Subjects and methods A cross-sectional study with female patients aged between 35 and 59 years old was conducted. Women were divided into two groups: premenopausal (n = 40) and postmenopausal (n = 36). Women enrolled in the study had serum PON1, total cholesterol, HDL, LDL, glucose and HbA1c, as well as the BMI measured. Additionally, women were genotyped for the PON1 T(-107)C polymorphism and the food intake profile was obtained through interview. Results Glucose (p = 0.03), HbA1c (p = 0.002) and total cholesterol (p = 0.002)concentrations were higher in post than premenopausal women, however PON1 activity was not different (p > 0.05). Carriers of the C allele had higher PON1 activity (CC: 88.9 ± 6.5 U/mL and CT: 79.9 ± 4.7 U/mL) than women of the TT genotype (66.6 ± 5.9 U/mL) (p < 0.05). However, the model predicting PON1 activity was slightly better when genotype, total fat and cholesterol content in the diet were all included. Conclusion In sum, we observed that the PON1 C(-107)T genotype was the major regulator of PON1 activity, and menopause had no effect on PON1 activity. The lipid and glycemic profile were altered in postmenopausal women.

Serum PTH reference values in an adult Brazilian population: implications for the diagnosis of hyperparathyroidism

ABSTRACT Objective: To define serum parathyroid hormone (PTH) reference values in carefully selected subjects following the recommended pre-analytical guidelines. Subjects and methods: First, 676 adults who would be submitted to thyroidectomy were evaluated. Patients using interfering medications or with malabsorption syndrome, hypomagnesemia, hyper- or hypophosphatemia, hypo- or hypercalcemia, 25-hydroxyvitamin D < 30 ng/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m2, urinary calcium/creatinine ratio ≥ 0.25, thyroid dysfunction, parathyroid adenoma detected during surgery were excluded. The sample consisted of 312 subjects. Results: The median, minimum, maximum, and 2.5th and 97.5th percentiles of the PTH values obtained were 30, 7.2, 78, 10.1, and 52 pg/mL, respectively. Thus, the reference range was 10 to 52 pg/mL. PTH > 65 pg/mL, the upper limit of normal according to the manufacturer of the kit, was observed in only one subject (0.3%). Considering the upper limit proposed by the kit's manufacturer, 1/6 hypercalcemic patients and 4/8 normocalcemic patients with PHPT had normal PTH. Using the upper limit established in this study, only one normocalcemic patient had normal PTH. Thus, the sensitivity of PTH in detecting asymptomatic primary hyperparathyroidism (PHPT) using the values recommended by the kit and established in this study was 64% and 93%, respectively (50% versus 87.5% for normocalcemic PHPT). Conclusion: The upper reference limit of PTH obtained for a rigorously selected sample was 20% lower than that provided by the assay, which increased its sensitivity in detecting PHPT.

Measurement of serum estrogen and estrogen metabolites in pre- and postmenopausal women with osteoarthritis using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry

Although 17β-estradiol (E2) deficiency has been linked to the development of osteoarthritis (OA) in middle-aged women, there are few studies relating other estrogens and estrogen metabolites (EMs) to this condition. We developed a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method to measure the levels of six EMs (i.e., estrone, E2, estriol, 2-hydroxyestrone, 2-hydroxyestradiol, and 16a-hydroxyestrone) in healthy pre- and postmenopausal women and women with OA. This method had a precision ranging from 1.1 to 3.1% and a detection limit ranging from 10 to 15 pg. Compared to healthy women, serum-free E2 was lower in the luteal and postmenopausal phases in women with OA, and total serum E2 was lower in postmenopausal women with OA. Moreover, compared to healthy women, total serum 2-hydroxyestradiol was higher in postmenopausal women with OA and total serum 2-hydroxyestrone was lower in both the luteal and follicular phases in women with OA. In conclusion, our HPLC-ESI-MS/MS method allowed the measurement of multiple biochemical targets in a single assay, and, given its increased cost-effectiveness, simplicity, and speed relative to previous methods, this method is suitable for clinical studies.

