Effects of continuous medroxyprogesterone acetate on lipoprotein metabolism in postmenopausal women receiving estrogen

Objective: To investigate the effects of medroxyprogesterone acetate (MPA) on the beneficial effects of estrogen therapy on lipid metabolism in postmenopausal women. Methods: Postmenopausal women were administered either conjugated equine estrogen (CEE) 0.625 mg daily for 3 months (Group 1) or CEE 0.625 mg in conjunction with MPA 2.5 mg (Group 2) or MPA 5.0 mg (Group 3) daily for 3 months. Plasma levels of cholesterol, triglyceride, lipoprotein lipids, apolipoproteins, sex steroid hormones and lecithin cholesterol acyltransferase activity (LCAT) were determined. Lipoprotein lipase (LPL) and hepatic triglyceride lipase (H-TGL) activities were measured in postheparin plasma. Changes in the lipid concentrations and enzymatic activities were evaluated in each group. Results: Total, low-density lipoprotein (LDL) cholesterol, apolipoprotein B concentrations and LCAT activity were all significantly reduced by treatment in the three groups. The levels of high-density lipoprotein (HDL), HDL2, and HDL3 cholesterol as well as the levels of apolipoprotein AI and AII were significantly elevated in groups 1 and 2. The mean decrease in these parameters was related to the dose of MPA. Levels of triglyceride in the HDL and HDL2 were significantly increased in group 1. The levels of triglyceride in plasma, very low density lipoprotein (VLDL), LDL, HDL3 and VLDL cholesterol and LPL activity were unaffected. H-TGL activity was significantly inhibited only in groups 1 and 2. MPA produced a dose-dependent increase in H-TGL activity. A significant negative correlation was observed between the HDL cholesterol concentration and H-TGL activity (r = 0.58 P < 0.001). Conclusions: The administration of MPA 2.5 mg and 5.0 mg did not adversely affect the changes in VLDL-LDL metabolism produced by estrogen. However, MPA has dose-dependent negative effects on HDL metabolism by increasing H-TGL activity and the 5.0 mg MPA interferes with the favorable effects on lipids of estrogen in postmenopausal women.     

Comparative effects of estrogens plus androgens and tibolone on bone, lipid pattern and sexuality in postmenopausal women

BACKGROUND: The main goals of estrogen replacement therapy (ERT) are the prevention of osteoporosis and cardioprotection and the improvement of quality of life (QL). Androgens and tibolone therapy may increase bone mineral density (BMD) to a greater extent than ERT and offer an increase in QL. Lipid and cardiovascular effects, however, are still a major concern. AIM: To evaluate whether the addition of a weak androgen to ERT may improve postmenopausal bone loss and sexual activity without adverse effects on lipid pattern and to compare these effects with those observed after tibolone therapy. SUBJECTS AND METHODS: This prospective study enrolled 120 surgical postmenopausal women; of these, 96 completed the 1-year follow-up. Patients were allocated to one of four groups. The first group (A; n = 23) received 4 mg of estradiol valerate plus 200 mg of enanthate of dihydroandrosterone im monthly. The second group (E; n = 26) received 50 microg/day of transdermal 17-b-estradiol continuously; the third (T; n = 23) received 2.5 mg of tibolone every day; and finally, the fourth group (C; n = 24) constituted a treatment-free control group. Bone mass (dual X-ray absorptiometry), serum total cholesterol, HDL, LDL, triglycerides, apolipoproteins A1 and B and sexual activity were evaluated before starting therapy and at the end of follow-up. RESULTS: All active treatment groups showed an increase in BMD. This increase was higher in the A treatment group (4.08% P < 0.01). Sexuality improved significantly with therapy; however, tibolone and androgens increased scores to a greater extent than ERT. Androgen therapy was associated with significant increases in total cholesterol, LDL and triglycerides. Cholesterol and LDL fall into groups E and T, HDL into groups A and T and triglycerides in group T only. CONCLUSION: The combined regimen of androgens and ERT increased vertebral bone mass and enhance sexual activity in postmenopausal women equal to that of tibolone and to a greater extent than ERT alone; its effects on lipids, however, are clearly adverse.     

