Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The combined progestogen/estrogen oral contraceptive is the most common form of contraception in the US. They contain 1 of 5 synthetic progestogens (derived from 19-nortestosterone) and 1 of 2 estrogens. 3 new progestin compounds are in use in Europe and Asia. They are norgestimate, desogestrel, and gestodene. Estrogen seems to cause vascular complications. Progestin may cause atherosclerosis. Desogestrel and gestodene were studied for 6 months. They have little effect on glucose and lipid metabolism. Triphasal ethinyl estradiol/levonorgestrel and ethinyl estradiol/norethindrone (Ortho Novum 7/7/7) were compared in a 12-month prospective clinical trial. There seems to be no consensus of a pattern of increased breast cancer associated with oral contraceptive use. The UK National Case Control Study Group analyzed women younger than 36 years at the time breast cancer was diagnosed. 91% of their cohort had used pills. A significant trend was found when risk was analyzed with duration of taking pills. Women who had taken the pill for 4 years had no increased risk of breast cancer. However, there was an increased relative risk of 1.7 (P0.001) for women who took pills for more than 8 years. Among women using the pill for 8 years, the relative risk was 2.6 (p0.0001). AMong women using pills with 50 ug. of estrogen, the trend to increased risk was (P0.10). The 1988 National Survey of adolescent males showed that 60% of men never married were active sexually. Among 17- to 19-year-old-men who live in metropolitan areas, condom use has more than doubled, compared with 1979. In 1988, a "new" copper-containing IUD was approved for use in the US by the Food and Drug Administration, the Copper T 380 A. Pregnancy rates are less with this than with older devices. IUDs may cause pelvic inflammatory disease with resulting tubal infertility. However, the risk was overstated earlier. Women who have only 1 sexual partner in their lifetime had no significant risk of tubal infertility. "lost" IUDs continue to be a problem.
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PMID:Contraception. 210 26

Sex differences and steroid hormones are known to influence the vascular system as shown by the different incidence of atherosclerosis in men and premenopausal women, or by the increased risk of cardiovascular diseases in women taking birth control pills or men taking estrogens. However, the mechanisms for these effects in vascular tissues are not known. Since steroid actions in target tissues are mediated by receptors, we have looked for cytoplasmic steroid receptor proteins in vascular tissues of dogs. We find specific saturable receptors, sedimenting at 8S on sucrose density gradients for estrogens (measured with [3H]estradiol +/- unlabeled diethylstilbestrol), androgens (measured with [3H]R1881 +/- unlabeled R1881 and triamcinolone acetonide), and glucocorticoids (measured with [3H]dexamethasone +/- unlabeled dexamethasone); they are absent for progesterone (measured with [3H]R5020 +/- unlabeled R5020 and dihydrotestosterone). Progesterone receptors can, however, be induced by 1-wk treatment of dogs with physiological estradiol concentrations (100 pg/ml serum estrogen), indicating a functional estrogen receptor. Receptor levels range from 20 to 2,000 fmol/mg DNA. They are specific for each hormone; unrelated steroids fail to complete for binding. Low dissociation constants, measured by Scatchard analyses, show that binding is of high affinity. Steroid binding sites are in the media and/or adventitia since they persist when the intima is removed. Compared with the arteries, receptor levels are reduced 80% in inferior venae cavae of females, and are absent in the venae cavae of males. We hypothesize that steroid hormones can have direct effects on vascular tissues medicated by specific receptors present in arterial blood vessel walls.
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PMID:Canine vascular tissues are targets for androgens, estrogens, progestins, and glucocorticoids. 628 10

The effect of high dose medroxyprogesterone (MPA) on serum lipids was studied in 31 postmenopausal patients with endometrial cancer. After 3 months of MPA treatment, total cholesterol decreased by 18% (P less than 0.001), LDL cholesterol by 16% (P less than 0.01) and HDL cholesterol by 38% (P less than 0.001) from the respective pretreatment values; correspondingly, the ratio of HDL to total cholesterol decreased (P less than 0.001). Similar changes were found as early as 2 weeks after start of treatment. In the 15 controls receiving no progestin treatment, full dose intracavitary radiotherapy and gynecological surgery had no effect on these serum lipids.
Atherosclerosis 1983 Apr
PMID:Effect of high dose progestin on serum lipids. 687 Sep 84

Epidemiologically, an inverse relation between serum HDL-C level (high density lipoprotein cholesterol) and risk for coronary heart disease has been reported. HDL has also been known to serve as a vehicle for transporting cholesterol from the arterial wall to the liver for excretion. However, there are no clinical data for the concept that a drug-decreased serum HDL-C is unfavorable with respect to atherosclerosis and myocardial infarction. This study compares the serum HDL-C level in 23 women who received depot medroxyprogesterone acetate (DMPA) as a 12-weekly injectable progestational contraceptive with that of a comparable control group of 23 IUD users. Both groups were selected on the basis of age, bodyweight, and alcohol consumption. HDL-C and serum triglyceride levels were measured by an enzymatic method. The serum HDL-C level was significantly lower in the DMPA group than in the IUD group (t=4.30, p= 0.001). The difference was attributed to the progestational effect of the DMPA. The lapse of time after a DMPA injection did not affect the serum HDL-C level, an unexpected finding as the average serum MPA level rises steeply during the 1st week after DMPA injection and then declines gradually to a relatively low value after 12 weeks. DMPA should not be prescribed to women with abnormally high risk for atherosclerosis (eg, heavy smokers, and women with adiposity and/or diabetes mellitus).
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PMID:Serum high density lipoprotein cholesterol levels in women using a contraceptive injection of depot-medroxyprogesterone acetate. 744 84

