Long-term estrogen therapy abolishes acute estrogen-induced coronary flow augmentation in postmenopausal women

Deltamethrin (CAS registry No. 52918-63-5), a synthetic dibromo-pyrethroid insecticide is highly effective against a broad spectrum of insects, and is widely used on crops and in public health programs. Data on the genotoxicity and carcinogenicity of deltamethrin are rather controversial, depending on the genetic system or the assay used. The aim of the present study was to analyze previously demonstrated metabolic changes using aspecific noninvasive methods in rats which are potentially applicable for monitoring occupational exposure. Since human exposure to pesticides occurs not only to active principles but to all chemicals present in a commercial formulation, we tested both the pure compound and a deltamethrin-based commercial formulation. Groups of rats were treated, i.p., consecutively for 7 days. The daily doses tested were 5 and 10 mg/kg body weight for pure deltamethrin, corresponding to volumes of 178.57 and 377.14 microliter/kg body weight for the commercial formulation (containing 2.8% deltamethrin). Urine was analyzed for mutagenic metabolites, thioethers, and D-glucaric acid content. Faeces extracts were tested for mutagenicity. Results show that DGA urinary excretion values did not mirror the phase I enzyme induction capability of the insecticide. Results obtained for urinary thioethers do not agree completely with those obtained on the influence of deltamethrin on glutathione S-transferase activity in rat liver. In fact, after administration of the deltamethrin commercial formulation, highest thioether excretion values were obtained during the treatment time for treated animals, as compared to controls. The mean values (+/-SEM) of thioether excretion were 0. 033 +/- 0.002 micromole -SH/24 h for control animals, 0.122 +/- 0. 004 and 0.185 +/- 0.025 for the two treatment groups. Thence, thioether determination in urine samples seems to be a suitable aspecific noninvasive method for assessing exposure to deltamethrin-based formulations, particularly those containing xylene and mesitylene as solvents, as in the tested formulation. Negative or toxic results obtained in the urinary and faecal mutagenicity test seem to exclude the formation and excretion of mutagenic metabolites following treatment with deltamethrin.     

Effects of estrogen replacement therapy on the lipoprotein profile in postmenopausal women with ESRD

BACKGROUND: Patients with ESRD have excessive cardiovascular morbidity and mortality. In postmenopausal women with normal renal function, estrogen replacement therapy decreases cardiovascular mortality by 50%, in part because of their beneficial effects on the lipoprotein profile. Because of similarities in the lipoprotein profile between healthy, postmenopausal women, and women with ESRD, we examined the effects of estrogen replacement on lipoproteins in 11 postmenopausal women with ESRD. METHODS: In a randomized, placebo-controlled crossover study (8 week treatment arms) using 2 mg daily of oral, micronized estradiol, 11 postmenopausal women with ESRD were treated. Neither baseline lipid nor lipoprotein abnormalities were used as entry criteria for study participation. RESULTS: Blood estradiol levels were 19 +/- 4 with placebo and 194 +/- 67 pg/ml (P = 0.024) with estradiol treatment. Total HDL cholesterol concentrations increased from 52 +/- 19 mg/dl to 61 +/- 20 mg/dl (16%), with placebo and estradiol treatments, respectively (P = 0.002). Apolipoprotein A1 increased by 24.6% (P = 0.0002) with estradiol intervention. HDL2 concentrations were 19 +/- 13 with placebo and 24 +/- 16 with estradiol treatment (P = 0.046). There were no differences in total or LDL cholesterol, other lipoprotein fractions including Lp(a), and triglycerides with 2 mg daily estradiol treatment. No significant side effects were observed. CONCLUSIONS: Therefore, using standard dosage regimens for estrogen replacement therapy in postmenopausal women with ESRD, HDL cholesterol is increased to an extent that would be expected to improve their cardiovascular risk profile. Further studies are needed to assess whether estrogen replacement therapy decreases the incidence or severity of cardiovascular disease in ESRD patients to a similar degree compared with other women.     

