Estradiol and norgestimate: a review of their combined use as hormone replacement therapy in postmenopausal women.

The focus of this review is hormone replacement therapy (HRT) with continuous administration of micronised, oral 17beta-estradiol 1 mg/day (herein referred to as continuous estradiol) plus micronised, oral norgestimate 90 microg/day administered for 3 days then withdrawn for 3 days in a 6-day repeating sequence (herein referred to as intermittent norgestimate). According to data from randomised, comparative trials of 1 year's duration, continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day relieves climacteric symptoms (vasomotor symptoms and vulvovaginal atrophy) in postmenopausal women. Continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day appeared as effective as estradiol 1 mg/day alone or continuous estradiol 2 mg/day plus continuous norethisterone acetate 1 mg/day in the treatment of postmenopausal women with vasomotor symptoms. Continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day was as effective as continuous estradiol 1 mg/day in causing the maturation of vaginal epithelial cells. In a randomised, double-blind study, bone mineral density (BMD) increased to a significantly greater extent and the rate of bone turnover was slower in postmenopausal women treated with continuous oral estradiol 1 mg/day plus intermittent norgestimate 90 microg/day than in placebo-treated patients. Two randomised, double-blind studies indicated that the addition of norgestimate 90 microg/day to continuous estradiol 1 mg/day did not attenuate the beneficial effects of estradiol on lipid parameters. Continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day was associated with increases in mean serum high density lipoprotein (HDL)-cholesterol levels and decreases in total cholesterol, low density lipoprotein (LDL)-cholesterol and lipoprotein (a) levels, compared with baseline. There was no statistically significant increase in triglyceride levels. In comparative trials, continuous oral estradiol 1 mg/day plus intermittent oral norgestimate 90 microg/day was well tolerated. Headache, breast pain or discomfort, abdominal pain or discomfort, uterine bleeding, dysmenorrhoea, oedema, nausea and depression were the most commonly reported adverse events. Continuous estradiol 1 mg/day plus intermittent oral norgestimate 90 microg/day was associated with a favourable uterine bleeding profile that improved over time. In a randomised trial, 80% of women were free from bleeding (irrespective of spotting) during month 12 of treatment. Norgestimate 90 microg/day was effective in protecting postmenopausal women against induction of endometrial hyperplasia by continuous estradiol 1 mg/day. In conclusion, data from a limited number of randomised studies indicate that HRT with continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day is effective in relieving climacteric symptoms, increasing BMD and slowing the rate of bone turnover in postmenopausal women. This HRT regimen is well tolerated and is associated with a similar incidence of adverse events to that reported in recipients of continuous estradiol 1 mg/day. The norgestimate component of the regimen provides good endometrial protection and is associated with a favourable bleeding profile. Long-term studies investigating the associated risk of breast cancer and thromboembolic events in recipients of continuous estradiol plus intermittent norgestimate are needed. In the meantime, continuous oral estradiol plus intermittent oral norgestimate can be regarded as an effective new option for HRT in postmenopausal women.     

Glycaemic control and hormone replacement therapy: implications of the Postmenopausal Estrogen/Progestogen Intervention (PEPI) study

Despite evidence that supports the beneficial effects of postmenopausal hormone replacement therapy (HRT), concerns remain about its possible adverse effects. However, entry into the postmenopausal state is associated with many characteristics of the insulin resistance syndrome, including increased cardiovascular morbidity and mortality, accretion of generalised and visceral adiposity and insulin resistance. Studies carried out in postmenopausal women have revealed that an increase in visceral obesity is associated with an increase in androgenicity that, in turn, is associated with type 2 (non-insulin-dependent) diabetes mellitus. Short term studies of HRT containing conjugated estrogens (CEE) and medroxyprogesterone (MPA) have shown prevention of the accretion of visceral fat. However, longer term studies using other techniques suggest that these effects may be evanescent. A few trials suggest that oral estrogen therapy reduces postmenopausal insulin resistance, as suggested by reductions in fasting insulin and glucose levels and an increase in glucose metabolism rates, whereas most studies do not show an adverse effect upon carbohydrate metabolism. MPA may decrease these beneficial effects. Transdermal estrogen is essentially neutral with regard to insulin sensitivity and oral estradiol (17beta-estradiol) may also be neutral or enhance sensitivity. Different progestogens vary in their effects upon carbohydrate metabolism. The Postmenopausal Estrogen/Progestogen Intervention (PEPI) Study was a prospective, 3-year, randomised trial in 875 women that compared placebo, unopposed CEE, CEE plus continuous MPA, CEE plus cyclical MPA, and CEE plus cyclical micronised progesterone. Fasting insulin and glucose levels decreased significantly by 16.1% and 0.122 mmol/L, respectively, in all drug treatment groups. However, after a 75g glucose load, glucose levels at 2 hours increased by 0.33 mmol/L in the active treatment groups without a corresponding increase in insulin levels. No beneficial effects on waist/hip ratio could be demonstrated. Data from the PEPI trial also suggested that the maximum benefit regarding carbohydrate metabolism was achieved in patients who were the most hyperglycaemic and hyperinsulinaemic at the start of therapy. It can be concluded, therefore, that HRT has few, if any, harmful effects on carbohydrate metabolism and that it may be of benefit in women in modifying the long term complications of the postmenopausal state.     

