LycoRed as an alternative to hormone replacement therapy in lowering serum lipids and oxidative stress markers: a randomized controlled clinical trial

AIM: Menopause is a pro-atherogenic state with a sharp rise in the incidence of coronary artery disease. This pilot study was designed as an equivalence randomized clinical trial to explore the potential of LycoRed (containing 2000 microg lycopene) as an alternative to hormone replacement therapy (HRT) for the prevention of coronary artery disease in postmenopausal women. METHODS: Forty-one healthy postmenopausal women were randomly allocated to receive either continuous combined HRT (n = 21) or LycoRed (n = 20) for six months. Serum lipid profile, marker of lipid peroxidation (malondialdehyde), and the level of endogenous antioxidant (glutathione) were measured at the baseline, and 3 and 6 months after the intervention in both groups. RESULTS: At 6 months, HRT resulted in a significant decrease in total cholesterol (TC) level by 23.5%, low-density lipoproteins (LDL) by 19.6%, and an increase in high-density lipoproteins (HDL) by 38.9%. The LycoRed group showed similar changes in TC (-24.2%), LDL (-14.9%) and HDL (+26.1%). Triglyceride levels showed a smaller though significant increase at 6 months, but not at 3 months, in both groups. There was no significant change in the very LDL (VLDL) level in either group. Malondialdehyde levels decreased significantly by 16.3% and 13.3%, whereas glutathione levels increased significantly by 5.9% and 12.5% in HRT and LycoRed groups, respectively. CONCLUSION: Both HRT and LycoRed had a favorable effect on serum lipids and oxidative stress markers which were comparable. LycoRed can be used as an alternative to HRT to reduce the risk of atherosclerosis in postmenopausal women.     

Lipid and lipoprotein changes associated with oral contraceptive use: a randomized clinical trial

To determine the effects of oral contraceptives on lipids and lipoproteins over a six-month period, we randomized 266 women into four oral contraceptive groups: ethinyl estradiol 35 micrograms plus ethynodiol diacetate 1 mg, ethinyl estradiol 30 micrograms plus levonorgestrel 0.15 mg, ethinyl estradiol 35 micrograms plus norethindrone 1 mg, and ethinyl estradiol 35 micrograms plus norethindrone 0.5 and 1 mg (biphasic). For all groups, total cholesterol increased 5.9-9.1% from baseline values over the six months. Triglycerides increased with all preparations, with the ethynodiol diacetate group (37.6%) and the biphasic norethindrone group (45.3%) showing the greatest increase. Low-density lipoprotein cholesterol increased 10-15.6% among the groups; low-density lipoprotein-apolipoprotein B changed proportional to the low-density lipoprotein cholesterol increases. All groups except the ethynodiol diacetate group showed a decrease of high-density lipoprotein cholesterol, with the levonorgestrel group (8.7%) and biphasic norethindrone group (4.5%) showing the largest declines. Apolipoprotein A-1 increased in all groups, with the ethynodiol diacetate preparation (19.3%) showing the greatest increase and the levonorgestrel preparation (3.2%) showing the smallest increase from baseline values. The changes in apolipoprotein A-1 were out of proportion to the changes in high-density lipoprotein cholesterol, suggesting that the high-density lipoprotein particle may be undergoing some type of metabolic alteration.     

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.     

Effect of conjugated equine estrogen in combination with two different progestogens on the risk factors of coronary heart disease in postmenopausal Chinese women in Taiwan: a randomized one-year study