Effects of transdermal estrogen replacement therapy on plasma levels of nitric oxide and plasma lipids in postmenopausal women

OBJECTIVE: Our purpose was to assess the effects of transdermal estrogen replacement therapy (TERT) on plasma levels of nitric oxide (NO) and plasma lipids in postmenopausal women. MATERIALS AND METHODS: The study designed as a randomized, double-blind, placebo-controlled trial, involved 43 postmenopausal healthy women who had previously undergone hysterectomy. Women received either transdermal 100 microg 17beta-estradiol (Climara forte TTS) or placebo once a week for 3 months. Plasma levels of NO metabolites, estradiol (E2), total cholesterol (TC), triglicerides (TG), low-density lipoproteins (LDL), high-density lipoproteins (HDL), HDL2 and HDL3 were measured in blood samples of all women which were collected before, after 24 h and after 3 months of therapy. RESULTS: We found significantly increased NO levels 24 h after therapy in TERT group. Moreover significantly higher NO levels were determined at 3rd month of therapy. Serum HDL and HDL2 levels of ERT group were significantly increased at 3rd month of therapy. Alteration of serum levels of HDL3, LDL and TC were not significantly different in groups. TG levels were significantly decreased in TERT group. DISCUSSION: NO-related mechanism may help to explain the cardio-protective effect of TERT in the postmenopausal period. TERT seems to have favorable effects on plasma lipids in surgical menopausal women.     

Effects of continuous combined conjugated estrogen/medroxyprogesterone acetate and 17beta-estadiol/norethisterone acetate on lipids and lipoproteins

OBJECTIVES: Various estrogen/progestogen combinations used in hormonal replacement therapy (HRT) have been reported to influence lipid and lipoprotein fractions differently. This motivated a comparative study where the two continuous combined regimens most commonly used in Sweden during the 1990s have been studied regarding effects on lipid profile. METHODS: In a 1-year prospective, double-blind study, 62 post-menopausal women were randomized to conjugated estrogen (CE), 0.625 mg, and medroxyprogesterone acetate (MPA), 5 mg, or 17beta-estradiol (E2), 2 mg, and norethisterone acetate (NETA), 1 mg. Serum concentrations of lipids and lipoproteins were measured at baseline and after 1 year of treatment. RESULTS: Both treatment groups significantly lowered the lipoprotein(a) (Lp(a)) levels. The CE/MPA group showed no significant changes in total cholesterol (TC), high-density (HDL) and low-density lipoprotein (LDL), but a significant increase of triglyceride (TG) levels. The E2/NETA group developed a significant lowering of total cholesterol, HDL, and LDL, but no significant changes of TG levels. The magnitude of change in serum concentrations of total cholesterol, HDL and TG differed significantly between the two treatment groups. CONCLUSIONS: Continuous combined treatment with CE/MPA and E2/NETA equally lowered Lp(a), an important risk factor for cardiovascular disease in women. Apart from this, the two treatments produced different effects on lipids and lipoproteins, findings that are more delicate to interpret.     

Changes in lipid and lipoprotein profile in postmenopausal women receiving low-dose combinations of 17beta-estradiol and norethisterone acetate

