雌激素替代治疗对绝经后妇女冠心病者血脂代谢及抗氧化作用的研究

对32例绝经后妇女（PMW）冠心病患者（CHD组）进行雌激素替代治疗（ERT），以观察对其血脂代谢及机体抗氧化水平的影响。另选取绝经后健康妇女30例为对照组。CHD组口服尼尔雌醇（CEE3）每月2次，每次2mg，连用6个月，分别于用药前、用药后3个月及6个月检测总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL－C）、低密度脂蛋白胆固醇（LDL－C）、脂蛋白（a）［LP（a）］、氧化修饰低密度脂蛋白（Ox－LDL）、丙二醛（MDA）及超氧化物歧化酶（SOD）。结果表明ERT前CHD组与对照组比较LP（a）、Ox－LDL及MDA水平明显升高（P＜0．05），而SOD总活力显著降低；CHD组于ERT后TC无明显变化，TG呈升高趋势（P＞0.05），而LDL-C、TC／HDL－C和LDL－C／HDL－C显著下降（P＜0．01），LP（a）也明显降低（P＜0．05），而HDL－C显著上升（P＜0．01）；血浆Ox－LDL、血清MDA显著下降（P＜0．01），血清SOD总活力明显上升（P＜0．05），提示ERT不仅能显著改善PMW之CHD患者血脂紊乱，而且能有效地提高机体抗氧化水平。     

Hormone replacement therapy enhances postprandial lipid metabolism in postmenopausal women.

Postmenopausal estrogen therapy reduces cardiovascular morbidity and mortality, except in women with advanced coronary disease. This beneficial effect is partly attributed to a reduction of fasting plasma total and low-density lipoprotein cholesterol (LDL-C) and an elevation of plasma high-density lipoprotein cholesterol (HDL-C) concentrations. Since postprandial lipemia seems to play a role in the pathogenesis of coronary artery disease, we evaluated the effect of hormone replacement therapy (HRT) on postprandial lipoprotein metabolism in 14 normolipemic postmenopausal women. A vitamin A fat-loading test before and after three cycles of treatment with a sequential combination of conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) was used to label chylomicrons and chylomicron remnants with retinyl palmitate (RP), and RP clearance was assessed over an 8-hour period postprandially. Following 3 months of HRT, fasting total cholesterol and LDL-C levels were reduced 9.8% (P = .049) and 16.5% (P = .023), respectively. Fasting HDL-C levels increased 18.9% (P = .001). Fasting triglycerides (TGs) increased, but not significantly. Postprandial integrated plasma TGs did not change significantly. The integrated RP levels in whole plasma and chylomicron (Svedberg flotation units [Sf] > 1,000) and nonchylomicron (Sf < 1,000) fractions were reduced 58% (P = .043), 78% (P = .041), and 75% (P = .001), respectively, after hormonal treatment. Enhanced clearance of chylomicrons and chylomicron remnants by HRT may contribute to the protective effect of estrogens against cardiovascular disease in normolipemic postmenopausal women.     

雌激素替代治疗对绝经后女性血脂代谢及血浆内皮素的影响

目的 探讨雌激素替代治疗(ERT)对绝经妇女血脂及血浆内皮素的影响。方法 选择自然停经妇女60例,其中30例用ERT,另30例用安慰剂治疗30天。治疗前后均检测促卵泡激素(FSH)、雌二醇(E_2)、孕酮(P)、睾酮(T)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)及血浆内皮素-1(ET-1)。结果 ERT组妇女血清E_2水平较治疗前明显升高,P、T水平无明显变化,TC、TG及LDL-C下降,HDL-C升高,ET-1水平显著下降;安慰剂组妇女上述指标均无显著变化。线性相关分析显示:绝经妇女E_2与TC、TG、LDL-C及ET-1负相关,与HDL-C正相关;TC与ET-1明显正相关。结论 ERT能改善绝经妇女血脂代谢和降低其血浆内皮素-1水平。两者相互促进和补充,从而发挥心血管保护作用。     

The prevention of bone mineral loss with hormonal replacement therapy in premenopausal women on dialysis with estrogen deficiency

