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.

Relationship between sexual hormones, quality of life and postmenopausal sexual function / Relação entre hormônios sexuais, qualidade de vida e função sexual na pós-menopausa

Abstract Objective To assess the relationship between sexual hormones, sexual function and quality of life in postmenopausal women. Method A cross-sectional study was conducted with a convenience sample of 36 postmenopausal women between the ages of 45 and 65 in follow-up at a climacteric outpatient clinic. Mood, quality of life, sexual function and hormonal profile were assessed. Results With regard to sexual hormones and sexual function, a relationship was found between orgasm and luteinizing hormone (r=0.37), orgasm and sex hormone-binding globulin (SHBG) (r=0.39), SHBG and less pain (r=0.44), dehydroepiandrosterone (DHEA) and desire (r=-0.45), as well as between prolactin and lubrication (r=0.33). Sexual hormones and quality of life were related as follows: progesterone and limitations due to physical aspects (r=0.35), SHBG and social aspects (r=0.35), cortisol and pain (r=0.46), DHEA and social aspects (r=-0.40). Finally, the following relationships were found between sexual function and quality of life: sexual desire and vitality, social aspects, state of general health and mental health (r=0.46, r=0.51, r=0.35, and r=0.38, respectively). Arousal, orgasm and satisfaction with sexual life showed a relationship with less physical pain (r=0.40, r=0.42, and r=0.43, respectively). Satisfaction with sexual life was correlated with vitality (r=0.33). Conclusion Different correlations than expected were found in this study regarding the effect of some hormones on sexual function and some aspects of the quality of life of postmenopausal women.

Resumo Objetivo Avaliar a relação entre hormônios sexuais, função sexual e qualidade de vida em mulheres na pós-menopausa. Métodos Estudo transversal com amostra de conveniência de 36 mulheres na pós-menopausa, com idades entre 45 e 65 anos, em seguimento ambulatorial de climatério. Humor, qualidade de vida, função sexual e perfil hormonal foram avaliados. Resultados Entre hormônios sexuais e função sexual, foi encontrada relação entre orgasmo e hormônio luteinizante (r=0,37), orgasmo e globulina ligadora de hormônios sexuais (SHBG) (r=0,39), SHBG e menos dor (r=0,44), desidroepiandrosterona (DHEA) e desejo (r=-0,45), bem como entre prolactina e lubrificação (r=0,33). Entre hormônios sexuais e qualidade de vida: progesterona e limitações por aspectos físicos (r=0,35), SHBG e aspectos sociais (r=0,35), cortisol e dor (r=0,46), DHEA e aspectos sociais (r=-0,40). Por fim, entre função sexual e qualidade de vida: desejo sexual e vitalidade, aspectos sociais, estado geral de saúde e saúde mental (r=0,46, r=0,51, r=0,35 e r=0,38, respectivamente). Excitação, orgasmo e satisfação com a vida sexual mostraram uma relação com menos dor física (r=0,40, r=0,42 e r=0,43, respectivamente). A satisfação com a vida sexual foi correlacionada com a vitalidade (r=0,33). Conclusão Correlações diferentes das esperadas foram encontradas neste estudo em relação ao efeito de alguns hormônios sobre a função sexual e alguns aspectos da qualidade de vida de mulheres na pós-menopausa.

Body composition and nutritional and metabolic parameters in postmenopausal women sufficient, insufficient and deficient in vitamin D

ABSTRACT Objective We investigated changes in body composition and nutritional and metabolic parameters in a group of postmenopausal women who were classified as sufficient, insufficient and deficient in vitamin D. Subjects and methods A total of 106 postmenopausal women were included in this cross-sectional study and classified according to their serum levels of 25-OH-vitamin D as sufficient (≥ 30 ng/mL; group S), insufficient (20.1 and 29.9 ng/mL; group I) or deficient (≤ 20 ng/mL; group D) in vitamin D. Body composition was measured by dual-energy X-ray absorptiometry (DXA); dietary recall questionnaires were completed; and blood samples were analysed to compare the metabolic and nutritional status of the study groups. Results Eleven (10.4%) of the women were classified in group S, 50 (47.2%) in group I and 45 (42.4%) in group D, with a mean serum level for 25-OH-D of 21.1 ± 7.0 ng/mL in all participants. Body composition did not differ among the groups. Serum levels of 25-OH-D were negatively correlated with serum levels of triglycerides, total cholesterol and LDL cholesterol. Conclusions Vitamin D insufficiency and deficiency were highly prevalent in our group of postmenopausal women, showing an association with an unfavourable lipid profile.

