The effect of estrogen replacement therapy with or without progestogen on the fibrinolytic system and coagulation inhibitors in postmenopausal status

OBJECTIVE: The aim of this study was to analyze several fibrinolytic components and coagulation inhibitors in postmenopausal women and to evaluate the effect of hormone replacement therapy.STUDY DESIGN: Several hemostatic parameters were evaluated in 75 postmenopausal women before and after 3 to 4 and 12 months of hormone therapy.RESULTS: An increase in plasma fibrinolytic activity primarily related to a significant increase in tissue-type plasminogen activator and a decrease in plasminogen activator inhibitor type 1 was observed in women receiving hormone replacement therapy. A significant decrease in protein S and lipoprotein(a) was detected under therapy. No modifications in tissue-type plasminogen activator/plasminogen activator inhibitor-1 and activated protein C/α₁-antitrypsin complexes, urokinase activity, plasminogen, and antithrombin III were detected.CONCLUSIONS: The increase in fibrinolytic activity and the decrease in lipoprotein(a) levels observed in women receiving hormone replacement therapy could help decrease the risk of coronary disease associated with the postmenopausal state.     

A comparison of the effects of sequential transdermal versus continuous orally administered hormone replacement therapies on plasma total homocysteine levels in postmenopausal women: a randomized, placebo-controlled study

OBJECTIVE: The objective was to determine the effects of transdermal and oral hormone replacement therapies on plasma total homocysteine levels in postmenopausal women. MATERIAL AND METHODS: One hundred and ten postmenopausal patients were enrolled in the study. Participants were randomized into three groups: in Group A (n = 31) oral continuous combined therapy and in Group B (n = 30) transdermal sequential hormone replacement therapy were given for 6 months. A placebo was administered orally to the control group (Group C, n = 30). Serum homocysteine levels were studied prior to and after 6 months of treatment in all groups. RESULTS: There were no statistical significant differences in mean serum homocysteine levels among the groups prior to the study. The mean homocysteine levels after 6 months in Groups A-C were also similar. CONCLUSIONS: Serum homocysteine levels alter with neither oral continuous nor sequential transdermal hormone replacement therapy.     

Effects of low-dose oral and transdermal estrogen replacement therapy on hemostatic factors in healthy postmenopausal women: a randomized placebo-controlled study

OBJECTIVE: This study was undertaken to investigate the effect of transdermal and oral estrogen replacement therapy in healthy postmenopausal women on markers of coagulation and fibrinolysis associated with coronary artery disease. STUDY DESIGN: In a randomized, placebo-controlled, double-blind study, healthy hysterectomized postmenopausal women received daily either placebo (n=49), transdermal 17beta-estradiol (E(2)) 50 microg (tE(2) group, n=33), oral E(2) 1 mg (oE(2) group, n=37), or oral E(2) 1 mg combined with gestodene 25 microg (oE(2)+G group, n=33) for thirteen 28-day treatment cycles. Hemostatic variables were measured in blood samples collected at baseline and in cycles 4 and 13. RESULTS: No significant changes versus baseline and placebo were found in the tE(2) group, except for plasminogen activator inhibitor type-1 (PAI-1) in cycle 13 (-32.4%, P=.01). In the oE(2) group, significant percentage changes from baseline versus placebo in cycle 13 were found in fibrinogen, -5.4% (P<.05); factor VII, -7.3% (P<.05); thrombin-antithrombin III complexes, -13.3% (P<.05); tissue-type plasminogen activator (t-PA), -17.3% (P<.001); and PAI-1, -54.3% (P<.001). In the oE(2)+G group, respective changes were factor VII, -17.6% (P<.001); t-PA, -14.5% (P=.01); PAI-1, -36.4% (P<.01); and D-dimer, +21.8% (P<.05). No significant changes were observed in prothrombin fragment 1+2 and plasmin-alpha(2)-antiplasmin complexes. CONCLUSION: Low-dose oral estradiol therapy was associated with an increase in fibrinolysis and small decreases in procoagulant variables. Transdermal therapy had minor effects.     

Assessment of mammographic density in postmenopausal women during long term hormone replacement therapy

Abstract

Objective: To assess long-term effects of different hormone replacement therapy (HRT) regimens on mammographic density.

