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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This is a review and presentation of recent clinical trials designed to ascertain the effects of estrogen or estrogen plus progesterone on the risks of heart disease. The framework of the epidemiologic evidence that estrogen is cardioprotective is reviewed and the impact of these data on apparent findings from clinical trials discussed. The Heart and Estrogen/Progestin Replacement Study is examined in detail, and the most frequent criticisms of its findings are presented. Findings from other clinical trials are presented and the clinical implications from the data discussed in relation to the larger body of literature pertaining to hormone replacement therapy and heart disease.
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PMID:The controversy over estrogen replacement therapy: an update on clinical trials. 1211 7

Several biases in studies of estrogen replacement therapy suggest that claims that estrogen replacement therapy reduces the risk of heart disease are exaggerated. Women who have taken part in these studies are usually healthier than the average woman. In fact, for many years, physicians had not prescribed hormones to women whom they considered to be in less than excellent health. Thus, women on estrogen replacement therapy would tend not to suffer heart disease. Even though hormonal therapy does protect against osteoporosis in postmenopausal women, physicians should not prescribe hormonal therapy just to protect women from heart disease. The American Heart Association reported in the autumn of 1993 that estrogen use has been linked to a 50% reduction in the risk of coronary heart disease and stroke, but it also warns that one must be cautious when interpreting these studies, since physicians may prescribe hormones to primarily healthier women to relieve symptoms of menopause. Women must visit a physician before beginning hormone replacement, and they are more likely to enter heart disease prevention programs than women not on estrogen. Women on hormone replacement therapy have higher incomes and more education than women who are not on this therapy. In fact, higher income and education make women more healthy than poor, less educated women. Since 10 times more women die of heart disease in the US than of osteoporosis, we need to know whether hormone replacement therapy really prevents heart disease. The Heart Estrogen Replacement Study and the Women's Health Initiative have recently begun carefully controlled studies examining whether hormone replacement therapy protects against heart disease. They should produce results in 5-6 years.
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PMID:Estrogen's protection against heart disease may be overstated. 1217 78

The 3 main methods of oral contraception (OC) are: 1) the sequential method, reproducing the hormonal sequence of the normal cycle; with this method the estrogen component is the one which inhibits ovulation; 2) the combined method, using estrogen and progesterone agents, and whose effectiveness is practically absolute; 3) the minipill, or low-dose progestin method. Other methods include the use of medroxyprogesterone acetate, which is 100% effective but has too numerous side effects, and the morning after pill. Estrogens utilized for OC are mestranol and ethinyl estradiol, while progestational agents can be derived from the natural progesterone, such as medroxyprogesterone, chlormandinone, and megestrol or from nor-19 testosterone. The minipill entails much fewer side effects than regular estroprogestational drugs, such as lower risk of thromboembolitic and metabolic processes; it does cause, however, a number of serious anomalies in the menstrual cycle. OC with low-dose progestin agents are recommended for women with pathologic antecedents, such as diabetes, cardiopathy, and hyperlipidemia.
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PMID:[Pills and minipills]. 1226 67

Over 60 million women use highly efficient and safe modern combined oral contraceptives (OCs) every day. A women who takes the oral contraceptive for 5 years before the age of 30 will actually live 12 days longer, although a woman taking the pill for the 1st time for 5 years after the age of 30 will have her life span reduced on the average by 80 days. OC related morbidity and mortality mostly occur in women over 35 who smoke. Combined low dose OCs are safe for women who do not smoke, at least to 45 years of age and probably to the menopause. The prescription of OCs is also safe to the young adolescent. The pill does not interfere with maturation of the hypothalamic-pituitary ovarian axis and does not increase the incidence of amenorrhoea, oligomenorrhoea or infertility in later life. Patients with contraindications to estrogen therapy are excluded from OC use (history of thromboembolism, major heart disease, liver disease, breast cancer). Low-dose (30-35 mcg estrogen-containing monophasic or triphasic) pills are recommended. Combined oral contraceptives contain either ethinyl estradiol (1.7 to 2 times more potent) or mestranol. After absorption the progestagens, norethisterone acetate, ethynodiol diacetate and lynoestrenol are all metabolized to norethisterone. The progestagen-only pill has about a 2% failure rate and poorer cycle control than the combined pill, but it lacks estrogenic, progestagenic and androgenic side effects. This pill is suitable for the lactating mother, for smokers over 35, for hypertensive patients, and for those with a history of thrombosis. The efficacy of the progestagen-only pill is restored in 3 days of pill taking. Postcoital contraception is an alternative: treatment can be given for at least 72 hours after intercourse. The Yuzpe method calls for the patient to take 2 combined oral contraceptive tablets containing levonorgestrel and ethinyl estradiol (Eugynon or Ovral) followed by a further 2 tablets 12 hours later. This regimen probably reduces the risk of pregnancy about tenfold and it is generally well tolerated.
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PMID:Oral contraceptives. 1231 13

