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。     

The effect of the phytoestrogen genistein and hormone replacement therapy on homocysteine and C-reactive protein level in postmenopausal women

BACKGROUND: The aim of the study was to evaluate the effect, in postmenopausal women, of the phytoestrogen genistein and hormone replacement therapy (HRT) on circulating two independent factors of cardiovascular risk: homocysteine and C-reactive protein (CRP). METHODS: Ninety healthy postmenopausal women, from 50 to 60 years of age, were randomly assigned to receive genistein (n = 30; 54 mg/die) or continuous combined estrogen/progestin therapy (17-beta-estradiol 1 mg plus norethisterone acetate 0.5 mg) or placebo. Plasma homocysteine and serum CRP were measured at baseline and after 6 months of treatment. RESULTS: In the genistein group, plasma homocysteine and serum CRP showed no statistically significant difference from baseline (homocysteine: 11.36 +/- 0.39 micromol/l; CRP: 1.73 +/- 0.31 mg/l) to 6 months treatment (homocysteine: 10.72 +/- 0.46 micromol/l; CRP: 2.13 +/- 0.45 mg/l), without any significant difference versus the placebo group (homocysteine: 11.25 +/- 0.43 micromol/l; CRP: 1.74 +/- 0.22 mg/l). In the HRT group there was a slight, but not significant reduction, of plasma homocysteine mean value from baseline (11.21 +/- 0.44 micromol/l) to 6 months treatment (10.45 +/- 0.38 micromol/l); whereas CRP mean value at the end of treatment (3.30 +/- 0.55 mg/l) was significantly higher from baseline (1.61 +/- 0.25 mg/l) (P < 0.01). However, after 6 months, no significant difference existed with the other two groups. CONCLUSIONS: The phytoestrogen genistein, after 6 months treatment, does not modify the independent cardiovascular risk linked to circulating homocysteine or CRP level. Our experience confirms critical increase of CRP serum level after HRT treatment, but not plasma homocysteine significant variation.     

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.     

Failure of the combination of sequential oral and transdermal estradiol plus norethisterone acetate to affect plasma homocysteine levels

Objective: A high level of plasma homocysteine may be deleterious to vascular health. We therefore compared the effect of combinations of sequential oral and transdermal estradiol plus norethisterone acetate on plasma homocysteine.

Design: Prospective, randomized study.

Setting: Outpatient department of obstetrics and gynecology in a university hospital.

Patient(s): Forty-two healthy, nonsmoking postmenopausal women starting hormone replacement therapy (HRT) to control climacteric symptoms.

Intervention(s): In a randomized order, the women started using either oral HRT (2 mg of estradiol on days 1–12, 2 mg of estradiol plus 1 mg of norethisterone acetate (NETA) on days 13–22, and 1mg of estradiol on days 23–28; N = 21) or transdermal HRT (50 μg/d of estradiol on days 1–28 and 250 μg/d of norethisterone acetate on days 15–28, N = 21) for 1 year.

Main Outcome Measure(s): Fasting plasma levels of homocysteine were measured before the treatment and during the combined estradiol-plus-NETA phases of the sixth and 12th treatment cycles.

Result(s): Basal homocysteine levels in the oral group (8.2 ± 3.1 μmol/L, mean plusmn;SD) and transdermal group (8.7 plusmn; 1.8 μmol/L, mean plusmn;SD) were not affected by the estradiol-plus-NETA combination.

Conclusion(s): Neither an oral nor a transdermal combination of sequential estradiol and NETA causes significant changes in plasma homocysteine in Finnish postmenopausal women with normal baseline homocysteine levels.     

Effects of tibolone on plasma homocysteine levels in postmenopausal women

OBJECTIVE: To investigate the effects of tibolone on levels of plasma homocysteine, an independent risk factor for cardiovascular disorders, in postmenopausal women. DESIGN: Prospective, randomized clinical study. SETTING: University hospital. PATIENT(S): Postmenopausal healthy women. INTERVENTION(S): Tibolone (2.5 mg/d) or calcium (1250 mg/d) and conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (5 mg/d) were administered orally for 6 months. Blood samples were collected at the start and the end of therapy. MAIN OUTCOME MEASURE(S): Plasma homocysteine levels. RESULT(S): Administration of tibolone and calcium caused only a 4% decrease in plasma homocysteine levels compared with initial levels. In contrast, conjugated equine estrogens plus medroxyprogesterone acetate caused a 29% decrease in plasma homocysteine levels. CONCLUSION(S): Despite the reported beneficial effect of tibolone on the serum lipid profile, tibolone had no statistically significant effect on serum homocysteine levels in postmenopausal women. The possible cardiovascular protective role of tibolone might be unrelated to its effects on homocysteine levels.     

