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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many preclinical and clinical studies reveal that changes in lipoprotein metabolism are a major contributing factor to atherosclerosis. Hormones in oral contraceptive (OC) formulations strongly influence lipoprotein metabolism. Specifically, estrogens bring about increases in plasma triglycerides which then cause a rise in the very low density lipoprotein. They also decrease levels of the intermediate and low density lipoprotein which cause build up of plaque on arterial walls. Estrogens also lead to rising high density lipoprotein (HDL) levels, especially the HDL2 subspecies. Increased HDL levels are associated with lower mortality rates from cardiovascular conditions in women who have already experienced menopause and are on hormone replacement therapy. Combination OCs used in the US increase plasma triglycerides, low density lipoprotein, and HDL3. The estrogen dose and the relative androgenicity of the progestin together influence the changes in HDL and HDL2. Even though low dose combined OCs bring about lipoprotein changes which are lower than those of higher dose OCs, the changes often remain significant. The progestin component of OCs is responsible for most changes in carbohydrate metabolism. Specifically OC use can lead to increased levels of plasma insulin, insulin resistance, and relative glucose intolerance. A curve analysis of glucose tolerance tests reveals this intolerance effect of OCs. The changes in carbohydrate metabolism are not as great in women using the lower dose OCs or formulations using the new progestins, however.
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PMID:The metabolic impact of oral contraceptives. 141 43

Epidemiological data have revealed that the progestogen in oral contraceptives (OCs) is involved in hypertension, ischemic heart diseases, and stroke. Atherosclerotic lesions were implicated owing to the androgenic properties of progestogens. However, atherosclerosis did not develop despite reduced high density lipoprotein (HDL) and elevated low density lipoprotein (LDL), presumably because of the strong effect of ethinyl estradiol (EE) upon induction of hepatic LDL- and remnant-receptors. A series of findings indicate that vasospasms caused by the effect of progestogens are involved in arterial thromboses. In postmenopausal women, the addition of progestogens to the estrogen treatment may trigger ischemic diseases. Estrogens exert a vasodilatory effect and stabilize the vascular tonus through the responsiveness of the endothelium, neurotransmitter release, and direct blocking of calcium channels. Progestogens increase the sensitivity of arteries to vasoconstrictory compounds and reduce blood flow. In women treated with ovulation inhibitors, and EE-induced activation of the renin-angiotensin-aldosterone system was observed. Aldosterone acts vasodilatorily, while progestogens with high affinity to the aldosterone receptor may exert a strong vasoconstrictory effect. If vascular lesions are present, the vasoconstrictory action of progestogens may cause acute ischemic attacks. Therefore, the lowest effective dose of the progestogen has to be used for replacement therapy. In hysterectomized women, the extra administration of progestogens should be avoided and in women with arterial diseases they should be prescribed with discretion. Additional progestogens given for 14 days 3 months apart may suffice for the prevention of endometrial hyperplasia. Both the EE and progestogen doses in OCs should be reduced. Progestogen-dominant ovulation inhibitors should be restricted to cases with an additional indication.
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PMID:[Hormonal contraception and substitution therapy: the importance of progestogen for cardiovascular diseases]. 145

Ovarian steroids have effects on blood circulation involving the mechanisms which control blood flow and the changes that occur in the pathogenesis of atherosclerosis. Estrogens appear to protect women from cardiovascular disease through their effects on lipid metabolism as well as more direct effects on arterial walls which appear to inhibit atherosclerotic plaque formation. There is increasing evidence that estrogen replacement after menopause can markedly reduce female mortality due to vascular disease. Effects of hormone imbalance and deficiency on vasomotor control are clinically significant and hormone treatment appears to be effective in the management of a variety of conditions due to abnormal blood flow including vasomotor instability, migraine, vaginal dryness and, perhaps, some forms of angina. Most review articles have focused on the effects of ovarian steroids and lipid metabolism as well as the findings of recent epidemiologic studies. This is understandable as those investigations have proved so valuable in understanding the protective effects of estrogens. The present discussion, in contrast, focuses on the effects of ovarian steroids, estrogens in particular, on circulatory mechanisms. At the present time there is increasing interest in these studies. Findings thus far appear to contribute to understanding estrogen cardioprotection and also raise awareness of a variety of clinical conditions in which estrogen treatment could be indicated because of its effects on circulation.
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PMID:Ovarian hormones and the circulation. 221 71