A novel concept to preserve the beneficial effects of hormone replacement therapy in bilaterally female ovariectomized rats: role of lovastatin therapy.

Estrogen replacement therapy (ERT) is claimed to reduce cardiovascular mortality by about 50% in postmenopausal women. This improvement is caused by favorable changes in lipid and lipoproteins metabolism, however, it also increases the incidence of the endometrial hyperplasia. Addition of progestin to ERT, referred to as hormone replacement therapy (HRT), has been shown to successively reduce this risk to the endometrium. Unfortunately, it has an adverse effect on high-density lipoprotein cholesterol (HDLC) concentration, thus compromising the benefits of ERT. Therefore the issue here whether HRT given alone and/or concomitantly with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (lovastatin) could exert any significant additional favorable effect on the lipid profile in bilaterally ovariectomized female rats. Sixty female Wistar rats were ovariectomized and treated with ERT (0.625 mg kg (-1)estradiol, E (2), IM every 2 weeks), HRT (estradiol plus progesterone, E (2)+ P, 0.625 mg kg (-1)estradiol and 5 mg progesterone kg (-1) respectively, IM every 2 weeks), and lovastatin (20 mg kg (-1)day (-1)orally) plus HRT (L + HRT) for 6 weeks. Blood aliquots were collected for serum and plasma separation. Serum vitamin E and plasma levels of C-reactive protein (CRP), nitric oxide (NO), lipid profile, and the susceptibility of non-HDLC to oxidation were determined. Moreover, thoracic aortas were dissected and directed for measurement of its lipid peroxide and NO contents. Treatment of ovariectomized rats with HRT showed a significant decrease ( P< 0.0001) in HDLC concentration compared to the group treated alone with ERT and increase ( P< 0.0001) in CRP levels compared to ovariectomized rats. HDLC and CRP are two powerful and significant predictors for increased cardiovascular risk in postmenopausal women. Addition of lovastatin as a complementary therapy to HRT revealed a significant 27% increment in HDLC and 48% decrement in CRP concentrations. Moreover, it significantly increased vitamin E, each of plasma and tissue content of NO and decreased atherogenic indexes (TC/HDLC, LDLC/HDLC), aortic lipid peroxide and susceptibility of non-HDLC to oxidation. In conclusion, this current study demonstrated that lovastatin together with continuous combined HRT seems to be more effective in the secondary prevention of coronary heart disease not only due to lipid lowering properties but also related to several other additive effects such as modification of endothelial function and inflammatory responses.     

Effect of conjugated equine estrogens on oxidative metabolism in middle-aged and elderly postmenopausal women

The effects of conjugated equine estrogens (CEE) 0.625 mg daily on cytochrome P450 (CYP) were quantified in 12 middle-aged and 13 elderly postmenopausal women at baseline and 6 months later. CYP phenotype was characterized by caffeine (CYP1A2), chlorzoxazone (CYP2E1), dapsone (CYP, N-acetyltransferase 2), dextromethorphan (CYP2D6), and mephenytoin (CYP2C19) metabolism. CEE significantly decreased CYP1A2 (caffeine metabolic ratio: 0.57 +/- 0.20 before, 0.40 +/- 0.20 after, P = .001) and significantly increased CYP2D6 (dextromethorphan/dextrorphan ratio: 0.0116 +/- 0.0143 before, 0.0084 +/- 0.0135 after, P = .022) metabolism. CEE had no overall effect on CYP2C19, CYP2E1, CYP-mediated dapsone metabolism, and N-acetyltransferase 2. The dextromethorphan metabolic ratio decreased only in the seniors. The dapsone recovery ratio decreased in the middle-aged group and increased in the seniors. CEE significantly influenced CYP1A2, CYP2D6, and CYP-mediated dapsone oxidative metabolism but not CYP2C19, CYP2E1, or N-acetyltransferase 2 metabolism in postmenopausal women. Age influenced CYP2D6 metabolism and dapsone hydroxylation.     