BACKGROUND: To compare the effect of hormone replacement therapy (HRT) using estrogen plus dydrogesterone or estrogen plus medroxyprogesterone acetate (MPA) on the risk factors for coronary heart disease (CHD) in postmenopausal women. METHODS: A randomized, prospective 1-year clinical trial was designed. All of the postmenopausal women (n = 279) received sequential conjugated equine estrogen (CEE) at a dose of 0.625 mg/day for 25 days (days 1-25) of each month. These women were also randomly assigned to receive either dydrogesterone 10 mg/day (E + D group, n = 140) or MPA 5 mg/day (E + P group, n = 139) for 14 days (days 12-25) of each month. Serum biochemical markers, lipoproteins, plasma prothrombin time (PT), partial prothrombin time (PPT) and antithrombin III-antigen (ATIII-Ag) were analyzed at baseline, and after 6 and 12 months of treatment. RESULTS: Liver function, renal function, PT and PPT did not change significantly during the 12-month trial. The E + D group had a more pronounced increase in high density lipoprotein cholesterol (HDL-C) than the E + P group (10.6% vs. 2.7%) after 12 months of treatment (p < 0.05). Both groups showed reduced concentrations of total cholesterol (T-CHO), low density lipoprotein cholesterol (LDL-C) and ATIII, whereas triglyceride (TG) was increased at the end of the trial (without intergroup difference). CONCLUSIONS: Our study demonstrated a favorable effect on lipoprotein profiles with both hormone replacement therapy regimens. Dydrogesterone appears to be superior to medroxyprogesterone acetate from the perspective of modification of coronary heart disease risk factors.     

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 raloxffene 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, dimacteric 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 17beta-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 diferent 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.     

Treatment-induced cyclic variations in serum lipids, lipoproteins, and apolipoproteins after 2 years of combined hormone replacement therapy: exaggerated cyclic variations in smokers.

OBJECTIVE: To study the long-term effect of cigarette smoking on cyclic variations in serum lipids, lipoproteins, and apolipoproteins following combined hormone replacement therapy. METHODS: One hundred eighteen healthy, early postmenopausal women were followed for 2 years in a randomized, placebo-controlled study. Four treatment groups received estradiol, either sequentially combined with levonorgestrel (75 micrograms), medroxyprogesterone acetate (10 mg), or desogestrel (150 micrograms), or continuously combined with cyproterone acetate (1 mg). Two groups received placebo. Serum lipids, lipoproteins, and apolipoproteins were measured at well-defined times. Information on smoking habits was elicited by questionnaire. RESULTS: We found statistically significant cyclic variations in apolipoprotein A1 in the levonorgestrel group (6.7%; 95% confidence interval [CI] 1.1-12.7%) and the desogestrel group (7.4%; 95% CI 2.9-12.1%). The cyclic variations in high-density lipoprotein (HDL) cholesterol were highly statistically significant in the levonorgestrel group (24.9%; 95% CI 10.2-39.2%). When women from sequential regimens were combined, further analysis showed that smokers had significantly larger cyclic variations in HDL cholesterol (P less than .01) and apolipoprotein A1 (P less than .05) than non-smokers. CONCLUSIONS: Sequentially combined hormone replacement therapy produces cyclic variations in HDL cholesterol and apolipoprotein A1 for at least 2 years. In addition, cigarette smoking is associated with an exaggeration of the cyclic effect of treatment on these indices.     

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.     

Comparison of the effects of raloxifene and low-dose hormone replacement therapy on bone mineral density and bone turnover in the treatment of postmenopausal osteoporosis.

OBJECTIVE: The aim of the present study was to compare the effects of raloxifene and low-dose hormone replacement therapy (HRT) on bone mineral density (BMD) and bone turnover markers in the treatment of postmenopausal osteoporosis. METHODS: Forty-two postmenopausal osteoporotic women, who were randomized to receive raloxifene 60 mg or estradiol 1 mg/norethisterone acetate 0.5 mg daily for 1 year, were studied. All women received calcium 600 mg/day and vitamin D 400 IU/day. BMD and markers of bone turnover were measured at baseline and at 12 months. RESULTS: After 12 months of treatment, there were statistically significant increases in BMD in both groups at all sites (all p < 0.05). For the lumbar spine, the increase in BMD was 2.3% for raloxifene compared with 5.8% for low-dose HRT and corresponding values for total body BMD were 2.9% for raloxifene and 4.6% for low-dose HRT; the increases being significantly greater in the low-dose HRT group (p < 0.001 and p = 0.02, respectively). Although the increase in BMD at the hip was significant for both raloxifene (2.1%) and low-dose HRT (3.2%) compared with baseline, the difference between the two regimens did not reach statistical significance. The decrease in serum C-terminal telopeptide fragment of type I collagen and serum osteocalcin levels for the low-dose HRT group (-53% and -47%, respectively) was significantly greater than for the raloxifene group (-23% and -27%, respectively; both p < 0.01). CONCLUSIONS: In postmenopausal women with osteoporosis, low-dose HRT produced significantly greater increases in BMD of the lumbar spine and total body and greater decreases in bone turnover than raloxifene at 12 months.     