Prevalence of hypovitaminosis D in postmenopausal women: a systematic review

SUMMARY BACKGROUND: Hypovitaminosis D is considered a global public health issue. Knowledge of its true dimensions will allow us to design interventions and plan preventive measures that can have a significant impact on human health. OBJECTIVES: The aim of this study was to evaluate the prevalence of hypovitaminosis D, defined as a serum 25-hydroxyvitamin D concentration < 30 ng/ml, in postmenopausal women around the world, as well as to identify the potential associated factors. METHODS: A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses recommendations. Specific search terms were consulted in Medline, Excerpta Medica, and Latin-American and Caribbean Health Sciences Literature databases, with no restriction for the year or language of publication. RESULTS: Of 451 studies initially identified, 32 were selected for analysis. Collectively, those 32 studies evaluated 21,236 postmenopausal women, of whom 16,440 (77.4%) had serum 25-hydroxyvitamin D concentrations < 30 ng/ml. The reported prevalence of hypovitaminosis D ranged from 29% (in the United States) to 99.4% (in China). In six of the studies, the prevalence was above 90%. CONCLUSIONS: If the criterion is the 30 ng/ml cut-off point, the majority of postmenopausal women in the world could be classified as having hypovitaminosis D. Among the studies evaluated, the lowest prevalence reported was nearly 30%. Neither latitude, region of the world, nor laboratory methodology were found to be associated with the prevalence of hypovitaminosis D.

RESUMO INTRODUÇÃO: A hipovitaminose D é considerada um problema de saúde pública global. O conhecimento de suas verdadeiras dimensões nos permitirá projetar intervenções e planejar medidas preventivas que possam ter um impacto significativo na saúde humana. OBJETIVO: O objetivo deste estudo foi avaliar a prevalência de hipovitaminose D, definida como concentração sérica de 25-hidroxivitamina D <30 ng/ml, em mulheres na pós-menopausa em todo o mundo, bem como identificar os potenciais fatores associados. MÉTODOS: Uma revisão sistemática foi realizada de acordo com as recomendações de Itens de Relatórios Preferenciais para Revisão Sistemática e Meta-Análises. Os termos de pesquisa específicos foram consultados nas bases de dados Medline, Excerpta Medica e Literatura Latino-Americana e do Caribe em Ciências da Saúde, sem restrição para o ano ou idioma de publicação. RESULTADOS: Dos 451 estudos inicialmente identificados, 32 foram selecionados para análise. Coletivamente, esses 32 estudos avaliaram 21.236 mulheres na pós-menopausa, das quais 16.440 (77,4%) apresentavam concentrações séricas de 25-hidroxivitamina D <30 ng/ml. A prevalência relatada de hipovitaminose D variou de 29% (nos Estados Unidos) a 99,4% (na China). Em seis dos estudos, a prevalência foi superior a 90%. CONCLUSÕES: Se o critério é o ponto de corte de 30 ng/ml, a maioria das mulheres na pós-menopausa no mundo poderia ser classificada como tendo hipovitaminose D. Entre os estudos avaliados, a menor prevalência relatada foi de quase 30%. Nem latitude, região do mundo, nem metodologia laboratorial foram encontrados para ser associados com a prevalência de hipovitaminose D.

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.

Estudio comparativo de la absorción neta de calcio de dos formulaciones distintas de carbonato de calcio en mujeres posmenopáusicas / Comparative study of net calcium absorption of two different pharma¬ceutical formulations of calcium carbonate in posmenopausal women