Oral hormone replacement therapy: factors that influence the estradiol concentrations achieved in a multiracial study population

The assumption that estradiol (E2) concentrations are reliably increased to therapeutic levels in postmenopausal women receiving hormone replacement therapy (HRT) has not been explicitly tested. Nor have factors that may modulate the E2 levels achieved been evaluated. The author examined E2 concentrations in a multiracial study population of 309 postmenopausal women treated with oral HRT and observed that 51.1% had achieved estradiol levels of at least 45 pg/ml (achievers). The odds of being an achiever were significantly elevated among non-Caucasian women by a HRT dose greater than 0.625 mg, current moderate drinking, and increasing duration of HRT use. The odds were significantly decreased by having a high school education or less and increasing time since last HRT dose. White postmenopausal women had significantly reduced odds of being an achiever, and both a dose of less than 0.625 mg and a dose equal to 0.625 mg significantly reduced the odds of being an achiever. Increasing body mass index and menopause duration were both associated with lower odds. This report demonstrates not only that women treated with HRTdo not all achieve therapeutic levels of estradiol but also that factors can be identified that modulate the E2 concentration achieved in response to HRT administration.     

Bioequivalence assessment of three different estradiol formulations in postmenopausal women in an open, randomized, single-dose, 3-way cross-over study.

OBJECTIVE: The aim of the study was to assess the bioavailability of estradiol (E2) following oral, single-dose administration of equimolar doses of three HRT preparations in a 3-way cross-over study in postmenopausal women. METHODS: 18 healthy subjects were enrolled. Free E2 and estrone (E1) serum concentrations were determined using commercially available immunoassay kits. Bioequivalence testing was performed between the following oral formulations: (a) 1.5 mg E2 tablets versus 2 mg E2V tablets; and (b) 1.5 mg E2 plus 0.15 mg DSG tablets versus 1.5 mg E2 tablets. RESULTS: For both E2 and E1 the E2 tablet was bioequivalent with both the E2V and the E2/DSG tablet with respect to the rate and extent of absorption (bioavailability). Although the mean tmax values of the three tablet formulations were similar, the variability was too large to prove formal bioequivalence. CONCLUSION: E2 tablets and E2/DSG tablets were bioequivalent and also bioequivalence of E2 tablets with commercially available E2V was found, which ensures a sequential HRT preparation without large variations in estrogen serum concentrations.     

骨吸收抑制剂治疗绝经后骨质疏松的临床评价

目的　评价不同类型骨吸收抑制剂在临床原发性骨质疏松症治疗中的疗效。方法　30 0例原发性骨质疏松症患者分成三组 ,每组 10 0例 ,所有患者均排除继发性骨质疏松。性激素类组 :服用利维爱 2 5mg ,隔日 1次 ;降钙素组 :密钙息 5 0IU ,肌注 ,第 1周每天 1次 ,第 2周隔日 1次 ,以后每周 2次 ;二膦酸盐组 :阿仑膦酸钠 10mg ,每天 1次。治疗 2年后随访 :腰椎骨密度 (BMD)、胫骨骨超声 (QUS)、尿羟脯氨酸 (HOP)、骨钙素和新骨折。结果　临床骨痛降钙素缓解速度最快 ,性激素类药物可迅速有效地缓解妇女更年期症状。治疗 2年后 ,腰椎骨密度明显上升 (P <0 0 5 ) ,二膦酸盐组上升 5 1% ,性激素类组上升 4 2 % ,降钙素上升 0 97% ;胫骨骨超声显著提高 (P <0 0 5 ) ,性激素组上升 2 1% ,降钙素组 1 8% ,二膦酸盐组 1 7% ;新骨折共 4例 :二膦酸盐组 2例 ,降钙素组和性激素组各 1例 ;尿羟脯氨酸仅二膦酸盐组明显下降 ;骨钙素各组无明显变化。结论　骨吸收抑制剂是骨质疏松治疗的重要手段 ,性激素类药物是治疗伴有绝经后综合症骨质疏松患者的首选药物 ,二膦酸盐对骨量较低且伴有骨痛的患者有良好的疗效 ,降钙素治疗骨质疏松疼痛临床疗效显著。     