In 25-30% of premenopausal dialysis women low serum estrogen concentrations are observed. This "premature menopause" can significantly contribute to accelerated bone loss. The aim of the study was to evaluate the effect of estrogen-gestagen replacement therapy on bone mineral density (BMD) in hemodialysis women with secondary to uremia estrogen deficiency. Among 20 hemodialysis women, aged 18-45 years, with serum 17 beta-estradiol < 30 pg/ml, ten (group I) received transdermal estradiol with cyclic addition of noretisterone acetate (Estracomb TTS 50/0.25), and another ten formed the control group (group II). BMD was evaluated by dual photon x-ray absorptiometry (DEXA, Lunar) in: lumbar spine (L2-L4), 1/3 distal radius and femoral neck, before and after the study. Serum 17 beta-estradiol concentrations were measured before, and after 1, 3, 6 and 12 months of the study. After one year, in group I, in which serum 17 beta-estradiol normalized already during the first month (p < 0.001), an increase of in BMD was noted, although significant only in L2-L4 (p < 0.05). In group II, no change in serum 17 beta-estradiol and mild but insignificant decrease in BMD were observed. However, a comparison of BMD values after 12 months in both groups revealed the marked differences in all studied sites (p < 0.01, p < 0.02, p < 0.05 in L4-L2, distal radius and femoral neck, respectively). The mean serum calcium, phosphate, PTH and alkaline phosphatase activity were similar in both groups and did not change during the study. In premenopausal hemodialysis women with estrogen deficiency, hormonal replacement therapy inhibits bone demineralization and can be useful in prevention of early osteoporosis.     

雌激素替代疗法对绝经后妇女血清血管 紧张素转化酶及血脂代谢的影响

目的　探讨雌激素替代疗法 (ERT)对绝经后妇女血清血管紧张素转化酶 (ACE)含量及血脂代谢的影响。方法　测定 30例健康绝经后妇女应用ERT(治疗组 )前及应用ERT 14周后血清ACE、雌二醇 (E2 )及血清甘油三酯 (TG)、总胆固醇 (TC)、高密度脂蛋白胆固醇 (HDL C)、低密度脂蛋白胆固醇 (LDL C)、脂蛋白 (a) [Lp(a) ]含量 ,并与 30例健康绝经后妇女应用安慰剂 (对照组 )进行对照。结果　对照组应用安慰剂前后 ,ACE及血脂各项含量无变化 ;治疗组应用ERT后 ,ACE含量明显降低且与E2 呈负相关 ,血清TC、LDL C及Lp(a)含量降低 ,HDL C含量升高 ,TG无变化。结论　绝经后妇女补充雌激素 ,可通过降低血清ACE水平及改善血脂代谢共同发挥对心血管系统的保护作用。     

Combined estrogen replacement therapy on metabolic control in postmenopausal women with diabetes mellitus

Previous studies have shown that the incidence of diabetes is higher when women come to menopause. This study was carried out to examine the effects of combined estrogen replacement therapy (ERT) on diabetes in postmenopausal women. PubMed/MEDLINE was searched for English-language articles published between January 1997 and June 2011. Studies that examined ERT on the incidence of diabetes and randomized clinical trials that evaluated combined ERT (estrogen plus progesterone) on diabetic indices in postmenopausal women were included. Pooled relative risks were calculated using a random- or a fixed-effects model. Sixteen studies comprising 17,971 cases were included. Based on the pooled data, ERT significantly reduced the incidence of diabetes [odds ratio (OR), 0.61; 95% confidence interval (CI), 0.55–0.68, ERT past/current/continuous use vs. never use; OR, 0.57; 95% CI, 0.51–0.65, ERT current/continuous use vs. past/never use]. Women with combined ERT have significantly lower levels of fasting plasma glucose (mean difference, –1.41 mM/L; 95% CI, –2.49 to ?0.33 mM/L) and HbA1c (mean difference, –0.73%; 95% CI, from ?1.28 to ?0.18%) compared with placebo. Furthermore, combined ERT dramatically reduced plasma total cholesterol (mean difference, –0.34 mM/L; 95% CI, from ?0.53 to ?0.15 mM/L) and low-density lipoprotein (mean difference, –0.43 mM/L; 95% CI, from ?0.71 to ?0.14 mM/L) but slightly increased high-density lipoprotein (mean difference, 0.02 mM/L; 95% CI, from ?0.07 to 0.12 mM/L) levels as compared with placebo control. This systemic review and meta-analysis provides evidence that postmenopausal women taking low-dose combined ERT have a decreased risk of developing diabetes and have better diabetic control.     