Library research reports from Sweden, England, and other countries have been studied in an effort to determine the effect of oral contraceptives (OCs) on lipoprotein metabolism. The results are conflicting, possibly due to the fact that there are different amounts of estrogen and progesterone in the various kinds of pills. Estrogen is known to cause increased glycerides in the blood, but progesterone can reduce the concentration of the glycerides. Blood lipids and glycerides increase after taking OCs, and high density lipoproteins decrease. Cholesterol and phospholipids usually decrease, but reports on this are also conflicting. It has been widely reported that OCs increase the risk of heart disease, but data from Great Britian indicate that the pills may actually protect the user from heart disease. Because the results of the aforementioned research are not conclusive, in depth research should be carried out to determine the relationship between OCs and lipoprotein metabolism. All clinical tests regarding OCs should take this relationship into consideration, in order to gather large amounts of reliable data.
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PMID:[[Effect of oral contraceptives on lipid and lipoprotein metabolism]]. 1233 79

Cardiovascular disease is the leading cause of death in women. In pooled analysis, observational studies have shown a 50% reduction in death and myocardial infarction among users of hormone replacement therapy (HRT) for the primary and secondary prevention of cardiovascular disease. The first randomized trial of HRT for secondary prevention of heart disease found no benefit to therapy (Heart and Estrogen/progestin Replacement Study ). Even after 6.8 years of follow-up, there was still no cardiovascular benefit from the use of HRT (HERS II). HRT was associated with a 50% increased risk of heart attacks within the first year as well as an increased risk of deep venous thrombosis (DVT) and pulmonary embolism (PE) (relative risk 2.89) and gallbladder disease (RR 1.38). The Estrogen Replacement and Atherosclerosis trial found no evidence that HRT slowed the progression of subclinical angiographic disease either. This was despite a favorable effect on high-density lipoprotein and low-density lipoprotein. The first randomized trial of HRT for the primary prevention of heart disease found no overall benefit (Women's Health Initiative). The combination of estrogen and progestin resulted in a 29% increase in heart attacks, 41% increase in stroke, a doubling of thrombotic events (DVT and PE), as well as a 26% increase in breast cancer. The risk for thrombotic events was greatest in the first year whereas the risk of breast cancer increased progressively with duration of therapy. HRT is no longer recommended for the primary or secondary prevention of cardiovascular disease or stroke. It may still be considered for short-term relief of menopausal symptoms in women without high-risk conditions, but alternatives exist.
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PMID:Hormone Replacement Therapy for Primary and Secondary Prevention of Heart Disease. 1268 16

We evaluated the association of hemostatic factors with insulin resistance in relation to reproductive hormones including FSH, estradiol, testosterone, and SHBG. SHBG was used to calculate the free estradiol index and free androgen index. We studied 3,200 women, aged 42-52 yr, in the Study of Women's Health Across the Nation, a prospective multiethnic study of the menopausal transition. We measured the hemostatic factors, fibrinogen, factor VIIc, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor type 1 (PAI-1), as well as glucose and insulin to calculate insulin resistance. After adjustment for body mass index, site, and ethnicity, SHBG was correlated with PAI-1 (partial r = -0.30) and t-PA (partial r = -0.12). Although testosterone was associated with t-PA (partial r = 0.13) and PAI-1 (partial r = 0.07), free androgen index was strongly correlated with t-PA (partial r = 0.18) and PAI-1 (partial r = 0.26). SHBG modified the association of hemostatic factors with insulin resistance. Women with greater insulin resistance had lower SHBG and higher PAI-1. Estrogen measures were not associated with insulin resistance. The influence of sex hormones on hemostatic factors and insulin resistance is poorly understood. SHBG, which influences the amount of bioavailable hormone, significantly modified the association of PAI-1 and t-PA with insulin resistance. The longitudinal Study of Women's Health Across the Nation will help us discern whether this interaction contributes to heart disease and diabetes among postmenopausal women.
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PMID:Insulin resistance, hemostatic factors, and hormone interactions in pre- and perimenopausal women: SWAN. 1455 72

