Acute hemodynamic effects of estrogen administration in postmenopausal women

The hemodynamic effects of estrogens in replacement doses have not been fully clarified; therefore, we studied the acute hemodynamic changes after 0.625 and 1.25 mg of conjugated estrogens, administered intravenously, using a thermodilution catheter, in postmenopausal women without structural heart disease. Pulmonary and systemic pressures and resistances and stroke volume did not change compared with baseline, but heart rate and cardiac output decreased significantly, which may be associated with estrogen's previously described calcium-blocking effect or with a more recently contemplated beta-blocking action.     

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 exercise and estrogen therapy on lipid profiles of postmenopausal women

PURPOSE: We compared the effects of aerobic exercise training on lipid and lipoprotein levels in 18 postmenopausal women who were (N = 8) or were not (N = 10) receiving estrogen replacement therapy (ERT). METHODS: Each group was tested for lipids, diet recall and VO2max before and after a 12 wk exercise program, consisting of 30-50 min of an aerobic activity at 75-85% of VO2max, 3-4 sessions per week. RESULTS: Both groups increased VO2max by 8% and neither group changed their diet. The ERT group had higher levels of triglycerides and lower levels of low density lipoprotein (LDL-C) (P < 0.01) before training. There were no mean group changes in any of the lipid variables with training. However, individual changes in LDL-C and Total Cholesterol (TC) were strongly related to baseline weight in the nonestrogen group (r = 109.91, r = -0.82) but not in ERT (r = -0.30, r = -0.51). Subsequently, all subjects were redivided into two groups based on BMI (< or = 27 or > or = 27) regardless of ERT status. TC decreased significantly (P < 0.05) in the < or = 27 BMI group. CONCLUSIONS: Exercise training had little effect on the lipid profiles of the ERT and the nonestrogen groups, but body weight seems to be a modulating factor. Heavier subjects did not respond as favorably to 12 wk of exercise training as postmenopausal women with less body mass, regardless of the presence of exogenous estrogen.     

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 continuous medroxyprogesterone acetate on lipoprotein metabolism in postmenopausal women receiving estrogen

Seed storage globulins of the 7S and 11S type are synthesized in the seeds of angiosperms and gymnosperms. We have isolated and characterized a vicilin-like gene expressed in the cycad Zamia furfuraceae. Sequence comparisons reveal clear similarities to a sucrose-binding protein isolated from soybean. We suggest the existence of a superfamily of related genes including both vicilin-like and legumin-like seed globulin genes as well as genes coding for spherulins, germins and sucrose-binding-proteins.     

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.     

Exercise echocardiography in postmenopausal hormone users with mild systemic hypertension

Rest and exercise echocardiography (at dynamic and isometric exercise) were performed in 30 postmenopausal women (aged 54 +/- 4 years) with borderline to mild hypertension. They were then divided into 2 groups: 17 women who started oral hormone replacement therapy (0.625 mg/day conjugated estrogens or 2 mg/day estradiol) and a control group of 13 nonusers. After 6 to 9 months, a second echocardiography was performed in 26 women (4 withdrew). There were only a few changes in values obtained in the 12 controls at the end of follow-up compared with baseline. Primarily, these changes included a slight decrease in systolic blood pressure at rest and on exercise. Several significant morphologic and hemodynamic alterations appeared in 14 hormone users. Left ventricular cavity dimensions and mass became smaller: mean end-diastolic diameter decreased from 45.9 +/- 3 mm at baseline to 44.4 +/- 3 mm at study termination (p = 0.007). The corresponding values for end-systolic diameter were 25.8 +/- 4 mm and 23.9 +/- 4 mm (p = 0.006); for left atrium diameter, it was 34.5 +/- 4 mm and 32.5 +/- 4 mm (p = 0.001); for left ventricular wall width, it was 19.9 +/- 2 mm and 19.3 +/- 2 mm (p = 0.02); for left ventricular mass, it was 197 +/- 28 g and 179 +/- 32 g (p = 0.006). The resting aortic blood flow velocity and acceleration increased: 119 +/- 18 cm/s before therapy versus 129 +/- 23 cm/s while on hormone substitution (p = 0.04), and 13.6 +/- 3 m/s2 versus 16.5 +/- 4 m/s2 (p = 0.008), respectively. Mean rest to peak exercise systolic blood pressure difference became smaller after hormones: 39 +/- 19 mm Hg versus 28 +/- 13 mm Hg (p = 0.03) during dynamic exercise, and 43 +/- 22 mm Hg versus 25 +/- 13 mm Hg (p = 0.004) during isometric exercise. The above data probably indicate that with hormone replacement therapy, there is an improvement in cardiac function both at rest and during exercise.     