Effect of estrogen replacement therapy on patella cartilage in healthy women

OBJECTIVES: Patellofemoral osteoarthritis (OA) is a significant cause of morbidity. Epidemiological data suggests that the use of oestrogen replacement therapy (ERT) may protect against tibiofemoral knee OA. However, the effect on patellofemoral OA is unknown. The aim of this study was to test the hypothesis that long term ERT (greater than 5 years) is associated with increased patella cartilage in post menopausal women. METHODS: We studied 81 women (42 current users (> 5 yrs) of oestrogen replacement therapy and 39 never users). Articular cartilage volumes were determined by post-processing images acquired in the sagittal plane using a T1-weighted fat suppressed magnetic resonance sequence on an independent workstation. RESULTS: There was no difference in the amount of patella cartilage in women on ERT compared to women on no ERT. After adjusting for patella bone size, years since menopause, body mass index, age of menopause and smoking, ERT users had 2.07 +/- 0.76 ml of patella cartilage compared to 1.93 +/- 0.89 ml in non-users (P = 0.24 for difference). CONCLUSIONS: This study suggests that use of ERT for more than 5 years does not have a significant effect on patella cartilage, in contrast to the previously described effect on tibial cartilage. The reasons for this are unknown, but may indicate that there are differences in the mechanisms for development of knee OA at these sites.     

Effects of estrogen replacement therapy on serum lipid values and angiographically defined coronary artery disease in postmenopausal women.

To examine the effects of estrogen replacement on lipids and angiographically defined coronary artery disease (CAD) in postmenopausal women, lipid profiles were obtained in 90 consecutive postmenopausal women undergoing diagnostic coronary angiography. Eighteen women (20%) were receiving estrogen and 72 (80%) were not. CAD (defined as greater than or equal to 25% luminal diameter narrowing in a major coronary artery) was present in only 22% of women (4 of 18) receiving estrogen and in 68% (49 of 72) who were not (p less than 0.001), with an odds ratio of 0.13. Mean high-density lipoprotein (HDL) cholesterol level was significantly higher (63 +/- 6 vs 48 +/- 2; p less than 0.01) and mean total/HDL cholesterol ratio significantly lower in women receiving estrogen than in those who were not (4.2 +/- 0.5 vs 5.1 +/- 0.2; p less than 0.05). The other lipid values were similar in both groups. On multiple logistic regression analysis, absence of estrogen use was the most powerful independent predictor of the presence of CAD (p less than 0.001), with total/HDL cholesterol ratio as the only other variable selected (p less than 0.01). Thus, among 90 consecutive postmenopausal women undergoing diagnostic coronary angiography, estrogen replacement therapy was associated with an 87% reduction in the prevalence of CAD, and those receiving estrogen had a significantly higher mean HDL cholesterol level and lower mean total/HDL cholesterol ratio.     

雌激素替代治疗对绝经后冠心病妇女血脂和胰岛素抵抗的影响

目的 :观察雌激素替代治疗对绝经后冠心病 （CHD）妇女血脂谱和胰岛素抵抗的改善作用。方法 :对确诊为CHD的绝经后妇女 ,口服尼尔雌醇 2 m g/2周 ,治疗 6个月。分别于治疗前后测定血糖、胰岛素 （INS）、性激素结合球蛋白 （SHBG）、促卵泡素 （FSH）、黄体生成素 （L H）、雌二醇 （E2 ）、总胆固醇 （T- CH）、甘油三酯 （TG）、高密度脂蛋白胆固醇 （HDL- C）、低密度脂蛋白胆固醇 （L DL- C）等 ,并计算胰岛素敏感指数 （SI）。结果 :雌激素替代后 ,CHD患者的 FSH,L H,T- CH,TG,L DL- C,INS明显下降 ;而 E2 ,SHBG,HDL- C,SI明显升高。结论 :雌激素替代治疗能改善 CHD患者血脂谱紊乱和胰岛素抵抗     

Mechanisms regulating LDL metabolism in subjects on peroral and transdermal estrogen replacement therapy

