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1.
Effects of conjugated estrogens/bazedoxifene on lipid and coagulation variables: a randomized placebo- and active-controlled trial.
Skouby, SO, Pan, K, Thompson, JR, Komm, BS, Mirkin, S
Menopause (New York, N.Y.). 2015;(6):640-9
Abstract
OBJECTIVE This study aims to evaluate the effects of conjugated estrogens (CE)/bazedoxifene (BZA) on lipid and coagulation variables in a randomized, double-blind, placebo- and active-controlled phase 3 study of nonhysterectomized postmenopausal women. METHODS The Selective estrogens, Menopause, And Response to Therapy (SMART)-5 trial evaluated the efficacy and safety of CE/BZA in postmenopausal women (N = 1,843) with menopausal symptoms. Lipid (N = 1,843) and coagulation (N = 590) variables were assessed in women receiving daily CE 0.45 mg/BZA 20 mg, CE 0.625 mg/BZA 20 mg, BZA 20 mg, CE 0.45 mg/medroxyprogesterone acetate (MPA) 1.5 mg, or placebo for 12 months. RESULTS At 12 months, CE 0.45 mg/BZA 20 mg, CE 0.625 mg/BZA 20 mg, BZA 20 mg, and CE 0.45 mg/MPA 1.5 mg decreased total cholesterol and low-density lipoprotein cholesterol compared with placebo (P < 0.01 for all). Both CE/BZA doses and CE/MPA increased high-density lipoprotein cholesterol compared with placebo (P < 0.05 for all). CE 0.45 mg/BZA 20 mg had a neutral effect on triglycerides; CE 0.625 mg/BZA 20 mg and CE/MPA increased triglycerides compared with placebo (P < 0.05). Both CE/BZA doses were associated with small but significant effects on hemostasis variables, including reductions in antithrombin, plasminogen activator inhibitor-1, and fibrinogen activity, and an increase in plasminogen activity relative to placebo at 12 months. Incidences of cardiovascular and venous thromboembolic events were similar among treatment groups. CONCLUSIONS This study provides reassurance that CE/BZA does not adversely affect lipid metabolism or hemostatic balance. In accordance, the incidences of venous thromboembolic events and cardiovascular events in postmenopausal women are similar to those observed with placebo.
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2.
Effects of hormone replacement therapy on glucose and lipid profiles and on cardiovascular risk parameters in postmenopausal women.
Bingol, B, Gunenc, Z, Yilmaz, M, Biri, A, Tiras, B, Güner, H
Archives of gynecology and obstetrics. 2010;(5):857-64
Abstract
OBJECTIVES The aim of this study was to evaluate the effects of hormone replacement therapy (HRT) on carbohydrate and lipid metabolisms and cardiovascular risk parameters in healthy postmenopausal women. METHODS Forty women receiving and 38 women not receiving HRT were included and baseline and sixth month blood pressure, weight, body mass index, waist/hip ratio, blood lipid profile, inflammatory markers (homocysteine, C-reactive protein (CRP) and fibrinogen), hemoglobin A1c (HbA1c) and insulin, and oral glucose tolerance test (OGTT) results were evaluated. RESULTS The mean age was 52.6+/-4.9 and 52.2+/-5.0 years in the HRT and Control Groups, respectively. Whereas there was no change in the Controls, the weight, waist/hip ratio, and BMI increased and diastolic blood pressure decreased in the HRT patients. LDL-c, VLDL-c and lipoprotein (a) levels were significantly higher in the HRT Group in the sixth month; however, total cholesterol and LDL-c increased in the Controls but VLDL-c and lipoprotein (a) did not. CRP and homocysteine significantly increased and fibrinogen decreased, whereas in the Control Group no significant change was detected. A significant improvement in HbA1c and OGTT was found in both the groups, whereas a significant reduction was measured only in the HRT Group. CONCLUSIONS In response to 6 months of HRT, there was an increase in weight, BMI, and waist/hip ratio as known cardiovascular risk factors, but no significant impact on lipid profile and glucose metabolism could have been clearly demonstrated. A mixed effect profile of HRT on the state of inflammation (increase in CRP and homocysteine, decrease in fibrinogen) was observed.