La suplementación con calcio reduciría, sola o asociada a otra medicación para osteoporosis, la pérdida de masa ósea y el riesgo de fracturas. Sin embargo, su tasa de adherencia es baja debido a la poca tolerancia. Objetivo: comparar la tasa de absorción neta de calcio entre dos formulaciones distintas de carbonato de calcio (500 mg): comprimidos vs. mousse. Material y métodos: 11 pruebas fueron realizadas en mujeres posmenopáusicas de 58,9±3 años. El diseño fue exploratorio abierto, aleatorizado, prospectivo cruzado de fase 4. Intervención: las participantes fueron aleatorizadas en dos grupos para recibir las dos formulaciones previa suplementación con vitamina D3. La tasa de absorción neta de calcio fue estudiada por la prueba de inhibición de hormona paratiroidea (PTH). Se obtuvieron muestras de sangre: basal y en la 1a, 2a y 3a hora posadministración del calcio asignado, y de orina de 2 horas basal y al final de la prueba. Determinaciones bioquímicas: calcio, fósforo, albúmina, 25-hidroxivitamina D y hormona paratiroidea intacta y calciuria. Análisis estadístico: método de los trapecios para calcular el área bajo la curva (AUC) de la concentración de calcio en el tiempo (R Development Core Team (2008). http://www.Rp-project.org) y Anova con dos términos de error para evaluar el efecto secuencia, período y formulación. Resultados: la mayor inhibición de PTH se observó a dos horas de la toma de ambas formulaciones (comprimidos -39,2% vs. mousse -38,0%; p=ns), con similar AUC0-3 h (comprimidos 3,35; IC 95%: 3,32; 3,37 vs. mousse 3,36; IC 95%: 3,33; 3,38). Cuando analizamos tolerancia y preferencias no se observaron diferencias estadísticamente significativas entre ambas formulaciones. Conclusión: el carbonato de calcio en mousse mostró similar tasa de absorción intestinal, preferencia y tolerancia gastrointestinal que en comprimido. (AU)

Calcium supplementation, administered alone or in combination with a specific medication for osteoporosis, would reduce bone mass loss and fracture risk in postmenopausal women. However, the adherence rate to calcium supplements is low, mainly due to low tolerance. Objective: comparisson of net calcium absorption rate between two different pharmaceutical formulations of calcium carbonate (PFCa) in postmenopausal women. Materials and Methods: 11 tests were performed in postmenopausal women aged 58.9±3 yrs. Design: Comparative, randomized, prospective, open-label exploratory crossover study of calcium mousse versus calcium pills. Intervention: Participants were randomized in 2 groups to receive the 2 different PFCa (500mg): pills vs. mousse, with previous vitamin D3 supplementation. The parathyroid hormone (PTH) inhibition test and the area-under-thecurve (AUC) of calcium were analyzed. Blood samples were taken at baseline and 1, 2 and 3 hrs after intake of the assigned PFCa. Urine samples (2hs) were obtained at -baseline, after 2hs of PFCa intake and at the end of the test. Biochemical Determinations: Serum: calcium, phosphorus, albumin, 25-hydroxyvitamin D, and intact PTH. In urine: calcium. Statistical Analysis: The trapezoid rule was applied to assess AUC in time (R Development Core Team (2008). http://www.Rp-project.org). An ANOVA model with 2 error terms was used to assess the effect of sequence, period, and formulation. Results: The highest inhibition PTH rates were observed after 2 hrs of PFCa (pills -39.2% vs. mousse -38.0%; p=ns). The AUC0-3hrs for both PFCa was similar (pills 3.35; 95%CI: 3.32; 3.37 vs. mousse 3.36; 95%CI: 3.33; 3.38). No statistically significant differences were observed when we analyze tolerance and predilection. Conclusion: The calcium carbonate in mousse showed an adequate rate of intestinal absorption, similarly predilection and gastrointestinal tolerance than the pill presentation. (AU)

The role of moderate-to-vigorous physical activity in mediating the relationship between central adiposity and immunometabolic profile in postmenopausal women

ABSTRACT Objectives To analyze the role of moderate-to-vigorous physical activity (MVPA) in mediating the relationship between central adiposity and immune and metabolic profile in postmenopausal women. Materials and methods Cross-sectional study comprising 49 postmenopausal women (aged 59.26 ± 8.32 years) without regular physical exercise practice. Body composition was measured by dual-energy X-ray absorptiometry. Fasting blood samples were collected for assessment of nonesterified fatty acids, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), adiponectin, insulin and estimation of insulin resistance (HOMA-IR). Physical activity level was assessed with an accelerometer (Actigraph GTX3x) and reported as a percentage of time spent in sedentary behavior and MVPA. All analyses were performed using the software SPSS 17.0, with a significance level set at 5%. Results Sedentary women had a positive relationship between trunk fat and IL-6 (rho = 0.471; p = 0.020), and trunk fat and HOMA-IR (rho = 0.418; p = 0.042). Adiponectin and fat mass (%) were only positively correlated in physically active women (rho = 0.441; p = 0.027). Physically active women with normal trunk fat values presented a 14.7% lower chance of having increased HOMA-IR levels (β [95%CI] = 0.147 [0.027; 0.811]). Conclusions The practice of sufficient levels of MVPA was a protective factor against immunometabolic disorders in postmenopausal women.