OBJECTIVE: To evaluate the modification of lipid and lipoprotein by use of low doses of continuous-combined formulations of 17beta-estradiol (E ) and norethisterone acetate (NETA) in healthy postmenopausal women. DESIGN: The study was designed as a double-blind, randomized, placebo-controlled trial. A total of 120 healthy postmenopausal women were randomized to one of three treatment arms: (1) placebo group ( = 40); (2) E /NETA 0.25-mg group-subjects receiving oral continuous-combined E 1 mg and NETA 0.25 mg ( = 40); (3) E /NETA 0.5-mg group-women who were treated with E 1 mg and NETA 0.5 mg ( = 40). The duration of study was 12 months. Plasma levels of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and very low-density lipoprotein (VLDL) cholesterol, triglycerides, lipoprotein(a), apolipoprotein A and apolipoprotein B were determined on four occasions (i.e., baseline, 3-, 6-, and 12-month visits). RESULTS: There were no differences in the baseline characteristics among the three groups. A total of 102 women completed the study, resulting in a compliance rate of 85%. There was a significant reduction of total cholesterol, LDL cholesterol, and lipoprotein(a) in both combined groups when compared with placebo. The level of apolipoprotein B declined significantly only in the E /NETA 0.25-mg group. Decrements were observed within 3 months of treatment and maintained thereafter. No significant changes were found in triglycerides, VLDL cholesterol, HDL cholesterol, apolipoprotein A, and LDL/HDL ratio. Between the two active combined groups, no statistically significant differences were noted. CONCLUSION: Favorable changes in lipids and lipoproteins were associated with the low dose of E /NETA combinations. These effects may contribute to the reduction or prevention of atherogenesis in postmenopausal women.     

Serum lipids, lipoproteins and apolipoproteins in pregnant non-diabetic patients.

AIMS--To investigate the effect of pregnancy on serum concentrations of lipids, lipoproteins, and apolipoproteins. METHODS--Fasting serum concentrations of total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), apolipoproteins AI, AII, and B, and lipoprotein (a) were measured in 178 women with normal glucose tolerance in the second and third trimesters of pregnancy and in a control group of 58 non-pregnant women of similar age. Data were analysed using the unpaired t test and by one-way analysis of variance. RESULTS--The pregnant women had significantly higher concentrations of total cholesterol, triglyceride, LDL cholesterol, HDL cholesterol, and apolipoproteins AI and B (p < 0.001) and apolipoprotein AII (p = 0.003) than the control women. The ratio of apolipoprotein B:apolipoprotein AI was significantly higher in the pregnant women than in the controls (p < 0.001), but the total cholesterol:HDL cholesterol ratio was not significantly different. No significant difference was found in the concentration of lipoprotein (a). CONCLUSIONS--Hyperlipidaemia is common in the second half of pregnancy. This may be a purely physiological response to pregnancy or it may be indicative of pathology in some women. These results warrant a follow up study to investigate whether the hyperlipidaemic response to pregnancy is variable and if so, whether it can predict future hyperlipidaemia in a manner analogous to that of impaired glucose tolerance during pregnancy, predicting non-insulin dependent diabetes in later life.     

National differences in lipid response to postmenopausal hormone replacement therapy

Objective: To compare the response of serum lipids and lipoproteins to the transdermal hormone replacement therapy (HRT) in five European countries. Methods: Five-hundred and sixty-seven healthy postmenopausal women from Belgium, Finland, the Netherlands, Sweden, and the UK received transdermal estradiol 50 μg daily for 12 months. In addition, two groups received transdermally norethisterone acetate (NETA) continuously, two groups sequentially (170 or 350 μg/day); one group received sequentially oral NETA (1 mg/day), and one group dydrogestrone (20 mg/day). Serum total cholesterol, HDL-, HDL2-, LDL-cholesterol, lipoprotein(a) (Lp(a)), and triglycerides were assessed before and at the end of treatment. Results: No significant national differences existed in the pretreatment levels of lipids and lipoproteins. Mean cholesterol, LDL, Lp(a), and triglycerides decreased during HRT, and HDL and HDL2 increased. Individual changes in responses to HRT were strongly dependent on pretreatment values. In this regard, British women differed from the others: their cholesterol, HDL, HDL2, and Lp(a) responses, when related to the pretreatment levels, were smaller than those of the others. Conclusion: A national difference discovered in response of serum lipids to HRT calls for caution in generalization of lipid data from one nation to another during HRT.     