Alveolar bone mass in pre- and postmenopausal women with serum calcium as a marker: A comparative study.

Context: In most women bone mass reaches its peak in the third decade of life and declines thereafter with the onset of menopause and might lead to osteoporosis. Osteoporosis may result in reduced jaw bone mass and alterations of the mandibular structure. Qualitative and quantitative indices have been used for panoramic radiographs to assess the alveolar bone quality. Aims: The purpose of this study was to compare the alveolar bone quality of premenopausal and postmenopausal women using the panoramic mandibular index (PMI). This study also aimed to estimate the levels of serum calcium in premenopausal and postmenopausal women. Settings and Design: Single centre case control study. Materials and Methods: A total of 30 patients were divided into three groups of ten each - the healthy group, control group, and study group. Alveolar bone mass was evaluated by the PMI. Serum calcium was also assessed for all the patients. Statistical analysis used: The results obtained were subjected to statistical analysis by one-way analysis of variance using Statistical Software SPSS version 17, Tukey test for comparision, Pearson's correlation coefficient was employed. Results: Premenopausal women had the highest values for alveolar cortical bone mass as recorded by the PMI, followed by postmenopausal women with a healthy periodontium. The lowest values were recorded in the group of postmenopausal women with chronic generalized periodontitis. Similar results were found for serum calcium values. Conclusion: Postmenopausal women exhibit a reduced alveolar bone mass and lowered levels of serum total calcium with the increasing age. These changes may be useful indicators for low skeletal bone mineral density or osteoporosis.

Effects of the Transition from Premenopause to Postmenopause on Lipids and Lipoproteins: Quantification and Related Parameters

BACKGROUND/AIMS: The aim of this study was to quantitatively measure changes in lipids and lipoproteins during perimenopause and to identify variables related to these changes. METHODS: Among women who had three regular health evaluations over a span of 2-4 years, 34 women remained in the premenopausal state, 34 premenopausal women transitioned to the postmenopausal state, and 36 postmenopausal women were enrolled. The menopausal state was determined not only by a history of amenorrhea but also by levels of female sex hormones. Yearly changes in lipids were calculated using a linear regression of the three measurements. RESULTS: The transition from premenopause to postmenopause was associated with increased total cholesterol and low-density lipoprotein (LDL) cholesterol levels by 7.4 +/- 8.0 mg/dL (4.2 +/- 4.9%) and 6.9 +/- 6.5 mg/dL (6.8 +/- 7.0%) over one year, resulting in an elevation of 19.6 +/- 22.6 mg/dL (10.9 +/- 13.0%) and 18.9 +/- 19.5 mg/dL (18.6 +/- 20.3%), respectively, during perimenopause. There were no changes observed in premenopausal and postmenopausal women. Body weight, blood pressure, high-density lipoprotein (HDL) cholesterol, and triglycerides did not change in any of the three groups. In all women, changes in both total cholesterol and LDL cholesterol were associated with changes in follicle stimulating hormone (r = 0.40, p < 0.001 and r = 0.38, p < 0.001, respectively). Changes in triglycerides were associated with changes in body weight (r = 0.28, p = 0.005). CONCLUSIONS: During perimenopause, total and LDL cholesterol levels increase and these changes in cholesterol are mainly dependent on changes in female sex hormones.