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3.
An open-label study of subdermal implants of estradiol-only versus subdermal implants of estradiol plus nomegestrol acetate: effects on symptom control, lipid profile and tolerability.
Barbosa, IC, Coutinho, EM, Oladapo, L, Noronha, CF, Mota, RL, Lopes, AC, Lopes, RC
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2009;(4):269-75
Abstract
OBJECTIVE To compare the effects of continuous 17-beta estradiol-only silastic implants with those of continuous 17-beta estradiol plus continuous nomegestrol acetate silastic implants on symptom control, lipid profile and tolerability in postmenopausal women. METHODS This was an open-label, parallel-group study. Women with and without uterus and no contraindications to hormone therapy (HT) in this study, we consider as HT the replacement of Estrogens-only and Estrogens + Progestogens Therapy, were enrolled. Each subject was assigned to receive four 17-beta estradiol-only silastic implants (women without uterus), or four 17-beta estradiol plus one nomegestrol acetate silastic implant (women with intact uterus), for 1 year. RESULTS A total of 40 subjects were enrolled and received, the silastic implants of which 40 (100.0%) subjects completed the study (n = 20, estradiol only; n = 20, estradiol plus nomegestrol acetate). The incidence of postmenopausal symptoms decreased significantly. No significant decreases in total cholesterol (1.3%), low-density lipoprotein cholesterol (1.1%), triglycerides (1.2%) and fasting glucose ((1.3%) serum levels were observed in both groups, whereas high-density lipoprotein (HDL) cholesterol increased significantly (2.8%), during the study in both groups. The incidences of adverse events were similar in both treatment groups. CONCLUSIONS Women treated with 17-beta estradiol-only silastic implants or 17-beta estradiol plus nomegestrol acetate silastic implants showed significant improvement of postmenopausal symptoms, including urogenital and sexual health symptoms and a significant increase in HDL cholesterol and no significant differences in other lipid profiles and tolerability.
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4.
Which progestogen is more likely to increase the risk of fatal myocardial infarction: a combination of epidemiological and trial evidence.
Al-Azzawi, F, Thompson, J, Stevenson, J
Maturitas. 2006;(2):154-63
Abstract
OBJECTIVES To evaluate the impact of metabolic effects of different progestogens on the risk of fatal myocardial infarction is evaluated. METHODS The changes in (apo)lipoproteins obtained from a randomized trial of three hormone therapy regimens were applied to three models for predicting fatal myocardial infarction derived from the apolipoprotein-related mortality risk (AMORIS) study. In our trial, 487 postmenopausal women were randomized to oral estradiol, with sequential addition of two trimegestone (TMG) doses or norethisterone acetate (NETA), and studied at baseline and after 3, 6, and 12 months. RESULTS The change from baseline in risk of fatal myocardial infarction, using AMORIS model 3, containing total cholesterol, triglycerides, and apolipoprotein AI, was a 10% reduction for the two TMG doses; NETA had no apparent impact. The differences between treatments were significant at all three time points. When apoB was added in AMORIS model 4, the difference between treatments (5% reduction in the two doses of TMG, compared to NETA) decreased over time, probably due to the effect of dropouts in the NETA group. CONCLUSIONS This analysis shows different metabolic responses to progestogens in terms of risk of fatal myocardial infarction. Generalization of health benefits or adverse effects seen in trials of hormone therapy to other progestogens could be misleading.
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5.
Bone response to treatment with lower doses of conjugated estrogens with and without medroxyprogesterone acetate in early postmenopausal women.