正常妊娠及妊娠期糖尿病患者血脂代谢特点

目的观察妊娠期糖尿病（gestational diabetes mellitus,GDM）孕妇和正常妊娠孕妇不同孕期的血脂代谢特点,探讨妊娠早中期血脂变化与GDM的关系。方法选择在我院门诊就诊的正常健康孕妇（A组）及GDM孕妇（B组）,两组分别于孕14-19周、28-34周抽取空腹静脉血测定血浆总胆固醇（TC）、甘油三脂（TG）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、载脂蛋白AI（APOAI）、载脂蛋白B（APOB）、脂蛋白A（LPA）。结果 （1）正常妊娠组与GDM组孕妇随着孕周的增加,TC、TG、APOB、LDL值显著升高（P〈0.01）,APOAI值明显升高（P〈0.05）,正常妊娠组中LPA值随孕周增加明显升高（P〈0.05）;（2）GDM组孕妇在孕14-19周及孕28-34周,TG值较同孕周的正常妊娠组显著升高（P〈0.01）,APOB值在GDM组孕14-19周时明显高于同期正常妊娠组（P〈0.01）;（3）TC、LDL、HDL、APOAI、LPA在两组不同孕周间比较均无显著性差异（P〉0.05）,HDL值随两组孕周增加升高不明显（P〉0.05）。结论GDM孕妇在不同孕周的甘油三酯水平均高于正常妊娠孕妇;GDM孕妇在孕早中期较正常妊娠孕妇存在更早期、更明显的脂代谢紊乱。在孕早中期监测血糖、血脂水平,及时制定合理的饮食计划,可减少GDM的发生和尽早防治其可能带来的母婴危害。     

Acute effects of estradiol and progesterone on insulin, lipids and lipoproteins in postmenopausal women: a pilot study

OBJECTIVES: To examine the acute effects of estradiol-17beta (E(2)) and progesterone (P) on serum levels of insulin, lipids and lipoproteins in estrogen-deficient postmenopausal women, whereby, a direct cause-effect relationship could be established without the influence of lifestyle changes. MATERIALS AND METHODS: Nine postmenopausal women were given oral E(2) (Estrace) 2 mg/day for 28 days and oral micronized P (Prometrium) 200 mg/day in the last 14 days of E(2) treatment. Fasting blood samples were obtained before starting E(2) (day 1) and P (day 15) and on day 29. Serum levels of insulin, triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL) and lipoprotein (a) (Lp(a)) at the three time points were compared by Friedman analysis of variance (ANOVA). Corresponding levels of glucose, the apolipoproteins (Apo) A1 and B and serum androgen levels were also evaluated. RESULTS: E(2) decreased while P increased fasting levels of insulin (32.45+/-3.57, 26.36+/-2.90 and 37.36+/-3.67 pmol/l on day 1, 15 and 29 respectively; P<0.01). Fasting glucose to insulin ratios changed inversely (P<0.01). E(2) increased HDL from 1.07+/-0.05 mmol/l on day 1 to 1.17+/-0.07 mmol/l on day 29 but decreased corresponding levels of Lp(a) from 261+/-93 to 211+/-83 U/l (P=0.03 for both). TC and LDL levels fell significantly after 14 days of E(2) treatment with no further decrease when P was added. Androgen levels remained unchanged during hormone treatment. CONCLUSION: The sequential, acute effects of E(2) and micronized P on insulin and lipids confirm a direct cause-effect relationship. The acute effects of P on insulin in particular, highlights the importance of standardizing the medication days according to estrogen and progestin in the clinical evaluation of their true metabolic impact in longer-term studies and may influence the choice of progestin type, dose and duration in hormone replacement.     

Lipoproteins and BMI: a comparison between women during transition to menopause and regularly menstruating healthy women

One hundred and forty-three women born 1942 were followed for 5 years during transition to menopause (49--54 years of age). Changes in menopausal status, body mass index (BMI) and circulating lipoproteins cholesterol, (chol), low density lipoprotein (LDL), high density lipoprotein, (HDL) and total triglycerides (TG) were measured, once yearly and compared with a control group of normally menstruating healthy, non-smoking women 23--39 years old. Results: Chol was significantly higher P<0.0001 in the study group visits 1--5 when compared with the controls and higher at visit 4 compared with visit 1(P<0.05) LDL was significantly lower in the study group and at visit 5 compared with visit 2 (P<0.05) HDL was significantly lower at visits 1--3 and 5 when compared with the controls (P<0.001) and to visit 4 (P<0.0001). TG was significantly higher in the study group (P<0.0001) and increased significantly during the 5-year study. BMI was significantly higher in the older women (P<0.001) and increased during 5-years of study (P<0.0001). When multiple stepwise regression analyses were performed at visit 5 using education, menopausal status, use of hormone replacement therapy (HRT), BMI and smoking as predictor variables, postmenopausal status was found to be significantly associated with high LDL (P<0.3), while high BMI significantly predicted low HDL and high TG levels. Perimenopausal status was significantly associated with high HDL levels. Conclusion: Age, BMI and menopausal status are significant predictors of circulating lipoprotein levels during transition to menopause.     

