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

A comparison of the effects of two low-dose oral contraceptives on lipid metabolism was undertaken in an open-group comparative design study at the Family Planning Clinic, Groote Schuur Hospital, Cape Town. Sixty healthy women aged 18-35 years requesting oral contraception were allocated alternately to use a monophasic oral contraceptive containing 30 micrograms ethinyloestradiol and 150 micrograms desogestrel (Marvelon, group A), or a triphasic oral contraceptive containing 30-40 micrograms ethinyloestradiol and 50-125 micrograms levonorgestrel (Triphasil, group B). The changes in the lipoprotein profile elicited by the two preparations differed significantly. Group A subjects had a much greater triglyceridaemic response (42.4%) than group B (14.6%) and had a significant increase in high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (Apo-A1). In group B, HDL-C decreased and Apo-A1 showed little change. Non-HDL-C (NHDL-C) and Apo-B levels hardly changed in either group. The atherogenic ratios, NHDL-C/HDL-C and Apo-B/Apo-A1 were higher in group B. This study confirmed a significant difference in the response of plasma lipoproteins to the two oral contraceptive preparations. The evidence suggests that the desogestrel-containing oral contraceptive elicits a less atherogenic lipoprotein profile than does the levonorgestrel-containing preparation. Although unsupported by direct clinical evidence that changes in the lipoprotein pattern induced by oral contraceptives cause atherosclerosis, these effects should be considered when prescribing oral contraceptives for women who have risk factors for cardiovascular disease.
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PMID:The clinical and biochemical effects of two combination oral contraceptive agents. 182 69

Many recent advances in fertility control have involved progestin-only contraception. The progestin-only oral contraceptive, which has a failure rate of 1-2.5%, is especially suited to women who are breastfeeding or cannot tolerate estrogen. The levonorgestrel implant, Norplant, is effective for 5 years and has a 1.5% failure rate. Currently under development is Norplant-2--a system that requires 2 rather than 6 capsules, lasts for 3 years, and is as effective as Norplant-1. Also under development is a biodegradable progestin-only implant. However, there are many side effects associated with these methods. Irregular bleeding occurs in 60-70% of Norplant acceptors and leads 12-20% of these women to discontinue implant use. Headaches and acne occur in 5-20% of users of levonorgestrel methods. More significant are concerns that progestin tends to increase low density lipoprotein levels. Although initial human trials have indicated a drop of 5-15% in both these levels, studies in macaque monkeys have found that progestin-only contraception is more likely to cause atherosclerosis than an estrogen-progestin formulation.
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PMID:Progestin-only contraception. 202 98

Female cynomolgus monkeys, a previously established model of carotid and coronary artery atherosclerosis, were used to study the relationships between potential risk factors and carotid artery atherosclerosis. Over a 24-month treatment period, one-third of the monkeys (n = 25) were given the oral contraceptive Ovral, one-third of the monkeys (n = 26) were given the oral contraceptive Demulen, and the remaining monkeys constituted a control group (n = 26). At necropsy, the atherosclerosis extent was measured in the left and right common carotid arteries and the left and right carotid bifurcations. Plasma lipid concentrations, regional adiposity, and social status were related to carotid artery atherosclerosis extent. The relationships between regional adiposity and social status and carotid artery atherosclerosis were accounted for, at least in part, by plasma lipid concentrations. Oral contraceptives had an adverse effect on plasma cholesterol concentrations and a protective effect against carotid artery atherosclerosis after adjusting for their effect on plasma lipids. The net result of these effects was little or no change in atherosclerosis extent in the carotid arteries due to oral contraceptive treatment.
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PMID:Carotid artery atherosclerosis in cholesterol-fed female cynomolgus monkeys. Effects of oral contraceptive treatment, social factors, and regional adiposity. 234 95

The effects on atherogenesis of stress, pregnancy, and oral contraceptive therapy were studied in a nonhuman primate model. The stress of social subordination was associated with ovarian dysfunction, unfavorable lipoprotein changes, and increased coronary artery atherosclerosis compared with nonstressed (socially dominant) or normal monkeys. Although pregnant animals exhibited lower high-density lipoprotein cholesterol concentrations, they had only one half as much diet-induced coronary artery atherosclerosis as their nonpregnant counterparts. Monkeys treated with an Ovral-like regimen also exhibited adverse lipoprotein changes. Nevertheless, prevalence and extent of coronary artery plaques decreased. We conclude that estrogen is an important factor in the animals' "female protection" against diet-induced atherosclerosis. We also suggest that the lowering of high-density lipoproteins by the progestin component of higher-dose contraceptives is not necessarily atherogenic if a sufficiently potent exogenous estrogen is administered concomitantly.
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PMID:From menarche to menopause: coronary artery atherosclerosis and protection in cynomolgus monkeys. 271 67

