Effect of hormone replacement therapy,tibolone and raloxifene on serum lipids,apolipoprotein A1, apolipoprotein B and lipoprotein(a) in Greek postmenopausal women

The aim of this study was to assess the effect of estrogen, two regimens of continuous combined hormone replacement therapy (HRT), tibolone and raloxifene on serum lipid, apolipoprotein A1 and B and lipoprotein(a) levels in Greek postmenopausal women. A total of 350 postmenopausal women were studied in a prospective open design. Women were assigned to one of the following regimens depending on the presence of risk factors for osteoporosis, climacteric symptoms and an intact uterus: conjugated equine estrogen 0.625 mg (CEE, n=34), continuous combined CEE 0.625 mg plus medroxyprogesterone acetate (MPA) 5 mg, (n=80), continuous combined 17β-estradiol 2 mg plus norethisterone acetate (NETA) 1 mg (n=58), tibolone 2.5 mg (n=83) and raloxifene HCl 60 mg (n=50). Forty-five postmenopausal women with no indications for HRT served as controls. Total cholesterol (TC), low-density lipoprotein (LDL) cholestrol and high-density lipoprotein (HDL) cholesterol, triglyceride (TG), apolipoprotein A1 (ApoA₁), apolipoprotein B (ApoB) and lipoprotein(a) (Lp(a)) levels were assessed in each subject at baseline, and at 6 and 12 months of therapy. All therapy regimens lowered TC levels compared to baseline (4.2-8.0% decrease). This effect was more prominent in the subgoup of women with high baseline TC levels (9.1-20.4% decrease). LDL cholesterol decreased significantly in CEE, CEE/MPA and raloxifene groups (?11.2%, ?11.9% and ?11.0%, respectively). Hypercholesterolemic women exhibited a steeper decrease in LDL cholesterol (10.6-27.8% in all therapy groups). TG levels increased significantly in the CEE and CEE/MPA groups (23.7% and 21.8%, respectively), while estradiol/NETA had no effect on TG levels. Tibolone decreased TG levels markedly, by 20.6%, while raloxifene had no TG-lowering effect. HDL cholesterol and ApoA₁ were increased by CEE and CEE/MPA (HDL cholesterol, 7.4% and 11.8%, respectively; ApoA₁, 17.8% and 7.9%, respectively) and decreased by tibolone (HDL cholesterol, ?13.6%; and ApoA₁, ?9.9%). All therapy regimens except raloxifene lowered Lp(a) levels, with tibolone having the more pronounced effect (?13.2 to ?29.0%). In conclusion, each therapy regimen had a different effect on lipid-lipoprotein levels, exerting favorable and unfavorable modifications. Hypercholesterolemic women seemed to benefit more from the cholesterol-lowering effect of estrogen replacement therapy/HRT. The choice for a particular regimen should be based on individual needs, indications and lipid-lipoprotein profile.     

The effect of hormone replacement therapy on the levels of serum lipids, apolipoprotein AI, apolipoprotein B and lipoprotein (a) in Turkish postmenopausal women