The effect of hormone replacement therapy on metabolism of lipoprotein remnants in postmenopausal women

OBJECTIVE: The measurement of remnant-like particles reflects chylomicron and very low density lipoprotein remnants which are most likely atherogenic particles. We investigated the effects of menopausal status and postmenopausal hormone replacement on metabolism of remnant lipoprotein-cholesterol. METHODS: We measured remnant lipoprotein-cholesterol by an immunoseparation assay in 20 premenopausal, 40 postmenopausal, and 30 bilaterally oophorectomized women. Of 70 postmenopausal subjects, 21 surgically menopausal women (with total hysterectomy) were started on hormone replacement with conjugated equine estrogen, 0.625 mg/day, and 36 naturally postmenopausal women were begun on a combination of conjugated equine estrogen 0.625 mg/day, plus medroxyprogesterone acetate, 2.5 mg/day. Plasma levels of remnant lipoprotein-cholesterol and other common lipids were measured after 6 and 12 months of treatment. RESULTS: Plasma remnant lipoprotein-cholesterol levels in postmenopausal and surgically menopausal women were significantly higher than in premenopausal women (P < 0.005). Plasma total and low-density lipoprotein cholesterol levels decreased and high-density lipoprotein cholesterol increased significantly (P < 0.01) in both treatment groups, respectively. Plasma triglyceride levels were not changed by treatment; however, remnant lipoprotein-cholesterol levels decreased in both treatment groups (estrogen group; P = 0.07, estrogen-progestin group; P < 0.05). No side effects of therapy were consistently reported. CONCLUSIONS: We confirmed that remnant lipoprotein-cholesterol increases after menopause. Hormone replacement therapy improves disordered lipoprotein metabolism and exerts a favorable effect on lipoprotein remnant metabolism in postmenopausal women.     

Perimenopausal changes in serum lipids and lipoproteins: A 7-year longitudinal study

Although cross-sectional studies suggest considerable influence of menopause on serum lipids and lipoproteins in women, it is not exactly clear. During our 7-year longitudinal study, serum concentrations of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and low-density lipoprotein (LDL) cholesterol were measured in 16 healthy perimenopausal women (aged 47–56 years at menopause) who had undergone annual examinations 4 years before and 3 years after menopause under a health examination system in Osaka. Longitudinal design enabled us to study the natural course of serum lipids and lipoproteins. The results show that from 4 years before to 1 year after menopause, the serum concentration of total cholesterol and LDL cholesterol increased on average by 25 mg/dl (14%) and 20 mg/dl (19%), respectively. Serum concentrations of triglycerides and of HDL cholesterol remained virtually unchanged during the perimenopausal and postmenopausal periods. It was concluded that serum lipids and lipoproteins are thus significantly altered as a consequence of menopause, resulting in a more atherogenic profile in the postmenopausal period.     