Peripheral blood lymphocyte subpopulations of postmenopausal women with hormone replacement therapy]

The effect of hormone replacement therapy on cellular immunity of postmenopausal women was studied by flow cytometry (FACS). Lymphocyte subsets in peripheral blood before and after hormonal replacement therapy (HRT) were measured. After 6 months of HRT with the sequential combined drug Klimonorm(R) (2 mg estradiol valerate and 0,15 mg levonorgestrel) the cytotoxic T-cells (CD8) were reduced and the CD4/CD8 ratio was increased significantly (p < 0,05).     

Testosterone addition to estrogen therapy – Effects on inflammatory markers for cardiovascular disease

Objective.?To analyze the effects of testosterone addition to estrogen therapy in comparison with estrogen alone on cardiovascular risk factors in postmenopausal women.

Methods.?Fifty surgically postmenopausal women were included in this double-blind, placebo-controlled and randomized study to receive daily oral treatment with estradiol valerate 2?mg + placebo (E/P) or estradiol valerate 2?mg + testosterone undecanoate 40?mg (E/T) for 24 weeks and then switched to the other regimen for another 24 weeks. Sex hormones, High sensitivity CRP (hsCRP), Interleukin-6 (IL-6), Tissue necrosis factor (TNF)-α, Insulin-like growth factor binding globulin (IGFBP-1), vascular cell adhesion molecule (VCAM)- 1, and homocysteine were analyzed at baseline and after 6 and 12 months.

Results.?Estradiol and androgens increased as expected during the treatments. After 6 months of E/P, increases of hsCRP and IGFBP-1 and a decline of VCAM were recorded, whereas IL-6, TNF-α, and homocysteine were unchanged. When testosterone was added to estrogen, the increase of IGFBP-1 and decline in VCAM was similar as with estrogen treatment alone. However, testosterone addition counteracted the estrogen-induced rise in hsCRP but had no effects on IL-6, TNF-α, and homocysteine.

Conclusion.?Data suggest that testosterone addition to estrogen treatment in postmenopausal women has a modest influence on inflammatory markers and there were no apparent adverse effects. On the contrary, the estrogen-induced increase in hsCRP was suppressed.     

Effects of low-dose 17-beta-estradiol plus norethisterone acetate and tibolone on fasting plasma homocysteine levels in postmenopausal women

BACKGROUND: Many postmenopausal women currently receive hormone replacement therapy. The use of low-dose 17beta-estradiol plus norethisterone acetate and tibolone for hormone replacement therapy is not uncommon in postmenopausal women. Homocysteine, which is known to be an independent risk factor for the development of cardiovascular disease, is found in increased levels postmenopause. This study compared the effects of low-dose 17beta-estradiol plus norethisterone acetate and tibolone on the fasting plasma homocysteine level in healthy postmenopausal women. METHODS: Healthy postmenopausal women (n = 44) were enrolled in the study. Women randomly assigned received 1 mg of 17beta-estradiol plus 0.5 mg of norethisterone acetate or 2.5 mg tibolone during a period of 12 weeks. Fasting plasma homocysteine levels were measured at baseline, the 4th week, and the 12th week of therapy. RESULTS: In the 4th week there were no significant changes in plasma homocysteine levels in both groups (p > 0.05). However at the end of the 12th week the plasma homocysteine levels were reduced significantly in both groups (p < 0.05). CONCLUSION: Low-dose 17beta-estradiol plus norethisterone acetate and tibolone lower the fasting plasma homocysteine levels in healthy postmenopausal women.     

Effect of different hormone replacement therapy regimens on circadian blood pressure profile and active renin in postmenopausal women.