Factors associated with secondary hyperparathyroidism in premenopausal women undergoing Roux-en-Y gastric bypass for the treatment of obesity / Fatores associados com hiperparatireoidismo secundário em mulheres na pré-menopausa submetidas a bypass gástrico em Y de Roux para tratamento de obesidade

OBJECTIVE: To evaluate bone metabolism, bone density (BMD) and vertebral fractures in morbidly obese individuals. SUBJECTS AND METHODS: Case series of 29 premenopausal obese patients, 15 of whom had been submitted to bariatric surgery. Serum calcium, albumin, PTH and 25-hydroxy vitamin D (25OHD) were measured as well as bone densitometry of the lumbar spine and proximal femur, and lateral spine x-rays. RESULTS: High parathyroid hormone (PTH) levels were recorded in 46.6 percent of the surgical patients and in 21.4 percent of the non-surgical patients (p = 0.245); 26.7 percent of the former and 28.6 percent of the latter revealed levels 25OHD < 30 ng/mL (p = 1.000). Calcium intake was higher in the surgical group (p = 0.004) along with lower serum calcium concentrations (p = 0.019). There were no significant differences in bone mineral density (BMD) or in the prevalence of vertebral fractures between groups. CONCLUSION: In premenopausal women undergoing Roux-en-Y gastric bypass there is important intestinal calcium mal absorption which seems to be the main factor causing secondary hyperparathyroidism.

OBJETIVO: Avaliar o metabolismo ósseo, a densidade mineral óssea (DMO) e as fraturas vertebrais em obesos mórbidos. SUJEITOS E MÉTODOS: Série de casos de 29 mulheres obesas e na pré-menopausa das quais 15 foram submetidas à cirurgia bariátrica. Realizadas dosagem sérica de cálcio, albumina, hormônio da paratireoide (PTH) e 25-hidróxi-vitamina D (25OHD), densitometria óssea de coluna lombar e fêmur e radiografia de coluna vertebral. RESULTADOS: Os níveis de PTH estavam elevados em 46,6 por cento das pacientes operadas e em 21,4 por cento das pacientes não operadas (p = 0,245); 26,7 por cento das operadas e 28,6 por cento das não operadas apresentavam 25OHD < 30 ng/mL (p = 1,000). A ingestão de cálcio foi maior no grupo operado (p = 0,004) e o cálcio sérico foi menor neste grupo (p = 0,019). Não houve diferenças significativas na densidade mineral óssea (DMO) e na prevalência de fraturas vertebrais entre os grupos. CONCLUSÃO: Em mulheres na pré-menopausa, submetidas ao bypass gástrico em Y de Roux, há considerável má absorção intestinal de cálcio, que parece ser o principal fator causador do hiperparatireoidismo secundário.

Déficit de Vitamina D en mujeres adultas de la Ciudad de Buenos Aires / Vitamin D deficit in adult women living in Buenos Aires City

El déficit de vitamina D se asocia con importante morbilidad. El objetivo de este estudio fue investigar la frecuencia de este déficit en una población de mujeres adultas y su asociación con distintas variables. Se evaluaron 224 mujeres mayores de 30 años atendidas en tres consultorios de clínica médica de la Ciudad de Buenos Aires entre octubre de 2006 y marzo de 2008. El nivel de 25 OH vitamina D, por radioinmunoanálisis, se clasificó como suficiente (> 30 ng/ml), déficit leve (entre 20 y 30 ng/ml) y déficit grave (< 20 ng/ml). La edad media fue de 58.3 ± 12.9 años; 77% eran posmenopáusicas. Presentaron déficit leve de vitamina D el 29.9% y déficit grave el 26.8%. El déficit grave se asoció con mayor edad promedio (62 años vs. 56 años, p = 0.003), con falta de exposición al sol (25.8 ng/ml vs. 31.7 ng/ml, p < 0.005), con mayor peso promedio (70 kg vs. 61 kg, p < 0.05), con inactividad física (27.8 ng/ml vs. 31.04 ng/ml, p = 0.0007) y con menor calcemia (9.26 mg/dl vs. 9.51 mg/dl, p < 0.01). No se asoció con tabaquismo ni con los valores de fósforo, creatinina ni TSH plasmáticas. El déficit de vitamina D es frecuente, en especial en mujeres añosas, sedentarias, poco expuestas al sol, obesas y con bajos niveles de calcio.