It has been well documented that low-density lipoproteins and intermediate-density lipoproteins play a role in the development of atherosclerosis. Data also indicate that high-density lipoproteins (HDLs), have potentially antiatherogenic effects. The individual estrogen and progestogen components of oral contraceptives (OCs) have been shown to affect plasma lipoproteins in both cross-sectional and longitudinal studies. This effect depends on both the type of steroid used and the dose of each of the OC components. Estrogen and progestogen have opposing effects on lipoprotein physiology. Estrogens raise the level of HDL cholesterol, while progestogens tend to lower HDL levels. Thus, in OC formulations, as the ratio of estrogen to progestogen increases in favor of estrogen, there is a greater increase in HDL cholesterol--a potentially beneficial effect. Although there is no direct evidence that favorable lipoprotein changes produced by OCs are cardioprotective, the physician prescribing an OC should minimize adverse lipoprotein effects by prescribing a balanced low-dose, low-impact formulation.
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PMID:The effects of oral contraceptives on plasma lipids and lipoproteins. 290 39

To summarize, estrogens have powerful effects on certain biologic parameters, the alteration of which could influence cardiovascular disease risk. Estrogens have long been known to influence lipid and lipoprotein levels by decreasing LDL (the atherogenic lipoprotein) and by increasing HDL (the protective lipoprotein). THese lipid alterations could favorably influence the risk of cardiovascular disease. Estrogens also temporarily increase glucose intolerance and lower fasting glucose levels; although the former event could adversely affect cardiovascular disease risk, the clinical significance of increased glucose intolerance with low fasting levels has not been determined. There is no consistent evidence that menopausal estrogens adversely affect coagulation or blood pressure levels, although both of these parameters could be affected in selected individuals. Overall, the estrogenic effects on lipid/lipoprotein levels appear to be the most consistent and the most powerful; given this assumption, estrogens should protect against cardiovascular disease. There is another interpretation of the biologic effect of estrogens on cardiovascular risk. It is possible that estrogens may increase the risk of a thromboembolic event due to an adverse influence on coagulation parameters and, at the same time, decrease the risk of an atherogenic event (via favorably altered lipid/lipoprotein levels). This proposed dual action of estrogens may explain the apparently conflicting results of increased risks of thromboembolism and decreased risks of atherosclerosis or myocardial infarction in men treated with high doses of estrogen (36, 196, 197). In women, there is some suggestion that (low-dose) postmenopausal estrogens may increase the risk of thromboembolism (79, 204), although the majority of studies report no such increase. The difference in risk of thromboembolism between men and women using estrogens may be due to several factors. First, the dose (potency) of the estrogen used by men is usually higher than that used by postmenopausal women, and the risk of estrogen-induced thrombus formation may be dose-dependent. Second, men tend to have more atherosclerotic lesions than women and thus would have more substrate available for thrombus formation. (This hypothesis is supported by the observation that the increased risk of thromboembolism was evident in men using estrogens for the secondary prevention of cardiovascular disease.) Indirect evidence supporting the hypothesis that endogenous estrogen levels are protective against cardiovascular disease is most consistent for women.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Noncontraceptive estrogen use and cardiovascular disease. 299 19

Endogenous sex hormone activity results in higher levels of VLDL, LDL, and apo B in males than in females, while HDL and particularly HDL2, and apo A1 levels are lower, apo A2 being reduced to a lesser degree. This sex-related difference appears progressively during puberty. There is increasing elevation of LDL cholesterol, apo B, and VLDL TG in women at the menopause, HDL cholesterol levels either diminishing or remaining constant. These differences in lipoprotein and apoprotein concentrations probably play a major role in protecting women against atherosclerosis development during the period of gonadal activity. Similar differences are provoked by exogenous hormone activity: the androgens increase LDL cholesterol and reduce HDL cholesterol, and total cholesterol is therefore only slightly altered. Estrogens provoke elevation of VLDL TG only at supraphysiological doses of the order of 30-50 mcg ethinyl estradiol. In contrast, reductions in LDL cholesterol and increases in HDL cholesterol occur even after low physiological doses of estrogens. This latter increase is dose-related and can be as high as 20%. The action of progestogens is less clearly defined and depends on the molecule administered, the dosage, and its possible androgenic action. When the latter activity is marked, lipoprotein and apoprotein variations are similar to those resulting from testosterone effects. The influence of sex hormones on the course of idiopathic hyperlipidemias varies. They may have a beneficial effect, but this is a fairly rare event and occurs only in very precise situations: improvement of type 3 hyperlipidemia by low dose estrogen therapy; improvement of moderate isolated hypercholesterolemia in menopausal women with low doses of estrogens, and improvement of type 5 mixed hypertriglyceridemia by certain progestogens such as oxandrolone. They usually produce the opposite effect, however, with marked increases of type 1, 4, and 5 hyperlipidemia under estrogens, sometimes leading to attacks of pancreatitis and elevation of preexisting hypercholesterolemias or mixed hyperlipidemias resulting in vascular accidents due to thrombosis. (author's modified)
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PMID:[Sex hormones and metabolism of lipoproteins]. 634 27