Non-HDL cholesterol is a good predictor of the risk of increased arterial stiffness in postmenopausal women in an urban Brazilian population

OBJECTIVES: Increased arterial stiffness is an important determinant of the risk of cardiovascular disease. Lipid profile impairment, especially hypercholesterolemia, is associated with stiffer blood vessels. Thus, the aim of this study was to determine which of the five circulating lipid components (high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL), total cholesterol (TC) and triglycerides) is the best predictor of increased arterial stiffness in an urban Brazilian population. METHODS: A random sample of 1,662 individuals from the general population of Vitoria, Brazil (25-64 years), was selected, and lipid components were measured using standard methods. Pulse wave velocity was measured using a non-invasive automatic device, and increased arterial stiffness was defined as a pulse wave velocity ≥10 m/s. RESULTS: In men, only total cholesterol (OR=1.59; CI=1.02 to 2.48, p=0.04) was associated with the risk of increased arterial stiffness. In women, HDL-C (OR=1.99; CI=1.18 to 3.35, p=0.01) and non-HDL-C (OR=1.61; CI=1.01 to 2.56, p=0.04) were good predictors of the risk of increased arterial stiffness. However, these associations were only found in postmenopausal women (OR=2.06; CI=1.00 to 4.26, p=0.05 for HDL-C and OR=1.83; CI=1.01 to 3.33, p=0.04 for non-HDL-C). CONCLUSION: Our findings indicate that both HDL-C and non-HDL-C are good predictors of the risk of increased arterial stiffness in postmenopausal women in an urban Brazilian population and may be useful tools for assessing the risk of arterial stiffness.

Efecto del 27- hidroxicolesterol en la acción antiplaquetaria de estradiol en mujeres postmenopáusicas / 27- Hydroxycholesterol reverses estradiol induced inhibition of platelet aggregation in postmenopausal women

Background: The decline of estrogen levels increases cardiovascular risk in women. Platelets express estrogen receptors and 17β-estradiol- (E2) can produce a protective effect on thrombus formation. The hydroxylation of cholesterol generates several sterols and 27-hydroxycholesterol (27HC) predominates in circulation. Aim: To evaluate the effect of 27HC as an endogenous antagonist of the anti-aggregating properties of E2 in platelets of postmenopausal women. Material and Methods: Platelet function of postmenopausal women was evaluated ex-vivo. Platelets pre-incubated with 27HC in the presence or absence of E2, were stimulated with collagen. Aggregation was evaluated using turbidimetry using a Chrono-log aggregometer. Results: Collagen-stimulated platelet aggregation was significantly inhibited by E2. The inhibitory effect of E2 on collagen-stimulated platelet aggregation was significantly reversed in the presence of 27HC. Conclusions: The suppressive effect of E2 on platelet aggregation is inhibited by 27HC, which could contribute to increase cardiovascular risk in postmenopausal women.

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.

Vitamin D Repletion in Korean Postmenopausal Women with Osteoporosis

PURPOSE: Up to 71% of South Korean postmenopausal women have vitamin D deficiency {serum 25-hydroxyvitamin D [25(OH) D] level <50 nmol/L}. Data on vitamin D supplementation was collected during the screening phase of an efficacy/safety study of denosumab in Korean postmenopausal women with osteoporosis. This report describes the effect of vitamin D supplementation on repletion to 25(OH)D levels ≥50 nmol/L in Korean postmenopausal women with osteoporosis. MATERIALS AND METHODS: Vitamin D levels of Korean postmenopausal women (60-90 years old) were measured by extracting 25(OH)D2 and 25(OH)D3 from serum samples via protein precipitation and using liquid chromatography with tandem mass spectrometry detection. Calibration curves were constructed from the mass chromatograms to obtain total vitamin D levels. Subjects with serum 25(OH)D levels <50 nmol/L were supplemented with 1000 IU of vitamin D tablets during the 2.5-month-long screening period. Dose, frequency, and duration were determined by the investigator. If repletion was achieved (≥50 nmol/L) on retest, subjects were eligible to be rescreened for study entry. RESULTS: Of 371 subjects screened, 191 (52%) required vitamin D supplementation, and 88% (168 of 191) were successfully repleted. More than half of the subjects (58%) who were successfully repleted received doses of 2000 IU daily. The mean time to successful repletion was 31 days (standard deviation 8.4 days; range 11-48 days). CONCLUSION: Supplementation with daily median doses of 2000 IU vitamin D successfully repleted 88% of Korean postmenopausal women with osteoporosis within 48 days to a serum vitamin D level of 50 nmol/L.

