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      La terapia hormonal de reemplazo y la prevención cardiovascular en la menopausia.: Principales estudios realizados y sus resultados Translated title: Replacement hormone therapy and cardiovascular prevention in the menopause: Main studies conducted and their results

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          Abstract

          Siempre ha sido señalada la influencia del hipoestronismo como factor de riesgo en el aparato cardiovascular en la mujer en la etapa del climaterio y la menopausia; sin embargo, existen diferencias importantes en las investigaciones observacionales realizados en la década de los años 80 y primera mitad de los 90 del pasado siglo, que resaltaban la protección de la terapia hormonal sobre el sistema cardiovascular y las investigaciones que se han hecho a partir de 1998 hasta la fecha, cuyos resultados han señalado que la terapia hormonal no solamente no protege el aparato cardiovascular, sino que puede tener un efecto negativo sobre el mismo, lo que ha sembrado muchas dudas ante esas diferencias.

          Translated abstract

          The influence of hypoestrogenism has always been considered as a risk factor in the cardiovascular system of women during the climacteric and menopause; however, there exist important differences between the observational researches made during the 80's and the first half of the 90's of the last century that stressed the protection of replacement hormone therapy on the cardiovascular system, and the researches carried out from 1998 on up to now that show that hormone therapy does not protect the cardiovascular system and may have a negative effect on it. These differences have sown many doubts so far.

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          Most cited references 22

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          Secular trends in cardiovascular disease risk factors according to body mass index in US adults.

          Prevalence of obesity in the United States has increased dramatically in recent decades, but the magnitude of change in cardiovascular disease (CVD) risk factors among the growing proportion of overweight and obese Americans remains unknown. To examine 40-year trends in CVD risk factors by body mass index (BMI) groups among US adults aged 20 to 74 years. Analysis of 5 cross-sectional, nationally representative surveys: National Health Examination Survey (1960-1962); National Health and Nutrition Examination Survey (NHANES) I (1971-1975), II (1976-1980), and III (1988-1994); and NHANES 1999-2000. Prevalence of high cholesterol level (> or =240 mg/dL [> or =6.2 mmol/L] regardless of treatment), high blood pressure (> or =140/90 mm Hg regardless of treatment), current smoking, and total diabetes (diagnosed and undiagnosed combined) according to BMI group (lean, or =30). The prevalence of all risk factors except diabetes decreased over time across all BMI groups, with the greatest reductions observed among overweight and obese groups. Compared with obese persons in 1960-1962, obese persons in 1999-2000 had a 21-percentage-point lower prevalence of high cholesterol level (39% in 1960-1962 vs 18% in 1999-2000), an 18-percentage-point lower prevalence of high blood pressure (from 42% to 24%), and a 12-percentage-point lower smoking prevalence (from 32% to 20%). Survey x BMI group interaction terms indicated that compared with the first survey, the prevalence of high cholesterol in the fifth survey had fallen more in obese and overweight persons than in lean persons (P<.05). Survey x BMI changes in blood pressure and smoking were not statistically significant. Changes in risk factors were accompanied by increases in lipid-lowering and antihypertensive medication use, particularly among obese persons. Total diabetes prevalence was stable within BMI groups over time, as nonsignificant 1- to 2-percentage-point increases occurred between 1976-1980 and 1999-2000. Except for diabetes, CVD risk factors have declined considerably over the past 40 years in all BMI groups. Although obese persons still have higher risk factor levels than lean persons, the levels of these risk factors are much lower than in previous decades.
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            Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II).