Long-term effects of transdermal and oral estrogens on serum lipids and lipoproteins in postmenopausal women

The transdermal and oral administration of estrogens for one year were compared with respect to the effects on lipid metabolism. Eighty-one postmenopausal women (1.5-3 years after menopause) were randomly divided into three groups. The first two groups received sequential estrogen treatment with either transdermal estradiol (Estraderm TTS, Ciba Geigy; 50 μg/day; 24 women) or 0.625 mg/day conjugated estrogens (Premarin, Wyeth; 20 subjects), respectively. In both groups medroxyprogesterone (10 mg/day per os) was added for 12 days of each cycle. Thirty-five subjects served as control group without therapy. No significant changes in the lipid profile was observed in control subjects after 1 year of follow-up. Serum triglycerides decreased significantly (-10.9 ± 26% S.D.; P < 0.05) in transdermal treated women, whereas it slightly rose in oral estrogen group. Comparable significant decreases in total and low density lipoprotein (LDL) cholesterol (mean range -6.5/-18.0%) were observed in women on estrogen replacement therapy. High density lipoprotein (HDL) cholesterol significantly diminished in transdermal estradiol group, but it rose slightly in the oral estrogen group. Thus the fraction of HDL cholesterol over LDL cholesterol did not change in the transdermal group whereas it significantly rose in subjects treated with oral estrogens. It remains to be established to what extent these differences on lipid metabolism are relevant for the prevention of cardiovascular diseases.     

Effects of menopause and hormone replacement therapy on plasma lipids, lipoproteins and LDL-receptor activity

A cross-sectional study of ninety six women was conducted to examine the effect of menopause and hormone replacement therapy (HRT) on plasma lipids, lipoproteins and oxidation of low density lipoproteins. The sample consisted of 26 premenopausal women, 26 postmenopausal women taking no replacement hormones and 43 postmenopausal women on hormone replacement therapy. Postmenopausal women not taking replacement hormones had significantly higher plasma cholesterol, low density lipoprotein (LDL) cholesterol and lipoprotein[a] (Lp[a]) levels compared to premenopausal women or postmenopausal women on HRT [6.00±0.15, 5.36±0.17 (P<0.01), 5.63±0.13 (P<0.05) mmol/l, respectively for total cholesterol; 4.13±0.15, 3.64±0.15 (P<0.05), 3.82±0.12 (P<0.05) mmol/l, respectively for LDL-cholesterol; 48.19±9.90, 26.59±5.53 (P<0.03), 25.12±4.62 (P<0.03) mg/dl, respectively for Lp[a]]. The differences in LDL cholesterol concentrations were inversely related to changes in LDL receptor activity (r=−0.27, P<0.01). HRT use was found to be associated with a significantly smaller LDL particle size. Plasma triglyceride was significantly higher in women on HRT (1.16±0.07 mmol/l) than in the premenopausal group (0.96±0.07) or postmenopausal group not using HRT (0.87±0.06). There were no differences in LDL oxidation between the groups when LDL was oxidised in the presence of copper. Nor was there any difference in the uptake of copper-oxidised or macrophage-modified LDL into J774 macrophages. These results confirm the effect of menopause and exogenous hormones on plasma lipids and lipoproteins, and suggest that HRT modifies the activity of the LDL receptor. Hormone replacement did not appear to protect LDL from oxidation.     

Evaluation of mammographic density and (99m)Tc-sestamibi scintimammographic uptake in postmenopausal women on hormone replacement therapy

OBJECTIVE: To evaluate changes in mammographic density and (99m)Tc-sestamibi scintimammographic uptake in postmenopausal women on hormone replacement therapy (HRT). METHODS: Seventy-five postmenopausal women were prospectively studied and allocated into three groups: 50 women were randomized to either Group 1 (G1, n=25), which received 2mg of 17beta-oestradiol continuously combined with 1mg of norethisterone acetate (E2/NETA, Kliogest, Medley) or Group 2 (G2), which received 2.5mg/day of tibolone (Livial, Organon). The remaining 25 women, who were asymptomatic and had no desire to undergo HRT, constituted the control group (G3). Each patient was submitted to both mammography and scintimammography at baseline and after six months. Mammographic density was evaluated by using the BI-RADS classification system. The classification system of Barros et al. was used in the interpretation of scintimammography. For statistical analysis, the Chi-square test, ANOVA and Pearson's correlation were used. RESULTS: At six months, increased mammographic density was observed in 48% of G1, 12% of G2 and 16% of G3 patients (p<0.001). The increase in sestamibi uptake was 56% in G1, 28% in G2 and 24% in G3 (p<0.001). Increases in both density and uptake were significantly higher in the group on E2/NETA than among tibolone users and the controls. CONCLUSION: In postmenopausal women, HRT with E2/NETA was associated with increased mammographic density and increased (99m)Tc-sestamibi scintimammographic uptakes, suggesting greater mithochondrial activity in the cells of the mammary duct. This was not observed in users of 2.5 mg of tibolone, demonstrating that the effects on the breast were reduced. The same was observed in the control group.     