The short-term effects of different regimens of hormone replacement therapy on left ventricular structure and performance in healthy postmenopausal women. A prospective,controlled echocardiographic study

OBJECTIVE: To compare the short-term effects of different hormone replacement therapy (HRT) regimens on left ventricular structure and function in healthy postmenopausal women. METHODS: Forty-two apparently healthy postmenopausal women were evaluated prospectively in this controlled study. Subjects were divided into 4 groups. Ten subjects, who did not accept HRT or any other treatments, formed the control group. The remaining subjects were assigned to receive oral estradiol (2 mg/day) + norethisterone acetate (1 mg/day) (n = 11), transdermal estradiol (0.05 mg) + norethisterone acetate (0.25 mg) (n = 11) or tibolone (2.5 mg/day) (n = 10) therapy during 12 weeks. Echocardiography and Doppler techniques were used to assess the cardiac effects of different HRT regimens. RESULTS: After 12 weeks of treatment, there were significant increases in left ventricular ejection fraction (transdermal group: p = 0.008, oral group: p = 0.003, tibolone group: p = 0.005) and cardiac output (transdermal group: p = 0.003, oral group: p = 0.003, tibolone group: p = 0.021) in all treatment groups. In addition, in the transdermal group, a slight increase in left ventricular end-diastolic volume was significant (p = 0.046). CONCLUSION: These data suggest that oral and transdermal HRT regimens and tibolone may contribute to the improvement in left ventricular systolic function without having an effect on left ventricular structure after short-term administration in healthy postmenopausal women.     

Assessment of the metabolic tolerance in postmenopausal women over a 1-year period of two hormone replacement therapies containing estradiol in combination with either norgestrel or trimegestone

This double-blind, randomized, multi-center study compared the metabolic tolerance of a combined formulation containing estradiol (E2) and trimegestone (TMG) with a standard hormone replacement therapy (HRT) containing estradiol valerate (EV) and norgestrel (NG). Blood lipids, glucose and fibrinogen concentrations were measured in the study which was conducted over 13 cycles, each of 28 days, and included 634 subjects in two randomized groups. A total of 481 subjects completed the study. The circulating concentrations of high density lipoprotein (HDL), HDL2, HDL3 cholesterol and apolipoprotein A1 were increased in the E2 + TMG group and reduced in the EV + NG group. Total cholesterol, low density lipoprotein (LDL) cholesterol, apolipoprotein B and lipoprotein(a) concentrations were decreased in both treatment groups; however, the reduction in LDL cholesterol was greater in the E2 + TMG group. Similar lipid findings were found in a subgroup that excluded subjects who had less than 3 months washout from a previous HRT, who provided a blood sample outside the day 17-28 window, or who were taking beta-blockers or thiazide diuretics. Blood glucose concentrations were reduced slightly in both treatment groups. A significant reduction in fibrinogen was also seen in both groups over the course of the study. The changes in lipid profile, especially HDL cholesterol, were more beneficial in the E2 + TMG group in comparison with the EV + NG group. This reflects the lack of androgenic action of trimegestone in comparison with norgestrel, which exhibits an androgenic effect and prevents the estrogen-induced increase in HDL cholesterol. The results of the study suggest that the use of trimegestone in combination with E2 may be preferable to norgestrel because of the more favorable lipid profile.     