激素替代治疗对绝经后妇女心血管危险因素的影响

目的 探讨不同的激素替代治疗（ＨＲＴ）方案对绝经后妇女心血管危险因素的影响。方法 ９１例绝经后妇女分为：（１）结合雌激素（ＣＥ）Ａ组,（２）ＣＥ Ｂ组;（３）７－甲基异炔诺酮 Ａ组;（４）Ｏｒｇ ＯＤ１４ Ｂ组;（５）炔雌醇（ＥＥ）Ａ组;（６）ＥＥ Ｂ组。     

激素替代疗法联合阿仑膦酸钠治疗绝经后骨质疏松的临床研究

目的观察激素替代疗法(HRT)联合阿仑膦酸钠治疗绝经后骨质疏松患者的疗效。方法采用随机、对照研究。69例绝经后骨质疏松症患者,随机分为联合用药组(联合组)、雌激素替代治疗组(雌激素组)和阿仑膦酸钠治疗组(阿仑膦酸钠组),每组23例。联合组每2周服尼尔雌醇片1mg,每3个月末10d加服安宫黄体酮6mg/d,同时给予阿仑膦酸钠70mg,每周1次口服。雌激素组为安慰剂+尼尔雌醇片和安宫黄体酮,阿仑膦酸钠组为安慰剂+阿仑膦酸钠。所有受试者均加服钙尔奇D600mg/d(每片含元素钙600mg和VitD125IU)。观察各组治疗后患者腰椎骨密度、血钙、血磷等骨代谢指标的变化及疼痛症状改善情况。结果通过1年治疗,3组患者的L1～4骨密度均有显著上升,其中联合组骨密度的上升更为明显(P<0.01),骨痛症状明显缓解,总有效率为100%,联合组的显效率高于其他两组。结论HRT联合阿仑膦酸钠治疗绝经后骨质疏松症,较单独用药更能有效地改善骨痛,提高骨密度值。     

盐酸雷洛昔芬防治绝经后骨质疏松症随机双盲对照研究

目的:评价雷洛昔芬(RLX)对绝经后妇女骨密度及骨代谢生化标志、脂代谢的影响及使用12个月的安全性观察.方法:采用随机、双盲安慰剂对照研究,68例绝经后妇女分为试验(n=34)及安慰剂组(n=34),每日分别服用RLX 60mg 或安慰剂,疗程12个月.结果:RLX组用药后腰椎及髋部骨密度均显著增加,腰椎骨密度升高2.30%,髋部骨密度升高2.07%,与安慰剂组比较骨密度变化的百分数差异有显著性(P<0.01).2组血清骨钙素、C端交联肽、总胆固醇、低密度脂蛋白胆固醇水平均下降,其变化百分率2组比较差异均有显著性(P<0.01).结论:RLX能增加绝经后妇女骨密度,降低骨转换率及血清总胆固醇、低密度脂蛋白胆固醇水平.     

Lipid-modifying effects of rosuvastatin in postmenopausal women with hypercholesterolemia who are receiving hormone replacement therapy

OBJECTIVE: To evaluate the efficacy and safety of rosuvastatin in postmenopausal women with hypercholesterolemia who are receiving hormone replacement therapy (HRT) in a randomized, double-blind, placebo-controlled trial. METHODS: After a 6-week dietary lead-in period, 135 postmenopausal women who had been taking a stable HRT regimen for at least 3 months were randomized to receive rosuvastatin 5 mg, 10 mg or placebo for 12 weeks. Fasting levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG) were assessed at weeks 0, 2, 6, 10, and 12; apolipoprotein (Apo) B and Apo A-I were measured at weeks 0 and 12. RESULTS: Rosuvastatin 5 mg and 10 mg significantly reduced LDL-C by 38% (SE = 2.1) and 49% (SE = 2.1), respectively, compared with placebo (1% [SE = 2.1]; p < 0.001). TC, TG, Apo B, and all lipid ratios examined (LDL-C/HDL-C, TC/HDL-C, non-HDL-C/HDL-C, and Apo B/Apo A-I) were also reduced significantly by both rosuvastatin doses (p < 0.001). HDL-C levels increased significantly in the rosuvastatin groups (11% and 8% for 5 mg and 10 mg, respectively, vs. -0.5% for placebo; p < 0.001), as did Apo A-I levels (p < 0.05). The combination of rosuvastatin plus HRT was well tolerated with no apparent differences among treatments in the numbers or types of adverse events reported. CONCLUSIONS: Rosuvastatin 5 mg or 10 mg once daily is a well-tolerated and highly efficacious lipid-lowering therapy in postmenopausal women receiving HRT.     