Effects of estrogen therapy of postmenopausal women on cytokines measured in peripheral blood

Estrogen replacement therapy (ERT) is known to prevent bone loss following the menopause, but the mechanism for this is unclear. Estrogen may suppress the secretion of certain bone-resorbing cytokines. The aim of this study was to assess the effect of ERT on the levels of cytokines measured in peripheral blood. We measured cytokines in 10 postmenopausal women (ages 56-59, 3-9 years since menopause) treated with ERT and 10 age-matched (54-59 years, 4-10 years since menopause) untreated women as controls. Samples of blood were taken and used for mononuclear cell cultures, whole blood (WB) cultures, and the separation of serum. The cultures were treated with lipopolysaccharide (LPS; 500 ng/ml) and hydrocortisone (10(-6) M). The conditioned medium from cultures and the serum were then assayed for interleukin-6 (IL-6), IL-1alpha IL-1beta, IL-1 IL-1ra, tumor necrosis factor alpha (TNF-alpha), and granulocyte macrophage colony stimulating factor (GM-CSF) by enzyme-linked immunosorbent assay. M-CSF and the soluble cytokine receptors soluble IL-6 receptor (sIL-6r) and soluble TNF receptor type 1 (sTNFr1) were also measured in serum and M-CSF in stimulated WB cultures. Measurements were corrected for mononuclear cell count. We also measured serum bone-specific alkaline phosphatase (ibAP) in all subjects. We found that LPS stimulated secretion of all cytokines both in WB and isolated cell cultures, and that this was attenuated by hydrocortisone. A significantly higher ratio of IL-1beta/IL-1ra (p = 0.02) in LPS stimulated WB cultures was seen in the untreated women. Levels of IL-1beta and IL-1alpha measured in WB cultures were lower and IL-1ra was higher in the ERT-treated group but these results were not significant. BAP was higher in the untreated group (p = 0.005) and correlated with IL-alpha/IL-1ra in the whole group (r = 0.49, p = 0.03). Results of other measurements showed no significant differences between groups. We conclude that estrogen may prevent bone loss following the menopause by altering the balance between IL-1beta and IL-1ra.     

Effects of estrogen replacement therapy on PET cerebral blood flow and neuropsychological performance

Reports that estrogen may protect against age-associated memory decline and Alzheimer's Disease have kindled interest in the effects of estrogen replacement therapy (ERT) on cognition and brain function. As part of a 9-year study in the Baltimore Longitudinal Study of Aging, we are performing annual magnetic resonance imaging, positron emission tomography (PET), and neuropsychological assessments to examine brain structure and function in individuals aged 55 and older. PET measurements of regional cerebral blood flow (rCBF) are obtained under 3 conditions: rest and verbal and figural delayed recognition memory tasks. Fifteen women receiving ERT (with or without the addition of progesterone) were compared with a matched sample of 17 untreated women. There were no significant differences between groups in regional brain volumes or ventricular size. However, ERT users and nonusers showed significant differences in PET-rCBF relative activation patterns during the memory tasks. During verbal memory processing, there were significant interactions in rCBF activations for the right parahippocampal gyrus, right precuneus, right frontal regions, and left hypothalamus. During figural memory processing, significant interactions were observed for right parahippocampal and inferior parietal regions and for left visual association and anterior thalamic regions. ERT users also showed better performance on neuropsychological tests of figural and verbal memory and on some aspects of the PET activation tests, although the two groups did not differ in education, overall verbal ability, or performance on other neuropsychological tests. These findings confirm our previous observation of the beneficial effects of ERT on figural memory. Moreover, differences in rCBF activation patterns between ERT users and nonusers suggest an area for future research to examine mechanisms through which ERT may influence memory and other cognitive abilities.     