To study the mechanisms of low density lipoprotein (LDL) cholesterol lowering by peroral and transdermal estrogen replacement therapy (ERT), 79 hysterectomized postmenopausal women aged 48 to 62 years were randomized in a double-blind double-dummy trial to receive either peroral estradiol valerate (2 mg/d) or transdermal estradiol gel (1 mg/d) for 6 months. Plasma LDL cholesterol decreased from 4. 19+/-0.83 (mean+/-SD) to 3.39+/-0.78 mmol/L (P<0.001) in the peroral group and from 4.11+/-0.86 to 3.72+/-0.78 mmol/L (P<0.001) in the transdermal estrogen group. Peroral estrogen did, but transdermal treatment did not, enhance the fractional catabolic rate (FCR) and production of LDL apolipoprotein B (apoB). However, the decrease of LDL cholesterol was related to an increase in FCR for LDL apoB on both peroral and transdermal ERT (r=-0.645, P<0.001 and r=-0.627, P<0.001, respectively). These changes were associated with changes in the serum estrogen level. Both therapies reduced absorption of dietary cholesterol by 6% to 10% (P<0.05). The effects of estrogen were not modified by the polymorphisms of apoE and apoB or cholesterol 7alpha-hydroxylase. In conclusion, the ERT-induced LDL cholesterol-lowering effect is related to changes in estrogen level, which presumably enhance LDL receptor activity, which is manifested as an increase in FCR for LDL apoB. The small decrease in the absorption efficiency of dietary cholesterol does not seem to contribute largely to the cholesterol lowering on either transdermal or peroral ERT.     

Differential effect of transdermal estrogen plus progestagen replacement therapy on insulin metabolism in postmenopausal women: relation to their insulinemic secretion

OBJECTIVE: To evaluate the impact on glucose and insulin metabolism of transdermal estrogen patches before and after the addition of cyclic dydrogesterone in postmenopausal women. DESIGN: We studied 21 postmenopausal women seeking treatment for symptomatic menopause. All patients received transdermal 50 micrograms/day estradiol for 24 weeks. After 12 weeks of treatment, 10 mg/day dydrogesterone were added. METHODS: During both regimens, insulin and C-peptide plasma concentrations were evaluated after an oral glucose tolerance test (OGTT); insulin sensitivity was evaluated by a hyperinsulinemic euglycemic clamp technique. Insulin and C-peptide response to OGTT were expressed as area under the curve (AUC) and as incremental AUC; insulin sensitivity was expressed as mg/kg body weight. Fractional hepatic insulin extraction (FHIE) was estimated by the difference between the incremental AUC of the C-peptide and insulin divided by the incremental AUC of the C-peptide. Plasma hormone and lipid concentrations were assessed at baseline and at 12 and 24 weeks of treatment. RESULTS: Nine patients proved to be hyperinsulinemic and 12 were normoinsulinemic. Transdermal estrogen treatment significantly decreased the insulin AUC (P < 0.05) and the insulin incremental AUC in hyperinsulinemic patients; addition of dydrogesterone further decreased both the AUC and incremental AUC of insulin. Estrogen alone and combined with dydrogesterone evoked a significant increase in C-peptide AUC in hyperinsulinemic (79.2%) and normoinsulinemic (113%) patients. The treatment increased the values for FHIE and insulin sensitivity in all patients (P < 0.04) and in the hyperinsulinemic group (P < 0.01), whereas it did not affect such parameters in normoinsulinemic patients. CONCLUSIONS: Transdermal estrogen substitution alone and combined with cyclical dydrogesterone may ameliorate hyperinsulinemia in a selected population of postmenopausal women.     

Individualizing therapy to prevent long-term consequences of estrogen deficiency in postmenopausal women.

BACKGROUND: Alendronate sodium and raloxifene hydrochloride were recently approved for the prevention of postmenopausal osteoporosis, but data on their clinical efficacy are limited. We compared these drugs with hormone replacement therapy (HRT) to help women and physicians guide postmenopausal treatment decisions. OBJECTIVE: To help physicians understand how they can best help women choose the most beneficial therapy after menopause based on their individual risk profile. METHODS: We developed a decision analytic Markov model to compare the effects of alendronate therapy, raloxifene therapy, and HRT on risks of hip fracture, coronary heart disease (CHD), breast cancer, and life expectancy. Regression models linked individual risk factors to future disease risks and were modified by drug effects on bone density, lipid levels, and associated breast cancer effects. RESULTS: Hormone replacement therapy, alendronate therapy, and raloxifene therapy have similar predicted efficacies in preventing hip fractures (estimated relative risk, 0.57, 0.54, and 0.58, respectively). Hormone replacement therapy should be more than 10 times more effective than raloxifene therapy in preventing CHD, but raloxifene therapy may not induce breast cancer. Women at low risk for hip fracture, CHD, and breast cancer do not benefit significantly from any treatment. Among women at average risk, HRT was preferred unless raloxifene therapy could reduce the risk of breast cancer by at least 66%, compared with a 47% increase for HRT. Women at high risk for CHD benefit most from HRT; women at high risk for breast cancer but low risk for CHD benefit most from raloxifene therapy, but only if it lowers the risk of breast cancer. CONCLUSION: Because of significant differences in the impact of these drugs, treatment choice depends on an individual woman's risk for hip fracture, CHD, and breast cancer.     