Assessment of the metabolic tolerance in postmenopausal women over a 1-year period of two hormone replacement therapies containing estradiol in combination with either norgestrel or trimegestone.

This double-blind, randomized, multi-center study compared the metabolic tolerance of a combined formulation containing estradiol (E2) and trimegestone (TMG) with a standard hormone replacement therapy (HRT) containing estradiol valerate (EV) and norgestrel (NG). Blood lipids, glucose and fibrinogen concentrations were measured in the study which was conducted over 13 cycles, each of 28 days, and included 634 subjects in two randomized groups. A total of 481 subjects completed the study. The circulating concentrations of high density lipoprotein (HDL), HDL2, HDL3 cholesterol and apolipoprotein A1 were increased in the E2 + TMG group and reduced in the EV + NG group. Total cholesterol, low density lipoprotein (LDL) cholesterol, apolipoprotein B and lipoprotein(a) concentrations were decreased in both treatment groups; however, the reduction in LDL cholesterol was greater in the E2 + TMG group. Similar lipid findings were found in a subgroup that excluded subjects who had less than 3 months washout from a previous HRT, who provided a blood sample outside the day 17-28 window, or who were taking beta-blockers or thiazide diuretics. Blood glucose concentrations were reduced slightly in both treatment groups. A significant reduction in fibrinogen was also seen in both groups over the course of the study. The changes in lipid profile, especially HDL cholesterol, were more beneficial in the E2 + TMG group in comparison with the EV + NG group. This reflects the lack of androgenic action of trimegestone in comparison with norgestrel, which exhibits an androgenic effect and prevents the estrogen-induced increase in HDL cholesterol. The results of the study suggest that the use of trimegestone in combination with E2 may be preferable to norgestrel because of the more favorable lipid profile.     

A randomized trial of oral contraceptive and hormone replacement therapy on bone mineral density and coronary heart disease risk factors in postmenopausal women

OBJECTIVE: To identify the effects of oral contraceptive (OC) and hormone replacement therapy (HRT) on bone mineral density and coronary heart disease risk factors in postmenopausal women. METHODS: Eighty healthy postmenopausal women were randomly assigned to a cyclic regimen of OC containing 30 microg of ethinyl estradiol and 150 microg of desogestrel or HRT containing 0.625 mg of conjugated equine estrogens 21 days per cycle and 5 mg of medrogestone 10 days per cycle for 12 months. Bone mineral density of lumbar spine and hip, biochemical markers of bone turnover, lipid-lipoprotein profiles, coagulation profiles, fasting plasma glucose, and blood pressure were evaluated. RESULTS: Both regimens caused significant increase in bone mineral density of lumbar spine, trochanter, intertrochanteric region, total hip, and Ward triangle. Only OC therapy was associated with a significant increase in femoral neck bone mineral density (mean score +/- standard error 2.5% +/- 0.7%, P < .01). Biochemical markers of bone turnover, total cholesterol, and low-density lipoprotein cholesterol decreased significantly in both groups. Posttreatment levels of those bone markers and lipid-lipoprotein were significantly lower after OC therapy than HRT. Fasting plasma glucose and systolic blood pressure decreased significantly in both groups; however, only the OC group showed a significant decrease in diastolic blood pressure. CONCLUSION: Both OC and HRT increased bone mineral density of lumbar spine and hip, but OC suppressed bone turnover more than HRT. Both methods favorably affected lipid-lipoprotein metabolism, fasting plasma glucose, and blood pressure during the 12 months of treatment.     