Vitamin D deficiency is a common cause of morbidity. We prospectively studied 224 consecutive female patients in order to evaluate the prevalence of vitamin D deficiency and to assess the utility of various clinical and biochemical markers in predicting the deficiency. All of them were outpatients, 30 years old or older, and were evaluated from October 2006 through March 2008. Levels of 25 OH vitamin D > 30 ng/ml were considered sufficient. Mild deficiency was considered between 20 and 30 ng/ml and severe deficiency < 20 ng/ml. The mean age was 58 ± 12.9 years; 77% were menopausal. Twenty nine percent of the patients had mild deficit and 26.8% had severe deficit of the vitamin. Severe deficit was associated with increasing age (62 vs. 56 years, p = 0.003), absence of sun exposure (25.82 ng/ml vs. 31.7 ng/ml, p < 0.005), obesity (70 vs. 61 kg, p < 0.05), absence of physical activity (27.8 ng/ml vs. 31.04 ng/ml, p = 0.0007) and slightly low levels of serum calcium (9.26 mg/dl vs. 9.51 mg/dl, p 0.01). We did not find any association between smokers and non-smokers patients, levels of serum phosphorus, creatinine and TSH. Vitamin D deficiency is a common disorder. It correlates with older age, absence of physical activity, sun exposure, obesity and slightly low levels of serum calcium. Improving diagnosis of this condition may enable us to improve the management of this disease.

Estrogen receptor 1 gene polymorphisms in premenopausal women: interaction between genotype and smoking on lipid levels

Estrogen has multiple effects on lipid and lipoprotein metabolism. We investigated the association between the four common single nucleotide polymorphisms in the estrogen receptor 1 (ESR1) gene locus, -1989T>G, +261G>C, IVS1-397T>C and IVS1-351A>G, and lipid and lipoprotein levels in southern Brazilians. The sample consisted in 150 men and 187 premenopausal women. The women were considered premenopausal if they had regular menstrual bleeding within the previous 3 months and were 18-50 years of age. Exclusion criteria were pregnancy, secondary hyperlipidemia due to renal, hepatic or thyroid disease, and diabetes. Smoking status was self-reported; subjects were classified as never smoked and current smokers. DNA was amplified by PCR and was subsequently digested with the appropriate restriction enzymes. Statistical analysis was carried out for men and women separately. In the study population, major allele frequencies were _1989*T (0.83), +261*G (0.96), IVS1-397*T (0.58), and IVS1-351*A (0.65). Multiple linear regression analyses indicated that an interaction between +261G>C polymorphism and smoking was a significant factor affecting high-density lipoprotein cholesterol (HDL-C) levels (P = 0.028) in women. Nonsmoking women with genotype G/C of +261G>C polymorphism had mean HDL-C levels higher than those with G/G genotype (1.40 ± 0.33 vs 1.22 ± 0.26 mmol/L; P = 0.033). No significant associations with lipid and lipoprotein levels in women and men were detected for other polymorphisms. In conclusion, the +261G>C polymorphism might influence lipoprotein and lipid levels in premenopausal women, but these effects seem to be modulated by smoking, whereas in men ESR1 polymorphisms were not associated with high lipoprotein levels.

Genotypes of vitamin D and estrogen receptors in pre and perimenopausal women from Córdoba, Argentina