The use of hormone replacement therapy in women with acute myocardial infarction: an audit of current practice

We undertook criterion-based audit of the current practice of prescribing hormone replacement therapy for women with acute myocardial infarction; the audit included 181 consecutive women admitted to one hospital with this diagnosis in one calendar year. The set standard was that, barring any contraindication, all postmenopausal women with acute myocardial infarction should be prescribed hormone replacement therapy before discharge from hospital. The evidence base of this standard derives from more than 30 epidemiological and clinical studies and a large body of biological data. Only 4.7% of the women were current users of hormone replacement therapy and the set standard was met in only 3% of eligible nonusers. Professionals caring for women who have had a myocardial infarction need to consider hormone replacement therapy as a secondary prophylaxis of myocardial infarction. Gynaecologists should liaise with colleagues in other specialties and general practice to ensure that information on the nongynaecological benefits of hormone replacement therapy is widely disseminated.     

Technetium-99m MIBI to assess coronary collateral flow during acute myocardial infarction in two closed-chest animal models

Collateral flow is an independent determinant of infarct size in both animal and clinical studies of myocardial infarction. The purpose of this study was to quantitatively evaluate, in a closed-chest animal model, a noninvasive method of measuring coronary collateral flow over a wide spectrum of collateral flow rates from a tracer that can be injected during occlusion but measured after reperfusion. METHODS: Fourteen animals underwent 40 min of coronary occlusion using a closed-chest technique. Two closed-chest models representing different rates of collateral flow were used: canine and porcine. Coronary blood flow was measured by radiolabeled microspheres. Collateral blood within the risk zone was estimated from the severity of 99mTc-sestamibi tomographic perfusion defect. RESULTS: Collateral blood flow was significantly higher in the canine model than it was in the porcine model. There was close agreement (r = 0.90) between absolute collateral flow by microspheres and the severity of the tomographic perfusion defect. CONCLUSION: These results suggest that an accurate noninvasive estimate of collateral blood flow can be provided by an intravenous injection of 99mTc-sestamibi.     

Redistribution of collateral blood flow from necrotic to surviving myocardium following coronary occlusion in the dog

Early changes in collateral blood flow after acute coronary occlusion may be critical for survival of ischemic myocardium. We used 15-mum radioactive microspheres to study myocardial blood flow in thoracotomized dogs 10 minutes and 24 hours after occlusion of the left anterior descending coronary artery (LAD). The ischemic area was delineated by dye injected into the distal artery, and indentification of potentially ischemic samples was confirmed by a newly developed technique in which microspheres were excluded from the normally perfused LAD. Layers were separated into necrotic or normal as defined by gross inspection and confirmed by histological examination and creatine phosphokinase assay. Infarction always involved endocardial layers and extended toward the epicardium. Average myocardial blood flow in 48 necrotic samples from 16 dogs either remained low (less than 0.05 ml/min g-1) or declined, falling from 0.11 +/-0.02(SE) at 10 minutes to 0.05 +/-0.01 ml/min g-1 at 24 hours (P less than 0.001). In contrast, in the 32 normal-appearing samples which were ischemic at 10 minutes, flow increased from 0.24 +/-0.03 to 0.39 +/-0.04 ml/min g-1 (P less than 0.001). Flow in control myocardium was 1.43 +/-0.12 and 1.04 +/-0.07 ml/min g-1, respectively. Peripheral mean coronary arterial pressure increased from 26 +/- 3 to 35 +/- 3 mm Hg, largely because of enlargement of collateral vessels; collateral conductance calculated from retrograde flow in 14 dogs increased from 0.023 +/- 0.005 after occlusion to 0.051 +/- 0.009 ml/min mm Hg-1 24 hours later (P less than 0.001). Thus, coronary collateral blood flow is redistributed from necrotic endocardial layers to surviving epicardial ones. In combination with a developing collateral supply this process may be essential for sparing myocardium after coronary occlusion.     