Methods: One hundred sixty-five postmenopausal women were treated with the same HRT during 5 years: 38 received transdermal estradiol, 78 cyclic combined therapy and 49 continuous combined therapy. Mammograms were obtained at baseline, at 1-year and 5-year treatment. Breast density changes were categorized as slight focal increased density, considerable focal increased density, slight diffuse increased density and considerable diffuse increased density.

Results: Mammographic density increased in 7.9% of women receiving estrogen alone versus 25.2% of women receiving combined therapy (p?<?0.022) during 1 year, and in 7.9% of women versus 28.3% of women (p?<?0.009) after 5 years of therapy, respectively. There were significant statistical differences in women treated with estrogen alone versus those treated with combined HRT after 1 and 5 years. After 5 years of HRT, breast density increased 21.8% in women receiving cyclic combined therapy versus 38.8% in those under continuous combined therapy (p?<?0.039).

Conclusion: An increase in breast density is significantly more frequent in women receiving combined estrogen-progestin therapy than in women receiving estrogen alone. There are differences between cyclic and continuous combined therapy at 5 years of treatment.     

A one-year randomized double-blind,multicentre study to evaluate the effects of an oestrogen-reduced,continuous combined hormone replacement therapy preparation containing 1 mg oestradiol valerate and 2 mg dienogest on metabolism in postmenopausal women

Objectives To evaluate the impact of an oestrogen-reduced, continuous combined hormone replacement therapy preparation containing 1 mg oestradiol valerate (1EV) and 2 mg dienogest (2DNG) on metabolism.

Methods In a randomized double-blind study, 1EV/2DNG was compared with a reference preparation containing 1 mg 17ß-oestradiol and 0.5 mg norethisterone acetate (E2/NETA). For the primary variable, i.e. the ratio of HDL cholesterol (week 52 to baseline), at least 98 case evaluations were planned. Secondary variables were other lipid parameters, haemostasis factors and carbohydrate metabolism.

Results After 1 year of treatment, the mean HDL cholesterol levels had decreased by 4.5 ± 14.8% in the 1EV/2DNG group and by 6.1 ± 13.9% in the E2/NETA group (treatment difference NS). The ratio of HDL cholesterol (week 52 to baseline) was 0.944 for 1EV/2DNG and 0.929 for E2/NETA (geometric means). The primary efficacy variable, the ratio of the geometric means of the two treatments (1EV/2DNG/E2/NETA) was 1.016, with a lower one-sided 95% confidence limit of 0.973, which was clearly above the prespecified non-inferiority bound of 0.85 (p-value < 0.001). HDL2 cholesterol increased by 0.3 ± 34.4% (1EV/2DNG) and decreased by 6.2 ± 34.3% (E2/NETA; treatment difference NS); HDL3 cholesterol decreased by 4.4 ± 19.9% (1EV/2DNG) and 8.2 ± 17.7% (E2/NETA; treatment difference NS). Changes in the haemostasis and carbohydrate variables were very similar in both treatment groups.

Conclusion This study provides evidence that a new oestrogen-reduced HRT preparation containing 1 mg oestradiol valerate and 2 mg dienogest has no major impact on lipid variables. Minimal changes were seen in haemostatic and carbohydrate variables.     

成都市围绝经期和绝经后妇女对激素替代治疗的认知和接受程度

目的 :调查成都市中老年妇女绝经状况和激素替代治疗 (HRT)的使用和认知状况 ,为有针对性地开展生殖健康服务提供依据。方法 :经调查表对成都市市区和郊县的190 6名 4 4岁以上妇女进行横断面研究。结果 :成都市妇女平均绝经年龄为 4 8岁 ,2 5 .4 %的妇女应用过HRT。近 1/3的妇女了解HRT。 5 0 %的妇女希望得到这方面的教育。获得信息的主要途径是医生、亲友、医学书籍和传媒。结论 :成都市中老年妇女的生殖健康知识较为贫乏 ,应将宣传教育和医学服务相结合 ,提高妇女的生活质量     