El propósito del estudio fue determinar la frecuencia de los genotipos de los receptores de vitamina D y de estrógeno y su relación con la densidad mineral ósea en mujeres sanas pre y perimenopáusicas de la ciudad de Córdoba y alrededores. Los genotipos se determinaron con la técnica de reacción en cadena de la polimerasa y análisis de los polimorfismos de longitud de fragmentos de restricción. Se usaron como restrictasas Bsm I y Fok I para el gen del receptor de vitamina D y Pvu II y Xba I para el gen del receptor de estrógeno. Se reclutaron y agruparon por edad doscientos diez mujeres pre y peri-menopáusicas. Sus niveles séricos de Ca y de hormona paratiroidea fueron similares, pero los de fósforo y b-Cross Laps disminuyeron con la edad. La densidad mineral ósea de cuello femoral disminuyó después de los 30 años. Las frecuencias genotípicas de ambos receptores fueron similares a aquéllas de otras mujeres caucásicas. No hubo asociación entre los genotipos de los receptores y la densidad mineral ósea. Los análisis de interacción entre ambos genes no evidenciaron influencia sobre la densidad mineral ósea, utilizándose edad, talla e índice de masa corporal como covariables. Los estilos de vida y hábitos de fumar y beber alcohol tampoco afectaron la densidad mineral ósea. En conclusión, estos datos no sostienen la hipótesis de que los genotipos de los receptores de vitamina D y de estrógeno influencian la densidad mineral ósea de columna lumbar y cuello femoral en mujeres sanas pre y perimenopáusicas de esta región de Argentina.

The aim of this study was to determine the frequency of vitamin D receptor and estrogen receptor genotypes and their relationship with the lumbar spine or femoral neck bone mineral density in healthy pre and perimenopausal women from Córdoba (Argentina) and adjacent areas. Genotypes were assessed by restriction fragment length polymorphism-polymerase chain reaction technique. Bsm I and Fok I for vitamin D receptor gene and XbaI and PvuII for estrogen receptor gene were used as restrictases. Two hundred and ten healthy pre and perimenopausal women were recruited and analyzed by age. Calcemia and serum parathyroid hormone did not change, but serum P and b-CrossLaps decreased with age. Femoral neck bone mineral density decreased significantly after 30 years old. Vitamin D receptor and estrogen receptor genotype frequencies were similar to those from other Caucasian women. No association between vitamin D receptor and estrogen receptor genotypes with the lumbar spine or femoral neck bone mineral density has been detected. Analysis of interaction between vitamin D receptor and estrogen receptor genes using covariates such as age, height and body mass index did not show any influence of the combination of those genotypes on bone mineral density. Lifestyle, smoking and alcohol intake had no effect on lumbar spine and femoral neck bone mineral density. To conclude, these data do not support the hypothesis that vitamin D receptor and estrogen receptor genotypes influence on lumbar spine and femoral neck bone mineral density in healthy pre and perimenopausal women from this area of Argentina.

Relationship of body composition and circulatory adiponectin to bone mineral density in young premenopausal women.

OBJECTIVE: Adiponectin is a recently discovered hormone secreted by adipocytes. Adiponectin plays an important role in the regulation of insulin sensitivity as well as the propensity to inflammation and atherosclerosis. In the present study, the authors explore the relationship between adiponectin and bone mass in premenopausal women. The relationship of fat mass compared to lean body mass to bone mass was also investigated MATERIAL AND METHOD: Two hundred premenopausal women aged between 20 and 40 years were studied. Bone mineral density (BMD) was measured at L2-4 and femoral neck by dual-energy X-ray absorptiometry (DEXA). Serum adiponectin concentrations were measured by radioimmunoassay. RESULTS: At the lumbar spines, factors associated with BMD were age (p < 0.01) and lean body mass (p < 0.001). No independent association with fat mass was demonstrated Likewise, at the femoral neck, only lean body mass was related to BMD (p < 0. 01). In terms of the relation of serum adiponectin to BMD, no association of serum adiponectin to BMD at the lumbar spines or femoral neck was found CONCLUSION: Altogether, the present findings do not suggest the independent role of adiponectin in the accrual of bone mass in females, although such a role still cannot be excluded in men or postmenopausal women.