Thirty postmenopausal women were randomly treated with desogestrel (DG) or levonorgestrel (LN) 125 micrograms/day for 3 weeks. Desogestrel reduced the serum total and free (non-protein bound) testosterone concentrations. It caused a small decrease in the sex hormone binding globulin capacity (SHBG) but did not influence the free testosterone index (testosterone/SHBG ratio). Levonorgestrel, on the other hand, did not influence the free testosterone concentration, but caused a significant increase in the free testosterone index. Levonorgestrel reduced the HDL and particularly the HDL2 cholesterol concentrations (mean change from 1.75 to 1.45 mmol/l for HDL and from 0.73 to 0.50 mmol/l for HDL2, P less than 0.001). It also caused a reduction in the VLDL triglyceride (P less than 0.05) but not the total serum triglyceride concentration. Desogestrel did not cause any significant changes in HDL or HDL2 cholesterol concentrations, but it reduced the VLDL triglyceride (P less than 0.01) and total serum (P less than 0.05) triglyceride concentrations. Neither of the two progestins influenced the postheparin plasma lipoprotein lipase (LPL) activity or the serum cholesterol esterification rate by lecithin:cholesterol acyltransferase (LCAT). It is therefore possible that both steroids decreased the hepatic output of triglycerides, which may be clinically important since both progestins are used in combination with ethinylestradiol (EE) which increases the hepatic TG synthesis. The failure of desogestrel to change HDL levels is consistent with earlier data on the lack of effects on HDL by non-androgenic progestins. Levonorgestrel increased the mean activity of postheparin plasma hepatic lipase (HL) from 23.3 to 28.0 mumol X h-1 X ml-1 (P less than 0.05). In contrast, this activity was not influenced by desogestrel. The magnitude of the changes in postheparin plasma HL activity and the free testosterone index (testosterone/SHBG ratio) showed significant positive correlation (+ 0.41, P less than 0.05). On the other hand, the changes in the HDL2 cholesterol and the postheparin plasma HL activity were inversely interrelated (r = 0.52, P less than 0.01). These relationships are consistent with the idea that the effects of different progestins on the HDL cholesterol are mediated by the sex steroid sensitive hepatic endothelial lipase.
Atherosclerosis 1985 Mar
PMID:Effects of two progestins with different androgenic properties on hepatic endothelial lipase and high density lipoprotein2. 315 21

The progestin, levonorgestrel administered orally to fed female rats significantly lowers both plasma total and very low density lipoprotein triglycerides. In contrast, plasma total cholesterol and low density lipoprotein cholesterol rose significantly. Suspensions of isolated hepatocytes were used to study the effects of levonorgestrel on triglyceride synthesis by examining the incorporation of labelled precursors [( 9,10- 3H]palmitate and [U-14C]glycerol) into triglycerides. Levonorgestrel (10(-4) M) significantly inhibited the incorporation of both precursors into hepatocyte triglycerides and also reduced their incorporation into the triglycerides (nearly all in d less than 1.006) released into the medium. These results suggest that inhibition of hepatic triglyceride synthesis and release can account at least for part of the lowering of plasma VLDL which occurs during administration of levonorgestrel.
Atherosclerosis 1984 Sep
PMID:Hypotriglyceridemic effects of levonorgestrel in rats. 643 17

Two progestins with different androgenic activity were compared for their effects on plasma high density lipoproteins and postheparin plasma lipase activities in premenopausal women. Levonorgestrel, a nortestosterone-derived steroid with androgenic activity reduced plasma HDL cholesterol by 17% (P less than 0.05) and HDL2 cholesterol by 30% (P less than 0.05), without changing the HDL3 cholesterol concentration. At the same time the postheparin plasma hepatic lipase activity was increased by 56% (P less than 0.01) whereas the lipoprotein lipase was not changed. None of these effects was reproduced during administration of medroxyprogesterone acetate, a progestin with low androgenic activity. The results suggest, first, that the decrease of HDL cholesterol observed during treatment with progestins is related to the androgenic activity of the steroid used, and, second, that the change in HDL (HDL2) is caused by androgen-induced increase of hepatic lipase activity.
Atherosclerosis
PMID:Different effects of two progestins on plasma high density lipoprotein (HDL2) and postheparin plasma hepatic lipase activity. 646 May 9