Effects of three low-dose oral contraceptive formulations on lipid metabolism

Three oral contraceptive preparations were studied in 60 healthy women. This randomized, comparative, baseline controlled study was designed to investigate the effects of the preparations on plasma lipids and lipoproteins. The following formulations were studied: a monophasic preparation containing ethinylestradiol and desogestrel (M-DSG) and two triphasic formulations containing ethinylestradiol and gestodene or levonorgestrel respectively (T-GSD and T-LNG). These preparations were studied for six treatment cycles. Total cholesterol and apoprotein B did not change in any group. Low density lipoprotein (LDL) cholesterol was significantly decreased in the groups of women treated with M-DSG and T-GSD respectively. No changes were observed in the T-LNG group. With M-DSG, significant increases were observed in high-density lipoprotein (HDL) cholesterol and HDL3 cholesterol, whilst HDL2 cholesterol did not change. With both T-GSD and T-LNG, no changes were observed in HDL cholesterol, whilst a significant increase in HDL3 cholesterol together with a trend to decrease in HDL2 cholesterol were observed. Apolipoprotein AI increased with the following ranking M-DSG greater than T-GSD greater than T-LNG. The LDL/HDL cholesterol ratio significantly decreased with both M-DSG and T-GSD. In the T-LNG group there was no change in this ratio. Triglycerides increased to the same extent in all treatment groups. As far as concerns the risk of arterial diseases, these three oral contraceptive formulations mostly induced negligible and/or partly favorable changes in plasma lipids and lipoproteins; however, the lipoprotein pattern during M-DSG treatment resulted better than during T-GSD, and the latter turned out to be better than during T-LNG.     

盐酸氟西汀联合激素与单纯激素补充治疗绝经期抑郁症的疗效比较

目的　观察盐酸氟西汀及激素补充治疗 (HRT)用于绝经期抑郁症的疗效。方法　将已绝经并符合抑郁症诊断的患者 5 4例 ,随机分为两组 ,每组 2 7例。盐酸氟西汀联合HRT组 :每 2 8天为1个周期 ,应用结合雌激素 0 6 2 5mg/d与安宫黄体酮 5mg/d ,盐酸氟西汀 2 0mg/d ;单纯HRT组 :每 2 8天为 1个周期 ,应用结合雌激素 0 6 2 5mg/d与安宫黄体酮 5mg/d。两组均治疗 8周。于治疗开始日及治疗第 1、2、3、4、6、8周各随访 1次 ,应用汉密尔顿抑郁量表 (HAMD)评价抑郁症程度 ,应用Kupperman绝经指数 (KMI)评价绝经期症状。结果　治疗前HAMD评分 ,盐酸氟西汀联合HRT组与单纯HRT组分别为 (2 3± 5 )分和 (2 4± 5 )分 ,两组比较 ,差异无显著性 (P >0 0 5 )。治疗第 3周 ,盐酸氟西汀联合HRT组为 (10± 6 )分 ,与治疗前比较 ,差异有极显著性 (P <0 0 0 1) ;单纯HRT组为 (15± 7)分 ,与治疗前比较 ,差异有显著性 (P <0 0 5 ) ;但两组治疗后比较 ,差异无显著性 (P >0 0 5 )。治疗 3周后 ,两组HAMD评分比较 ,差异有显著性 (P <0 0 5 )。至治疗第 8周HAMD评分 ,盐酸氟西汀联合HRT组与单纯HRT组分别为 (3± 2 )分和 (11± 6 )分 ,两组比较 ,差异有极显著性 (P <0 0 0 1)。治疗前KMI评分 ,盐酸氟西汀联合HRT组与单纯HRT     

Resistance of pelvic arteries and plasma lipids in postmenopausal women: comparative study of tibolone and continuous combined estradiol and norethindrone acetate replacement therapy