Hormone replacement therapy (HRT) was considered as main prevention of cardiovascular disease (CVD) in postmenopausal women. Mechanisms of vasoprotective effect of this treatment are complex. However, recent data give rise to some uncertainties about HRT benefits and risks. Little is known about the effects of oral and transdermal HRT regimens on the renin-angiotensin-aldosterone system (RAS) and blood pressure (BP). This 3-month study comprised 28 menopausal women (age range 45-55 years) divided into two groups: Group 1: 12 normotensive women with natural occurrence of menopause receiving oral treatment with Climen (Schering) containing estradiol valerate and cyproterone acetate; Group 2: 16 normotensive women with surgically induced menopause receiving transdermal application of Climara (Schering) containing 17beta-estradiol. There were no significant differences in office BP before and after treatment with Climara or Climen. However, ambulatory monitoring showed a significant fall in systolic BP (day-time, night-time and total 24-h) when estradiol alone was used. A similar trend towards lower values of systolic BP that was significant only for the night-time BP was observed after treatment with Climen. There were no significant changes in diastolic BP after both treatment regimens. Heart rate (day-time and 24-h) was significantly lower after transdermal estradiol treatment. There was no significant change in active renin after both treatment regimens. The present study showed that both treatment regimens resulted in lower ambulatory BP in normotensive postmenopausal women with more notable reduction in night-time BP. Increase in nocturnal dipping may account in part for the beneficial cardiovascular effects of HRT including decreased end-organ damage.     

Vasoactive biomarkers and oxidative stress in healthy recently postmenopausal women treated with hormone replacement therapy.

BACKGROUND: Despite biologically plausible mechanisms for cardiac protection from estrogen therapy, recent clinical trials have suggested possible cardiovascular risk rather than benefit. However, it has been speculated that cardioprotective benefits from hormone replacement therapy (HRT) may be more evident in the early postmenopausal period. We have previously reported early beneficial effects on biochemical markers of endothelial function in healthy women after short-term estradiol replacement therapy. In this study we aimed to evaluate the effect of long-term HRT on different vasoactive factors and oxidative stress in healthy recently postmenopausal women. METHODS: Fifteen women (age 50 +/- 1 years, time since menopause 1.6 +/- 0.1 years) were randomized to a sequential oral and transdermal estradiol regimen (2 mg oral micronized 17beta-estradiol/day or 1.5 mg 17beta-estradiol gel/day). Oral dydrogesterone (10 mg/day, 12 days/month) was then cyclically combined with either of the estrogen therapies for 1 year. Blood samples were collected at baseline and after 1, 2, 6 and 12 months of therapy to evaluate levels of follicle stimulating hormone (FSH), estradiol, 6-keto PGF1alpha (prostacyclin metabolite), nitrite/nitrate, epinephrine, norepinephrine, 8-isoprostane (8-epi PGF2alpha) and lipid profile values. RESULTS: FSH levels decreased (p < 0.001) while estradiol levels increased (p < 0.001) during HRT. Levels of epinephrine (p < 0.001), norepinephrine (p < 0.01), mean blood pressure (p < 0.01) and low density lipoprotein (LDL) cholesterol (p < 0.01) decreased, and nitrite/nitrate levels increased (p < 0.01) during HRT, which did not significantly affect 8-epi PGF2alpha levels. CONCLUSIONS: One-year HRT significantly reduced the levels of catecholamines, mean blood pressure and LDL cholesterol while it increased levels of nitrite/nitrate, indicating cardiovascular benefit in healthy recent postmenopausal women. Levels of 8-epi PGF2alpha did not change, suggesting no evident relationship between HRT and oxidative stress.     

Continuous combined hormone replacement therapy compared with tibolone

Objective: To compare relief of vasomotor symptoms, changes in lipoproteins, and bleeding patterns in postmenopausal women receiving either continuous combined hormone replacement therapy (HRT) of estradiol valerate and norethisterone or tibolone 2.5 mg/day.Methods: In a multicenter, randomized, open-label study, 235 postmenopausal women received one of the above-mentioned treatments. Fasting lipoproteins were measured at baseline and at 3, 6, and 12 months. At each visit, participants completed Greene climacteric questionnaires and recorded any bleeding episodes. Data are presented as mean ± standard deviation if normally distributed, median and interquartile range if non-normally distributed, or as frequency count. For menopausal symptoms and diary card data, the differences were tested by Wilcoxon rank-sum test.Results: One hundred sixteen women received continuous combined HRT and 119 women received tibolone; 72 and 76 women, respectively, completed 12 months of therapy. Both treatments effectively relieved vasomotor symptoms and reduced serum total cholesterol. Continuous combined HRT, but not tibolone, significantly reduced low-density lipoprotein levels. Both treatments reduced high-density lipoprotein levels, but the effect was more profound with tibolone. The initial bleeding score was higher for women taking continuous combined HRT; however, by the end of the study, the percentages of amenorrheal women were comparable. Endometrial histology was similar for both treatments at the end of the study, although two cases of proliferative endometrium were found in the tibolone group.Conclusion: Estradiol valerate–norethisterone continuous combined HRT controls symptoms and is associated with a safe lipid profile.     