A study of the prevalence of hyperlipidemia has been conducted among female telephone company employees using oral contraceptives (OCs) or estrogenic hormones. This paper relates hormone formulation and estrogen/progestin potency to striglyceride and cholesterol concentrations in total plasma and lipoprotein fractions and relative lipid composition. Changes in these lipid parameters are of interest because they may predict atherosclerosis risk. Results in 148 hormone users are compared with those in 306 nonhormone users. All data are adjusted for the effects of age, relative body weight, cigarette smoking, and alcohol intake. Triglyceride concentrations in whole plasma, very low density lipoprotein (VLDL), and high density lipoprotein (HDL) are elevated 1.5-2.5 fold with increasing estrogen potency. Low density lipoprotein (LDL) triglyceride concentration is elevated to a similar degree among OC users regardless of estrogen potency, but there is no significant effect of postmenopausal estrogen use on LDL triglyceride concentrations. The LDL cholesterol concentration shows an increasing trend with increasing estrogen potency in a random sample of OC-treated women, but is slightly lower than control in postmenopausal women treated with estrogen alone. The HDL cholesterol concentration in plasma is highest with hormones having the greatest estrogen potency and lowest with those having the greatest progestin potency. The VLDL cholesterol to triglyceride ratio adjusted for triglyceride concentration is significantly increased with the use of Ovral, a progestin-predominant contraceptive preparation. The LDL cholesterol to triglyceride ratio is reduced with the use of all OCs examined, except for Ovral, where the ratio is above average. The HDL cholesterol to triglyceride ratio is reduced for all combination OCs examined. The use of a sequential OC or postmenopausal estrogens is not associated with a significant alteration in the cholesterol to triglyceride ratio in any lipoprotein fraction. Knowledge of estrogen and progestin potency and kind of progestin are important in predicting the effect of OCs on plasma and lipoprotein lipids. On the basis of observed differences in lipoprotein lipid concentrations and relationships, the potential arteriosclerotic risk from sex hormones may vary among OC formulations.
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PMID:Oral contraceptive and postmenopausal estrogen effects on lipoprotein triglyceride and cholesterol in an adult female population: relationships to estrogen and progestin potency. 729 96

In the present study the effect on the urinary excretion of vasoactive markers of two oral contraceptives (OCs), i.e., Leios, containing 0.02 mg ethinyl estradiol and 0.1 mg levonorgestrel, and Stediril 30, containing 0.03 mg ethinyl estradiol and 0.15 mg levonorgestrel, was investigated. cGMP, prostacyclin and its antagonist thromboxane, serotonin, and urodilatin, a natriuretic and diuretic peptide formed in the kidney, were measured as markers. In a comparative, double-blind, randomized, parallel group study, 34 women received Leios and 33 women Stediril 30. Nocturnal urine was collected before treatment and during cyclic treatment after 3 and 12 cycles. Both contraceptives significantly enhanced cGMP excretion after 12 cycles. The prostacyclin metabolite remained unchanged for both formulations, but the excretion of the thromboxane metabolite was significantly decreased after 12 cycles. Thus, the ratio of prostacyclin to thromboxane, crucial for the resulting effect on vascular tone, increased significantly. For the serotonin metabolite, no changes were observed for both contraceptives. The excretion of urodilatin significantly increased for both preparations after 12 cycles compared to the pretreatment values. These results indicate that the low-dose OCs Leios and Stediril 30 may stimulate the production of some vasoactive markers, at least after 12 cycles of treatment. The positive influence of these contraceptives on the various markers investigated may improve vascular tone, impede development of atherosclerosis and arterial thrombosis, and improve water and electrolyte homeostasis. These effects most likely can be attributed to the estrogenic component. Levonorgestrel may elicit no impact on these estrogen-induced changes that, however, seem only to be manifested after a longer treatment period.
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PMID:Effect of two oral contraceptives with different ethinyl estradiol and levonorgestrel concentrations on the urinary excretion of biochemical vasoactive markers. 1183 34

As part of a longterm surveillance of the progestogen-only Norplant implant system, the metabolic functions in a representative Southeast Asian population of 100 Singaporean women were investigated. Prior research has identified the increased risk of arterial atherosclerosis complications and changes in serum lipids due to progestogens in contraceptives. Differences in liver function, lipid metabolism, and carbohydrate metabolism were recorded for this population of healthy, nonsmoking, nonalcohol drinking, and nonlactating women. Medical testing methods are identified and statistical differences are reported as the paired t test, and observation of % changes between pre- and postinsertion levels. Skewed results are subjected to the Wilcoxon signed rank test of significance suing median distribution. The resulting analyses found that the mean levels of bilirubin, total protein, and globulin remained within the normal clinical range, and no individual values fell outside the normal range. There was a highly significant increase in bilirubin during the 1st year of use, a decline in the 2nd, increase in the 3rd, and stabilization at increased levels after 4 years, suggesting that the system is returning to normal. Most prior studies have shown no significant changes in liver function. Total triglycerides and total cholesterol had a highly significant decrease in 4 years, which is comparable to other published results. The LDL cholesterol was decreased after 2 years and then reached preinsertion levels after 3 years and stabilized. Preinsertion levels of HDL cholesterol were reached after 2 years, then a decrease and stabilization in year 4. These HDL changes have been observed in other studies. HDL to total cholesterol ratio returned to preinsertion levels after 2 years after a reassuring and significant increase after 1 year, and decreased to .255 after 4 years. The ratio always remained above .200. It does not appear that lipid metabolism contributes to increased cardiovascular risk. It is cautioned that without controls for nonsteroid use the observed changes may be related to extraneous environmental effects. The absolute levels in the oral glucose intolerance test showed no clinically significant changes for 4 years. Only in years 1 and 2 on a paired basis were there differences after 1 hour.
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PMID:Metabolic changes in Singapore women using Norplant implants: a four year review. 1228 15


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