Impact of hormone replacement therapy on postprandial lipoproteins and lipoprotein(a) in normolipidemic postmenopausal women

In 43 normolipidemic postmenopausal women we studied fasting and postprandial (oral fat load with 50 g fat per square meter; blood sampling for 5 h) lipoprotein components and lipoprotein(a) levels before and with the administration of conjugated equine estrogens opposed by medrogestone (on days 11–21). Data was compared intraindividually; the second testing was performed during the last 5 days of the combined estrogen/progestogen phase of the third cycle. Fasting low-density lipoprotein (LDL) and total cholesterol concentrations decreased significantly; high-density lipoprotein (HDL) cholesterol, including subfractions HDL₂ and HDL₃, was not changed. Fasting triglyceride concentrations increased. All lipoprotein fractions measured showed a postprandial elevation with the exception of chylomicron cholesterol concentrations. There was a significant effect of hormone replacement therapy on the postprandial course of total cholesterol (decrease; P < 0.001), VLDL cholesterol (increase; P = 0.025), and the triglyceride proportion in the LDL plus HDL fraction (increase; P < 0.001). With hormone replacement therapy the postprandial curve of total triglycerides was increased only 1 h after the fat load while chylomicron triglyceride concentrations were lowered after 5 h. VLDL triglycerides were not influenced. In all patients with lipoprotein(a) levels above 10 mg/dl, this parameter decreased (about 25%). Although increasing fasting triglyceride concentrations, hormone replacement therapy does not bring about an exaggerated postprandial increase in triglycerides. Postprandial chylomicron clearance is evidently promoted. Hormone replacement therapy leads to a small increase in triglycerides in the LDL plus HDL fraction by inhibiting hepatic lipase activity. Moreover, the decrease in lipoprotein(a) levels may contribute to the antiatherosclerotic effect.Abbreviations: CEE conjugated equine estrogens - HDL high-density lipoproteins - HRT hormone replacement therapy - LDL low-density lipoproteins - TG triglycerides - VLDL very low density lipoproteins Correspondence to: U. Julius     

Tibolone and risk of endometrial polyps: a prospective, comparative study with hormone therapy

OBJECTIVE: To assess the incidence of endometrial polyps during postmenopausal replacement therapy with tibolone, using an appropriate control group. DESIGN: A total of 485 postmenopausal women were included in this open, prospective, comparative study for a duration of 36 months. Of this group, 249 women received 2.5 mg/day of tibolone and 244 women served as controls, receiving continuous-combined estrogen-progestogen therapy (HT). Transvaginal ultrasound, hysteroscopy, and directed biopsies were performed before treatment was initiated and at the end of the study. RESULTS: Two hundred twenty-one of the women receiving tibolone and 203 receiving continuous-combined HT completed the study. Endometrial polyps were detected in 74 women (33.4%) from the tibolone group and in 22 women (10.8%) from the HT group (P < 0.01). The vaginal bleeding rate did not differ between the groups. The frequency of atrophic polyps was significantly higher in the tibolone group (P < 0.01). No difference was found in the size of the polyps. CONCLUSIONS: Tibolone increases by threefold the risk for endometrial polyps.     

Hormone replacement therapy: lipid responses to continuous combined oestrogen and progestogen versus oestrogen monotherapy.