Serum testosterone does not affect bone mineral density in postmenopausal women

Objective The purpose of the present study was to investigate the correlation between serum testosterone levels and bone mineral density (BMD) in postmenopausal women.Materials and methods The study group was made up of postmenopausal women admitted to our tertiary center. Serum calcium, phosphorus, albumin, parathyroid hormone (PTH), thyrotropin (TSH), 25-OH vitamin D, and total testosterone concentrations were measured. Subjects were categorized into three groups regarding bone mineral density (BMD) values: normal (n = 22), osteopenia (n = 21), and osteoporosis (n = 21). Subjects were also categorized into three groups according to serum testosterone levels: low testosterone (n = 10), normal testosterone (n = 42), and high testosterone (n = 12).Results No significant difference was found for serum testosterone, TSH, calcium, phosphorus, albumin, PTH, and 25-hydroxyvitamin D levels among patients with normal BMD, osteopenia, and osteoporosis (p > 0.05). Lumbar spine, total femur, femoral neck, trochanteric, intertrochanteric, and Ward’s triangle BMD values were similar for the different testosterone levels (p > 0.05).Conclusion There was no correlation between serum testosterone levels and patient age, body-mass index, or any measured BMD values. Given the findings in our study, which failed to demonstrate a statistically significant relationship between testosterone and BMD, adjustment of other risk factors for osteoporosis might have a more distinctive effect in this setting.

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.

What is the influence of hormone therapy on homocysteine and crp levels in postmenopausal women?

OBJECTIVE: To evaluate the influence of estrogen therapy and estrogen-progestin therapy on homocysteine and C-reactive protein levels in postmenopausal women. METHODS: In total, 99 postmenopausal women were included in this double-blind, randomized clinical trial and divided into three groups: Group A used estrogen therapy alone (2.0 mg of 17β-estradiol), Group B received estrogen-progestin therapy (2.0 mg of 17 β-estradiol +1.0 mg of norethisterone acetate) and Group C received a placebo (control). The length of treatment was six months. Serum measurements of homocysteine and C-reactive protein were carried out prior to the onset of treatment and following six months of therapy. RESULTS: After six months of treatment, there was a 20.7% reduction in homocysteine levels and a 100.5% increase in C-reactive protein levels in the group of women who used estrogen therapy. With respect to the estrogen-progestin group, there was a 12.2% decrease in homocysteine levels and a 93.5% increase in C-reactive protein levels. CONCLUSION: Our data suggested that hormone therapy (unopposed estrogen or estrogen associated with progestin) may have a positive influence on decreasing cardiovascular risk due to a significant reduction in homocysteine levels. .

Ovarian Leydig cell tumor in a post-menopausal patient with severe hyperandrogenism / Tumor ovariano de células de Leydig em paciente em pós-menopausa com hiperandrogenismo grave

Leydig cell tumors are rare ovarian steroid cell neoplasms. More than 75% of patients show signs of virilization due to overproduction of testosterone. We report a case of an 8-year-old woman with progressive signs of virilization, and presenting vaginal bleeding. Clinical analyses revealed high levels of serum testosterone, delta 4-androstenedione and estradiol, and also inappropriate low levels of gonadotrophins for a post-menopausal woman. Transvaginal ultrasound showed no evidence of ovarian tumor, but pelvic and abdominal computerized axial tomography imaging revealed a left ovarian solid nodule, and no evidence of alteration in the adrenal glands. Total hysterectomy and bilateral salpingoophorectomy were performed. Histopathology and immunohistochemistry confirmed the diagnosis of Leydig cell tumor. After surgery, androgen levels returned to normal, and there was regression of the signs of virilization.

Tumores ovarianos de células de Leydig são neoplasias raras de células ovarianas esteroidogênicas. Mais de 75% dos pacientes apresentam sinais de virilização devido à produção excessiva de testosterona. Relatamos aqui o caso de uma mulher de 81 anos de idade com sinais progressivos de virilização e ocorrência de sangramento vaginal. As análises clínicas mostraram altos níveis de testosterona sérica, delta 4-androstenediona e estradiol, além de níveis inadequadamente baixos de gonadotrofinas para uma mulher em pós-menopausa. O ultrassom transvaginal não apresentou evidências de tumor ovariano, mas a tomografia axial computadorizada da região pélvico-abdominal mostrou um nódulo sólido no ovário esquerdo e nenhuma evidência de alteração nas adrenais. Foi feita uma histerectomia total e salpingooforectomia bilateral. Os exames histopatológicos e a imuno-histoquímica confirmaram o diagnóstico de tumor de células de Leydig. Após a cirurgia, os níveis de androgênios voltaram ao normal, e os sinais de virilização regrediram.

