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.

Prevalencia de causas secundarias de baja masa ósea en una población de mujeres premenopáusicas / Prevalence of secondary causes in a population of premenopausal women with low bone mass

La osteoporosis es un trastorno común en las mujeres posmenopáusicas; sin embargo, también puede afectar a hombres y mujeres jóvenes premenopáusicas. El objetivo del presente trabajo fue evaluar la prevalencia de causas secundarias de baja masa ósea en un grupo de mujeres premenopáusicas que consultaron en una Institución especializada en Osteología. Material y métodos: se realizó un estudio retrospectivo, de corte transversal, descriptivo y observacional. Se analizaron las historias clínicas de 88 pacientes que consultaron por baja masa ósea durante un período de 19 meses, con la finalidad de encontrar posibles causas secundarias. A su vez, se definió como pacientes con diagnóstico de baja masa ósea idiopática aquellas en las cuales no se encontró ninguna causa secundaria de pérdida ósea. Resultados: de las 88 mujeres evaluadas, el 48,9% presentaba al menos una causa secundaria para baja masa ósea (amenorrea secundaria, hipercalciuria, tratamiento con glucorticoides, hipovitaminosis D y enfermedad celíaca) y el 51,1% fueron consideradas idiopáticas. Conclusiones: es esencial evaluar exhaustivamente a las mujeres premenopáusicas con baja masa ósea a fin de descartar posibles causas secundarias y tomar las medidas preventivas necesarias para mejorar esa condición. (AU)

Objective: osteoporosis is a common disorder in postmenopausal women, however it can also affect men and premenopausal young women. The purpose of this study was to evaluate the prevalence of secondary causes of low bone mass in premenopausal women that consulted physicians in an institution specialized in osteology for a period of 19 months. Material and methods: this is a retrospective, transversal, descriptive and observational study. The clinical history of 88 patients who consulted a physician due to low bone mass for a period of 19 months in an institution specialized in osteology. Were analyzed the patient's clinical history in order to find secondary causes. We define as suffering Low Bone Mass those patients who did not have secondary causes. Results: of the 88 women tested, 48,9% had one or more secondary causes or risks factors for low bone mass (secondary amenorrea, hypercalciuria, treatment with glucocorticoids, hypovitamiosis D and celiac disease) and 51,1% patients were considered idiopathic. Conclusions: we conclude that it is essential to exhaustively search for secondary causes of low bone mass in premenopausal women, due to the high prevalence of secondary osteoporosis in this population. (AU)

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.

Genes responsible for vaginal extracellular matrix metabolism are modulated by women's reproductive cycle and menopause

Objectives To analyze the expression of genes involved in extracellular matrix (ECM) biogenesis and remodeling in vaginal tissue of women with clinically normal pelvic floor support (defined as controls) according to the phase of menstrual cycle and postmenopausal women with and without pelvic organ prolapse (POP). Materials and Methods This study examined the expression of matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), and the Lysyl oxidase (LOX) family genes in the anterior vaginal wall of Caucasian women by real-time RT-PCR. Initially, mRNA expression was assessed in premenopausal controls in the secretory (group 1, n = 10) vs. proliferative (group 2, n = 8) phase of menstrual cycle. In addition, we compared premenopausal controls in the proliferative phase (group 2) vs. postmenopausal controls (group 3, n = 5). Finally, we analyzed postmenopausal controls (group 3) vs. postmenopausal women with advanced POP (group 4, n = 13). Results According to the phase of menstrual cycle, MMP1 was significantly reduced (p = 0.003), whereas the expression of TIMP1 and LOXL4 was significantly up-regulated during proliferative phase (both p < 0.01) when compared to the secretory phase in premenopausal control women. Regarding menopausal status/ageing, all MMPs were down-regulated, while TIMP3, TIMP4 and LOXL2 were significantly up-regulated in postmenopausal control women when compared to premenopausal controls (p = 0.005, p = 0.01 and p < 0.001, correspondingly). TIMP4 and LOXL2 mRNA levels were significantly decreased in postmenopausal POP patients compared to asymptomatic postmenopausal controls (p < 0.01 for both). Conclusions Our results indicate that ovarian cycle and age-related changes influence the expression of genes encoding proteins responsible for ECM metabolism in human vagina. Moreover, POP is associated with alteration in vaginal ECM components after menopause. .

Hormonioterapia neoadjuvante no câncer de mama / Neoadjuvant endocrine therapy in primary breast cancer

A hormonioterapia neoadjuvante tem sido cada vez mais utilizada na prática clínica para melhorar as opções cirúrgicas para mulheres pós-menopáusicas com tumores localmente avançados, com receptores hormonais fortemente positivos. Estudos recentes indicam que a resposta do tumor nesta população pode prever o resultado em longo prazo de pacientes em terapia endócrina adjuvante, defendendo a sua ampla aplicação no tratamento da doença nas pacientes com receptores hormonais positivos. Nas pacientes na pré-menopausa, mais estudos são necessários para estabelecer o real benefício desta abordagem. Do ponto de vista de investigação, a hormonioterapia neoadjuvante pode proporcionar uma oportunidade única para os estudos preditores de resposta, além de proporcionar o desenvolvimento de novos agentes terapêuticos.

