Effects of hormone replacement therapy on plasma homocysteine and C-reactive protein levels.

In order to investigate the effect of hormone replacement therapy (HRT) on plasma homocysteine and C-reactive protein (CRP) levels 46 healthy postmenopausal women were prospectively enrolled. HRT, which was either 0.625 mg/day conjugated equine estrogen (CEE) plus 2.5 mg/day medroxyprogesterone acetate (MPA) or 0.625 mg/day CEE alone were administered. After 6 months, estrogen alone significantly increased serum CRP concentrations (p = 0.039), however, estrogen plus progesterone therapy did not significantly alter serum CRP levels. Both regimens significantly decreased plasma homocysteine levels (CEE group p = 0.034, CEE+MPA group p = 0.007). It was concluded that the reduction in plasma homocysteine levels with both regimens might contribute to the cardiovascular benefit of HRT and the CRP raising effect of estrogen might be partially prevented by the addition of progesterone.     

Hormone replacement therapy and plasma homocysteine levels.

OBJECTIVE: To compare the effects of 4 and 12 weeks of combined estradiol-progestogen replacement with unopposed estradiol therapy on fasting plasma total homocysteine concentrations in healthy postmenopausal women. METHODS: In this prospective, 12-week study in healthy postmenopausal women, we randomly assigned 59 women to sequentially combined daily 2 mg estradiol (E2) plus either trimegestone 0.5 mg daily or dydrogesterone 10 mg daily (n = 28), or to unopposed daily 2 mg estradiol (n = 16), or to placebo (n = 15). RESULTS: Fasting plasma total homocysteine concentrations decreased by 9.4% in the combined estradiol-progestogen group and by 5.1% in the estradiol-only group, and they increased by 2.4% in the placebo group (analysis of covariance: combined hormone replacement therapy compared with placebo (P = .02); combined therapy compared with estradiol (P = .23); and estradiol compared with placebo (P = .26). Reductions were detectable after 4 weeks of combined estradiol-progestogen treatment. The data suggest an additional progestogen-related reduction in homocysteine levels of 0.7 micromol/L and 0.4 micromol/L after 4 and 12 weeks, respectively. Women with a baseline homocysteine concentration in the highest quartile had significantly greater reductions in homocysteine compared with women with an initial homocysteine value in the lowest quartile. CONCLUSION: Fasting total homocysteine concentrations were significantly reduced by combined estradiol-progestogen replacement. Women with high homocysteine levels at baseline benefit the most. The progestogens used in this study did not have an unfavorable effect on homocysteine metabolism.     

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

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

Effect of long-term hormone replacement therapy on plasma homocysteine in postmenopausal women: a randomized controlled study

OBJECTIVE: The purpose of this study was to investigate the long-term effect of hormone replacement therapy on total homocysteine and to study whether there was any difference in effect between opposed and unopposed hormone replacement therapy or whether the methylenetetrahydrofolate reductase C677T polymorphism was associated with the effect of hormone replacement therapy on total homocysteine. STUDY DESIGN: Two hundred nine healthy postmenopausal women were randomized to hormone replacement therapy (n = 103) or no substitution (n = 106) 5 to 7 years earlier. RESULTS: Women who received hormone replacement therapy had significantly lower total homocysteine concentrations than women in the control group; median total homocysteine values were 8.6 micromol/L and 9.7 micromol/L, respectively, in a per-protocol analysis (P =.02). The effect was comparable in all methylenetetrahydrofolate reductase genotypes, and no difference between unopposed and opposed hormone replacement therapy could be demonstrated. Similar results were obtained when an intention-to-treat analysis was performed. CONCLUSION: Long-term hormone replacement therapy results in lower total homocysteine concentrations in all methylenetetrahydrofolate reductase genotypes without demonstrable difference in effect between unopposed and opposed hormone replacement therapy.     

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 hormone replacement therapy and methylenetetrahydrofolate reductase polymorphism on plasma folate and homocysteine levels in postmenopausal Japanese women

OBJECTIVE: To evaluate the relationships among the methylenetetrahydrofolate reductase (MTHFR) polymorphism, plasma folate, total homocysteine (Hcy) levels, lipids, and the reduction of Hcy levels resulting from hormone replacement therapy (HRT). DESIGN: Clinical study. SETTING: Outpatient department of obstetrics and gynecology in a general hospital. PATIENT(S): Two hundred seventeen postmenopausal Japanese women. INTERVENTION(S): Of the 217 women, 172 patients were under continuous treatment with oral conjugated equine estrogen and medroxyprogesteron acetate. MAIN OUTCOME MEASURE(S): Fasting Hcy, folate, methionine, lipids, and apolipoproteins were measured before and after 3 months of HRT. RESULT(S): The plasma Hcy concentration was significantly higher in the low folate than in the high-folate group only in patients with the homozygous (T/T) mutant. Plasma Hcy concentrations were significantly correlated with age (R = 0.64, P=.02) or years since menopause (R = 0.73, P=.02) only in the low-folate group with T/T. The plasma Hcy concentration decreased significantly in all genotypes after 3 months of HRT, but the levels of serum folate and methionine remained unchanged. CONCLUSION(S): The MTHFR polymorphism was associated with a higher Hcy concentration, and this association was related to the serum folate level. Hormone replacement therapy reduced the plasma Hcy concentration independently of the MTHFR polymorphism.     

