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

A randomized, comparative study of two low-dose oral contraceptives was carried out in 60 nonpregnant women for 12 cycles. Twenty-eight women took a preparation containing 150 micrograms of desogestrel and 30 micrograms of ethinyl estradiol; 32 took 75 micrograms of gestodene and 30 micrograms of ethinyl estradiol. Baseline values in the two groups were in good agreement. During the first three cycles, serum cholesterol levels remained unchanged, but triglyceride and high-density lipoprotein cholesterol levels increased significantly and to the same extent (about 20%). Low-density lipoprotein cholesterol levels decreased slightly. Apolipoproteins A1 and A2 and low-density lipoprotein B increased significantly and similarly. Except for continued increases in low-density lipoprotein B, no further changes were noted during subsequent cycles. We concluded that the two contraceptives have the same impact on lipid metabolism, with all lipid and apolipoprotein values remaining within the normal range. The changes with both pills reflect a mild estrogenic dominance. Implications for coronary artery atherosclerosis appear to be minimal.
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PMID:Effects of oral contraceptives on lipid metabolism. 214 70

Although the available scientific data on the undesired metabolic effects of sex steroids have accumulated rapidly, most are of a descriptive nature, and only a few studies elucidate the impact at the cellular level and the possible interrelationship between different metabolic systems. This review summarizes the influence of different contraceptive steroid combinations on glucose metabolism and points to the possible mechanisms behind a disturbance of the euglycemic homeostasis with a concomitant change in lipid metabolism. Today the general concept is that the influence of combined sex steroid products on glucose metabolism is mainly caused by the progestogen components, although artificial estrogens may act synergistically. The diabetogenic effects of the progestogens make it important to consider the development during the last decade of the new more selective progestogens of the gonane type. From recent studies it seems, however, that intake of contraceptive combinations of ethinyl estradiol in combination with these types of gonanes, such as desogestrel and gestodene, may also be accompanied by increased insulin resistance, specifically, a hyperinsulinemic response to a glucose challenge despite unchanged glucose values compared with a baseline test. This is similar to observations made with combinations of ethinyl estradiol and other more traditional types of progestogens of the gonane and estrane type. It is conceivable that the diabetogenic effects of the progestogens are caused by a change in insulin receptor binding or a postreceptor defect in the cellular insulin action. The clinical implications of the diabetogenic effects of the sex steroids are hard to interpret, but more long-term exposure of arterial tissue to elevated concentrations of glucose and insulin results in inhibition of lipolysis and synthesis of cholesterol and triglycerides, which result in the development of lipid-filled lesions--fatty streaks--similar to those of early atherosclerosis.
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PMID:Mechanism of action of oral contraceptives on carbohydrate metabolism at the cellular level. 219 6

A nonhuman primate model was developed to study the effects of oral contraceptives on lipoproteins and atherosclerosis. Cynomolgus macaques were selected because of their susceptibility to diet-induced atherosclerosis and because their reproductive physiology, menstrual cycle, and circulating sex hormone patterns are similar to those of human females. The first study compared a vaginal ring containing levonorgestrel and estradiol with an oral contraceptive containing norgestrel and ethinyl estradiol. A second study compared two oral combinations: norgestrel-ethinyl estradiol and ethynodiol diacetate-ethinyl estradiol. As predicted, use of all the contraceptives led to lowering of high-density lipoprotein cholesterol levels. However, contrary to what might be expected, use of the ethinyl estradiol-containing oral contraceptives did not lead to an increase in the prevalence or extent of atherosclerosis. We concluded that ethinyl estradiol neutralized the atherogenic influence of the progestin component of oral contraceptives.
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PMID:Oral contraceptives, lipoproteins, and atherosclerosis. 222 Sep 63