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。     

子宫内膜异位症根治术后激素替代治疗疗效观察

目的　探讨激素替代治疗Ⅲ～Ⅳ期子宫内膜异位症根治术后 (全子宫及双侧附件切除术后 )的临床疗效与安全性。方法　 2 0 0 1年 3月至 2 0 0 2年 12月将 30例患者随机分成两组 (各 15例 ) :观察组口服戊酸雌二醇0 5～ 1 0mg ,每日 1次。对照组口服利维爱 1 2 5mg ,每日或隔日 1次。治疗前后检查盆腔情况、肝肾功能、体内血清FSH(卵泡刺激素 )、血清E2 (雌二醇 )水平 ,记录治疗期间盆腔痛、性交痛等子宫内膜异位症相关症状和乳房胀痛等不良反应 ,Kupperman评分 (K评分 )每月 1次。 结果　两组用药后围绝经期症状均明显改善 ,无子宫内膜异位症复发表现 ,血浆E2 水平上升 ,治疗前后比较差异有显著性意义 (P <0 0 1)。治疗后E2 水平观察组高于对照组 ,两组比较差异有显著性意义 (P <0 0 1) ,但均在安全范围内。结论　小剂量戊酸雌二醇和利维爱用于Ⅲ～Ⅳ期子宫内膜异位症根治术后患者 ,均能安全、有效地控制围绝经期症状。     

Hormone replacement therapy in postmenopausal women with Alzheimer's disease: a randomized,prospective study

OBJECTIVE: To compare the therapeutic efficacy of hormone replacement therapy (HRT) and tacrine in Alzheimer's disease. DESIGN: Six-month, randomized, open-label study. SETTING: University hospital. PATIENT(S): Fifty-five women with mild to moderate Alzheimer's disease were randomly assigned to tacrine (n = 26) or HRT (n = 29). INTERVENTION(S): In the tacrine group, an initial dose of 40 mg/day was increased up to 160 mg/day. In the HRT group, conjugated equine estrogen was given to patients without uteri (n = 3) or together with micronized progesterone to patients with uteri (n = 26). MAIN OUTCOME MEASURE(S): Mini-Mental State Examination (MMSE), Hopkins Verbal Learning Test, Boston Naming Test, Controlled Oral Word Association Test, Geriatric Depression Scale, Hamilton Depression Scale (HDS), and Instrumental Activities of Daily Living (IADL). RESULT(S): Thirty-three patients who completed the outcome measures (tacrine, 17; HRT, 16) were included in an intent-to-treat analysis. The results did not differ between groups except for IADL, which rated more highly after HRT. Apolipoprotein E genotype effects were assessed. MMSE and HDS scores were improved after tacrine treatment in epsilon 4-negative patients. CONCLUSION(S): Overall efficacy of estrogen plus progesterone combination was similar to tacrine for cognition and mood, but greater for ADL. In epsilon 4-negative patients, tacrine is preferable for cognition and mood.     

Sequential combined transdermal and oral postmenopausal hormone replacement therapies: effects on bleeding patterns and endometrial histology

Objectives: To determine the endometrial response and bleeding patterns in postmenopausal women taking a sequential combined hormone replacement regimen either orally or transdermally. Methods: Seventy-two postmenopausal women with amenorrhea of 6 months or longer with follicle stimulating hormone and estradiol levels in the postmenopausal range and normal endometrium were included in the study. The patients randomly received sequential combined hormone replacement regimen with oral (n=37) or transdermal route (n=35). The total duration of treatment was 6 months (6 cycles of 28 d). The subjects kept daily bleeding diaries, and endometrial biopsies were taken at baseline and after 6 months of therapy. Results: The rates of adequate progestational response (secretory or atrophic) were 83.8% and 82.9% in the oral and transdermal hormone replacement groups, respectively (p>0.05). In the oral hormone replacement group, there were 16.2% of inadequate progestational response, 2.7% had endometrial hyperplasia and 13.5% proliferative endometrium. In the transdermal hormone replacement group, there were 17.1% of inadequate progestational response, 2.9% had endometrial hyperplasia and 14.3% proliferative endometrium. Cyclic bleedings occurred in 92.4% and 92% of all cycles in the oral and transdermal treatment groups, respectively. The mean duration of bleeding per cycle were 3.9±0.9 and 3.8±0.9 d in the oral and transdermal treatment groups, respectively. Conclusion: Sequential combined transdermal hormone replacement therapy is as effective as oral therapy in preventing the development of endometrial hyperplasia. Satisfactory control of bleeding is achieved with both regimens. Received: 6 June 2001 / Accepted: 12 July 2001     

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 sequential combined transdermal and oral hormone replacement therapies on serum lipid and lipoproteins in postmenopausal women