Bone and heart abnormalities of subclinical hyperthyroidism in women below the age of 65 years / Anormalidades ósseas e cardíacas do hipertireoidismo subclínico em mulheres com menos de 65 anos

The objective of the present study was to evaluate bone and cardiac abnormalities and symptoms and signs of thyroid hormone excess in women with subclinical hyperthyroidism (SCH) aged < 65 years. Forty-eight women with SCH were evaluated. The control group consisted of 48 euthyroid volunteers. The mean symptom rating scale score was significantly higher in patients. Cardiac involvement, both morphological and affecting systolic and diastolic functions, was also observed in patients. Women with SCH showed a significant increase in serum markers of bone formation and resorption. In addition, bone mineral density (BMD) was lower in the femoral neck but not in the lumbar spine in patients before menopause, whereas a lower BMD was observed at both sites in postmenopausal patients. SCH is not completely asymptomatic in women aged < 65 years, and is associated with heart abnormalities and with increased bone turnover and reduced BMD even before menopause.

O objetivo deste estudo foi avaliar as anormalidades ósseas e cardíacas, sintomas e sinais de excesso de hormônio tireoidiano em mulheres com hipertireoidismo subclínico (HSC) e menos de 65 anos de idade. Quarenta e oito mulheres com HSC foram avaliadas. O grupo-controle consistiu de 48 voluntárias eutireoidianas. A média do escore de sintomas foi significativamente maior em pacientes que em controles. Comprometimento cardíaco, morfológico e afetando as funções sistólica e diastólica, também foi observado. Mulheres com HSC apresentaram significativo aumento dos marcadores séricos de formação e reabsorção óssea. A densidade mineral óssea (DMO) foi menor no colo de fêmur, mas não em coluna lombar em mulheres antes da menopausa; enquanto e em ambos os sítios nas mulheres pós-menopausadas. HSC não é inteiramente assintomático em mulheres com menos de 65 anos, está associado a anormalidades cardíacas morfológicas e funcionais, incremento da remodelação óssea, e menor DMO, mesmo antes da menopausa.

Estudo da densidade mineral óssea em pacientes com lúpus eritematoso sistêmico antes e após uso de glicocorticóides / Study of the bone mineral density in patients with systemic lupus erythematosus before and after glucocorticoid treatment

OBJETIVO: Avaliar a variabilidade da densidade mineral óssea em pacientes com lúpus eritematoso sistêmico, antes do início e após 30 e 60 dias do início de glicocorticoterapia. MATERIAIS E MÉTODOS: Estudo efetuado em 15 mulheres em pré-menopausa com lúpus eritematoso sistêmico encaminhadas para realização de densitometria óssea e que fariam uso de corticosteróides logo após o exame. RESULTADOS: Demonstrou-se que a densidade mineral óssea, em g/cm², na coluna lombar reduziu-se significativamente entre a análise prévia ao uso e a análise em 60 dias de uso da medicação, mas no colo femoral não houve diferença significativa. CONCLUSÃO: Concluiu-se que o uso de corticoterapia em pacientes com lúpus eritematoso sistêmico, em curto prazo, reduz significativamente a densidade mineral óssea na coluna lombar, não somente em longo prazo como descrito anteriormente por outros autores.

OBJECTIVE: To evaluate the bone mineral density variability in patients with systemic lupus erythematosus, before the beginning and at 30 and 60 days from the beginning of glucocorticoid therapy. MATERIALS AND METHODS: Fifteen premenopausal women with systemic lupus erythematosus were referred for bone densitometry before being submitted to glucocorticoid therapy. RESULTS: It was demonstrated that the bone mineral density in g/cm² in the lumbar spine presented a significant decrease in the span between the first analysis previously to the beginning of the glucocorticoid therapy and the third analysis after 60 days under therapy. On the other hand no significant difference was found in the femoral neck. CONCLUSION: The authors conclude that, at short term, rather than only at long term as previously reported by other authors, corticotherapy in patients with systemic lupus erythematosus results in a decrease in the bone mineral density in the lumbar spine.

Insulin, insulin-like growth factor-I and breast cancer risk in Japanese women.