Objectives Estrogen replacement therapy alters the lipid profiles favorably for delaying atherosclerosis in postmenopausal women. The effects of estrogen plus progesterone combination therapy on lipids are controversial. This study was designed to evaluate the effect of female sex hormones on lipids and lipoproteins and to clarify the influence of progesterone on the effect of estrogen in postmenopausal women.Methods Of the 60 postmenopausal women admitted to our menopause clinic, 40 had intact uterus and received continuous 0.625 mg conjugated equine estrogen (CEE) plus 2.5 mg medroxyprogesterone acetate (MPA), whereas the remaining 20 were hysterectomized and received 0.625 mg CEE daily. To assess the alterations in lipids and lipoproteins during menopause, 45 healthy premenopausal women were investigated. Lipid and lipoprotein levels were assessed in each subject at baseline and at the 6th and 18th months of therapy.Results In menopause, a shift towards more atherogenic lipid and lipoprotein profiles than those of the premenopausal state was found. Following 18 months of treatment, both regimens reduced total cholesterol (TC) levels as compared with the baseline (6.4 vs. 6.9% in the CEE/MPA and CEE groups, respectively). The CEE group had a more pronounced increase in high-density lipoprotein (HDL) cholesterol than the CEE/MPA group (10.3 vs. 8.8%, respectively). Both groups displayed reduced TC, low-density lipoprotein (LDL) cholesterol and apolipoprotein-B (ApoB) concentrations, whereas triglycerides increased, with a greater tendency to increase in the CEE/MPA group at the end of the trial. Also, the lipoprotein (a) [Lp(a)] levels decreased significantly (27.6 vs. 24.5% in the CEE/MPA and CEE groups, respectively). This decrease was more pronounced in subjects with a relatively higher basal Lp(a) concentration.Conclusion Both treatment regimens caused positive alterations in the lipid and lipoprotein profiles. This association might play a pivotal role in the postmenopausal increases in atherosclerotic diseases and cardioprotective effect of estrogen in postmenopausal women.     

激素替代治疗对绝经后妇女血清脂蛋白(a)的影响

目的 探讨戊酸雌二醇和倍美力对心血管疾病独立危险因子脂蛋白(a)[Lp(a)]的影响。方法 60例绝经后病例,按1:1随机分成两组,行连续序贯方案治疗,其中倍美力组30例口服结合雌激素0.625mg/d加醋酸甲孕酮4mg/d;戊酸雌二醇组30例口服戊酸雌二醇1mg/d加醋酸甲孕酮4mg/d。两组均连续治疗16周,于用药前、用药9周、16周取血测定血Lp(a),同时测血雌二醇水平。结果 两组用药后9周和16周Lp(a)均显著下降(P<0.01);两组间用药各时相Lp(a)水平差异无显著性(P>0.05)。两组用药前后E_2水平均显著升高(P<0.01),达正常月经周期早卵泡期水平。结论 激素替代治疗可使心血管疾病独立危险因子Lp(a)降低。     

Effect of hormone replacement therapy and tibolone on serum total homocysteine levels in postmenopausal women

OBJECTIVE: To assess the effect of continuous combined hormone replacement therapy (HRT) or tibolone on serum total homocysteine (tHcy) levels in postmenopausal women. STUDY DESIGN: Ninety-five postmenopausal women aged 41-68 years were included in the study. Seventy-three women with climacteric complaints, osteopenia or osteoporosis received either conjugated equine estrogens 0.625 mg combined with medroxyprogesterone acetate 5 mg (CEE/MPA, n=31) or tibolone 2.5 mg (n=42). Twenty-two healthy women, matched for chronological and menopausal age, served as controls. Serum tHcy levels were assessed at baseline, 6, 12 and 18 months. RESULTS: No difference was recorded between groups regarding demographic characteristics or mean baseline serum tHcy. Serum tHcy levels decreased significantly in the CEE/MPA compared to baseline (change at 18 months: -3.9%, P<0.05). The magnitude of the decrease was higher in the subgroup of women with baseline tHcy levels above the median (change at 18 months: -15.0%, P<0.01). No change in tHcy levels was detected in the tibolone group throughout the study period, either in the whole group (change at 18 months: 1.9%, NS) or in the subgroup with baseline tHcy levels above the median (change at 18 months: -3.23%, NS). CONCLUSION: Continuous CEE/MPA reduces tHcy especially in women with high pretreatment tHcy levels. Tibolone has no effect on serum tHcy levels at least during the first 18 months of therapy. Larger studies with longer follow-up are required to confirm these results.     