Leptin levels in pre and post menopausal Pakistani women

To evaluate the correlation of fasting serum leptin levels with anthropometric measurements and menopausal status, in women. The study comprised of 80 non-obese women who were divided into 2 groups as pre-menopausal [n=46] and post-menopausal [n=34].Anthropometric measurements i.e. height, weight, waist and hip circumference were measured for all the subjects and the Waist-hip Ratio [WHR] and Body Mass Index [BMI] were calculated from these measurements. A fasting venous blood sample was taken from all the subjects and serum leptin concentrations were determined by ELISA. A comparison of the mean values for BMI and WHR between the two groups showed a non significant difference. Within each group, significant associations were noted between the fasting serum leptin level and values of BMI and WHR. A comparison of the mean serum leptin concentrations between the two groups, showed a highly significant difference [p<0.001]. Our results indicate that in the non-obese women of our population, leptin levels associate with BMI and WHR and together with menopausal status seem to be important determinants of serum leptin levels

Influence of menopause on high density lipoprotein-cholesterol and lipids

It has been generally accepted that high density lipoprotein cholesterol (HDL-C) level decreases with menopause in women. However, recent reports show different results. There is very little data concerning perimenopausal women. To verify these findings, lipids and lipoprotein(a) +AFs-Lp(a)+AF0- levels were compared among pre-, peri- and postmenopausal women of similar mean ages. Postmenopausal women had higher HDL-C levels than premenopausal women (p+ADw-0.001) and there was no difference between peri- and postmenopausal women. LDL-C level in perimenopausal women was lower than in postmenopausal women (p+ADw-0.001) and higher than in premenopausal women with borderline significance (p+AD0-.051). Total cholesterol levels showed stepwise elevation from premenopause to postmenopause. Perimenopausal women had lower Lp(a) levels than postmenopausal women (p+ADw-0.0005) and similar levels to premenopausal women. Lp(a) levels between 0.1 to 10.0 mg/dL were the most prevalent in pre- and perimenopausal women, and those between 10.1 to 20.0 mg/dL in postmenopausal women. In conclusion, menopause itself is associated with the elevation of HDL-C level, and the postmenopausal increase of coronary artery disease is not related to postmenopausal change of HDL-C level. Perimenopausal status, although transient, may favor Lp(a) and lipid profiles for delaying atherosclerosis.

Risk factors for decreased bone density in premenopausal women

Osteoporosis is a major health problem. Little is known about the risk factors in premenopause. Sixty 40-50 year old patients with regular menses were studied cross-sectionally. None of the patients were on drugs known to interfere with bone mass. Patients answered a dietary inquiry and had their bone mineral density (BMD) measured. The Z scores were used for the comparisons. A blood sample was taken for the determination of FSH, SHBG, estradiol, testosterone, calcium and alkaline phosphatase. Calcium and creatinine were measured in 24-h urine. A Z score less than -1 was observed for the lumbar spine of 14 patients (23.3 percent), and for the femur of 24 patients (40 percent). Patients with a Z score less than -1 for the lumbar spine were older than patients with a Z score ò-1 (45.7 vs 43.8 years) and presented higher values of alkaline phosphatase (71.1 + 18.2 vs 57.1 + 14.3 IU/I). Multiple regression analysis showed that a lower lumbar spine BMD was associated with higher values of alkaline phosphatase, lower calcium ingestion, a smaller body mass index (BMI), less frequent exercising, and older age. The patients with a Z score less than -1 for the femur were shorter than patients with a Z score ò-1 (158.2 vs 161.3 cm). Multiple regression analysis showed that a lower femoral BMD was associated with lower BMI, higher alkaline phosphatase and caffeine intake, and less frequent exercising. A lower than expected BMD was observed in a significant proportion of premenopausal women and was associated with lower calcium intake, relatively lower physical activity and lower BMI. We conclude that the classical risk factors for osteoporosis may be present before ovarian failure, and their effect may be partly independent of estrogen levels.

Les hemorragies organiques perimenopausiques d'origine uterine

The authors report the different aspects they have observed when they study 70 case histories of patients who has a histological examination of the endometrium and the myometrium for uterine bleeding during the perimenopause. Whatever the type of bleeding, the most common finding was hyperplasia [48.5%]. Benign lesions of the myometrium was observed in 60% for the leiomyoma and 33% for adenomyoses. Hysteroscopy alone or with curettage was very important for the diagnosis