Effects of hormone replacement therapy on plasma pro-inflammatory and anti-inflammatory cytokines and some bone turnover markers in postmenopausal women.

OBJECTIVE: The present study was undertaken to evaluate plasma TNFalpha, IL-1beta, IL-10; and urinary hydroxyproline (Hyp) and calcium (Ca) as bone resorption markers in postmenopausal women compared with premenopausal ones; and to assess the effects of HRT upon these cytokines and bone turnover markers. PATIENTS AND METHODS: The study involved 50 healthy postmenopausal women, and 25 healthy premenopausal women (control group). Postmenopausal women were randomly divided into two subgroups: women receiving cycle HRT schedule (0.625 mg conjugated estrogen from days 1 to 28+5 mg medroxyprogesterone acetate from days 18 to 28) for 2 months (n=25); and second subgroup consisted of women receiving continue HRT schedule (0.625 mg conjugated estrogen+2.5 mg medroxyprogesterone acetate from days 1 to 28) for 2 months (n=25). Plasma TNFalpha, IL-1beta and IL-10 concentrations were measured with ELISA kits. Fasting urinary Hyp was measured by Ehrlich's spectrophotometric reaction. Ca was determined by oxalate precipitation and the redox titration procedure. Statistical significance was analysed by Kruskal-Wallis plus post hoc Mann-Whitney U-tests for multiple comparisons, Wilcoxon signed ranks test for paired data, and Pearson correlation test. RESULTS: Compared with premenopausal individuals, postmenopausal women have increased plasma TNFalpha, IL-1beta, IL-10 (p<0.0001, p<0.0001, and p<0.001, respectively); and increased urinary Hyp and Ca concentrations (p<0.05). HRT (both cycle and continue schedules) lead to a significant decrease in TNFalpha, IL-1beta and urinary Hyp concentrations, and has no effect uppon IL-10 levels. HRT reverses increased urinary Hyp and Ca excretion to the premenopausal level. There is a significant positive correlation between pre- and post-HRT IL-1beta levels in both cycle and continue subgroups (r=0.437, p<0.05; and r=0.656, p<0.01, respectively), and between pre-HRT IL-1beta and urinary Ca (r=0.509, p<0.01; and r=0.415, p<0.05). There is a significant negative correlation between post-HRT IL-10 and TNFalpha levels in continue HRT receiving group (r=-0.446, p<0.05). Urinary Hyp in cycle and continue HRT received subgroups are correlated with post-treatment values (r=0.455, p<0.05; and r=0.776, p<0.01). CONCLUSIONS: Plasma TNFalpha, IL-1beta, IL-10; and urinary Hyp and Ca increase with menopause. We suggest that the increase of IL-10 is secondary to the elevation of TNFalpha and IL-1beta and that the increase of IL-10 is a compensatory mechanism, by which this anti-inflammatory cytokine counteracts to pro-inflammatory TNFalpha and IL-1beta, and thus balances their osteoclast activating and oxidative stress-related effects. Two months duration HRT (cycle and continue schedule) lead to the significant decrease in plasma TNFalpha, IL-1beta and urinary Hyp concentrations. HRT reverses increased Hyp and Ca excretion to the premenopausal level. So, HRT, decreasing Th1 cytokines (TNFalpha, IL-1beta) probably improve the aberation of Th1/Th2 balance that is implicated in various pathological conditions. However, because of the relatively small number of participants and short duration of the therapy, further studies are necessary to establish a risk/benefit ratio for HRT to view effects on cytokine pattern and bone metabolism.     