OBJECTIVE: We sought to compare vascular resistance and plasma lipids in postmenopausal women assigned to tibolone (a synthetic estrogen replacement steroid) therapy or continuous combined hormone replacement therapy. STUDY DESIGN: Pulsatility and resistance indexes in pelvic arteries (color Doppler transvaginal ultrasonography) and lipids were monitored in this double-blind 1-year trial of 100 women randomized to either 2.5 mg tibolone or 2 mg 17beta-estradiol plus 1 mg norethindrone acetate daily. RESULTS: Both indexes of the arcuate arteries (uterine arteries) were significantly reduced beyond 3 and 6 months (12 months) from baseline, respectively, by the combined regimen compared with tibolone alone. Tibolone increased the resistance index of arcuate arteries but did not affect uterine arteries. There was no effect of either regimen on the internal iliac arteries. The medians of the percentage changes from baseline of high-density lipoprotein cholesterol (triglycerides) were significant between groups after 1 year, as follows: -17% (-16%) in the tibolone group and -4% (+15%) in the combined group, respectively. Both regimens similarly reduced total and low-density lipoprotein cholesterol and lipoprotein Lp(a). CONCLUSION: Hormone replacement therapy may induce different or opposite changes of both vascular resistance and lipids. It is unknown whether these findings may modify cardiovascular risk.     

不同方法治疗围绝经期及绝经后妇女抑郁症的疗效分析

目的 探讨抗抑郁药物及性激素治疗围绝经期及绝经后妇女抑郁症的临床效果.方法 采用汉米尔顿抑郁量表(HRSD)及自评抑郁量表(SDS)对86例围绝经期及绝经后抑郁症妇女进行抑郁症程度评价,然后随机分为2组,每组43例.对照组应用抗抑郁药物,其中轻、中度(29例)患者应用氟哌噻吨美利曲辛(其他名称:黛力新)1～2片/d;重度患者(14例)应用盐酸氟西汀(其他名称:百忧解)20 mg/d;性激素治疗(HRT)组(轻、中度31例,重度12例)应用替勃龙1.25 mg/d.入选者每4周随访1次,共计12周.结果 (1)有效率:对照组轻、中度抑郁症患者,治疗总有效率为96%;HRT组治疗总有效率为93%.两组比较,差异无统计学意义(P＞0.05).重度抑郁症的治疗有效率对照组为93%,HRT组为42%,两组比较,差异有统计学意义(P＜0.01).(2)HRSD评分:轻、中度抑郁症患者用药前、用药第4、8、12周时,对照组分别为(26.8±5.7)、(10.7±3.6)、(6.4±3.6)、(3.5±2.5)分;HRT组分别为(25.3±4.7)、(15.2±5.3)、(11.4±4.4)、(4.4±3.8)分.两组内治疗后各时间点HRSD评分与治疗前比较,差异均有统计学意义(P＜0.01);对照组与HRT组用药前及用药第12周时HRSD评分比较,差异无统计学意义(P＞0.05).重度抑郁症患者用药前、用药第4、8、12周时,HRSD评分对照组分别为(37.6±5.6)、(21.4±5.2)、(14.2±4.2)、(7.3±2.3)分;HRT组分别为(38.2±4.8)、(32.6±5.4)、(28.2±4.6)、(24.3±4.5)分.对照组内治疗后各时间点比较,差异有统计学意义(P＜0.01),HRT组用药前与用药第12周比较,差异也有统计学意义(P＜0.05).两组用药后各时间点HRSD评分比较,差异有统计学意义(P＜0.01).(3)SDS评分:对照组轻、中、重度患者用药前与用药第4、8、12周各时间点SDS评分比较,差异均有统计学意义(P＜0.01).HRT组轻、中度患者用药前与用药第4、8、12周各时间点SDS评分比较,差异也有统计学意义(P＜0.01);HRT组重度抑郁症患者用药前与用药第12周比较,差异有统计学意义(P＜0.05).在重度抑郁症患者中,对照组用药后HRSD、SDS评分与HRT组比较,明显降低,差异有统计学意义(P＜0.01).结论 HRT可用于治疗围绝经期及绝经后轻、中度抑郁症,对于重度抑郁症患者,抗抑郁药物的治疗效果优于性激素.     