Effect of hormone therapy and raloxifene on serum VE-cadherin in postmenopausal women

OBJECTIVE: To investigate the effect of continuous combined hormone therapy and raloxifene on serum VE-cadherin. DESIGN: The study was double blinded, with a placebo run-in period of 28-50 days. SETTING: University menopause clinic. PATIENT(S): Twenty-eight healthy postmenopausal women devoid of climacteric complaints. INTERVENTION(S): Subjects were randomized to 17beta-estradiol (2 mg) + norethisterone acetate (1 mg; E(2)-NETA) or raloxifene hCL (60 mg) for a period of 6 months. MAIN OUTCOME MEASURE(S): Serum VE-cadherin, which was estimated at baseline and at month 6. RESULT(S): Serum VE-cadherin decreased significantly in both E(2)-NETA and raloxifene groups (raloxifene baseline +/- SD: 1.17 +/- 0.44 ng/mL, 6 months: 0.82 +/- 0.29 ng/mL; E(2)-NETA baseline: 1.19 +/- 0.47 ng/mL, 6 months: 0.92 +/- 0.49 ng/mL). Percentage changes from baseline were -21.7 +/- 24.3 for E(2)-NETA and -26.0 +/- 20.6 for raloxifene. CONCLUSION(S): The effect of E(2)-NETA and raloxifene suggests that these drugs may preserve interendothelial junction integrity and control vascular permeability. Although this effect may influence the progress of the atheromatous lesion, its clinical impact on coronary artery disease (CAD) remains uncertain.     

Effects of hormone replacement therapy on serum lipids and phospholipids in postmenopausal women.

Hormone replacement therapy (HRT) has been shown to reduce the risk of cardiovascular disease and the beneficial effects may be mediated in part by favourable changes in plasma lipid levels. Evidence exists concerning the effect of combined oestrogen and progestogen on lipids, nevertheless no such evidence can be found on the phospholipid profile, which is important the lipid metabolic pathways. In the present study, involving the serum lipids and lipoproteins, we observed an increase in the concentration of total cholesterol (P < 0.001), HDL-C (P < 0.001), HDL-C (P < 0.001), 2 HDL-C (P < 0.001) and a decrease in the ratio LDL-C/ 3 HDL-C (P < 0.001) in the subjects of Group B (oestrogen plus progestogens) compared with controls (baseline). Also, we found an increased in triglycerides (P < 0.01) and ApoA-1 (P < 0.01) concentrations in the subjects of Group A (oestrogen alone) compared with controls (baseline). With regard to the phospholipids, the main changes observed in their concentrations were: an increase in phosphatidyl choline (P < 0.001) and a decrease in phosphatidyl serine (P < 0.01) for both groups compared with controls. Also, a decrease in phosphatidylinositol (P < 0.01) in Group B compared with controls (baseline). The significance of these results are discussed.     

Decrease of serum endothelin levels with postmenopausal hormone replacement therapy or tibolone.

Endothelin is the most potent vasoconstrictor peptide known to date. Hormone replacement therapy (HRT) with estrogen reduces plasma endothelin levels. We measured endothelin in 51 postmenopausal patients before and during HRT. Patients were randomly allocated to receive either oral tibolone, oral or transdermal 17 beta-estradiol. A group of comparable volunteers served as controls. After 24 months, endothelin levels decreased in all treatment groups: tibolone, 18.2%; oral 23.1%; transdermal, 20.8%. Endothelin levels increased in the controls by 36.6% (p < 0.01). Tibolone decreases endothelin levels to a similar degree as conventional estrogen-progestogen-replacement therapy. These data provide another potential mechanism supporting the cardioprotective effects of tibolone.     

E-cadherin expression in cervical epithelial cells of postmenopausal women: association with hormone therapy, tibolone, and raloxifene

This study assesses the possible associations between postmenopausal therapy (hormone therapy, raloxifene, and tibolone) and E-cadherin expression in normal cervical Papanicolaou smears (squamous, glandular, and metaplastic cells). E-cadherin immunostaining was less intense in metaplastic cells of women on tibolone, whereas hormone therapy and raloxifene were not associated with altered E-cadherin expression.     

Effects of raloxifene, hormone therapy, and soy isoflavone on serum high-sensitive C-reactive protein in postmenopausal women.