Raloxifene: a review of its use in postmenopausal osteoporosis

Raloxifene is a selective estrogen receptor modulator that partially mimics the effects of estrogens in bone and the cardiovascular system, while functioning as an antiestrogen in endometrial and breast tissue. In randomised placebo-controlled studies involving postmenopausal women or patients with osteoporosis, raloxifene 60 to 150 mg/day was effective in increasing bone mineral density (BMD) over 12- to 36-month periods. At the 60 mg/day recommended dosage, increases of 1.6 to 3.4%, 0.9 to 2.3% and 1.0 to 1.6% were reported in lumbar spine, femoral neck and total hip, respectively, versus < or =0.5% with placebo. Raloxifene 60 or 120 mg/day decreased the risk of vertebral fractures over a 36-month period in postmenopausal patients with osteoporosis. Significant reductions in radiographic fracture risk versus placebo (30 and 50%) occurred regardless of whether patients had existing fractures at baseline. Although raloxifene did not affect the overall incidence of nonvertebral fractures, a reduction in the incidence of ankle fracture was reported in comparison with placebo. In postmenopausal women, raloxifene 60 mg/day significantly reduced serum levels of total and low density lipoprotein cholesterol from baseline, compared with placebo. High density lipoprotein cholesterol and triglyceride levels were unaffected. Raloxifene 60 or 120 mg/day reduced the risk of invasive breast cancer by 76% during a median of 40 months' follow-up in postmenopausal patients with osteoporosis and no history of breast cancer. A relative risk reduction of 90% was reported for estrogen-receptor positive invasive breast cancers; estrogen-receptor negative cancer risk was unaffected by raloxifene. Raloxifene was generally well tolerated in clinical trials at dosages up to 150 mg/day. Adverse events thought to be related to raloxifene treatment were hot flushes and leg cramps. Venous thromboembolism was the only serious adverse event thought to be related to raloxifene treatment and a relative risk of 3.1 compared with placebo treatment was reported in patients with osteoporosis. Vaginal bleeding occurred in < or =6.4% of raloxifene-treated women but was reported by 50 to 88% of those receiving estrogens or hormone replacement therapy (HRT). Raloxifene treatment was not associated with stimulatory effects on the endometrium. CONCLUSIONS: Raloxifene significantly increases BMD in postmenopausal women and reduces vertebral fracture risk in patients with osteoporosis. In clinical trials, raloxifene was generally well tolerated compared with placebo and HRT, although its propensity to cause hot flushes precludes use in women with vasomotor symptoms. In particular, the lack of stimulatory effects on the endometrium and the reduction in invasive breast cancer incidence indicate raloxifene as an attractive alternative to HRT for the management of postmenopausal osteonorosis.     

Effects of long-term, low-dose sex hormone replacement therapy on hippocampus and cognition of postmenopausal women of different apoE genotypes

Aim： To study the effects of long-term, low-dose sex hormone replacement therapy （HRT） on the volume and biochemical changes of the hippocampus in postmenopausal women carrying apolipoprotein E （apoE） gene ε3 or ε4. Methods： Eightythree postmenopausal women who had used a low dose of HRT for over 4 years were selected as the HRT group, and 99 postmenopausal women with matched age and education were enrolled as the control group. ApoE alleles were analyzed by PCR. Magnetic resonance imaging was performed to determine the volume of the brain hippocampus. Proton magnetic resonance spectroscopy was used to detect the biochemical changes in the anterior cingulate cortex and hippocampus in apoE ε4 and ε3 carriers. Six common cognitive tests were used to make an overall evaluation of cognitive function. Results： Analysis with the apoE ε4 carriers showed that the volume of the hippocampus of the control group were significantly lower than those of the HRT group, The biochemical analysis showed that there was an increase of N-acetylaspartate （NAA）/total creatine （tCr） and a decrease of myoinositol （mI）/tCr in the hippocampus of apoE ε4 carriers in the HRT group, compared with the control group. For the apoE ε3 carders, the least squares means （LSMEAN） of the HRT group was higher than that of the control group. Conclusion： This study showed that long-term, low dose HRT might be beneficial for reducing the risk of AD development in vulnerable postmenopausal women. Meanwhile, HRT could increase the LSMEAN of apoE ε3 carriers.     

雌激素加钙剂与钙剂对比治疗绝经后妇女骨质疏松症的骨密度测定分析

目的 对使用雌激素加钙剂与钙剂治疗绝经后骨质疏松症妇女的骨密度进行测定分析。方法 将绝经后患骨质疏松症的妇女分成两组,一组75例,每天口服结合型雌激素（贝美力）0.3mg加含钙元素1g的钙剂,连脬6个月;另一组37例,每天口服含钙元素1g的钙剂,连服6个月,用以色列MYRIAD-SOUNDSCAN-2000型骨量超声测定仪检测胫骨中段骨密度。结果 口服雌激素加钙剂组骨密度总有效率100%,口服钙剂组骨密度总有效率70.3%。结论 使用雌激素加钙剂与钙剂均可以达到增加绝经后妇女的骨密度,预防和治疗绝经后骨质疏松症的目的,使用雌激素加钙剂较单补钙剂疗效更好。     