Studies of both human and nonhuman primates show an inverse relationship between high-density lipoprotein (HDL) cholesterol concentrations and coronary artery atherosclerosis. For this reason, there has been concern that the HDL cholesterol-lowering effect of oral contraceptives might exacerbate coronary artery atherosclerosis. We studied three groups of adult female cynomolgus macaques fed a moderately atherogenic diet: a control group, a group given ethinyl estradiol and norgestrel, and another group given ethinyl estradiol and ethynodiol diacetate. Norgestrel and ethynodiol diacetate, co-administered with ethinyl estradiol, lowered the plasma concentrations of HDL cholesterol. However, the extent of coronary artery atherosclerosis was lessened by both contraceptives, especially among females at high risk based on their plasma lipid profiles.
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PMID:Oral contraceptives and coronary artery atherosclerosis of cynomolgus monkeys. 230 Mar 48

In 17 prostatic cancer patients, changes in the plasma lipoprotein pattern, including high density lipoprotein (HDL) subfractions, and in glucose tolerance were compared after 6 months on parenteral polyestradiol phosphate (PEP; Estradurin, 80 or 160 mg/month) with the respective changes in orchiectomized patients. In the estrogen group there was no change in the total serum cholesterol level, whereas in the orchiectomy group an increase of 10% was observed. Estrogen therapy resulted in a significant increase of serum HDL (11%) and HDL2 cholesterol (26%) levels; in the orchiectomy group these fractions remained unchanged. Estrogen therapy induced a significant decrease in total serum triglycerides (24%) and in low density lipoprotein triglycerides (27%); in the orchiectomy group reverse changes were observed. PEP treatment caused changes in the serum lipoprotein pattern, which apparently decreases the risk of atherosclerosis.
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PMID:Effects of orchiectomy and polyestradiol phosphate therapy on serum lipoprotein lipids and glucose tolerance in prostatic cancer patients. 235 Nov 92

The inhibition of atherosclerosis by estrogen has been shown clinically and experimentally, but the mechanism by which this occurs is unknown. Previous studies have shown that estrogen enhances the uptake of low-density lipoprotein (LDL) by bovine aortic endothelial cells (BAEC) while not altering membrane binding at saturating levels of LDL. In this study the effect of estrogen on LDL binding kinetics has been investigated. Computer-assisted Scatchard analysis of binding data suggests a single-site binding model. Estrogen-treated BAEC showed a lower binding affinity (Ka = 2.47 +/- 0.74 E7 M-1) than control cells (1.95 +/- 0.21 E7 M-1) (p = 0.0012). Estrogen-treated cells, however, had a greater binding capacity (Bmax = 1.26 +/- 0.07 E-10M) than control cells (Bmax = 8.49 +/- 0.44 E-11M) (p = 0.0004). The latter was due primarily to a difference in LDL binding at higher concentrations of LDL (greater than 40 micrograms/ml). These findings are consistent with an estrogen-stimulated increase in low-affinity binding of LDL to BAEC, which may not be directly receptor mediated and which appears to enhance the uptake of LDL at higher lipoprotein concentrations. Such alterations in LDL uptake by endothelial cells could influence the formation of atherosclerotic plaque.
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PMID:The effect of estrogen on low-density lipoprotein binding kinetics in aortic endothelial cells. 254 95

The means by which estrogen retards atherosclerosis cannot be explained solely by changes in circulating lipoprotein levels. We studied the effects of 17 beta-estradiol on the binding, incorporation, and degradation of low density lipoprotein (LDL) by cultured bovine aortic endothelial cells (BAEC). Estrogen receptors in the cytoplasm and nucleus of BAEC could be demonstrated by immunofluorescent staining. Estradiol was found not to affect surface binding of LDL to BAEC. However, at physiologic concentrations (50 pg/ml), estradiol did enhance LDL uptake by the BAEC (P less than 0.005). This enhancement was present but somewhat reduced at higher concentrations of estrogen (P less than 0.05). Only approximately 10% of incorporated LDL was trichloroacetic acid soluble, indicating a low rate of LDL degradation. The relative rate of LDL breakdown within the BAEC was not altered by estrogen. These results, showing estrogen stimulation of LDL uptake by the BAEC, do not clarify the protective effect of this hormone. It is speculated that estrogen may augment the cellular clearance of LDL.
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PMID:Effect of estradiol on low density lipoprotein uptake by bovine aortic endothelial cells. 265 94