We investigated the effects of 17 beta-estradiol (beta E2), alpha-estradiol (alpha E2), and progesterone (P) on baseline and vasopressin (AVP)-induced [Ca2+]i in human platelets obtained from healthy male and female volunteers. Platelets were treated with beta E2, alpha E2, P, or ethanol vehicle for 30 min at 37 degrees C. In males, both beta E2 and P at 10(-5) mol/L reduced the AVP-induced rise in [Ca2+]i, to 72 +/- 3% (mean +/- SEM) and 53 +/- 3%, respectively. However, at 10(-6) mol/L only beta E2 had a significant effect (P < .02). In females, 10(-6) and 10(-5) beta E2 reduced the AVP response to 85.3 +/- 4.6% and 80.8 +/- 5.4% of control values, respectively. Progesterone (10(-6) and 10(-5) mol/L) reduced the AVP response to 83.8 +/- 5.1% and 60.3 +/- 2.0% of control values, respectively. The inactive estrogen alpha E2 had no effect on basal or AVP-induced rise in [Ca2+]i in either subject population, suggesting hormonal specificity. Neither beta E2 nor P affected baseline [Ca2+]i in either population. Thus, by attenuating [Ca2+]i responses in platelets, beta E2 and P may modulate platelet aggregation and atherosclerosis.
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PMID:Effects of estradiol and progesterone on platelet calcium responses. 775 50

The chemotactic cytokine, monocyte chemoattractant protein-1 (MCP-1), and its murine homologue, JE, have been detected in atherosclerotic lesions but not in normal arteries, implicating that these proinflammatory cytokines may be involved in the pathogenesis of atherosclerosis. Epidemiologic studies reveal that postmenopausal women receiving estrogen replacement for treatment of osteoporosis have a greatly reduced risk of developing cardiovascular disease. Because JE/MCP-1 and estrogen play regulatory roles in the development of atherosclerotic lesions, we chose to examine the effect of estrogen treatment on JE/MCP-1 mRNA expression in macrophages. 17 beta-estradiol (E2) inhibited LPS-stimulated JE/MCP-1 mRNA expression in ANA-1 and J774A.1 murine macrophage cell lines and in thioglycolate-elicited murine peritoneal macrophages. Inhibition of JE/MCP-1 mRNA ranged from 50 to 90%, with a maximal effect occurring at a concentration of 300 pg/ml E2. Conversely, E2 had little effect on LPS-stimulated TNF-alpha mRNA production. Treatment of LPS-stimulated macrophages with moxestrol, an estrogen agonist, resulted in a similar inhibition, and the addition of the estrogen antagonist, tamoxifen, reversed E2 inhibition of JE/MCP-1 mRNA expression. Progesterone failed to inhibit LPS-induced JE/MCP-1 mRNA expression. Immunohistochemical analysis revealed the presence of estrogen receptors in ANA-1 cells, indicating that E2 inhibition of LPS-induced JE/MCP-1 mRNA expression in murine macrophages may be mediated through the estrogen receptor. Thus, another mechanism whereby estrogen exerts antiatherogenic effects may be through prevention of macrophage accumulation in the atherosclerotic lesion.
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PMID:Estrogen modulation of JE/monocyte chemoattractant protein-1 mRNA expression in murine macrophages. 783 68

A clinical trial was conducted in three centres to assess the effects of long-term use of the injectable contraceptive depot-medroxyprogesterone acetate (DMPA) on lipid metabolism. Fifty women who had used DMPA at a dose of 150 mg every three months for 3 to 9 years were recruited in Bangkok, Christchurch and Mexico City. They were compared to a control group of 120 IUD users. Total cholesterol, LDL-cholesterol, HDL-cholesterol, total triglycerides, apolipoproteins AI, AII and B were measured throughout one injection interval. Significant findings differed between centres. Compared to their own centre controls, DMPA users in Bangkok had higher LDL-cholesterol levels; those in Christchurch had lower HDL-cholesterol, apolipoprotein (apo) AI and apo AI/B ratio and higher apo B levels; those in Mexico City had a lower apo AI/B ratio. Further changes were observed during the injection interval, some of which were correlated to changes in serum MPA levels. It is concluded that long-term use of DMPA induces moderate changes in lipid metabolism which are unfavourable in terms of risk for atherosclerosis. This should be borne in mind when weighing the overall risks and benefits of this contraceptive method for a potential user.
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PMID:A multicentre comparative study of serum lipids and apolipoproteins in long-term users of DMPA and a control group of IUD users. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation Special Programme of Research, Development and Research Training in Human Reproduction. 844 18