Hormonal regulation of lipoprotein(a) levels: effects of estrogen replacement therapy on lipoprotein(a) and acute phase reactants in postmenopausal women

Estrogen lowers lipoprotein(a) [Lp(a)] levels, but the mechanisms involved have not been clarified. To address the relationship between estrogenic effects on Lp(a) and serum lipids, and on other plasma proteins of hepatic origin, 15 healthy postmenopausal women participated in a randomized, double-blinded, placebo-controlled, crossover study with 4 weeks of oral conjugated estrogens (0.625 mg/d) and placebo, separated by a 6-week period. Lp(a) levels decreased during estrogen treatment in 14 of the 15 subjects (mean decrease, 23%; P < .001). In response to estrogen, apolipoprotein A-I (apoA-I), HDL cholesterol, and triglyceride levels increased by 12% (P = .001), 11% (P < .001), and 10% (P = .02), respectively. Apolipoprotein B (apoB) and LDL cholesterol levels decreased by 7% (P = .01) and 12% (P = .03), respectively, ApoB, LDL cholesterol, and Lp(a) levels fell within 1 week of treatment, whereas apoA-I and HDL cholesterol levels rose more slowly. Levels of acid alpha 1-glycoprotein (AAG) and haptoglobin (HPT), two hepatically derived acute phase proteins, also decreased during estrogen treatment by 18% (P < .001) and 25% (P = .002), respectively. Although the changes in AAG and HPT in response to estrogen were highly correlated (r = .67, P = .009), we were unable to detect a correlation between change in either acute phase protein and change in Lp(a) (r = -.14 and -.24, P = .64 and .41). The lack of correlation between the changes in two acute phase reactants and Lp(a) suggests different underlying mechanisms for the effects of estrogen on these liver-derived proteins.     

Differences in prediction of mortality and non-fatal complications after acute myocardial infarction: a multivariate analysis

The global prognostic after acute myocardial infarction depends of the left ventricular function and the residual ischemia. However, there is controversy about the capacity of some variables reflecting this prognostic factors to predict futures complications. The main objective of this study is to know the influence of the kind of complications in the prognostic value of the variables more frequently used in the clinical practice. We studied 121 consecutive patients with acute myocardial infarction discharged from hospital. The previous and during acute infarction clinical variables were analyzed. The regional and global left ventricular function was studied by 2D echocardiography. An exercise test symptoms-limited was performed at 3rd week after discharge in 94 patients selected. The patients were followed during selected one year. The first year cardiac mortality rate was 8.6%. In the multivariate, the independent predictors of mortality were: age > 60 years (p = 0.02) and the impossibility to perform exercise test (p = 0.0002). In the univariate analysis the echocardiographic motility score > or = 17, eyection fraction < 35% and Killip class > or = II were also death predictors. Non fatal complications (angina, reinfarction o heart failure) were present in 47 patients (42.3%) of 111 survivors. The ischemic complications were predicted in multivariate analysis only by postinfarction angina (p = 0.0007), and heart failure by eyection fraction < 35% (p = 0.006), previous infarct (p = 0.002) and Killip class (p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hostility, aggression and the risk of nonfatal myocardial infarction in postmenopausal women

Integration of human papillomavirus type 16 DNA sequences into host DNA is a frequent event in cervical carcinogenesis. However, recent studies showing that HPV16 is present exclusively in an episomal form in many primary cervical cancers suggest that HPV16 can transform target cells by mechanisms that do not require viral integration. We have established a cervical carcinoma cell line that harbors episomal copies of HPV16 DNA of approximately 10 kb. Restriction enzyme and two-dimensional gel analysis confirmed that HPV16 DNA was extrachromosomal with both monomeric and multimeric forms present. HPV16 was maintained as episomes with passage both in culture and after subcutaneous growth in nude mice. The 10 kb viral genome, consisting of a full-length copy of HPV16 and a partial duplication of the long control region and the L1 open reading frame, exhibited transforming activity comparable to prototype HPV16. This cell line should provide a useful model system for studying the biological significance of the physical state of the HPV16 genome in cervical carcinoma cells.     