Pro-inflammatory effects of oestrogens during use of oral contraceptives and hormone replacement treatment

The effects of two third-generation monophasic combined oral contraceptives (COC) and a postmenopausal hormone replacement therapy (HRT) consisting of 2 mg 17 beta-oestradiol on the plasma level of the acute-phase indicator C-reactive protein (CRP) and other acute-phase reactants were analysed. Two studies were conducted: (1) a randomised, open-label study with two different oral contraceptive preparations with an equal dose of ethinylestradiol (30 micrograms) and a different progestogen, either 75 micrograms gestodene (GSD-EE) or 150 micrograms desogestrel (DSG-EE); blood samples of 39 young women were analysed before and after 3, 6, 12 treatment cycles; (2) a randomised, blinded placebo-controlled study with 2 mg 17 beta-oestradiol in postmenopausal women with non-insulin-dependent diabetes mellitus without signs of cardiac involvement; blood samples of 38 women were analysed before and after 6 weeks of treatment. The plasma concentration of CRP increased strongly during oral contraceptive use for both preparations; the increase persisted over 12 cycles. The already elevated CRP in postmenopausal diabetic women showed a moderate increase after 6 weeks of treatment with 17 beta-oestradiol. CRP increases during oral contraceptive use were associated with changes in some other acute-phase proteins (fibrinogen, ceruloplasmin, von Willebrand factor [vWF]) originating from the liver and vessel wall, but not in others (interleukin-6 [IL-6], serum amyloid A [SAA]). The results demonstrate an increase in a specific set of acute-phase reactants caused by oestrogen-containing preparations. It is proposed that the pro-inflammatory effect of oestrogens should be checked for a relationship with the increased risk of thromboembolism for both oral contraceptive and HRT.     

Physical performance and life quality in postmenopausal women supplemented with vitamin D: a two-year prospective study

Aim:

To investigate the effects of calcium and vitamin D supplementation on bone turnover marker levels, muscle strength and quality of life in postmenopausal Chinese women.

Methods:

A total of 485 healthy postmenopausal Chinese women (63.44±5.04 years) were enrolled in this open-label, 2-year, prospective, community-based trial. The participants were divided into group A, B, C, which were treated with calcium (600 mg/d) alone, calcium (600 mg/d) and cholecalciferol (800 IU/d) or calcium (600 mg/d) and calcitriol (0.25 μg/d), respectively, for 2 years. Serum levels of 25-hydroxyvitamin D, parathyroid hormone, β-CTX and P1NP were measured, and the muscle strength and quality of life were assessed at baseline and at 12- and 24-month follow-ups.

Results:

Four hundred and sixty one participants completed this study. Serum levels of 25-hydroxyvitamin D were significantly increased in group C, but not changed in groups A and B at 24-month follow-up. Serum levels of parathyroid hormone, bone turnover marker β-CTX and bone formation marker P1NP were significantly decreased in group C, while serum levels of β-CTX were increased in group A at 24-month follow-up. The participants in group C maintained the grip strength, while those in groups A and B exhibited decreased grip strength at 24-month follow-up. The quality of life for the participants in groups B and C remained consistent, but that in group A was deteriorated at 24-month follow-up.

Conclusion:

Supplementation with calcitriol and calcium modifies the bone turnover marker levels, and maintains muscle strength and quality of life in postmenopausal Chinese women, whereas supplementation with cholecalciferol and calcium prevents aging-mediated deterioration in quality of life.     

Economic impact of tibolone compared with continuous-combined hormone replacement therapy. In the management of postmenopausal women with climacteric symptoms in the UK