Effect of different hormone replacement therapy regimens on circadian blood pressure profile and active renin in postmenopausal women

Hormone replacement therapy (HRT) was considered as main prevention of cardiovascular disease (CVD) in postmenopausal women. Mechanisms of vasoprotective effect of this treatment are complex. However, recent data give rise to some uncertainties about HRT benefits and risks. Little is known about the effects of oral and transdermal HRT regimens on the renin-angiotensin-aldosterone system (RAS) and blood pressure (BP). This 3-month study comprised 28 menopausal women (age range 45-55 years) divided into two groups: Group 1: 12 normotensive women with natural occurrence of menopause receiving oral treatment with Climen^® (Schering) containing estradiol valerate and cyproterone acetate; Group 2: 16 normotensive women with surgically induced menopause receiving transdermal application of Climara^® (Schering) containing 17β-estradiol. There were no significant differences in office BP before and after treatment with Climara or Climen. However, ambulatory monitoring showed a significant fall in systolic BP (day-time, night-time and total 24-h) when estradiol alone was used. A similar trend towards lower values of systolic BP that was significant only for the night-time BP was observed after treatment with Climen. There were no significant changes in diastolic BP after both treatment regimens. Heart rate (day-time and 24-h) was significantly lower after transdermal estradiol treatment. There was no significant change in active renin after both treatment regimens. The present study showed that both treatment regimens resulted in lower ambulatory BP in normotensive postmenopausal women with more notable reduction in night-time BP. Increase in nocturnal dipping may account in part for the beneficial cardiovascular effects of HRT including decreased end-organ damage.     

Effect of oral hormone replacement therapy on plasma homocysteine levels

BACKGROUND: Various inherited or acquired conditions can lead to mild or severe hyperhomocysteinemia, which has toxic effects on the vascular endothelium. It has been reported that hormone replacement therapy is associated with decreased homocysteine plasma levels, but this is still a controversial issue. PURPOSE: To compare homocysteine plasma levels in women before and after 3 months of oral hormone replacement therapy. METHODS: Twenty-four women were selected to take part in the study. Blood samples were collected immediately before hormone replacement therapy (cyclic association of 2 mg of estradiol valerate and 1 mg of cyproterone acetate) and three months after the beginning of hormone replacement therapy. Samples collected before hormone replacement therapy were used as controls. Plasma homocysteine levels and the presence of C677T mutation in the methylene tetrahydrofolate reductase gene were evaluated in all participants. RESULTS: The methylene tetrahydrofolate reductase gene mutation was detected in 8 women (33.3%) in heterozygosis, in 3 (12.5%) in homozygosis, and 13 women (54.2%) did not present the mutation. No significant differences were observed in homocysteine levels before and after three months of oral hormone replacement therapy, regardless of the C677T genotype. CONCLUSIONS: The results obtained indicate that homocysteine plasma levels are not affected after three months of oral hormone replacement therapy.     

Effects of estrogen and psychological stress on plasma homocysteine levels

OBJECTIVE: To investigate the effects of estrogen (E) and psychological stress on plasma total homocysteine levels in relation to menopausal status. DESIGN: Double-blind, randomized, placebo-controlled study. SETTING: The General Clinical Research Center of a university hospital. PATIENT(S): Thirty-six postmenopausal women and 26 premenopausal women. Both samples were healthy nonsmokers. INTERVENTION(S): Both premenopausal and postmenopausal women were subjected to a 6-minute psychological stressor. Postmenopausal women were randomized to one of three treatment arms: 2 mg of E2 or 2 mg of E2 + 5 mg of medroxyprogesterone acetate (MPA), or a placebo, all of which were given orally for 3 months. The psychological stressor was readministered after the 3-month regimen. MAIN OUTCOME MEASURE(S): Plasma total homocysteine levels were measured before and after the psychological stressor on one occasion for premenopausal women and before and after hormone replacement or placebo for postmenopausal women. RESULT(S): There were no significant differences in homocysteine levels between premenopausal (7.2 +/- 1.7 micromol/L; mean +/- SD) and postmenopausal women (7.9 +/- 2.06; mean +/- SD). There was no effect of stress or hormone replacement on homocysteine levels. CONCLUSION(S): Psychological stress, menopausal status, and oral hormone replacement therapy (HRT) do not affect plasma total homocysteine levels in women with normal basal homocysteine levels.     