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

The effect of a triphasic combination of ethinyl estradiol and levonorgestrel upon various lipoprotein parameters was compared to that of a preparation that contained ethinyl estradiol and desogestrel on days 6, 11, 21, and 28 of a control cycle, the third cycle of treatment with either ethinyl estradiol/levonorgestrel or ethinyl estradiol/desogestrel (11 volunteers each), the third cycle of a 3-month washout period, and the third treatment cycle after crossover change of the preparations. Significant increases were found in total triglycerides (15% to 20%) and phospholipids (8%) with both preparations, whereas total cholesterol and lipoprotein Lp(a) were not altered. High-density lipoprotein triglycerides (50% to 60%) and high-density lipoprotein-3 cholesterol (10% to 15%) were elevated by both contraceptives, high-density lipoprotein cholesterol and alpha-lipoprotein cholesterol only by ethinyl estradiol/desogestrel (11%), whereas high-density lipoprotein phospholipids, high-density lipoprotein-2 phospholipids, high-density lipoprotein-3 phospholipids, and high-density lipoprotein-2 cholesterol were not influenced. Both ethinyl estradiol/levonorgestrel and ethinyl estradiol/desogestrel increased apolipoproteins A (14%), A-I (20% to 30%), and A-II (25% to 35%) significantly. Very low-density lipoprotein triglycerides were elevated (30%) only by ethinyl estradiol/desogestrel, and low-density lipoprotein phospholipids (20%) by both ethinyl estradiol/levonorgestrel and ethinyl estradiol/desogestrel, whereas the other parameters, very low-density lipoprotein phospholipids, very low-density lipoprotein cholesterol, pre-beta-lipoprotein cholesterol, low-density lipoprotein triglycerides, low-density lipoprotein cholesterol, beta-lipoprotein cholesterol, and apolipoprotein B, were not significantly changed. Provided that the assumption is correct that high low-density lipoprotein cholesterol and apolipoprotein B and low high-density lipoprotein subfractions and apolipoprotein A are associated with an elevated risk of atherosclerosis, the results seem to represent beneficial rather than deleterious side effects of the low-dose oral contraceptives.
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PMID:A randomized crossover comparison of two low-dose contraceptives: effects on serum lipids and lipoproteins. 293 88

The influence of two types of steroidal contraception on the extent of coronary, aortic, carotid, and iliaco-femoral atherosclerosis was assessed in 57 cynomolgus macaques with moderate diet-induced hyperlipoproteinemia. Thirteen animals were treated with an intravaginal ring that released 17 beta-estradiol and levonorgestrel. Fifteen females were treated with an oral contraceptive (OC) composed of ethinyl estradiol and norgestrel. Fifteen females received placebo vaginal rings, and 14 males were untreated. The contraceptive treatments resulted in similar large reductions in plasma high-density lipoprotein (HDL) cholesterol concentrations. Neither treatment influenced the prevalence of coronary artery atherosclerosis. However, treatment with the contraceptive vaginal ring was associated with increased extent of coronary artery atherosclerosis (plaque size) relative to untreated females, whereas treatment with the OC was not. The contrasting effects of the two treatments could not be explained by differences in total plasma cholesterol, HDL cholesterol, or blood pressure. The results suggest that the greater estrogenic influence associated with the ethinyl estradiol-containing OC resulted in inhibition of coronary artery atherosclerosis despite a pronounced progestin-induced lowering of plasma HDL cholesterol concentration and, further, that hormonal balance may have a marked influence on the relationship between plasma lipids and atherogenesis.
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PMID:Contraceptive steroids and coronary artery atherosclerosis in cynomolgus macaques. 310 54


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