OBJECTIVE: To compare the effects of raloxifene, estradiol valerate plus dienogest, and soy isoflavones (genistein) on serum concentrations of high-sensitive C-reactive protein in healthy postmenopausal women. METHODS: The 80 healthy postmenopausal women enrolled in the study were randomly allocated to receive 60 mg of raloxifene, 2 mg of estradiol valerate plus dienogest, 40 mg of genistein, or placebo (n=20 in each group). Blood samples were collected at the start of the study and at 3 and 6 months. Lipid profile was also determined. RESULTS: Only the group receiving estradiol valerate plus dienogest showed an increase in serum levels of high-sensitive C-reactive protein compared with baseline values and values in the control and other groups. All 3 treatments resulted in an increase in high-density lipoprotein cholesterol levels and a decrease in total, low-density, and very-low-density lipoprotein cholesterol levels. CONCLUSIONS: Estradiol valerate plus dienogest, but not raloxifene and genistein, increase serum high-sensitive C-reactive protein levels. All 3 treatments, however, have an estrogen-like effect on serum lipid profile.     

Uterine effects of raloxifene in comparison with continuous-combined hormone replacement therapy in postmenopausal women

OBJECTIVE: We sought to compare the uterine effects of raloxifene with those of continuous-combined hormone replacement therapy. STUDY DESIGN: This randomized, double-blind 24-month study involved 136 postmenopausal women who received raloxifene 150 mg/d or conjugated equine estrogens 0.625 mg/d with medroxyprogesterone acetate 2.5 mg/d. After baseline evaluations, endometrial biopsy specimens were obtained, and endometrial thickness was measured annually by means of transvaginal ultrasonography. Statistical analyses were performed with an intention-to-treat approach. RESULTS: In the raloxifene group at the end point of the study 94.4% of biopsy specimens showed normal benign postmenopausal endometrium and 5.6% were classified as benign stimulatory endometrium. In the continuous-combined hormone replacement therapy group at the end point of the study 78.7% of biopsy specimens showed normal benign postmenopausal endometrium, 19. 1% were classified as benign stimulatory endometrium, and 2.1% showed benign abnormal postmenopausal endometrium. Mean endometrial thickness was unchanged from baseline with raloxifene and was increased significantly by 0.5 mm at 12 months with continuous-combined hormone replacement therapy. CONCLUSION: Raloxifene 150 mg/d did not increase endometrial thickness or cause endometrial proliferation in healthy postmenopausal women.     

Effect of hormone replacement therapy on glucose tolerance in postmenopausal women.

Oral glucose tolerance tests were performed on 50 symptomatic postmenopausal women before and after three months of hormone replacement therapy. All patients were randomly allocated to one of five groups treated with various synthetic or so-called naturally occurring oestrogens. Therapy produced a significant deterioration of carbohydrate tolerance with sequential preparations containing 100 microgram of ethinyl oestradiol or graduated doses of mestranol up to 50 microgram. The conjugated equine oestrogen (1.25 mg daily) and oestrogen valerate (2 mg daily) treated groups did not show abnormal glucose tolerance. The decreased glucose tolerance may be due as much to dosage levels as to any metabolic characteristics of the various oestrogens prescribed.     

Cost-effectiveness of raloxifene and hormone replacement therapy in postmenopausal women: impact of breast cancer risk.