Estrogens are female sex hormones that may also protect against peroxidative damage of membrane lipids and low density lipoproteins (LDL). Studies have reported that female rats have greater protection against free radical induced lipid peroxidation and muscle damage consequent to exercise than do male rats. It has been suggested that the lower susceptibility to exercise induced oxidative stress and muscle membrane disruption of female rats may be due primarily to the antioxidant and membrane stabilizing properties of estrogens. Studies on humans have indicated that the lower incidence of atherosclerosis seen in premenopausal females in comparison to males is due at least in part to the ability of estrogens to diminish LDL peroxidation. However, there is little evidence as to the potential of estrogens to protect human females from free radical induced peroxidation and muscle damage due to exercise. This paper reviews the evidence for membrane stabilization potential of estrogens and their possible mechanisms, and speculates as to the potential significance of this for human exercise.
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PMID:Can estrogens diminish exercise induced muscle damage? 774 68

Sex hormones may play a role in the determination of cardiovascular disease. Recently lipoprotein(a) (Lp[a]) has been recognized as a risk factor for coronary heart disease. Estrogens and anabolic steroids have been reported to alter Lp(a) levels, yet no data are available on the association between in vivo concentrations of sex hormones and Lp(a) concentrations. We examined the possible associations of sex hormone-binding globulin, total and free testosterone, estradiol, and dehydroepiandrosterone sulfate to Lp(a) concentrations in men in two population-based studies (San Antonio Heart Study [n = 178] and a Finnish study on the association between insulin resistance and atherosclerosis [n = 87]). In neither study were sex hormones significantly related to Lp(a) concentrations. In addition, Lp(a) was significantly related to apolipoprotein(a) molecular weight (which was measured in the Finnish study only). These results were unchanged when Lp(a) concentrations were adjusted for apolipoprotein(a) molecular weight (a strong correlate of Lp[a] concentrations). We conclude that in vivo concentrations of sex hormones are unlikely to be associated with Lp(a) concentrations in men.
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PMID:Lack of association between sex hormones and Lp(a) concentrations in American and Finnish men. 827 74

Estrogens have been found to protect against atherosclerosis in a variety of animal models, and these antiatherogenic properties have been confirmed by epidemiological and clinical studies in women as well. Since the estrogen-induced changes of plasma lipid and lipoprotein levels do not fully account for the prevention of atherosclerosis, additional effects must be assumed. Experimental studies suggest various direct vascular actions. Estrogens enhance the endothelial degradation of low-density lipoprotein cholesterol, and preliminary data indicate antioxidative actions on low-density lipoprotein particles in macrophages. They suppress intimal proliferation and extracellular matrix production in the arterial wall and induce marked vasodilatation in systemic and coronary arteries. Adverse effects on hemostatic factors described with high doses and synthetic compounds are not evident during hormonal replacement in postmenopausal women, in whom an estradiol-induced inhibition of platelet aggregation may even have beneficial clinical effects. The role of progesterone and other progestogens in the progression of atherosclerosis is controversial. Despite a partial antagonism to estrogen-induced changes of plasma lipids, their addition to estrogens does not alter the anti-atherosclerotic properties, at least in animal experiments. The direct vascular actions of progestogens-although not as well documented-seem to be less pronounced than those of estrogens. The experimental data indicate that direct vascular effects play an important role in the antiatherogenic properties of ovarian sex steroids. However, the underlying cellular and molecular mechanisms remain largely unknown.
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PMID:Ovarian sex steroids and atherosclerosis. 850 11

This review summarizes recent data on the effects of endogenous and exogenous androgens, estrogens and progesterone on serum lipoproteins levels and composition in humans. Sex steroid hormones modulate serum lipoprotein metabolic mechanisms and influence atherosclerosis and coronary heart disease. In general, androgens lower HDL and raise LDL levels and Lp(a) thus promoting the atherogenic process. As it is true with estrogens, the lipoprotein effects of androgens are more pronounced with oral than with parenteral administration. Millions of women use oral contraception and postmenopausal women use more and more some form of hormone replacement therapy. The HDL-raising effect of estrogen replacement seems to be mediated by an increase in apoprotein AI production and not by a decrease in the clearance rate. Estrogens lower LDL levels by accelerating the rate of LDL catabolism which is due to an increase in the number of hepatic LDL receptors. They also improve endothelium-dependent vasodilatation which might be mediated by an antioxidant action of estrogens. These facts could explain well known cardioprotective effects of estrogens. Androgen progestins, especially older such as norgestrel, lower HDL and raise LDL thus diminishing or eliminating the benefits of estrogens on cardiovascular system while newer progestins have a lesser effect on circulating lipoproteins.
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PMID:[The effects of androgens and other sex hormones on serum lipoproteins]. 875 6


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