            The Heart and Estrogen/progestin Replacement Study (HERS) found no overall reduction in risk of coronary heart disease (CHD) events among postmenopausal women with CHD. However, in the hormone group, findings did suggest a higher risk of CHD events during the first year, and a decreased risk during years 3 to 5. To determine if the risk reduction observed in the later years of HERS persisted and resulted in an overall reduced risk of CHD events with additional years of follow-up. Randomized, blinded, placebo-controlled trial of 4.1 years' duration (HERS) and subsequent unblinded follow-up for 2.7 years (HERS II) conducted at outpatient and community settings at 20 US clinical centers. A total of 2763 postmenopausal women with CHD and average age of 67 years at enrollment in HERS; 2321 women (93% of those surviving) consented to follow-up in HERS II. Participants were randomly assigned to receive 0.625 mg/d of conjugated estrogens and 2.5 mg of medroxyprogesterone acetate (n = 1380), or placebo (n = 1383) during HERS; open-label hormone therapy was prescribed at personal physicians' discretion during HERS II. The proportions with at least 80% adherence to hormones declined from 81% (year 1) to 45% (year 6) in the hormone group, and increased from 0% (year 1) to 8% (year 6) in the placebo group. The primary outcome was nonfatal myocardial infarction and CHD death. Secondary cardiovascular events were coronary revascularization, hospitalization for unstable angina or congestive heart failure, nonfatal ventricular arrhythmia, sudden death, stroke or transient ischemic attack, and peripheral arterial disease. There were no significant decreases in rates of primary CHD events or secondary cardiovascular events among women assigned to the hormone group compared with the placebo group in HERS, HERS II, or overall. The unadjusted relative hazard (RH) for CHD events in HERS was 0.99 (95% confidence interval [CI], 0.81-1.22); HERS II, 1.00 (95% CI, 0.77-1.29); and overall, 0.99 (0.84-1.17). The overall RHs were similar after adjustment for potential confounders and differential use of statins between treatment groups (RH, 0.97; 95% CI, 0.82-1.14), and in analyses restricted to women who were adherent to randomized treatment assignment (RH, 0.96; 95% CI, 0.77-1.19). Lower rates of CHD events among women in the hormone group in the final years of HERS did not persist during additional years of follow-up. After 6.8 years, hormone therapy did not reduce risk of cardiovascular events in women with CHD. Postmenopausal hormone therapy should not be used to reduce risk for CHD events in women with CHD.
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              Effect of postmenopausal hormones on inflammation-sensitive proteins: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Study.

              Observational studies in healthy women suggest postmenopausal hormone therapy reduces risk of coronary events. In contrast, in a recent clinical trial of women with coronary disease, a subgroup analysis demonstrated increased risk during the early months of therapy. Because higher levels of inflammation factors predict vascular disease outcomes, the effect of hormones on these factors is of interest. Four inflammation-sensitive factors, C-reactive protein, soluble E-selectin, von Willebrand factor antigen, and coagulation factor VIIIc were measured at baseline, 12, and 36 months in 365 participants of the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial, a randomized, placebo-controlled trial of the effects of 4 hormone preparations on cardiovascular disease risk factors. Compared with placebo, all 4 active preparations resulted in a large sustained increase in the concentration of C-reactive protein and a decrease in soluble E-selectin (P=0.0001). There were no effects of treatment on concentrations of von Willebrand factor or factor VIIIc. There were no differences in effects among treatment arms. Relative to placebo, when combining active treatment arms, final concentrations of C-reactive protein were 85% higher whereas E-selectin was 18% lower compared with baseline. Postmenopausal hormones rapidly increased the concentration of the inflammation factor C-reactive protein. Such an effect may be related to adverse early effects of estrogen therapy. In contrast, hormones reduced the concentration of soluble E-selectin, and this might be considered an anti-inflammatory effect. Because PEPI was not designed to assess clinical endpoints, studies of the impact of hormone-mediated changes in inflammation on risk of subsequent coronary events are needed.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Journal
                gin
                Revista Cubana de Obstetricia y Ginecología
                Rev Cubana Obstet Ginecol
                Editorial Ciencias Médicas (Ciudad de la Habana )
                1561-3062
                August 2006
                : 32
                : 2
                : 0
                Affiliations
                [1 ] Policlínico Universitario 26 de julio Cuba
                Article
                S0138-600X2006000200011
                Product
                Product Information: website
                Categories
                OBSTETRICS & GYNECOLOGY

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