The action of female sex steroids on carbohydrate metabolism has clearly been demonstrated by numerous clinical and experimental studies. A beneficial effect of 17 beta oestradiol has been reported on insulin secretion and insulin sensitivity, inducing an improvement of glucose tolerance through an increase of glucose clearance by liver, muscle and adipose tissues. Progesterone has, to a lesser degree, the same stimulant effect on insulin secretion and improves glucose assimilation by the liver, although a relative insulin resistance is observed in the other two tissues. Menopausal hormonal privation does not significantly alter glucose tolerance in the absence of such predisposition factors as overweight or history of gestational or familial diabetes mellitus. The first trials of menopausal substitution with oral synthetic oestrogens, especially in doses of more than 50 micrograms per day, were responsible for the bad reputation of oestroprogestins due to their effects on metabolic parameters. As shown by prescription for contraceptive use, replacement therapy with oral synthetic oestrogens induces a diabetogenic tendency as well as hypertensive, dyslipidaemic and thrombogenic risks, especially when associated with progestins issued from nortestosterone. Reducing the oestrogen doses, using equine sulfoconjugates and selecting non-androgenic progestins has already minimized these deleterious effects. The present availability of oral or percutaneous natural 17 beta oestradiol and of norpregnanes calls for reconsideration of the glucidic risk due to oestroprogestin prescription. A few studies have already shown that in fact they can improve glucose tolerance. The recommended substitution of menopause to prevent atherosclerosis must lead to a better characterization of its glycaemic and insulinaemic effects.
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PMID:[Sex steroids. Effects on the carbohydrate metabolism before and after menopause]. 850 47

The aim of the study was to compare the effects of continuous oral estrogen/progestin therapy to the effects of transdermal estrogen therapy combined with cyclic oral progestin on the properties of LDL particles. Eighty postmenopausal women were randomly allocated to receive either oral (continuous 17-beta-estradiol 2 mg and norethisterone acetate 1 mg per day, E2/NETA) or transdermal therapy (patches delivering continuous 17-beta-estradiol, E2, 0.05 mg/day with sequential oral medroxyprogesterone acetate, MPA, 10 mg/day for 12 days/cycle). The groups had similar mean values and ranges of age, BMI and postmenopausal status. The blood samples were taken at baseline, and twice at 1 year before and after MPA administration. LDL particle size distribution was determined by gradient gel electrophoresis and LDL was isolated by sequential ultracentrifugation for compositional analyses. Concentrations of total LDL mass, LDL cholesterol and LDL protein decreased in the oral treatment group (p < 0.01, p < 0.001 and p < 0.01, respectively), whereas they remained unchanged during the transdermal therapy. Particle size of the major LDL peak remained unchanged during both transdermal and oral therapies. HDL cholesterol concentration decreased significantly in both treatment groups (p < 0.001 for both). Serum triglyceride and HDL cholesterol concentrations were the strongest determinants of LDL particle size ( r = -0.50 and r = 0.54, respectively, p < 0.001 for both). The cholesteryl esters and free cholesterol content of the LDL particles decreased in the oral treatment group (p < 0.05). Phospholipid content of LDL increased in both groups receiving either oral or transdermal therapy (p < 0.01 for both). In conclusion, oral administration of 17-beta-estradiol and norethisterone acetate caused a decrease in LDL mass by decreasing the number and cholesterol content of LDL particles. The concomitant decrease of HDL cholesterol by progestins may partly negate this beneficial effect of LDL lowering.
Atherosclerosis 1996 May
PMID:Effects of postmenopausal estrogen/progestin replacement therapy on LDL particles; comparison of transdermal and oral treatment regimens. 876 79

While estrogen is known to retard the development of atherosclerosis, the exact mechanism is unknown. The migration of monocytes into the arterial intima is important in the pathogenesis of atherosclerosis. Monocyte chemotactic protein 1 (MCP-1) is suggested to be a real chemotactic factor that is released from monocytes, endothelial cells, and smooth muscle cells. We investigated the effect of 17 beta-estradiol on the migration of human monocytes in response to MCP-1, using a modified Boyden chamber. A physiological concentration of 17 beta-estradiol (10(12) - 10(4)M) inhibited the migration of monocytes exposed to MCP-1. Two estrogen receptor antagonists, tamoxifen and clomiphene, each restored monocyte chemotaxis to MCP-1 to control level, even in the presence of 17 beta-estradiol, suggesting that estrogen receptors are related to the effect of 17 beta-estradiol. Progesterone and testosterone had no measurable effect on monocyte migration. These findings suggest that inhibition of the chemotactic response of monocytes exposed to MCP-1 may be one mechanism for the anti-atherogenic effect of 17 beta-estradiol.
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PMID:Physiological concentration of 17 beta-estradiol inhibits chemotaxis of human monocytes in response to monocyte chemotactic protein 1. 878 8


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