Níveis séricos de vitamina B12 não se relacionam com baixa densidade mineral óssea em mulheres brasileiras na pós-menopausa / Serum levels of vitamin B12 are not related to low bone mineral density in postmenopausal Brazilian women

INTRODUÇÃO: Osteoporose e deficiência de vitamina B12 são condições de prevalência crescente com o envelhecimento. A associação entre níveis séricos de vitamina B12, baixa massa óssea e risco aumentado de fraturas ósseas tem sido descrita, mas os estudos não são homogêneos e os resultados são controversos. OBJETIVO: Investigar a associação entre níveis plasmáticos de vitamina B12 e densidade mineral óssea em mulheres assintomáticas na pós-menopausa. MÉTODOS: Mulheres assintomáticas no período pós-menopausa foram consecutivamente incluídas neste estudo transversal. A densidade mineral óssea (coluna lombar e fêmur) foi avaliada pelo método DXA Lunar Prodigy Vision, e foram determinados níveis sanguíneos de vitamina B12, cálcio, fósforo, fosfatase alcalina óssea e hormônio paratireoidiano. Os critérios da Organização Mundial de Saúde foram considerados para o diagnóstico de osteoporose. RESULTADOS: Foram incluídas neste estudo 70 mulheres, com média de idade de 62,5 ± 7 anos. Do total, 18 (25,7%) apresentaram densidade mineral óssea normal, 33 (47,1%) tinham osteopenia e 19 (27,1%) tinham osteoporose. Seis (8,6%) pacientes haviam apresentado fratura de punho, duas (2,8%) reportaram diagnóstico de fratura vertebral e apenas uma (1,4%) paciente havia sofrido fratura de quadril. Os níveis de vitamina B12 (média ± DP; pg/mL) das mulheres com densidade mineral óssea normal, osteopenia e osteoporose foram 590,2 ± 364,3, 536,6 ± 452,3 e 590,2 ± 497,9, respectivamente (P = 0,881). A análise de regressão múltipla mostrou que o índice de massa corporal e a fosfatase alcalina óssea foram preditores da densidade mineral óssea na coluna lombar. CONCLUSÃO: Os resultados indicam que níveis de vitamina B12 não se relacionam à densidade mineral óssea neste grupo de mulheres brasileiras na pós-menopausa.

INTRODUCTION: Osteoporosis and vitamin B12 deficiency are conditions with an increasing prevalence over time. It has been described an association between low serum vitamin B12, osteoporosis and increased risk of bone fractures, but the studies are heterogeneous and the results are controversial. OBJECTIVE: To investigate the association between plasma levels of vitamin B12 and bone mineral density in a group of asymptomatic women after menopause. METHODS: Asymptomatic postmenopausal women were consecutively invited to participate in this cross-sectional study. Bone mineral density (lumbar spine and femur) was measured by DXA Lunar Prodigy Vision, and blood levels of vitamin B12, calcium, phosphorus, bone alkaline phosphatase (BAF), and parathyroid hormone were determined. For the diagnostic of osteoporosis the World Health Organization criteria were considered. RESULTS: Seventy women were included, mean age 62.5 ± 7 years. Eighteen (25.7%) women had normal bone mineral density, 33 (47.1%) had osteopenia and 19 (27.1%) had osteoporosis. Six (8.6%) patients had wrist fracture; two (2.8%) reported a diagnosis of vertebral fracture and only one (1.4%) patient had suffered a hip fracture. The levels of vitamin B12 (mean ± SD, pg/mL) of women with normal bone mineral density, osteopenia and osteoporosis were 590.2 ± 364.3, 536.6 ± 452.3, and 590.2 ± 497.9, respectively (P = 0.881). Multiple regression analysis showed that body mass index and BAF were the main predictors of lumbar spine bone mineral density. CONCLUSION: The results indicate that vitamin B12 serum levels are not related to bone mineral density in this group of Brazilian postmenopausal women.