Effects of long-term oral hormone replacement therapy on plasma nitric oxide and beta-endorphin levels in postmenopausal women

OBJECTIVES: The aim of this study is to evaluate the relationship between plasma nitric oxide (NO) and beta-endorphin levels in women using hormone replacement therapy (HRT) for 12 months. MATERIAL AND METHODS: Our study group was composed of 55 patients who were in at least their second postmenopausal year. Of the 55 patients, 25 were in the control group. All 30 women in the study group received 2 mg 17beta-estradiol + 1 mg norethisterone acetate tablets daily for 12 months. Plasma NO and beta-endorphin levels were measured both before and after the study period and possible relationships were analyzed. RESULTS: There was a significant increase in both beta-endorphin (p = 0.0001, 10.93 +/- 2.25 vs. 14.85 +/- 2.49) and NO (p = 0.0001, 19.79 +/- 4.01 vs. 27.83 +/- 10.27) levels measured after the study in the HRT group. A correlation was seen between the increments in beta-endorphin and NO levels in the HRT group. CONCLUSION: Continuous combined HRT raises both plasma NO and beta-endorphin levels and a close relationship was found between the two molecules after therapy. We postulate that the increment in these molecules may explain some of the beneficial effects of HRT on cognitive function and mood.     

Comparison of the effect of oral and transdermal hormone therapy on fasting and postmethionine homocysteine levels

OBJECTIVE: To compare the modifications on basal and post-methionine homocysteine (Hcy) levels induced by transdermal vs. oral continuous combined hormone therapy (HT). DESIGN: Prospective randomized study. SETTING: Outpatient service at university hospital. PATIENT(S): Twenty-four healthy postmenopausal women. INTERVENTION(S): Six-month administration of transdermal (50 microg/d of E(2) and 140-170 microg/d of norethisterone [NET] acetate; n = 12) or oral (2 mg of E(2) and 1 mg of NET acetate; n = 12) HT. MAIN OUTCOME MEASURE(S): Fasting levels of Hcy, cysteine (Cys), folate, and vitamin B12. Post-methionine Hcy concentrations. RESULT(S): During HT, a slight decrease of fasting Hcy (8.9 [6.7; 15.2] micromol/L vs. 8.3 [4.9; 12.0] micromol/L) and fasting Hcy/Cys, a possible index of Hcy trans-sulfuration (0.061 [0.039; 0.107] micromol/L vs. 0.048 [0.032; 0.093] micromol/L) was observed. Modifications were similar in the transdermal and oral group. Net decreases of Hcy and Hcy/Cys observed during HT were related linearly to pretreatment values (r = 0.821 and r = 0.775, respectively), and were significant for Hcy above, but not below, 9 micromol/L. Transdermal (33.5 [27.5; 75.9] micromol/L vs. 28.4 [17.4; 48.9] micromol/L) or oral HT (36.1 [17.7; 74.8] micromol/L vs. 29.9 [17.5; 50.3] micromol/L), decreased, similarly, post-methionine Hcy levels. CONCLUSION(S): Similarly to oral, transdermal HT reduces post-methionine Hcy and fasting Hcy when it is elevated.     

Interaction between hormone replacement therapy preparations and oral anticoagulant therapy

There is limited information regarding the interaction of hormone replacement therapy (HRT) and oral anticoagulants. Following the acute over-anticoagulation of two women shortly after the initiation of tibolone, we have undertaken a retrospective review of anticoagulated women to determine if the dose of oral anticoagulants and quality of anticoagulant control are affected by the introduction of HRT. We demonstrate that acute over-anticoagulation consistently occurs following the commencement of tibolone and requires anticoagulant dose modification to re-establish target international normalised ratio (INR). In contrast, non-tibolone HRT preparations do not consistently alter anticoagulant control or dose requirements.     

Effect of oral conjugated equine estrogen combined with medroxyprogesterone acetate on plasma homocysteine levels in postmenopausal women

Conjugated equine estrogen alone or combined with medroxyprogesterone acetate lowered homocysteine levels in postmenopausal women. Regardless of the dosage of progestin used, there was no impact on homocysteine metabolism after 3 years of therapy.     

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.     