Fifty-five postmenopausal women with climacteric complaints were randomly assigned to treatment with either 2 mg oestradiol valerate (E2V) (cyclic regimen: 21 days of treatment followed by a 7-day treatment-free interval), or 2 mg E2V combined with 1 mg cyproterone acetate (E2V+CPA) daily, over a 6-month period. Treatment was by the oral route in both cases. The aim was to compare the influence of these two hormone replacement therapy regimens on lipid metabolism. Blood samples were obtained before and after 1 and 6 months of treatment. Serum was analyzed for total cholesterol (TC), high-density lipoproteins (HDL), apolipoproteins A1 and B and triglycerides. The low-density lipoprotein (LDL) concentrations were derived by calculation. All parameters were evaluated in terms of mean +/- S.D. There was no significant difference in the response of the blood lipids to the two treatments, as assessed by analysis of variance (P greater than 0.05). Serum levels of TC were found to have fallen after month 1 and 6 by 5.3 and 5.6%, respectively, during E2V treatment and by 2.4 and 0.2% during E2V+CPA treatment. Serum HDL levels had increased after months 1 and 6 by 9.7 and 5.2%, respectively, in the E2V group and by 6.9 and 2% in the E2V+CPA group, which was also confirmed by the increase in apolipoprotein A1 levels. There was, however, a borderline increase in LDL and apolipoprotein B in the E2V+CPA group. Serum triglycerides were reduced and serum levels of SHBG increased during treatment in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Abfall der Serumlipoproteine und Anstieg der Apolipoproteine A-I und A-II nach oraler Zufuhr mehrfach ungesättigter Phospholipide

Summary Polyenylphosphatidylcholine was given orally in a dosage of 10 g per day to 10 healthy subjects for 4 weeks. The concentrations of cholesterol, triglycerides, phospholipids, apolipoproteins AI, AII, and B were measured in serum, as were very low density lipoproteins, low density lipoproteins, and high density lipoproteins every 3 h on the day before and after the 4 weeks of application. The diet was controlled 10 days before and during the experiment using the dietary recall method. The evaluation of the diet records showed that 5 subjects had increased and 5 subjects had decreased their fat consumption in exchange for carbohydrates during the experiment. Nevertheless body weight remained constant within ±1 kg. Cholesterol in serum and low density lipoprotein decreased, but the differences were not statistically significant. In spite of dietary changes apolipoprotein AI and AII in high density lipoproteins increased significantly. We conclude that the influence of drugs on serum lipids can only be evaluated in conjunction with reliable control of the diet.

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Abkürzungen PPC Polyenylphosphatidylcholin - VLDL Very low density lipoproteins - LDL Low density lipoproteins - HDL High density lipoproteins - LCAT Lecithin-Cholesterin-Acyl-Transferase     

Changes in lipid metabolism in women with age-related macular degeneration

Abstract Age-related macular degeneration (AMD) is one of the leading causes of visual loss among people aged 65 and older. At present the origin of AMD still remains unknown. The objective was to evaluate the chosen lipid and lipoprotein concentrations in blood of patients with AMD. Sixty women aged 55–71 (mean age 65.1±5.7) were treated in the outpatient ophthalmological clinic for more than two years because of AMD. We evaluated total serum cholesterol (TCH), triglycerides (TG), HDL-cholesterol (HDL), LDL-cholesterol (LDL), lipoprotein (a) (Lp(a)), apolipoprotein AI (Apo AI) and apolipoprotein B (Apo B) by direct spectrophotometry (Human and Randox standard kits, USA). We found a significant increase of TCH, LDL and TG (224.36±41.67 mg/dl, 159.02±39.66 mg/dl and 120.92±42.64 mg/dl), and a significant decrease of HDL (38.68±6.36 mg/dl) in the AMD patients when compared with the control group. We have not found a significant difference in the average TG level between the studied groups. The concentration of Apo B was markedly increased (164.66±46.46 mg/dl) and Apo AI concentration was markedly decreased (128.9±17.01 mg/dl) in the AMD patients when compared with the control group. There was no significant difference in the concentration of the Lp(a) between the two groups. The results of our present study could point to the fact that changes in the lipid metabolism could be one of the very important risk factors involved in the pathogenesis of AMD.The results of this study have been presented as a poster presentation at the XIII Congress of the European Society of Ophthalmology 3–7 June 2001, Istanbul, Turkey