Overweight and abdominal obesity increase mortality risk, although the risk may be mediated by traditional cardiac risk factors. The authors assessed the association of baseline measures, change in overall body weight and abdominal obesity (waist circumference), and weight and waist circumference cycling with total mortality among postmenopausal women with known heart disease. They used data from 2,739 US women who participated in the Heart and Estrogen/progestin Replacement Study between 1993 and 2001. Over 6.8 years of follow-up, 498 women died. In adjusted Cox models that included either baseline waist circumference or body mass index (BMI), each was associated with mortality. However, after further adjustment for diabetes, hypertension, and lipoproteins, these associations disappeared. In models including both waist circumference and BMI, larger waist circumference (hazard ratio=1.40 per standard deviation, 95% confidence interval: 1.16, 1.68) was associated with increased risk and higher BMI (hazard ratio=0.81 per standard deviation, 95% confidence interval: 0.67, 0.97) was associated with decreased risk of total mortality, independent of cardiac risk factors. Weight and waist circumference cycling were not associated with mortality. Results show that both BMI and waist circumference are associated with mortality among postmenopausal women with established heart disease, but waist circumference may be more important than BMI, and their effects may be largely mediated by other cardiac risk factors.
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PMID:Association of total and central obesity with mortality in postmenopausal women with coronary heart disease. 1465 1

Estrogen, with or without a progestin, is effective for the treatment of menopausal symptoms. Larger doses of estrogen/progestin have been used than required for the amelioration of menopausal symptoms. Both positive and negative outcomes of hormone therapy are reported in postmenopausal women. The positive aspects have been those associated with a reduction in menopausal symptoms such as hot flashes, and improvement in vulvovaginal atrophy with maintenance of bone mineral density. The problems have included an increased risk of venous thrombosis and breast cancer. The anticipation is that as the dose of oral estrogen and progestins is lowered, the benefits can be maintained and the side effects reduced. Recent clinical trials have found that lower doses of estrogen and/or progestin reduce or improve menopausal symptoms and maintain bone mineral density. The impact of lower doses of hormones on heart disease, and venous thromboembolism and stroke remain to be determined in future studies.
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PMID:Lower doses of oral estrogen and progestogens as treatment for postmenopausal women. 1585 5

The prevalence of hypertension and cardiovascular disease increases dramatically after menopause in women, implicating estrogen as having a protective role in the cardiovascular system. However, recent large clinical trials have failed to show cardiovascular benefit, and have even demonstrated possible harmful effects, of opposed and unopposed estrogen in postmenopausal women. While these findings have led to a revision of guidelines such that they discourage the use of estrogen for primary or secondary prevention of heart disease in postmenopausal women, many investigators have attributed the negative results in clinical trials to several flaws in study design, including the older age of study participants and the initiation of estrogen late after menopause.Because almost all clinical trials use oral estrogen as the primary form of hormone supplementation, another question that has arisen is the importance of the route of estrogen administration with regards to the cardiovascular outcomes. During oral estrogen administration, the concentration of estradiol in the liver sinusoids is four to five times higher than that in the systemic circulation. This supraphysiologic concentration of estrogen in the liver can modulate the expression of many hepatic-derived proteins, which are not observed in premenopausal women. In contrast, transdermal estrogen delivers the hormone directly into the systemic circulation and, thus, avoids the first-pass hepatic effect.Although oral estrogen exerts a more favorable influence than transdermal estrogen on traditional cardiovascular risk factors such as high- and low-density lipoprotein-cholesterol levels, recent studies have indicated that oral estrogen adversely influences many emerging risk factors in ways that are not seen with transdermal estrogen. Oral estrogen significantly increases levels of acute-phase proteins such as C-reactive protein and serum amyloid A; procoagulant factors such as prothrombin fragments 1+2; and several key enzymes involved in plaque disruption, while transdermal estrogen does not have these adverse effects.Whether the advantages of transdermal estrogen with regards to these risk factors will translate into improved clinical outcomes remains to be determined. Two ongoing clinical trials, KEEPS (Kronos Early Estrogen Prevention Study) and ELITE (Early versus Late Intervention Trial with Estradiol) are likely to provide invaluable information regarding the role of oral versus transdermal estrogen in younger postmenopausal women.
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PMID:Effects of transdermal estrogen replacement therapy on cardiovascular risk factors. 1639 17


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