To evaluate the effects of glucose metabolism related factors, such as insulin and insulin-like growth-factors (IGFs), on breast cancer development among Japanese women, we conducted a case-referent study comparing 187 women presenting with operable breast cancer and 190 women of the same age having no breast cancer. Odds ratios (OR) and 95% confidence intervals (95%CI) were determined by multiple logistic regression analysis. In the present study, no association in risk was observed with increasing levels of IGF-I or IGF binding protein-3 (IGFBP-3), before or after adjustment these factors. However, a suggestion of a positive association of an increased breast cancer risk was evident in postmenopausal women with elevated plasma insulin levels, particularly those with BMI>23.07. The OR for plasma insulin in the top tertile was 4.48 (95%CI:1.07-18.7) compared to the bottom tertile. For C-peptide, there was a similar positive association, with a corresponding OR of 2.28. In addition, we observed strong links between plasma insulin, C-peptide levels and estrogen receptor (ER) negative breast cancer, with ORs of 2.79(95%CI:1.09-7.16), and 2.52 (95%CI:0.91-6.97) respectively, for the top versus bottom tertiles. In conclusion, the present study suggested that plasma insulin level is a predictor of postmenopausal breast cancer in obese women and ER negative breast cancer. Additional studies are needed to clarify the role of glucose metabolism pathways in breast cancer development and interaction of IGF systems.

Efeitos de uma associacao estro-progestonica em mulheres hipertensas e normotensas na perimenopausa / Effects of an estrogenic-progestogenic association on hipertensive and normotensive perimenopausal women

Objetivo: O objetivo deste estudo foi avaliar os efeitos de uma associacao estro-progestogenica contendo valerato de estradiol associado a progestogeno derivado de 19-nortestosterona sobre os niveis presssoricos, perfil lipidico e outros...

Risk of coronary heart disease in women after menopause.

An increase in the incidence of coronary heart disease risk has commonly been reported in postmenopausal women. The study population comprised 263 adult healthy men and 237 women (104 premenopausal and 133 postmenopausal) ranging in age group of 21-70 years who were examined for coronary heart disease risk factors from Nellore district in Andhra Pradesh. Anthropometric measurements, blood pressure and serum lipids were analysed using standard procedures. There were no significant differences for anthropometric variables between postmenopausal and premenopausal women. Postmenopausal women had significantly higher levels of blood pressure, pulse rate, serum total cholesterol, triglycerides, low-density lipoprotein cholesterol and ratios of total cholesterol:high-density lipoprotein cholesterol and low-density lipoprotein cholesterol:high-density lipoprotein cholesterol as atherogenic indices than premenopausal women and the corresponding age group of male counterparts. However, the variation of high-density lipoprotein cholesterol levels between these groups were not statistically significant. The prevalence of hypertension, hypercholesterolaemia, hypertriglyceridaemia and atherogenic indices was significantly greater in postmenopausal women than in premenopausal women. This study confirms a higher prevalence of risk factors for coronary heart disease among women in older age group and suggests that when oestrogen production ceases in menopausal women, the risk of coronary heart disease increases.

Endocrinologia do ovário no climatério perimenopáusico / The ovarian endocrinology in the perimenopausal period

O climatério, período de transiçäo entre o menacme e a senectude, compreende uma série de fenômenos clínicos, biológicos e endocrinológicos, que se iniciam muito antes da instalaçäo da menopausa e prosseguem por anos após a mesma. A endocrinologia de transiçäo menopáusica, compreendida nesse período, é o objetivo do presente trabalho de revisäo da literatura. Observa-se, inicialmente, diminuiçäo na secreçäo de Inibina, um polipeptídeo produzido pelas células da granulosa, responsável por modulaçäo da secreçäo de FSH. Há aumento do FSH, seguido de aumento do LH e diminuiçäo da esteroidogênese ovariana, resultando em hipoestrogenismo e diminuiçäo dos níveis de progesterona, o que concorre para a série de alteraçöes que caracterizam esse período.

Marcadores bioquímicos del remodelamiento óseo en mujeres pre y postmenopáusicas / Biochemical markers of bone turnover in pre and postmenopausal women

La disminución o cese de la producción de estrógenos en lamenopausia, ocasiona alteraciones del metabolismo óseo, caracterizadas por la resorción acelerada de tejido óseo. Esta condición es responsable, comúnmente, de la presentación de osteoporosis. Con el objeto de evaluar el estado del remodelamiento óseo, se estudiaron tres grupos de 46 mujeres cada uno: premenopáusicas (A), postmenopáusicas naturales (B) y con ooforectomía bilateral (C) de 41.30 ñ 9.72, 55.93 ñ 7.11 y 50.24 ñ 8.66 años ñ D.E., respectivamente. La concentración (U/L x ñ DE) de fosfatasa alcalina total (FAt), marcador de formación ósea fue 125.88 ñ 65.67, 149.26 ñ 51.48 y 131.18 ñ 57.3 para los grupos A, B y C, respectivamente. Como marcador de resorción ósea se determinó fosfatasa ácida tartrato resistente (FATR), obteniéndose (UI/LxñD.E.) para A: 7,99ñ2.78, B: 9.82ñ2.15 y C: 8.68ñ2.23. Las diferencias entre las medias de los tres grupos fueron significativas para FAt y FATR (p < .001), entre los tres grupos estudiados. Se concluye que la determinación de FAt y FATR, así como de Ca, P y Mg séricos y Ca y P urinarios, permiten evaluar el estado del remodelamiento óseo