Sequentially combined estradiol valerate plus levonorgestrel therapy decreases 18:1 trans-fatty acid content of plasma lipids in healthy postmenopausal women.

Trans-fatty acids (TFA) have been classified as atherogenic dietary constituents but the effect of hormone replacement therapy (HRT) on their concentrations is not known. We used a washout protocol to study the effect of long-term estrogen and combined estrogen-progestin HRT on plasma elaidate (18:1t), which is the trans isomer of oleate and the major TFA in the diet. The study group comprised 15 women receiving estradiol valerate HRT and 15 women receiving combined HRT with estradiol valerate and levonorgestrel. The concentrations of elaidate in plasma phospholipids, cholesteryl esters and triglycerides were determined by gas chromatography. At baseline, the total plasma elaidate concentration was lower in the combined HRT group than in the estradiol valerate HRT group (p < 0.01). In the combined HRT group, the concentration of elaidate increased significantly after withdrawal of HRT (p < 0.001) and decreased again to the baseline level after restart of therapy (p < 0.001). These changes were due to decreases in the concentrations of phospholipids and triglycerides; in phospholipids there was also a proportional decrease of elaidate. There were no changes in elaidate in women receiving estradiol valerate alone. Our results suggest that long-term combined HRT treatment decreases plasma TFA, which is not achieved by estrogen alone.     

Randomized control study of the effects of raloxifene on serum lipids and homocysteine in older women

OBJECTIVE(S): Raloxifene, a selective estrogen receptor modulator, has beneficial estrogen agonist effects on bone and cardiovascular risk factors and estrogen antagonist effects on the breast and uterus. Limited clinical data have shown a sustained decrease in total cholesterol, low-density lipoprotein cholesterol, and homocysteine levels; an elevated homocysteine level is an independent risk factor for atherosclerosis. All of these studies were conducted in relatively young populations of women (mean age, 52-54 years). Raloxifene does not affect hot flushes, a major immediate symptom of menopause. This drug may therefore be useful in older women to prevent osteoporosis and cardiovascular disease. The aim of this clinical study was to evaluate the effects of raloxifene on plasma lipids and homocysteine in older women. STUDY DESIGN: The subjects were 45 healthy postmenopausal women, aged 60 to 70 years. The women were randomly assigned to therapy with raloxifene or placebo, 60 mg/d for 1 year. Twenty-six women received raloxifene and 19 received placebo. Checkups were performed every 3 months. At baseline and after 3, 6, 9, and 12 months of treatment we measured homocysteine, total serum cholesterol, triglycerides, and both high-density lipoprotein and low-density lipoprotein cholesterol. RESULTS: An effect on lipids was evident by 3 months with no significant additional modification at 12 months. Mean low-density lipoprotein cholesterol levels were lowered by 15% and total cholesterol was lowered by 8.5%. No reduction in high-density lipoprotein cholesterol or triglycerides was observed. After 3 months of therapy, homocysteine was significantly lower than at baseline (9.9 +/- 1.6 vs 11 +/- 2.1 micromol/L; P < .05). The greatest reduction with respect to baseline was reached after 6 months of therapy (-19.5% +/- 3%; P < .05). CONCLUSION(S): The results of our study show that raloxifene at a dose of 60 mg/d reduces serum concentrations of low-density lipoprotein cholesterol and total cholesterol in healthy older women. Our study shows that in older women raloxifene leads to a 19.5% +/- 3% reduction in fasting homocysteine levels. Raloxifene may have a favorable effect on the incidence of cardiovascular disease in older women.     

Menopause rather than estrogen modifies plasma homocysteine levels.