The long-term effects of low-dose 17beta-estradiol and dydrogesterone hormone replacement therapy on 24-h ambulatory blood pressure in hypertensive postmenopausal women: a 1-year randomized, prospective study.

OBJECTIVE: The aim of this study was to assess the long-term effects of low-dose oral hormone replacement therapy (HRT) on 24-h blood pressure in hypertensive postmenopausal women. STUDY DESIGN: In this 12-month, prospective study, 66 postmenopausal women with mild or moderate hypertension were randomly assigned to receive either HRT with 1 mg/day micronized 17beta-estradiol sequentially combined with 10 mg/day dydrogesterone for 14 days of each 28-day cycle, or no therapy. Ambulatory blood pressure measurements were recorded for a 24-h period at baseline and after 12 months of treatment or follow-up. RESULTS: Blood pressure did not differ significantly between the groups at baseline. After 12 months, there were falls in 24-h systolic, diastolic and mean arterial blood pressure in both the HRT and control groups; only the fall in mean arterial blood pressure in the HRT group achieved statistical significance (-2.0 +/- 0.8 mmHg, p < 0.01). While there was no significant decrease in daytime systolic or mean arterial blood pressure in either group, a significant decrease in diastolic blood pressure (-1.8 +/- 10 mmHg, p < 0.001) was observed in the HRT group. Night-time systolic and mean arterial blood pressure also decreased significantly (p < 0.001) in the HRT group (-3.0 +/- 1.5 mmHg and -2.2 +/- 0.6 mmHg, respectively), but no significant change was observed in the control group. Conclusion: Low-dose oral HRT caused significant falls in both daytime and night-time ambulatory blood pressure in postmenopausal women with mild or moderate hypertension.     

The influence of medroxyprogesterone acetate on the effects of transdermal oestradiol replacement therapy on plasma lipids.

A prospective study was carried out on 82 healthy menopausal women to determine whether or not there is an attenuation of the cardioprotective effects of continuous transdermal oestradiol on plasma lipid and lipoprotein concentrations with the use of sequential oral medroxyprogesterone acetate. Group 1 comprised 51 hysterectomised women on transdermal oestradiol (50 microg daily). Group 2 included 31 women with an intact uterus on oestradiol (50 microg daily) and medroxyprogesterone acetate (10 mg daily for the first 12 days of each calendar month). Women maintained on 50 microg throughout 6 months (group 1: n = 29; group 2: n = 20) were reviewed for changes in plasma lipids and lipoproteins at the end of 6 months (group 1), and in the combined phase of treatment in the seventh month (group 2). In group 1, there was a reduction in the concentrations of total cholesterol (- 6.3%, P = 0.004) and LDL-cholesterol (- 6.1%, P = 0.05). In group 2, there were no significant changes in total cholesterol (- 4.8%, P = 0.23) and LDL-cholesterol (- 5.8%, P = 0.30). HDL-cholesterol levels did not change significantly with unopposed oestradiol (+ 3.8%, P = 0.30), or with additional medroxyprogesterone acetate (0%, P = 0.94). Serum triglyceride concentrations decreased significantly in both the groups (- 14.3%, P = 0.001, and- 12.8%, P = 0.006, respectively). There were no statistically significant differences in the changes in the respective plasma lipid parameters on comparing the two treatment groups (P > 0.4 for all comparisons, Student's t -tests). The plasma lipid and lipoprotein profile encountered at the end of 6 months, was also generally maintained in 24 women (group 1: n = 13; group 2: n = 11) who completed 1 year of the study. Transdermal oestradiol may be of particular clinical benefit for women with hypertriglyceridaemia. Medroxyprogesterone acetate did not exert a significantly adverse influence on plasma lipid and lipoprotein concentrations.     

A comparison of continuous combined hormone replacement therapy, HMG-CoA reductase inhibitor and combined treatment for the management of hypercholesterolemia in postmenopausal women.