Lindsay, R, Gallagher, JC, Kleerekoper, M, Pickar, JH
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2005;(4):372-9
Abstract
Lower doses of conjugated estrogens (CE) alone or combined with lower doses of medroxyprogesterone acetate (MPA) increase mean bone mineral density (BMD) from baseline at the spine and hip in early postmenopausal women. However, not all women on therapy gain BMD. The incidence of continued bone loss (defined as a loss of BMD of > 2% from baseline) among women using lower doses of CE and CE/MPA is unknown. This randomized, double-blind, placebo-controlled, multicenter substudy of the Women's Health, Osteoporosis, Progestin, Estrogen (Women's HOPE) trial investigated the incidence of continued bone loss with lower-dose CE and CE/MPA. Eight hundred twenty-two healthy postmenopausal women with intact uteri received CE 0.625, CE 0.625/MPA 2.5, CE 0.45, CE 0.45/MPA 2.5, CE 0.45/MPA 1.5, CE 0.3, CE 0.3/MPA 1.5 (all doses in mg/day), or placebo for 2 years along with 600 mg/day of calcium. Changes from baseline in spine and total hip BMD were compared among treatment groups in an intent-to-treat analysis. At 12 months, < 10% of women on active treatment lost > 2% of spinal BMD (except CE 0.3/MPA 1.5 [15.6%]), compared with 41.2% of women on placebo. At 24 months, the percentages of women on active treatment who lost > 2% of spine BMD ranged from 4.5% with CE 0.45/MPA 1.5-15.6% with CE 0.3/MPA 1.5, compared with 55.2% of women taking placebo. More than 85% of women on active treatment did not experience continued BMD loss at the hip at 12 months and 24 months, in contrast to 30.6% of women on placebo at 12 months and 36.5% at 24 months. Women receiving active treatment who lost > 2% of spine or hip BMD also had a lesser reduction in biochemical markers of bone turnover. In summary, continued bone loss among early postmenopausal women treated with lower doses of CE or CE/MPA is uncommon.
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6.
Effects of conjugated equine estrogens or raloxifene on lipid profile, coagulation and fibrinolysis factors in postmenopausal women.
Dias, AR, Melo, RN, Gebara, OC, D'Amico, EA, Nussbacher, A, Halbe, HW, Pinotti, JA
Climacteric : the journal of the International Menopause Society. 2005;(1):63-70
Abstract
OBJECTIVES To compare the effect of conjugated equine estrogens (CEE) and raloxifene on lipid profile and hemostasis. MATERIALS AND METHODS A double-blind, randomized and parallel study was performed with 90 healthy postmenopausal women, aged 54 +/- 5 years, divided into three groups and submitted to daily therapy with either CEE 0.625 mg, raloxifene 60 mg or placebo for 4 months. The lipid profile, coagulation and fibrinolytic factors were analyzed. RESULTS CEE increased the levels of high density lipoprotein cholesterol (HDL-C) from 49.0 to 56.8 mg/dl (p < 0.001), very low density lipoprotein cholesterol (VLDL-C) from 17.2 to 22.3 mg/dl (p < 0.001), and triglycerides from 86.0 to 111.7 mg/dl (p < 0.001), and decreased the levels of low density lipoprotein cholesterol (LDL-C) from 121.0 to 106.5 mg/dl (p < 0.001). The only significant effect of raloxifene was an increase in the levels of HDL-C from 46.0 to 47.8 mg/dl (p = 0.019). There was no significant reduction in LDL-C, from 115.5 to 110.2 mg/dl (p = 0.06), VLDL-C, from 21.7 to 20.0 mg/dl (p = 0.201), and triglycerides, from 108 to 100 mg/dl (p = 0.201). CEE decreased the levels of fibrinogen, from 370.5 to 326.8 g/l (p = 0.039) and the levels of antithrombin III, from 99.5 to 93.2% (p < 0.001). Raloxifene decreased the levels of fibrinogen, from 354.7 to 302.0 g/l (p = 0.009) and the levels of antithrombin III, from 102.4 to 98.5% (p = 0.039). CEE increased levels of protein C from 103.7 to 115.3 mg/l (p < 0.001) and raloxifene did not change the levels of protein C (107.9 to 105.1 mg/l; p = 0.158). CEE decreased the antigen levels of tissue plasminogen activator (t-PA) from 8.8 to 6.8 U/ml (p < 0.001), and of plasminogen activator inhibitor (PAI-1) from 30.8 to 21.6 U/ml (p < 0.010), whereas raloxifene had no significant effect on either t-PA, from 9.6 to 9.2 U/ml (p = 0.235) or PAI-1 antigen levels, from 32.1 to 30.4 U/ml (p = 0.538). CONCLUSION Both CEE and raloxifene exert significant effects on the lipid and coagulation profile. CEE had a more significant effect on fibrinolysis than raloxifene. These effects may have a significant impact on the cardiovascular risk that needs to be confirmed in larger studies.