OBJECTIVES: To investigate the effects of transdermal estrogen replacement therapy (ERT) on plasma homocysteine levels in postmenopausal women who underwent total hysterectomy with bilateral oophorectomy. METHODS: In two-phase open longitudinal prospective study we compared 28 premenopausal women and 35 healthy postmenopausal patients to evaluate the effect of transdermal estrogen treatment (TTS 50 twice-weekly) on plasma homocysteine levels after 6 and 12 months of therapy. RESULTS: The study showed statistically relevant differences (P<0.05) in baseline plasma homocysteine concentration between the patients in premenopausal and in postmenopausal status. No difference in the plasma homocysteine levels was observed after 6 and 12 months of ERT on postmenopausal patients. CONCLUSIONS: Surgically postmenopausal women have higher plasma homocysteine concentrations than premenopausal women, but transdermal estrogen treatment for 12 months in postmenopausal women does not modify homocysteine levels.     

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.     

Serum osteocalcin and urinary crosslaps are suitable markers of bone turnover in response to short-term hormone replacement therapy.

In this study we evaluated the effect of short-term hormone replacement therapy (HRT) on bone formation (serum osteocalcin) and resorption markers (urinary type I collagen peptides (crosslaps), urinary total free pyridinoline (TPYRI) and urinary free deoxypyridinoline (DPYRI)) as well as female sex hormones (serum estradiol, follicle stimulating hormone (FSH) and luteinizing hormone (LH)) in a group of early postmenopausal women with severe estrogen deficiency. The 46 healthy postmenopausal women with serum estradiol levels < 10 ng/l were subsequently divided into two groups, according to their compliance with HRT. In the group taking HRT significant changes from baseline values could be observed in estradiol, FSH, urinary crosslaps and serum osteocalcin levels after 6 months, whereas no changes could be observed in LH, TPYRI and DPYRI from baseline values. In the group which refused HRT all values were increased relative to baseline values, indicating increased bone turnover. Serum osteocalcin and urinary crosslaps were significantly decreased in women taking HRT in comparison to the group refusing HRT. After 6 months the treated patients showed a decrease in urinary crosslaps of 42% (SD 12%) and in serum osteocalcin of 24% (SD 6%) in comparison with baseline values. In patients who refused HRT, urinary crosslaps were increased by 43% (SD 20%) and serum osteocalcin levels decreased by 2% (SD 9%) compared to baseline values. In postmenopausal women suffering from severe estrogen deficiency (estradiol < 10 ng/l) serum osteocalcin and urinary crosslaps are significantly increased, indicating a clear correlation between estrogen deficiency and an increase in bone resorption as well as bone formation. The recommended HRT dose was sufficient to reduce the rate of bone turnover to premenopausal values. Serum osteocalcin and urinary crosslaps are suitable candidates not only for the assessment of a high postmenopausal bone turnover, but also for monitoring the response to and for verifying the actual intake of HRT or other antiresorptive treatment.     

Hormone replacement therapy: estrogen and progestin effects on plasma C-reactive protein concentrations

OBJECTIVE: Our purpose was to assess the effect of hormone replacement therapy (HRT) on C-reactive protein blood concentrations with special reference to the progestin component. STUDY DESIGN: Changes from baseline and between groups in blood concentrations of C-reactive protein were determined during 12-month periods in 6 groups of postmenopausal women. Group A (the reference group) received no HRT; group B received 2 mg of estradiol valerate (E2V) daily combined with 1 mg of cyproterone acetate (CPA) for 10 days (28/10 days); group C received 2 mg of E2V plus 1 mg of CPA sequentially (21/10 days); group D received a combination of 2 mg of E2V and 1 mg of norethindrone acetate continuously; group E received 2 mg of E2V in combination with local delivery of levonorgestrel (20 microg/24 h); and group F received a long-cycle regimen consisting of 2 mg of E2V (84/91 days) plus 20 mg of medroxyprogesterone (14/91 days). RESULTS: No significant variation in CRP levels was observed in the reference group. HRT resulted in a significant increase in CRP concentrations in the women receiving the continuous combination of E2V plus norethindrone acetate and the continuous regimen of E2V plus local delivery of levonorgestrel. Cyclic or continuous intake of E2V plus CPA did not change CRP levels significantly. During the long-cycle regimen, the concentrations of CRP showed a significant variance over time. The concentrations increased during the estrogen phase but were modulated by the progestin intake throughout the study period. CONCLUSION: HRT can increase CRP levels in healthy women, and both the estrogen and the progestin component are of importance for the change. Whether the increase in CRP levels only reflects a changed steady-state metabolism is unknown. However, the clinical significance should be viewed from the perspective of changes in other inflammatory risk markers of importance for the evolution of cardiovascular disease.