OBJECTIVE: To examine the life expectancy and cost-effectiveness of hormone replacement therapy (HRT) and raloxifene therapy in healthy 50-year-old postmenopausal women. METHODS: We performed a cost-effectiveness analysis using a Markov model, discounting the value of future costs and benefits to account for their time of occurrence. RESULTS: Both HRT and raloxifene therapy increase life expectancy and are cost-effective relative to no therapy for 50-year-old postmenopausal women. For women at average breast cancer and coronary heart disease risk, lifetime HRT increases quality-adjusted life expectancy more (1.75 versus 1.32 quality-adjusted life years) and costs less ($3802 versus $12,968) than lifetime raloxifene therapy. However, raloxifene is more cost-effective than HRT for women at average coronary risk who have a lifetime breast cancer risk of 15% or higher or who receive 10 years or less of postmenopausal therapy. Raloxifene is also the more cost-effective alternative if HRT reduces coronary heart disease risk by less than 20%. CONCLUSIONS: Assuming the benefit of HRT in coronary heart disease prevention from observational studies, long-term HRT is the most cost-effective alternative for women at average breast cancer and coronary heart disease risk seeking to extend their quality-adjusted life expectancy after menopause. However, raloxifene is the more cost-effective alternative for women at average coronary risk with one or more major breast cancer risk factors (first-degree relative, prior breast biopsy, atypical hyperplasia or BRCA1/2 mutation). These results can help inform decisions about postmenopausal therapy until the results of large scale randomized trials of these therapies become available.     

Circulating levels of atherogenesis-associated adipocytokines and apoptotic markers are differentially influenced by hormone therapy, tibolone and raloxifene in healthy postmenopausal women.

OBJECTIVE: Estrogen agonist compounds may exert cardioprotective activity by modulating adipocytokine concentration and apoptosis. The objective of this study was to evaluate the effects of hormone therapy, tibolone and raloxifene on the serum adipocytokines resistin and adiponectin as well as on circulating markers of receptor-mediated apoptosis. Design Randomized, open-label, intervention study in the Menopause Clinic of a University Hospital. METHODS: One hundred healthy postmenopausal women were randomized to the following groups: conjugated equine estrogens 0.625 mg (CEE) (n = 16); 17 beta-estradiol 1 mg plus norethisterone acetate 0.5 mg (E(2)/NETA) (n = 15); tibolone 2.5 mg (n = 18); raloxifene HCl 60 mg (n = 20); and no treatment (n = 19). Eighty-eight women completed the 3-month study period. Main outcome measures were levels of serum adiponectin, resistin, soluble Fas and Fas ligand. RESULTS: Levels of serum adiponectin decreased significantly in the tibolone group (baseline: 10 556.7 +/- 4213.5 ng/ml; 3 months: 7856.3 +/- 3450.7 ng/ml; p = 0.0001) and increased in the CEE group (baseline: 9268.1 +/- 5158 ng/ml; 3 months: 11 302.6 +/- 4980.9 ng/ml; p = 0.01). Serum resistin values increased only in the tibolone group (baseline: 2.81 +/- 0.89 ng/ml; 3 months: 3.55 +/- 1.31 ng/ml; p = 0.04), while the level of Fas ligand decreased significantly in the E2/NETA (baseline: 70.4 +/- 21.9 pg/ml; 3 months: 62.1 +/- 18.6 pg/ml; p = 0.02) and tibolone group (baseline: 68.2 +/- 25.7 pg/ml; 3 months: 59.2 +/- 21.7 pg/ml; p = 0.01). CONCLUSIONS: Of the regimens investigated, only unopposed estrogens may exert an atheroprotective effect through the increase of adiponectin and a resultant favorable lipid and anti-inflammatory profile.     

Effect of hormone replacement therapy on lipids and left ventricular function in postmenopausal smokers.

OBJECTIVE: Menopause and smoking have negative effects on the cardiovascular system. The study was planned to investigate the influence of oral hormone replacement therapy (HRT) on heart function and lipids in postmenopausal smokers. METHODS: Lipid levels and left ventricular systolic and diastolic function by means of echocardiography were assessed before entering the study and at 6-month intervals during the 12 months of oral HRT in 62 postmenopausal women, 30 of whom were smokers and 32 were non-smokers. RESULTS: Oral HRT caused a significant decrease in levels of total cholesterol and low density lipoprotein (LDL) cholesterol and a significant increase in high density lipoprotein (HDL) cholesterol in non-smokers. This effect was not evident in smokers. Echocardiography revealed a significant improvement of systolic function (ejection fraction, left ventricular outflow tract velocity, forward velocity integral, acceleration time and mean systolic acceleration) and diastolic function (diastolic time, duration of the early filling phase, peak velocity of early mitral flow, and the ratio of late to early peak mitral flow) in non-smokers. In smokers, a significant increase in some parameters of systolic function (ejection fraction, acceleration time and mean systolic acceleration) and an insignificant change in diastolic function were observed. Oral HRT of 12 months' duration has very limited beneficial effects on CONCLUSION: lipids and left ventricular heart function in postmenopausal women who smoke.     