Vascular effects of estrogen and cholesterol-lowering therapies in hypercholesterolemic postmenopausal women

BACKGROUND: Lipoproteins affect endothelium-dependent vasomotor responsiveness. Because lipoprotein effects of estrogen and cholesterol-lowering therapies differ, we studied the vascular responses to these therapies in hypercholesterolemic postmenopausal women. METHODS AND RESULTS: We randomly assigned 28 women to conjugated equine estrogen (CE) 0.625 mg, simvastatin 10 mg, and their combination daily for 6 weeks. Compared with respective baseline values, simvastatin alone and combined with CE reduced LDL cholesterol to a greater extent than CE alone (both P<0.05). CE alone and combined with simvastatin raised HDL cholesterol and lowered lipoprotein(a) to a greater extent than simvastatin alone (all P<0.05). Flow-mediated dilation of the brachial artery (by ultrasonography) improved (all P<0.001 versus baseline values) on CE (4.0+/-2.6% to 10.2+/-3.9%), simvastatin (4.3+/-2.4% to 10.0+/-3.9%), and CE combined with simvastatin (4.6+/-2.0% to 9.8+/-2.6%), but similarly among therapies (P=0.507 by ANOVA). None of the therapies improved the dilator response to nitroglycerin (all P>/=0.184). Only therapies including CE lowered levels of plasminogen activator inhibitor type 1 and the cell adhesion molecule E-selectin (all P<0. 05 versus simvastatin). CONCLUSIONS: Although estrogen and statin therapies have differing effects on lipoprotein levels, specific improvement in endothelium-dependent vasodilator responsiveness is similar. However, only therapies including estrogen improved markers of fibrinolysis and vascular inflammation. Thus, estrogen therapy appears to have unique properties that may benefit the vasculature of hypercholesterolemic postmenopausal women, even if they are already on cholesterol-lowering therapy.     

Growth hormone in postmenopausal women after long-term oral estrogen replacement therapy

Studies of estrogen effects on growth hormone (GH) and its pulsatile release in postmenopausal women have typically utilized estrogen replacement therapy (ERT) of relatively short duration (days to weeks). The purpose of this study was to compare GH measures from healthy postmenopausal women who were on oral ERT for 3 years or more (n = 24; mean ERT duration = 16.1 years) with women not on ERT (NERT; n = 40). Blood samples were drawn remotely every 20 min for 24 h and then analyzed for mean 24-h GH, mean GH during sleep, and mean 24-h insulin-like growth factor-I (IGF-I). GH peak analyses were also performed. Mean 24-h GH and GH during sleep were significantly higher and IGF-I was significantly lower in ERT women compared with NERT women. In addition, use of long-term ERT was associated with more GH peaks relative to women not on ERT, but no change in GH peak amplitude or area. GH was not related to age in either group. GH was strongly and negatively correlated with measures of adiposity in NERT women but not in ERT women. In conclusion, long-term oral ERT is associated with increased circulating GH and decreased IGF-I levels, even after many years of treatment.     

Use of estrogen in women with systemic lupus erythematosus--should, should not?

Changes in sex hormone metabolism seem to play a role in the expression of systemic lupus erythematosus (SLE). Epidemiological studies have demonstrated an increased risk of developing SLE in women using oestrogens for more than ten years. Onset or aggravation of symptoms have been described in case reports and small retrospective series of SLE patients. Oestrogen replacement therapy is generally well tolerated whereas oral contraceptives containing oestrogen can induce flares in a small proportion of SLE patients. A generally negative attitude towards oestrogens seems inadequate since controlled prospective studies are lacking. Patients with stable disease may use oestrogen provided there is close follow-up, particularly during the first six months of treatment. Treatment with oestrogen is contraindicated in SLE patients with a history of thromboembolism, positivity for phospholipid antibodies, and in the presence of severe organ involvement.     

Differential impact of conventional oral or transdermal hormone replacement therapy or tibolone on body composition in postmenopausal women

OBJECTIVE: To compare the effects on body composition and body weight of tibolone vs two different sequential oral or transdermal oestrogen-progestogen hormone replacement therapies versus no therapy. PATIENTS AND METHODS: One hundred postmenopausal women were assigned to a control group (n = 26), or randomized to 1) tibolone (TIB) 2.5 mg/day (n = 28), 2) oral oestradiol 2 mg/day (PO) plus sequential dydrogesterone 10 mg/day for 14 of 28 days per cycle (n = 26), or 3) transdermal oestradiol patch (TTS) releasing 50 micrograms/day plus oral sequential dydrogesterone 10 mg/day for 14 of 28 days per cycle (n = 20). Body composition was measured at the base-line and every 6 months for 2 years by DXA (Hologic QDR 1000 W). RESULTS: Total body fat mass increased (P < 0.05) in controls (+3.6 +/- 1.5%) and in TTS treated (+4.7 +/- 2.2%), but not in PO (-1.2 +/- 2.4%) and TIB (-1.6 +/- 2.2%) treated subjects. This increase in total fat mass in controls and TTS treated women was mostly due to an increase in fat mass of the trunk (P < 0.05), but not legs. As a result, a redistribution of body fat to the trunk occurred in controls, TTS and TIB, but not in PO treated women (P < 0.05). Total lean body mass decreased (P < 0.02) in controls (-1.7 +/- 0.7%) and PO (-1.4 +/- 0.6%) but not in TTS (+0.3 +/- 0.8%) and TIB (+0.4 +/- 0.5%) treated subjects. CONCLUSIONS: The menopause is associated with an increase in total body fat and a decline in lean body mass. Oral oestradiol/dydrogesterone and tibolone prevent total body fat changes, whereas transdermal oestradiol/oral dydrogesterone and tibolone prevent the lean mass changes. Furthermore, oral oestradiol/dydrogesterone prevents the shift to a central, android fat distribution.     