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7.
Effects of two continuous hormone therapy regimens on C-reactive protein and homocysteine.
Barnes, JF, Farish, E, Rankin, M, Hart, DM
Menopause (New York, N.Y.). 2005;(1):92-8
Abstract
OBJECTIVE To compare the effects of two continuous hormone therapy (HT) regimens on the cardiovascular risk markers, C-reactive protein (CRP) and homocysteine. DESIGN A prospective study in which 43 postmenopausal women were randomly assigned to either tibolone 2.5 mg/day (n = 20) or 0.625 mg/day conjugated equine estrogens (CEE) plus continuous medroxyprogesterone acetate (MPA) 5 mg/day (n = 23). Serum levels of CRP, homocysteine, vitamin B12, and folate were determined before and during 12 weeks of therapy. RESULTS C-reactive protein levels were increased by tibolone (76%; P < 0.001) and CEE+MPA (81%; P < 0.001). Neither tibolone nor CEE+MPA had any significant effect on homocysteine levels, but there was a significant difference between the effects of treatment over time (P = 0.046). Both tibolone and CEE+MPA reduced vitamin B12 levels (11%; P < 0.001, and 8%; P < 0.01, respectively), but had no statistically significant effect on folate levels. Individual changes in homocysteine levels were negatively associated with changes in vitamin B12 levels (r = -0.68; P < 0.01) after tibolone therapy. CONCLUSION Both tibolone and CEE plus MPA increased CRP levels and reduced levels of vitamin B12. Neither therapy had any significant effect on homocysteine levels. Further long-term studies into the effect of HRT on these markers, and the relationship to cardiovascular disease risk, are required.
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8.
[Low dose estrogen replacement therapy (ERT) for postmenopausal hemodialysis (HD) patients].
Hamano, T, Fujii, N, Ito, T, Imai, E, Mikami, S, Katayama, M, Obi, Y
Clinical calcium. 2005;:161-6; discussion 166
Abstract
We studied the short-time effects of low dose estradiol (E2) on bone metabolism in hemodialysis (HD) patients. We prescribed transdermal E2 (0.36 mg every other day) to 17 non-diabetic postmenopausal osteoporotic HD patients and measured intact parathyroid hormone (iPTH), serum NTX (sNTX), intact osteocalcin (iOC), and bone resorptive cytokines including IL-6 and TNF-alpha. Serum E2 increased from 20 to approximately 40 pg/mL, which is comparable to that of male HD patients. Three-month treatment decreased serum calcium by 0.7 mg/dL followed by a significant elevation of iPTH and iOC. Despite the increase of iPTH, collagen breakdown product, sNTX did not change significantly, implying decreased skeletal sensitivity to PTH resorbing effect. IL-6 and TNF-alpha decreased, but this trend was not statistically significant. Bone pain and/or pain from carpal tunnel syndrome resolved by ERT. We needed to dose-up active vitamin D to control enhanced iPTH. Our data suggests that E2 attenuates the resorbing effect of PTH and stimulates bone formation, also in HD patients.
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9.
Effects of low and high dose oestradiol and dydrogesterone therapy on insulin and lipoprotein metabolism in healthy postmenopausal women.