糖皮质激素替代治疗对21-羟化酶缺陷症患者糖脂代谢的影响

目的 单纯男性化型和非经典型21-羟化酶缺陷症(21-OHD)患者常常合并糖脂代谢异常,本文研究接受糖皮质激素替代治疗的21-OHD患者的糖脂代谢的变化.方法 收集2004年至2010年期间接受糖皮质激素治疗的21-OHD患者32例,同时收集到未接受糖皮质激素治疗的新诊断的21-OHD患者31例,均经21-羟化酶(CYP21)基因测序突变分析证实为CYP21 A2基因突变.检测人体测量学指标和空腹血糖、血脂、胰岛素、性激素水平,以及口服葡萄糖耐量试验(OGTT)和胰岛素释放试验.结果 糖皮质激素治疗组睾酮[(0.61±0.12对4.10±0.66)ng/ml,P＜0.01]、17-羟孕酮[17-OHP,(14.83±3.48对48.52±4.72) ng/ml,P＜0.01]、硫酸脱氢表雄酮[DHEAS,(55.7±23.6对405.2±65.7)μg/dl,P＜0.01]、促肾上腺皮质激素[ ACTH,(105.8±44.7对617.4± 163.3)pg/ml,P＜0.01]水平明显下降,而体重指数[(23.2±0.9对21.1±0.5)kg/m2,P＜0.05]、收缩压[(120.5±1.3对115.5±1.8)mm Hg,P＜0.05,1mm Hg=0.133 kPa]和甘油三酯[(1.8±0.2对1.1±0.1)mmol/L,P＜0.05]却明显增高,并且糖皮质治疗组的稳态模型评估的胰岛素抵抗指数(HOMA-IR)也明显高于未治疗组[(2.07±0.27对1.16±0.12),P＜0.01].多因素回归分析表明体重指数与HOMA-IR的相关性最强.结论 糖皮质激素治疗增加21-OHD患者体重指数、血清甘油三酯水平、收缩压和降低胰岛素敏感性.其中体重指数增加是导致胰岛素抵抗的主要原因,因此21-OHD患者的糖皮质激素治疗需注意代谢紊乱问题.     

Alcohol,estrogen replacement therapy,and visuospatial processes in postmenopausal women

BACKGROUND: Studies suggest that moderate drinking may benefit cognition and the effect may favor women. This study investigated effects of moderate drinking on visuospatial functioning in postmenopausal women. Visuospatial processes are sensitive to alcohol abuse and are thought to be sensitive to hormonal fluctuations. Three questions were posed in order to: explore visuospatial processes in moderate-drinking and abstaining postmenopausal women, assess visuospatial differences in women using no estrogen replacement therapy (No-ERT), ERT alone (ERT-only), and ERT with progestin (ERT+Pro), and identify alcohol/ERT interactions associated with visuospatial performance. METHODS: Two hundred fourteen postmenopausal women participated (75 No-ERT; 63 ERT-only; 76 ERT+Pro. All were moderate drinkers or teetotalers and all received the Block Design test from the Wechsler Adult Intelligence Scale-Revised. A raw score was calculated and progress at 30-sec intervals was assessed. RESULTS: ANOVA revealed an alcohol main effect [F(3,202) = 4.74; p < 0.004] on 60- to 120-sec change scores. Teetotalers had significantly smaller change scores (less improvement) compared with all levels of drinkers. ANOVA on design 9 (the most difficult trial) revealed an ERT main effect [F(3,202) = 4.37; p < 0.02]. ERT nonusers scored significantly lower than ERT-only and ERT+Pro groups. A design 9 trend toward an alcohol x ERT interaction was noted [F(6,202) = 1.93; p < 0.08], and a design 9 time x alcohol interaction was revealed [F(6,404) = 2.65; p < 0.02]. CONCLUSIONS: These data suggest that moderate drinking may be positively associated with visuospatial processes in postmenopausal women. They also suggest that ERT, alone and with progestin, is positively associated with visuospatial processes, but only when the task is difficult. These findings support Kaplan's assertion that subtle performance deficits may not be detectible with traditional endpoint measures. A provocative alcohol x ERT trend suggests that alcohol consumption should be considered in studies of ERT effects on cognitive ability.