Development of endometrial cancer in women on estrogen and progestin hormone replacement therapy

The presenting symptoms, hormonal regimens, treatment modalities, tumor pathology, and follow-up of 25 women developing endometrial cancer while receiving postmenopausal estrogen and progestin therapy were investigated retrospectively. Patients were interviewed and hormone therapies were confirmed through medical records. Pathology specimens were reviewed. Patients received conjugated estrogens (n = 20) or another estrogen (n = 5). For those on conjugated estrogens, the mean daily dose was 0.68 mg, monthly duration was 24.9 days, and monthly dose was 17.0 mg. Women also received medroxyprogesterone acetate (n = 23) or norethindrone acetate (n = 2). The most common regimen was sequential medroxyprogesterone acetate, at a mean daily dose of 7.5 mg, monthly duration of 9.3 days, and monthly dose of 68 mg (mean duration = 5.7 years). Most tumors were low stage and grade, with few demonstrating grade 3 disease (n = 2) or greater than 50% myometrial invasion (n = 2). Twenty-three (92%) had disease limited to the uterus, while two had stage IIIA disease. All are alive and disease-free after a median follow-up of 26 months. Estrogen and progestin therapy does not prevent endometrial cancer in all patients. Women who developed this tumor on sequential therapy in general received less than the recommended guidelines for daily dosage and monthly duration of progestin. Most patients had early-stage and low-grade disease. Continued vigilance in the care of women on hormone replacement therapy is necessary even when combination therapy is prescribed.     

The effect of batroxobin on coronary segmental resistance and coronary blood flow in acute myocardial ischemic dogs

To study the effects of batroxobin on coronary circulation and cardiac performance in acute myocardial ischemia, Batroxobin was given intravenously to dogs with experimental coronary stenosis. A dose-dependent increase of coronary blood flow (CBF) was observed. Forty minutes after batroxobin (2 BU.kg-1 at infusion rate 0.1 BU.kg-1.min-1) administration, CBF increased by 12% (P < 0.05), small coronary resistance(RS) decreased from 4.1 +/- 0.5 to 3.2 +/- 0.5 mmHg.min.ml-1 (P < 0.01), while large coronary resistance(RL) changed insignificantly from 3.9 +/- 0.8 to 3.8 +/- 0.7 mmHg.min.ml-1 (P > 0.05). Two hours following drug administration, the changes in CBF, RS and RL still remained and RT decreased by 13% (P < 0.05). The + LV(dp/dt)max and -LV(dp/dt)max increased by 14% and 16% (P < 0.05) respectively compared with those in control group. It is concluded that batroxobin improves the ischemic canine coronary circulation and cardiac performance by way of lowering the small coronary resistance and thus increasing CBF. The data also suggest the benificial effect of batroxobin in acute myocardial ischemia.     

Combined pathology of the pancreas and myocardium in myocardial infarction and acute destructive pancreatitis

Pancreas was studied in 30 patients who died of myocardial infarction (MI). Total pancreonecrosis was found in 1 case (recurring MI), diffuse focal pancreonecrosis in 3 cases (the second MI). Local microcirculation disturbances, thrombosis of some interlobular veins, degenerative changes of the exocrine pancreocytes with translocation of zymogen granules and their parapedesis into the edematous interstitium were found in all other cases. Focal metabolic myocardial damage and circulation disturbances mainly in the subendocardium of the left ventricle myocardium were found in the heart of 3 patients who died of pancreonecrosis and 60 white rats with pancreatitis induced by chloroethyl. There was a redistribution of Ca2+ in the ultrastructural components of the cardiomyocytes with its accumulation in the cytosol and sarcoplasmic reticulum. The most pronounced and widespread myocardial damage was observed in the hemorrhagic stage of pancreatitis.     

Fluctuations of lipid and lipoprotein levels in hyperlipidemic postmenopausal women receiving hormone replacement therapy