OBJECTIVE: To compare the lipid-altering effects of hormone replacement therapy alone and in combination with HMG-CoA reductase inhibitor in postmenopausal women with hypercholesterolemia. METHODS: This was a prospective randomized controlled trial with 3 parallel groups. The patients (n = 35) were randomly assigned to receive pravastatin 20 mg/day (n = 12); continuous combined hormone replacement therapy (0.625 mg conjugated estrogen/day combined with medroxyprogesterone 5 mg/day) (n = 12); continuous combined hormone replacement therapy plus pravastatin (n = 11) for 16 weeks. RESULTS: Among patients treated with continuous combined hormone replacement therapy levels of total cholesterol (10.7%) and LDL cholesterol (12.6%) decreased significantly (p < 0.05), while levels of high density lipoprotein cholesterol (5%) and triglycerides (6.2%) increased insignificantly (p > 0.05). Patients in the pravastatin group achieved significant reductions of 18.8 and 21.4% in total cholesterol and low density lipoprotein cholesterol levels, respectively (p < 0.05). Among patients treated with a combination of continuous combined hormone replacement therapy plus pravastatin, levels of total cholesterol (20.5%) and low density lipoprotein cholesterol (23.8%) decreased the most, while levels of triglycerides (2.1%) decreased lower than the pravastatin-only group. The mean percentage of the differences between the baseline and treatment levels of the lipids and lipoproteins were not significant between the 3 study groups (p > 0.05). CONCLUSION: No significant difference between hormone replacement therapy alone and in combination with HMG-CoA reductase inhibitor in the treatment of postmenopausal women with hypercholesterolemia was noted in this study. The combination of hormone replacement therapy not only does not adversely affect the lipid-lowering effect of pravastatin alone, but hormone replacement therapy also offers additional benefits in the treatment of hypoestrogenic hypercholesterolemia in postmenopausal women.     

Effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate on plasma lipids and lipoproteins, coagulation factors, and carbohydrate metabolism.

OBJECTIVE: To determine the effects of lower doses of conjugated equine estrogens (CEE) alone or CEE and medroxyprogesterone acetate (MPA) on lipoproteins, carbohydrate metabolism, and coagulation/fibrinolytic factors. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Multicenter substudy of the Women's HOPE trial. PATIENT(S): Seven hundred and forty-nine healthy, postmenopausal women. INTERVENTION(S): Women were randomized to receive the following doses in milligrams per day: 0.625 CEE; 0.625 CEE/2.5 MPA; 0.45 CEE; 0.45 CEE/2.5 MPA; 0.45 CEE/1.5 MPA; 0.3 CEE; 0.3 CEE/1.5 MPA; or placebo. MAIN OUTCOME MEASURE(S): Assessment of lipids, lipoproteins, glucose tolerance, and coagulation/fibrinolytic factors at baseline, cycle 6, and year 1. RESULT(S): One year of treatment with any of the CEE or CEE/MPA regimens studied increased high-density lipoprotein cholesterol (HDL-C); the 10% increase in HDL-C for the CEE 0.45/MPA 1.5 group was similar to the CEE 0.625/MPA 2.5 group. Low-density lipoprotein cholesterol was significantly reduced in all of the active treatment groups except the CEE 0.3/MPA 1.5 group at cycle 13. Apolipoprotein A-I and triglyceride levels increased and apolipoprotein B levels decreased in all groups. The lipoprotein (a) level was reduced in the CEE 0.45/MPA 2.5, CEE 0.45/MPA 1.5, and CEE 0.625/MPA 2.5 groups. Minimal changes were observed in carbohydrate metabolism for all groups. Fibrinogen and PAI-1 activity decreased and plasminogen activity increased in all groups. Decreases in antithrombin III and protein S activities were significant for all active treatment groups except the CEE 0.3/MPA 1.5 group. CONCLUSION(S): Lower doses of CEE and CEE/MPA induce favorable changes in lipids, lipoproteins, and hemostatic factors with minimal changes in carbohydrate metabolism.