Effect of hormone replacement therapy and calcitonin on bone mass in postmenopausal women.

A total of 104 postmenopausal women were randomly assigned to different therapeutic regimens: (a) calcitonin, (b) estrogen/progestogen (HRT) plus calcitonin, (c) estrogen/progestogen (HRT), (d) and the control group. The bone mass of the lumbar vertebrae of all patients was assessed with a dual beam photon absorptiometer (Norland GD 153). The 73 patients who completed the 1-yr study showed that postmenopausal bone loss could be prevented by either estrogen/progestogen (HRT) or calcitonin. In addition, the combination of hormonal replacement therapy and calcitonin not only prevented post-menopausal bone loss but resulted in a significant 10% gain in bone mass (P < 0.001).     

绝经后妇女激素补充治疗后同型半胱氨酸及超声心动图改变的初步观察

目的　观察绝经后妇女激素补充治疗 (HRT)后血浆总同型半胱氨酸 [H(e) ]及超声心动图的改变。方法　将受试者分为 4组。Ⅰ组、Ⅱ组为自然绝经妇女 ,各 30例 ,其中Ⅰ组给予HRT(结合雌激素 0 6 2 5mg d ,安宫黄体酮 2mg d ,或者每月后 14d加安宫黄体酮 4mg d) 3个月 ;Ⅱ组不给予HRT ,为对照 ;Ⅲ组 2 0例 ,为已接受HRT1 5年的绝经后妇女 ;Ⅳ组 2 0例 ,为从未应用HRT的绝经后妇女。Ⅰ组、Ⅱ组受试者于接受HRT前及接受HRT 3个月后测定H(e) ;Ⅲ组、Ⅳ组受试者测定H(e) ,并行超声心动图检查。结果　Ⅰ组、Ⅱ组接受HRT 3个月前后H(e)无明显变化 ,Ⅰ组接受HRT前为(9 3± 2 5 ) μmol L ,Ⅱ组为 (9 4± 2 9) μmol L ;Ⅰ组接受HRT后H(e)为 (9 1± 2 8) μmol L ,Ⅱ组为(9 8± 3 6 ) μmol L。两组比较 ,差异无显著性 (P >0 0 5 )。Ⅲ组H(e)明显低于Ⅳ组 ,分别为 (8 0±1 3) μmol L及 (10 3± 3 2 ) μmol L。两组比较 ,差异有显著性 (P <0 0 5 )。Ⅲ组、Ⅳ组的超声心动图检查结果无明显改变。结论　短期应用HRT对H(e)无明显改善 ,长期应用HRT可降低H(e)水平。绝经后妇女应用HRT 1 5年 ,未见超声心动图有明显变化。     

Effects of tibolone on thromboxane B(2) levels in postmenopausal women.

This study was carried out in 16 premenopausal (control) and 24 postmenopausal women (study group) to investigate the effect of menopause and tibolone treatment (2.5 mg/day for 6 months) on plasma thromboxane B(2) (TxB(2)), a well-known vasoconstrictor and stimulator of platelet aggregation. The TxB(2) levels were measured using [(125)I] RIA kit. Statistical significance was analyzed by Student's t test for paired and unpaired data, and Pearson's correlation analysis. Plasma TxB(2) concentrations of postmenopausal women were higher than those of premenopausal women. Tibolone treatment decreased plasma TxB(2) in postmenopausal women. There was no correlation between TxB(2) and blood pressure and heart rate. It was concluded that tibolone, decreasing the plasma concentrations of TxB(2), might have beneficial effects on prostaglandin metabolism and thus reduce the risk of cardiovascular disease.