BACKGROUND: Fluctuations in lipid and lipoprotein levels are encountered quite often in hyperlipidemic patients. We examined the possibility that lipid and lipoprotein levels fluctuate due to the different effects of estrogen and progestogen in postmenopausal hyperlipidemic women receiving combined hormonal replacement therapy. METHODS: In an open-label study conducted during 3 consecutive hormonal cycles (3 months), levels of fasting total cholesterol, triglycerides, and low (LDLC)- and high-density lipoprotein cholesterol (HDLC) were determined in 36 postmenopausal hyperlipidemic women on day 13 of conjugated equine estrogen (1.25 mg/d) therapy and on day 25 after 12 days of receiving estrogen plus medroxyprogesterone acetate (5 mg/d). RESULTS: While receiving estrogen and combined therapies, means +/- SD total cholesterol levels increased from 6.50 +/- 0.97 mmol/L (251 +/- 37 mg/dL) to 6.88 +/- 1.42 mmol/L (266 +/- 54 mg/dL) (P<.001); LDLC levels, from 4.05 +/- 1.14 mmol/L (156 +/- 44 mg/dL) to 4.62 +/- 1.36 mmol/L (178 +/- 52 mg/dL) (P<.001). Mean +/- SD HDLC cholesterol levels decreased from 1.44 +/- 0.32 mmol/L (55 +/- 12 mg/dL) to 1.29 +/- 0.28 mmol/L (50 +/- 10 mg/dL) (P<.001); triglyceride levels, from 2.23 +/- 1.03 mmol/L (197 +/- 91 mg/dL) to 2.06 +/- 1.04 mmol/L (182 +/- 92 mg/dL) (P<.001). CONCLUSIONS: Hyperlipidemic postmenopausal women receiving combined sequential estrogen and progestogen replacement therapy demonstrate very significant fluctuations in their lipid and lipoprotein levels. These fluctuations depend on the hormonal phase, ie, estrogen alone or combined with progestogen.     

Acceptability of a substitution of estrogen replacement therapy to women enrolled in a health maintenance organization

This research examines the implications of an aging society on the demand for prehospital emergency medical services (EMS). Using a large comprehensive set of population-based EMS utilization data (N = 73874) and population data from the 1990 Census for the City of Dallas, Texas, rates of utilization for eight age groups were computed for total EMS incidents, incidents requiring transport services, and a sub-category of transport services for individuals requiring services for life-threatening conditions. The pattern of utilization associated with age was found to be tri-modal with rates rising geometrically with age for individuals aged 65 and over. Compared to the age group 45 to 64 years of age, rates of utilization for those aged 85 years and older were 3.4 times higher (P < 0.001) for total EMS incidents, 4.5 times higher (P < 0.001) for emergency transports and 5.2 times higher (P < 0.001) for incidents of a life-threatening nature. A broad categorization of all EMS incidents by reason for requiring services indicates that the observed age-associated increase in utilization is due primarily to medical conditions rather than incidents arising from trauma. Finally, gender and racial/ethnic differences in utilization are briefly considered.     

Alternation in the coronary blood flow velocity pattern in patients with no reflow and reperfused acute myocardial infarction

1. The effects of fluvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on the vascular angiotensin converting enzyme (ACE) activity in hyperlipidaemic rabbits were compared with those of enalapril, an ACE inhibitor. 2. Rabbits were fed a 1.5% cholesterol containing diet or normal diet for 16 weeks and treated with either fluvastatin or enalapril in the diet at the respective doses of 2 and 10 mg kg-1 day-1. The total cholesterol, triglyceride and phospholipid levels in serum were significantly increased in rabbits fed the high cholesterol diet. Treatment with fluvastatin but not enalapril resulted in a decrease in serum lipids. 3. The vascular ACE activities assessed via the cleavage rate from synthetic substrate in the aortic arches and upper thoracic aortae were increased by 8 to 10 times when the rabbits were made hyperlipidaemic. Fluvastatin as well as enalapril significantly lowered the tissue ACE in the aortae. 4. The ACE activities in serum did not alter in hyperlipidaemic rabbits either in the presence or absence of fluvastatin. The serum ACE activity was lowered by enalapril. 5. The lipid peroxide in serum as well as the plaque area in the thoracic aorta was significantly increased in the cholesterol diet-fed rabbits. Treatment with fluvastatin or enalapril reduced both serum lipid peroxide and plaque formation. The relaxant responses to acetylcoholine (ACh) were significantly suppressed in the cholesterol-fed rabbits. Treatment with fluvastatin or enalapril significantly reversed the suppression of ACh-induced relaxation. 6. It seems that the reduction of vascular ACE is not coupled to lipids and ACE activity in serum, but rather to lipid peroxidation. Thus, the decrease in vascular ACE activity by fluvastatin as well as the lipid-lowering effect may reduce the risk of atherosclerosis progression in the vasculature.     