Effect of the cessation of long-term hormone replacement therapy on plasma plasminogen activator inhibitor-1 and fibrinogen

OBJECTIVE: Hormone replacement therapy (HRT) has generally been documented to reduce plasminogen activator inhibitor-1 (PAI-1) and fibrinogen levels in plasma of postmenopausal women. We used a wash out protocol to study whether stopping long-term HRT with estrogen alone or a combination of estrogen-progestin have different effects on these markers of hemostasis. STUDY DESIGN: Thirty healthy postmenopausal women on HRT participated. Fifteen had estradiol valerate, and 15 had estradiol valerate and levonorgestrel. Each was studied after long-term HRT (period 1), four weeks after cessation of the treatment (period 2, wash out), and three weeks after reintroducing the therapy (period 3). RESULTS: In the estrogen group, PAI-1 increased by 18% during the wash out period (P=0.013) and decreased by 22% after reintroduction of therapy (P=0.001). In the combined therapy group, there was a trend of PAI-1 to increase by 18% when therapy was discontinued (P=0.17), and it decreased by 25% after reintroduction of hormone replacement therapy (P=0.036). Fibrinogen was initially lower in the estrogen group compared with the combined therapy group (p=0.014), and did not change during wash out. CONCLUSION: This wash out study shows that cessation of long-term HRT unfavorably increases PAI-1, but appears to have no adverse effect on fibrinogen.     

Postmenopausal changes in serum cytokine levels and hormone replacement therapy

OBJECTIVE: Our purpose was to investigate the effect of hormone replacement therapy on the postmenopausal changes in serum cytokine levels. STUDY DESIGN: Fifteen cytokines were measured by an enzyme-linked immunosorbent assay in 97 untreated and hormone replacement-treated women. Thirteen women were examined before and during hormone replacement therapy. RESULTS: Serum concentrations of macrophage colony-stimulating factor were significantly (P < .05) lower during the early postmenopausal period (< or = 10 years) than the values in premenopause and the elevated levels in the late postmenopausal period (< or = 30 years). A significant increase in tumor necrosis factor alpha and a decline in transforming growth factor beta1 were found in late postmenopausal women. Serum levels of macrophage colony-stimulating factor in women receiving hormone replacement therapy were significantly higher than those in untreated postmenopausal women. Furthermore, hormone replacement therapy induced a significant (P < .01) increase in serum levels of macrophage colony-stimulating factor, whereas serum levels of other cytokines were not affected. CONCLUSION: It is well documented that macrophage colony-stimulating factor lowers serum cholesterol concentrations and prevents atherosclerosis. Inducing the production of macrophage colony-stimulating factor is a possible additional mechanism of hormone replacement therapy in mediating the antiatherogenic effect.     

Long-term effects of continuous oral and transdermal estrogen replacement therapy on sex hormone binding globulin and free testosterone levels.

OBJECTIVE: To determine the long-term effects of estrogen replacement therapy on sex hormone binding globuline (SHBG) and free testosterone (fT) levels in surgical postmenopausal women. STUDY DESIGN: Forty patients with surgical menopause were enrolled in this prospective study. The women were randomly divided into two groups. The first group received oral therapy (continuous conjugated equine estrogens (CEE) - 0.625mg per day) and the second group received transdermal therapy (patches delivering continuous 17beta-estradiol (E2)--0.05mg per day). Serum SHBG and fT levels were determined at baseline and after first and second years of treatment. Two-way repeated measures analysis of variance with Bonferroni adjusted post-hoc test and unpaired-t-test were performed for statistical analysis with SPSS program. RESULTS: Serum SHBG levels increased significantly with oral CEE after first year of treatment (P<0.05) and remained at this level for the next year. Transdermal therapy did not affect SHBG levels after first and second years (P<0.05). Serum fT levels did not change significantly in either group at the end of the first or second years (P<0.05) although there was a significant difference between the groups after 2 years (P<0.05). CONCLUSION: Oral conjugated estrogens increased SHBG levels during therapy. This effect may balance the increased estrogen and androgen stimulation on breast tissue and may be more beneficial to the cardiovascular system in postmenopausal women.     

Role of postmenopausal hormone replacement therapy on body fat gain and leptin levels

During menopause women tend to gain body fat. The increase in adiposity seems to be a consequence of the decline in endogenous estrogens and the reduced energy expenditure. The role of post-menopausal hormone replacement therapy (pHT) in modulating visceral obesity is controversial. Some studies have shown that pHT has no effect on body weight while in other studies pHT increased body weight. Leptin is an adipocyte-derived hormone and its levels reflect the amount of adipose tissue. Obesity is associated with elevated serum leptin levels. The effect of pHT on leptin levels is also controversial. In some studies pHT increased leptin levels while other studies have not confirmed this increasing effect. The major problem encountered during administration of hormone therapy seems to be the timing of pHT initiation which is a strong confounder on the effect of pHT on leptin levels in postmenopausal women.     

A comparison of circulating hormone levels in postmenopausal women receiving hormone replacement therapy.

Seventeen postmenopausal subjects were randomized into this comparative study of esterified estrogen 0.625 mg (Estratab), esterified estrogen 0.625 mg plus 1.25 mg methyltestosterone (Estratest H.S.), or conjugated estrogen 0.625 mg (Premarin). Sixteen subjects completed the study in which plasma hormone concentrations of estrone and estradiol were assessed at various time points. There were no significant differences among the treatment groups.