OBJECTIVE: To estimate the economic impact of using tibolone 2.5 mg compared with 17 beta-estradiol 2 mg/norethisterone acetate 1 mg (E2/NETA) in postmenopausal women with climacteric symptoms. DESIGN AND SETTING: This was a modelling study performed from the perspective of the UK's National Health Service (NHS). METHODS: The clinical outcomes from a previously reported trial were used as the clinical basis for the analysis, which showed that 48 weeks' treatment with tibolone and E2/NETA significantly alleviated the climacteric symptoms experienced by postmenopausal women. These data were combined with resource utilisation estimates derived from a panel of 10 GPs and 3 gynaecologists, enabling us to construct a Markov model depicting changes in the health status of postmenopausal women. The model was used to estimate the expected NHS costs and consequences after 48 weeks' treatment with tibolone and E2/NETA. MAIN OUTCOME MEASURES AND RESULTS: The mean expected direct healthcare cost of using tibolone and E2/NETA to manage postmenopausal women for 48 weeks was estimated to be 260 Pounds and 239 Pounds (1997/1998 prices) per patient, respectively. Starting hormone replacement therapy (HRT) with tibolone instead of E2/NETA was equally effective in alleviating climacteric symptoms (65.9 and 62.2%, respectively; p = 0.516) over 48 weeks and significantly reduced the incidence of vaginal bleeding by 36% (p < 0.0001) and breast tenderness by 57% (p < 0.0001) for a mean additional cost of 21 Pounds (ranging between -3 Pounds and 42 Pounds) per patient. The acquisition cost of HRT was the primary cost driver for tibolone-treated patients, whereas the cost of managing adverse events was the primary cost driver for E2/NETA-treated patients. CONCLUSIONS: The true cost of prescribing tibolone and E2/NETA is impacted on by a broad range of resources, not only drug acquisition costs. Although the acquisition cost of tibolone is higher than that of E2/NETA, the difference in the expected NHS cost of the first year of treatment between the 2 HRTs is negligible. This is because of the higher incidence of adverse events among E2/NETA-treated patients, which also results in a higher continuation rate among tibolone-treated patients. Factors such as patient preferences should also be taken into consideration so that treatment choices are not decided solely on the basis of acquisition costs.     

The effects of one-year simvastatin therapy on women’s bone mineral density

Only few studies have reported that bone fracture risk is decreased in hypercholesterolemic postmenopausal women treated with statin therapy. Because of a lack of longitudinal studies on the effect of statins on bones, the aim of our investigation was to estimate the simvastatin therapy effects on bone mineral density in hypercholesterolemic postmenopausal women. Our investigation was carried out on 53 postmenopausal women with hypercholesterolemia. The women included in the study were divided into two groups. Group 1 was comprised of women with two or more (n=32) atherosclerosis risk factors, whereas group 2 had women with less than two (n=21) of these risk factors. All the women included in the study were placed on a hypocholesterolemic diet and the women in group 1 were additionally treated with 20 mg of simvastatin daily. The parameters of lipid status, body mass index, and L2–L4 densitometry were determined at baseline and then after one year. The simvastatin-treated group showed significant improvement of lipid parameters and increased bone mineral density. Finally, changes in bone mineral density between the groups showed significant differences (p<0.05). Although our investigation was carried out on a small group, our results showed a positive effect of the simvastatin therapy on the bone mineral density of postmenopausal women.     

Lipid-modifying effects of rosuvastatin in postmenopausal women with hypercholesterolemia who are receiving hormone replacement therapy*

SUMMARY

Objective: To evaluate the efficacy and safety of rosuvastatin in postmenopausal women with hypercholesterolemia who are receiving hormone replacement therapy (HRT) in a randomized, double-blind, placebo-controlled trial.

Methods: After a 6-week dietary lead-in period, 135 postmenopausal women who had been taking a stable HRT regimen for at least 3 months were randomized to receive rosuvastatin 5?mg, 10?mg or placebo for 12 weeks. Fasting levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG) were assessed at weeks 0, 2, 6, 10, and 12; apolipoprotein (Apo) B and Apo A-I were measured at weeks 0 and 12.

Results: Rosuvastatin 5?mg and 10?mg significantly reduced LDL-C by 38% (SE = 2.1) and 49% (SE = 2.1), respectively, compared with placebo (1% [SE = 2.1]; p < 0.001). TC, TG, Apo B, and all lipid ratios examined (LDL-C/HDL-C, TC/HDL-C, non-HDL-C/HDL-C, and Apo B/Apo A-I) were also reduced significantly by both rosuvastatin doses (?p < 0.001). HDL-C levels increased significantly in the rosuvastatin groups (11% and 8% for 5?mg and 10?mg, respectively, vs. –0.5% for placebo; p < 0.001), as did Apo A-I levels (?p < 0.05). The combination of rosuvastatin plus HRT was well tolerated with no apparent differences among treatments in the numbers or types of adverse events reported.

Conclusions: Rosuvastatin 5?mg or 10?mg once daily is a well-tolerated and highly efficacious lipid-lowering therapy in postmenopausal women receiving HRT.