Effects of alendronate on bone turnover markers in early postmenopausal women

BACKGROUND: Alendronate sodium (Fosamax, Merck, Sharp & Dohme, Whitehouse Station, NJ, USA) is an aminobisphosphonate that can inhibit osteoclast-mediated bone resorption activity to reduce bone turnover rate and improve progressive gains in bone mass. METHODS: This was a randomized, double-blind, placebo-controlled study comparing the effects on bone turnover markers between daily treatment with alendronate sodium 10 mg and placebo. Forty early postmenopausal women completed three months of treatment. The bone turnover rate was determined by measuring the biochemical markers at baseline, week 6 and at the end of the three-month treatment period. All adverse events were recorded during each follow-up visit. RESULTS: Patients receiving alendronate treatment had a significant decrease in urinary excretion of the bone resorption marker deoxypyridinoline (Dpd) as well as one of the bone formation markers, bone-specific alkaline phosphatase (AlkP-B). Patients receiving placebo tended to have increased urinary excretion of bone resorption and formation markers. At the end of three months, the mean percentage change of Dpd and AlkP-B from baseline in the group receiving 10 mg alendronate was 30.49% and 29.45% reduction, respectively. The placebo group had 2.39% and 1.52% increase, respectively. Overall, three biochemical markers (Dpd, AlkP-B and osteocalcin) differed significantly between the treatment and control groups after three months of treatment. The drug was well tolerated, without a significant increase in incidence of adverse effects such as gastrointestinal discomfort and esophageal irritation. CONCLUSIONS: Bone turnover rate decreased quickly following drug administration. The incidence of adverse effects did not differ significantly between the alendronate and placebo groups. Alendronate is, therefore, recommended as an effective nonhormonal treatment for postmenopausal osteoporosis.     

Effects of 1-year treatment with ipriflavone on bone in postmenopausal women with low bone mass

Genetic mosaic maize plants that contained dwarf1 sectors in otherwise normal plants were analyzed. The analysis of dwarf1 sector growth relative to the surrounding wild-type tissue should test the hypothesis that Dwarf1 controls the production of a diffusible factor. Maize dwarf1 sectors did not show altered growth relative to the surrounding tissue, indicating that Dwarf1 controls the production of a diffusible factor. As Dwarf1 has been proposed to control the conversion of GA20 to biologically active GA1, these results suggest that GA, itself is the diffusible factor.     

Effects of transdermal nitroglycerin on left ventricular function after acute myocardial infarction

Progressive left ventricular dysfunction in acute myocardial infarction patients is associated with a poor prognosis. It has been shown that some therapeutic measures which have the potential for limiting the infarct size and preserving ventricular function, are also able to reduce the incidence of congestive heart and improve survival. The aim of this protocol was to assess the effects of transdermal nitroglycerin administered within 72 hours after the onset of acute myocardial infarction and for the following 6 months, on left ventricular function. A total of 98 consecutive acute myocardial infarction patients were randomly allocated, within 72 hours of onset of symptoms, to a double-blind 6-month-therapy with either 10 mg/24 hour transdermal nitroglycerin or placebo. Patients underwent two-dimensional echocardiography at entry, after 2 weeks, 3 months and 6 months. In the nitroglycerin group, end-diastolic volume increased during the follow-up (+6.7%, p < 0.05) while end-systolic volume remained nearly unchanged; ejection fraction and stroke volume increased progressively (+6.3%, p < 0.05, +14.2%, p < 0.05, respectively) and a important reduction of percent of dyssynergic segments was present (-19.2%, p < 0.005). In the placebo group end-diastolic volume and end-systolic volume slightly increased during the follow-up (+2% and +4.9% respectively); ejection fraction and stroke volume remained nearly unchanged during the study; percent of dyssynergic segments showed an important decrease after 2 weeks and 6 months (-21.3%, p < 0.005). A clinically relevant increase (> 20%) in ejection fraction was present more frequently in the nitroglycerin than in the placebo group (p < 0.001). In conclusion, the early (within 72 hours) and prolonged (6 months) administration of transdermal nitroglycerin in acute myocardial infarction improves ejection fraction and stroke volume but does not modify ventricular remodeling.