The aim of this study was to compare the effects of sequential combined transdermal and oral postmenopausal hormone replacement therapies on serum lipid-lipoprotein profiles risk markers for cardiovascular disease. A prospective randomize study was designed: Ninety-six healthy nonhysterectomised postmenopausal women were randomized to receive either transdermal continuous 17β-estradiol, 0.05 mg/d (Estraderm TTS, Novartis, Basel, Switzerland), with transdermal sequential norethisterone acetate, 0.25 mg/d (Estragest TTS, Novartis, Basel, Switzerland), or oral continuous conjugated equine estrogens, 0.625 mg/d (Premarin 0.625 mg, Wyeth, Philadelphia, U.S.A.), with oral sequential medroxyprogesterone acetate, 10 mg/d (Farlutal 5 mg, Deva, Istanbul, Turkey). 84 women completed the trial, 42 in oral and 42 in the transdermal group. The serum levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apolipoproteins AI and apolipoproteins B at 6 months after starting treatment were compared with baseline values for both therapies. Both oral and transdermal therapies significantly reduced serum levels of total cholesterol (208– 190 mg/dL and 216–199 mg/dL, respectively, p=0.0001) and LDL-cholesterol (128–112 mg/dL and 140– 127 mg/dL, respectively, p=0.001). The serum levels of triglycerides did not show any significant change with oral therapy, whereas this lipid fell (128–101 mg/dL, p=0.0001) significantly with transdermal therapy. We found significant decrease in HDL-cholesterol with transdermal therapy while there was no significant change with oral therapy. Apolipoproteins AI, the major protein component of HDL₂ subfraction, was increased by oral therapy and lowered by transdermal therapy. As a conclusion, we have found that serum total cholesterol and LDL-cholesterol were lowered by both therapies, with no significant differences between treatments, whereas there were significant differences between treatments according to effects on serum triglycerides and apolipoproteins AI. Received: 15 May 2001 / Accepted: 20 July 2001     

激素补充治疗对绝经后妇女血液流变学的影响

目的探讨不同剂量结合雌激素(倍美力)配伍安宫黄体酮(MPA)的连续联合方案对绝经后妇女血液流变学的影响,以便更合理地为绝经后妇女的激素补充治疗提供指导和咨询.方法将60例绝经1～4年的健康妇女随机分为3组,A、B组分别口服结合雌激素0.625mg/d或0.3mg/d配伍MPA2mg/d,加复方碳酸钙(钙尔奇-D)600mg/d;C组口服复方碳酸钙600mg/d,为期半年,对比3组用药前、后以及用药后各组间血液流变学各项指标的变化.结果治疗前3组血液流变学各项指标比较,差异无显著性(P＞0.05).用药后,A组的全血高切粘度从(5.23±0.37)毫帕@秒(mPa@s)降至(5.03±0.43)mPa@s(P＜0.05),血浆粘度从(1.66±0.19)mPa@s降至(1.58±0.15)mPa@s(P＜0.05),红细胞变形能力从(4.76±0.32)mPa@s降至(4.54±0.34)mPa@s(P＜0.05),有明显改善.B组全血高切粘度从(5.10±0.30)mPa@s降至(4.87±0.30)mPa@s(P＜0.05),红细胞变形能力从(4.65±0.34)mPa@s降至(4.43±0.29)mPa@s(P＜0.05),也有明显改善.C组各项指标无明显变化.治疗后,A组血浆粘度及纤维蛋白原水平低于C组(P＜0.05);B组全血高切粘度、全血低切粘度及血浆粘度低于C组(P＜0.05).血栓弹力图于治疗前及治疗后各组间比较及治疗前后自身对比,差异无显著性(P＞0.05).结论两种剂量结合雌激素配伍MPA连续联合方案,均可降低血浆粘度、提高红细胞变形能力、改善微循环.     