Godsland, IF, Manassiev, NA, Felton, CV, Proudler, AJ, Crook, D, Whitehead, MI, Stevenson, JC
Clinical endocrinology. 2004;(5):541-9
Abstract
OBJECTIVE Menopause diminishes insulin secretion and elimination, increases risk of diabetes and adversely affects lipoprotein metabolism. This study was undertaken to establish whether oral oestradiol plus dydrogesterone postmenopausal hormone therapy can modify these changes. DESIGN Randomized prospective trial of postmenopausal women taking low dose therapy (1 mg/day oestradiol-17 beta with 5 or 10 mg/day dydrogesterone for days 17-28 of each cycle, n = 15) or high dose therapy (2 mg/day oestradiol-17 beta with 10 or 20 mg/day orally administered dydrogesterone, n = 9). MEASUREMENTS Patients underwent measurement of glucose, insulin and C-peptide in the fasting state and during an intravenous glucose tolerance test (IVGTT) at baseline and after 12 and 24 cycles of treatment. Modelling analysis was used to derive measures of insulin secretion, elimination and sensitivity. Fasting serum lipids, lipoproteins and apolipoproteins were also measured. RESULTS In both groups there were significant reductions in fasting glucose, insulin and C-peptide. Pancreatic insulin secretion during the IVGTT was increased by treatment (ranging from 45% to 92%, P < 0.01). Insulin elimination was increased at both the peripheral (16% to 43%, P < 0.05) and hepatic (18% to 31%, P < 0.05) levels. Insulin sensitivity was unaffected. Low density lipoprotein (LDL) cholesterol was reduced and high density lipoprotein (HDL) cholesterol increased with treatment. CONCLUSIONS Postmenopausal hormone therapy with oestradiol plus dydrogesterone can favourably affect lipoprotein concentrations and can reverse menopause-associated changes in insulin secretion and elimination.
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10.
Comparison of the effect of oral and transdermal hormone therapy on fasting and postmethionine homocysteine levels.
Cagnacci, A, Malmusi, S, Zanni, AL, Alessandrini, C, Caretto, S, Volpe, A
Fertility and sterility. 2004;(1):99-103
Abstract
OBJECTIVE To compare the modifications on basal and post-methionine homocysteine (Hcy) levels induced by transdermal vs. oral continuous combined hormone therapy (HT). DESIGN Prospective randomized study. SETTING Outpatient service at university hospital. PATIENT(S): Twenty-four healthy postmenopausal women. INTERVENTION(S): Six-month administration of transdermal (50 microg/d of E(2) and 140-170 microg/d of norethisterone [NET] acetate; n = 12) or oral (2 mg of E(2) and 1 mg of NET acetate; n = 12) HT. MAIN OUTCOME MEASURE(S): Fasting levels of Hcy, cysteine (Cys), folate, and vitamin B12. Post-methionine Hcy concentrations. RESULT(S): During HT, a slight decrease of fasting Hcy (8.9 [6.7; 15.2] micromol/L vs. 8.3 [4.9; 12.0] micromol/L) and fasting Hcy/Cys, a possible index of Hcy trans-sulfuration (0.061 [0.039; 0.107] micromol/L vs. 0.048 [0.032; 0.093] micromol/L) was observed. Modifications were similar in the transdermal and oral group. Net decreases of Hcy and Hcy/Cys observed during HT were related linearly to pretreatment values (r = 0.821 and r = 0.775, respectively), and were significant for Hcy above, but not below, 9 micromol/L. Transdermal (33.5 [27.5; 75.9] micromol/L vs. 28.4 [17.4; 48.9] micromol/L) or oral HT (36.1 [17.7; 74.8] micromol/L vs. 29.9 [17.5; 50.3] micromol/L), decreased, similarly, post-methionine Hcy levels. CONCLUSION(S): Similarly to oral, transdermal HT reduces post-methionine Hcy and fasting Hcy when it is elevated.