Tratamento pós-menopausa reduz a atividade da catalase e atenua o risco cardiovascular / Postmenopausal therapy reduces catalase activity and attenuates cardiovascular risk

FUNDAMENTO: A menopausa pode levar a alterações na saúde feminina, com mudanças no estado oxidativo de mulheres pós-menopausadas, para as quais são limitadas as informações relativas à influência da hormonioterapia (HT) sobre as atividades das enzimas antioxidantes. OBJETIVO: Avaliar a influência da HT sobre a atividade da catalase, concentrações de lipídeos e lipoproteínas, proteína de transferência de colesteril éster, substâncias reativas ao ácido tiobarbitúrico, nitratos, proteína C-reativa ultrassensível e espessura da carótida em mulheres pós-menopausadas. MÉTODOS: Foram alocadas 94 mulheres para um de quatro grupos com ou sem HT. O último grupo foi subdividido em mulheres sendo tratadas com estrógeno e outras com estrógeno mais progestágeno. Foram realizadas medidas de parâmetros bioquímicos plasmáticos e da espessura da íntima-média da carótida. RESULTADOS: A HT antagonizou a redução na atividade da catalase após a menopausa, mas não teve efeito sobre os níveis da proteína de transferência de colesteril éster, substâncias reativas ao ácido tiobarbitúrico, peróxido lipídico, nitrato e proteína C reativa ultrassensível, nem sobre a espessura da íntima-média da carótida. A análise multivariada mostrou que a HT baseada em estrógeno atenuou a relação entre os fatores de risco cardiovasculares e a espessura da íntima-média da carótida comum. CONCLUSÃO: Este estudo mostra que a HT em mulheres pós-menopausadas produz efeitos antioxidantes e antiateroscleróticos benéficos por melhorar as concentrações séricas de lipídios e lipoproteínas, aumentar a atividade da catalase sérica e atenuar a associação entre os fatores de risco cardiovasculares e a aterosclerose precoce.

BACKGROUND: Menopause can lead to alterations in women's health, with changes in the oxidative status of postmenopausal women in whom information regarding the influence of hormone therapy (HT) on antioxidant enzyme activities is limited. OBJECTIVE: To evaluate the influence of HT on catalase activity; concentrations of lipids and lipoprotein, cholesteryl ester transfer protein, thiobarbituric acid-reactive substances, nitrates, high-sensitivity C-reactive protein and carotid thickness in postmenopausal women. METHODS: Ninety-four consecutive women were allocated to one of four groups, without HT and with HT. The latter group was subdivided into women using estrogen and those using estrogen plus progestogen therapy. Plasma biochemical parameters and common carotid intima-media thickness measurements were performed. RESULTS: HT antagonized the decrease in catalase activity after menopause, but had no effect on the levels of cholesteryl ester transfer protein, thiobarbituric acid-reactive substances, lipid peroxide, nitrate, high-sensitivity C-reactive protein, or on the common carotid intima-media thickness. Multivariate analysis showed that estrogen-based HT attenuated the relationship between cardiovascular risk factors and the intima-media thickness of the common carotid. CONCLUSION: This study indicates that HT in postmenopausal women produces beneficial antioxidant and anti-atherosclerotic effects by ameliorating the plasma lipid and lipoprotein profiles, increasing plasma catalase activity and attenuating the association between cardiovascular risk factors and early atherosclerosis.

Mayor frecuencia de aberraciones cromosómicas en linfocitos expuestos o no a mitomicina C, de mujeres posmenopáusicas obesas en comparación con mujeres no obesas del departamento del Cauca, Colombia / High frequency of chromosome aberrations observed in lymphocytes in postmenopausal obese women

Introducción. Los estudios epidemiológicos indican que la obesidad está asociada en el 25 al 30 % con varios tipos de cáncer. Objetivo. Evaluar la frecuencia de aberraciones cromosómicas en linfocitos de mujeres posmenopáusicas obesas y no obesas, mediante la prueba de reto celular (challenge assay) como biomarcador de inestabilidad genómica. Materiales y métodos. Cuarenta mujeres posmenopáusicas fueron incluidas en el estudio (20 obesas y 20 no obesas). Los grupos fueron pareados según edad (± 5 años) y procedencia. Después de la firma voluntaria del consentimiento informado, las mujeres fueron entrevistadas y se les tomó una muestra de 5 ml de sangre periférica. Se establecieron cultivos de linfocitos con tratamiento con mitomicina C y sin él (prueba de reto celular) y, posteriormente, se registró la frecuencia de aberraciones cromosómicas para cada grupo y tratamiento. Resultados. En general, las mujeres obesas presentaron una mayor frecuencia de aberraciones cromosómicas en comparación con las no obesas. Después de exponer los cultivos celulares a mitomicina C, las mujeres obesas presentaron un incremento en el número de aberraciones cromosómicas totales en comparación con las no obesas (3,74±0,63 Vs. 2,70±0,61; p=0,001). Conclusiones. La mayor frecuencia de aberraciones cromosómicas en los linfocitos de mujeres posmenopáusicas obesas que en no obesas, sugiere diferencias en la capacidad de reparación del ADN, lo cual podría explicar la asociación entre la inestabilidad genómica y la mayor incidencia de cáncer en esta población.