Changes in hemostatic parameters after oral and transdermal hormone therapy in postmenopausal women

Hormone therapy (HT) can be prothrombotic risk factor. We compared the effects of oral HT (o-HT) and transdermal HT (t-HT) on the kinetic of clot formation and fibrinolysis in postmenopausal women after 6 months HT using a multiparameter test. We observed that after HT, the level of fibrinogen was higher than in controls (Fg 3.12 g/l vs. 4.24 g/l (o-HT); 3,7?g/l (t-HT); p?<?0.001) and values of velocity of polymerization in o-HT group were increased (95.84 mOD/min vs. 146.50 mOD/min, p?<?0.001) compared to controls. Maximum absorbance of formed clots was higher in o-HT group (0.279 vs. 0.312, p?<?0.001) than in controls, but in t-HT group was lowest (0.268). Fibrin lysis half-time increased in both HT groups (controls 17.16?min vs. 31.43?min (o-HT); 23.34?min (t-HT) p?<?0.001) compared to values in controls. The results of our study show that o-HT caused the changes in clot formation and fibrinolysis than t-HT in postmenopausal women. The increased level of fibrinogen and its accelerated kinetics of polymerization as well as a lower rate of clot lysis may partly explain the increase in venous thrombosis and cardiovascular events reported after the use of HT, especially the oral form of that.     

A cross-sectional study of the effects of hormon replacement therapy on the cardiovascular disease risk profile in healthy postmenopausal women

OBJECTIVE: To assess risk factors for cardiovascular disease in healthy postmenopausal women who had been uninterruptedly on menopausal hormone replacement therapy (HRT) for at least 5 years or who had not received any HRT. DESIGN: Cross-sectional study. SETTING: The Royal Free Hospital and The Middlesex Hospital. PATIENT(S): A total of 256 healthy postmenopausal women were analyzed: 73 were taking tibolone, 60 were taking transdermal E(2), 58 were taking conjugated equine estrogens (E), and 65 were not taking any menopausal therapy. INTERVENTION(S): Cardiovascular disease risk factors measurement. MAIN OUTCOME MEASURE(S): Total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, lipoprotein(a), insulin, glycated hemoglobin, high sensitivity C-reactive protein, fibrinogen, total antioxidants, and endothelin-1. RESULT(S): The different types of HRT induced disparate changes in the various markers of cardiovascular disease. Significantly higher high sensitivity C-reactive protein concentrations were found in women receiving conjugated equine E and tibolone than in women who were not taking any therapy. Glycated hemoglobin was significantly lower in women receiving transdermal E(2) and tibolone compared to women not on HRT. Women on tibolone had significantly higher systolic blood pressure. CONCLUSION(S): Because high sensitivity C-reactive protein has recently emerged as an important predictor of cardiovascular disease, the higher high sensitivity C-reactive protein levels observed in women on conjugated equine estrogens and on tibolone have potential important clinical implications.     

Sequentially combined hormone replacement therapy reduces impedance to flow within the uterine and central retinal arteries in healthy postmenopausal women

OBJECTIVE: The purpose of this study was to investigate the long-term effects of combined hormone replacement therapy on the impedances of the uterine, central retinal, and ophthalmic arteries in healthy postmenopausal women. STUDY DESIGN: In a prospective controlled study we randomly assigned 30 healthy postmenopausal women (mean age, 52 +/- 3 years) to 2 groups. Women in the hormone replacement therapy group (n = 15) received 1 mg micronized 17beta-estradiol daily sequentially combined with 5 or 10 mg dydrogesterone for 14 days of each 28-day cycle during 12 months and 2 mg 17beta-estradiol combined with 10 mg dydrogesterone thereafter for a period of 3 months. The control group (n = 15) received no treatment. Color Doppler ultrasonography was used to measure the impedance to flow (pulsatility index) within the uterine, central retinal, and ophthalmic arteries in the 17beta-estradiol phase at baseline and after 3, 12, and 15 months. RESULTS: With respect to values in the control group, 12 months of hormone replacement therapy was associated with a significantly lower (by 39%) mean pulsatility index of the uterine artery (decrease from baseline of 25% in hormone replacement therapy group and increase of 14% in control group) and a significantly lower (by 29%) mean pulsatility index of the central retinal artery (decrease of 9% in hormone replacement therapy group and increase of 20% in control group). After 3 months this effect was already evident. During hormone replacement therapy the reductions in mean pulsatility index values of the uterine and central retinal arteries with respect to baseline were larger (both P =.002) in the women with high pretreatment pulsatility index values than in those with low pretreatment values. The baseline pulsatility index of the uterine artery correlated positively with age and with duration of amenorrhea (r = 0.42, P =. 01; r = 0.48, P =.008; respectively). CONCLUSION: These results suggest that 12 months of sequentially combined hormone replacement therapy with a low dose of estradiol (1 mg) lowers arterial impedance in specific vascular territories. These data may help in understanding the effects of hormone replacement therapy on the cerebral circulation.