Age-related deterioration in arterial structure and function in postmenopausal women: impact of hormone replacement therapy

Epidemiological evidence suggests that hormone replacement therapy (HRT) reduces morbidity and mortality from cardiovascular diseases in postmenopausal women. In this study, indices of arterial function [total systemic arterial compliance (SAC) and carotid arterial distensibility coefficient (DC)], structure [carotid intima-media thickness (IMT)], and lipid profiles were compared in postmenopausal women on long-term HRT and aged-matched controls. One hundred nine women aged 44 to 77 years taking HRT and an age-matched group of 108 female controls were entered into the study. The two groups were similar for body mass index, smoking status, exercise level, alcohol intake, and blood pressure. Fasting cholesterol, low density lipoprotein, and lipoprotein(a) were reduced and high density lipoprotein increased in the HRT group. IMT increased with age; SAC and DC were reduced with age in both groups. The HRT group had a higher mean SAC (0.42+/-0.02 versus 0.34+/-0.02 U/mm Hg, P=0.0001) and a lower mean IMT (0.67+/-0.01 versus 0.74+/-0.02 mm, P=0.006) than did controls. Subgroup analysis for estrogen versus estrogen plus progestin revealed no differences for SAC and IMT; DC, however, was greater in estrogen-only users. Smokers on HRT had a higher mean SAC (0.41+/-0.02 versus 0.31+/-0.01 U/mm Hg, P=0.008) and a lower IMT (0.65+/-0.02 versus 0.75+/-0.03 mm, P=0.002) than did smokers not taking such therapy. A protective effect of long-term estrogen therapy on age-related changes in arterial structure and function in postmenopausal women was evident in smokers and nonsmokers alike. Progestin appeared to counteract the effects of estrogen on carotid compliance only. Long-term controlled trials are needed to determine the significance of these findings.     

A comparison of estrogen replacement, pravastatin, and combined treatment for the management of hypercholesterolemia in postmenopausal women

OBJECTIVES: To evaluate and compare the lipid-altering effects of conjugated estrogens and pravastatin, alone and in combination, in postmenopausal women with hypercholesterolemia. METHODS: This was a double-blind, randomized, placebo-controlled clinical trial with 4 parallel groups. Participants (N = 76) were randomly assigned to receive conjugated estrogens, 0.625 mg/d; pravastatin sodium, 20 mg/d; conjugated estrogens plus pravastatin; or a placebo for 16 weeks. RESULTS: Primary end points were changes in serum lipid parameters. Among participants treated with conjugated estrogens, levels of non-high density lipoprotein cholesterol (non-HDL-C) (13.0%) and calculated low density lipoprotein cholesterol (LDL-C) (13.5%) decreased, while levels of HDL-C (22.5%) and triglycerides (4.2%) increased. Participants in the pravastatin group achieved reductions of 23.7% and 25.4% in non-HDL-C and calculated LDL-C levels, respectively. Levels of HDL-C increased slightly (3.7%) and triglycerides decreased by 12.1%. Among participants treated with a combination of conjugated estrogens plus pravastatin, the non-HDL-C (-25.2%) and calculated LDL-C (-28.7%) responses were similar to those of the pravastatin group, and the HDL-C response (21.2%) was similar to that observed in the conjugated estrogens group. Triglyceride levels remained similar to baseline (-0.9%) in the combined treatment group. CONCLUSIONS: Administration of conjugated estrogens resulted in potentially antiatherogenic changes in levels of non-HDL-C, HDL-C, and calculated LDL-C. The HDL-C response to combined treatment was similar to that observed in women taking conjugated estrogens alone, while the non-HDL-C and LDL-C responses to combined treatment were similar to those produced by pravastatin therapy alone. These findings support the position of the National Cholesterol Education Program that estrogen replacement, with a progestin where indicated, should be given consideration as a therapeutic option for the management of hypercholesterolemia in postmenopausal women.