Introduction. Epidemiological studies indicate that obesity is associated with an increased risk of 20-25% with several types of cancer. Objective. The frequency of chromosome aberrations was evaluated in lymphocytes from postmenopausal obese and non-obese women. Materials and methods. Twenty obese and 20 non-obese women, all post-menopause, were recruited. The groups were matched according to age (± 5 years) and place of origin. After signing the consent form, women were interviewed using a structured questionnaire, and a blood sample (5 ml) was drawn into vacutainer tubes. From each sample, lymphocyte cell cultures were established with and without mitomycin C (challenge assay). Afterwards, the frequency of chromosome aberrations were recorded for each group and treatment. Data were analyzed using the statistical program SPSS, v. 14.0. Results. Obese women had a higher frequency of chromosome aberrations when compared with non-obese women. After exposing the cell cultures to mitomycin C, obese women presented an increase in the number of total chromosome aberrations in comparison to non-obese women (3.7± 0.6 vs. 2.70±0.6; p=0.001). Conclusions. The higher frequency of chromosome aberrations in lymphocytes from postmenopausal obese women compared to non-obese women suggested differences in the DNA repair capacity. This may indicate an association between genomic instability and the higher incidence of cancer in this population.

Perfil dos hormônios da tireoide em pacientes com câncer de mama em estado de menopausa / Thyroid hormone profile in breast cancer patients in postmenopause

OBJETIVO: Verificar o perfil dos hormônios tireóideos (HTs) em pacientes pós-menopausa portadoras de carcinoma de mama (CaM). SUJEITOS E MÉTODOS: Participaram 12 pacientes com CaM em estádio I ou II sem intervenções que pudessem interferir na progressão tumoral e um grupo controle com 18 pacientes em pós-menopausa sem CaM. Foram dosados os níveis séricos de anticorpo antitiroperoxidase (TPOAB), hormônio estimulante da tireoide (TSH), tiroxina livre (T4L), estradiol (E2), hormônio folículo estimulante (FSH) e hormônio luteinizante (LH) antes e após a cirurgia, e realizada a imunoistoquímica dos receptores de estrógeno (ER) e progesterona (PR). RESULTADOS: Quatro pacientes com CaM apresentaram alterações do perfil hormonal tireoidiano: dois hipertireoidismo, um hipotireoidismo e positividade TPO-AB, todas com ER e PR positivos. Os níveis de TSH dessas pacientes não foram diferentes dos níveis encontrados no grupo controle (1,89 ± 1,56 vs. 2,86 ± 3,12 mUI/mL), porém os níveis de T4L nas pacientes com CaM foram estatisticamente maiores que o controle (1,83 ± 0,57 vs. 1,10 ± 0,20 ng/dL). CONCLUSÃO: Esses resultados reforçam a necessidade de avaliação do status tireoidiano em pacientes com CaM, uma vez que, na ausência de E2, mudanças clínicas nos HTs podem atuar em vias controladas pelo E2.

OBJECTIVE: The aim of this study was to determine thyroid hormone (TH) profile in postmenopausal patients with breast cancer (BC). SUBJECTS AND METHODS: 12 CaM patients stages I or II, without interventions that could interfere with tumor progression were selected, as well as and a control group with 18 postmenopausal women without CaM. We measured serum anti-thyroperoxidase antibody (TPOAB), thyroid-stimulating hormone (TSH), free thyroxine (T4L), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH), before and after surgery, besides immunohistochemistry for estrogen (ER) and progesterone (PR) receptors. RESULTS: Four patients with CaM showed changes in thyroid hormone profile: two had hyperthyroidism, one hypothyroidism, and one was positive for TPO-AB. All of them positive for ER and PR. TSH levels in breast cancer patients were not different from levels found in the control group (1.89 ± 1.56 vs. 2.86 ± 3.12 mIU/mL), but the levels of T4L in patients with CaM were statistically higher than those of the control group (1.83 ± 0.57 vs. 1.10 ± 0.20 ng/dL). CONCLUSION: These results reinforce the need for assessment of thyroid status in CaM patients, since in the absence of E2, changes in clinical HTs can act in E2-controlled processes.