Clinical efficacy of raloxifene in postmenopausal women.

A new class of compounds known as selective estrogen receptor modulators (SERMs) may possess the optimal combination of characteristics desirable in a drug designed for use in postmenopausal women. Among this class of compounds, raloxifene is the most studied and is currently available for clinical use in some countries for the prevention of osteoporosis in post-menopausal women. Raloxifene is a non-steroidal benzotiophene derivative shown to prevent bone loss at axial and appendicular sites and reduce serum cholesterol, like estrogen, in oophorectomized rats and in postmenopausal women. In animal models, unlike estrogen, raloxifene does not stimulate breast or uterine tissues. These appealing attributes make raloxifene a potential treatment for osteoporosis and other menopause related risks in middle aged and elderly women. Multicenter studies have been performed in early postmenopausal women, randomly assigned to receive raloxifene 30, 60, or 150 mg/day or placebo. All subjects received a calcium supplement. Bone mineral density, which was measured twice a year over 24 months by dual X-ray absorptiometry, decreased significantly at all skeletal sites with placebo, and significantly increased with raloxifene at the spine, hip, and total body at the three doses. At 24 months, the mean increase with raloxifene 60 mg compared with placebo was 2.4% at the lumbar spine and at the total hip, and 2% at the total body. Markers of bone formation (serum osteocalcin and bone specific alkaline phosphatase) and of resorption (urinary CrossLaps) decreased significantly to the premenopausal range within 3-6 months of treatment with raloxifene. In addition, total serum and low-density lipoprotein cholesterol decreased significantly in all raloxifene therapy groups in a dose-related fashion. Serum HDL-cholesterol and triglycerides were not significantly changed by therapy. The most commonly observed side-effect was hot flushes, with patients taking raloxifene reporting a slightly higher rate of flushes (25%) than those on placebo (18%). This adverse event usually occurred within the first few months of therapy, was generally mild, and did not result in excess study dropout (raloxifene 1.5%, placebo 2.1%). Preliminary 2-year data indicated that raloxifene is not associated with an increased risk of breast cancer. In summary, the clinical efficacy and safety of raloxifene is very promising and this compound will offer a particularly attractive choice for postmenopausal women.     

Desogestrel and gestodene in oral contraceptives: 12 months' assessment of carbohydrate and lipoprotein metabolism.

We examined the influence on carbohydrate and lipoprotein metabolism of oral contraceptives (OCs) containing two new third-generation progestogens, desogestrel and gestodene. This was a prospective randomized study in which monophasic combinations of 20 micrograms ethinyl estradiol (E2) and 150 micrograms desogestrel or 30 micrograms ethinyl E2 plus 75 micrograms gestodene were administered to 15 and 19 healthy women, respectively. An oral glucose tolerance test including measurement of insulin response was performed before treatment and after 3, 6, and 12 months of treatment. We also determined fasting plasma concentrations of total cholesterol; high-density lipoprotein cholesterol, including the subfractions high-density lipoprotein2 cholesterol and high-density lipoprotein3 cholesterol; low-density lipoprotein cholesterol; very low-density lipoprotein cholesterol; and triglycerides. A transient deterioration of glucose tolerance was observed despite unchanged levels of insulin after treatment with both compounds for 3 months. In both groups plasma levels of triglycerides, very low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol increased significantly after 3 months. After 12 months, a significant increase in the high-density lipoprotein cholesterol/total cholesterol ratio was observed in the ethinyl E2-desogestrel group, and no persistent changes in low-density lipoprotein cholesterol could be demonstrated in any of the groups. Our results indicate that treatment with either compound for 12 months has no effect on carbohydrate or lipoprotein metabolism known to increase the risk of cardiovascular disease.     

Comparison of transdermal and oral estrogen-progestin replacement therapy: effects on serum lipids and lipoproteins.

OBJECTIVE: We attempted to ascertain whether transdermal postmenopausal estrogen-progestin therapy has the typical effects of oral therapy on serum lipoprotein risk markers for cardiovascular disease. STUDY DESIGN: Sixty-one postmenopausal women were randomized to receive either transdermal continuous 17 beta-estradiol, 0.05 mg/day, with transdermal cyclic norethindrone acetate, 0.25 mg/day, or oral continuous conjugated equine estrogens, 0.625 mg/day, with oral cyclic dl-norgestrel, 0.15 mg/day. Twenty-nine untreated subjects served as controls. Lipoprotein profiles at 3 and 6 months were compared with baseline values by means of analysis of variance. RESULTS: In the estrogen-alone phase both therapies reduced serum levels of total and low-density lipoprotein cholesterol; high-density lipoproteins were largely unchanged. Oral therapy increased triglycerides whereas this lipid fell with transdermal therapy. In the combined phase of the cycle both therapies reduced triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. CONCLUSION: Transdermal and oral therapies had similar effects on lipoprotein cholesterol but different effects on triglycerides.     

HMR 3339, a novel selective estrogen receptor modulator, reduces total cholesterol, low-density lipoprotein cholesterol, and homocysteine in healthy postmenopausal women

OBJECTIVE: To investigate the short-term effects of HMR 3339 in comparison with raloxifene and placebo on cardiovascular risk factors. DESIGN: A multicenter, randomized, placebo-controlled, double-blind, dose-ranging study. SETTING: Gynecologic outpatient department. PATIENT(S): One hundred eighteen healthy nonhysterectomized postmenopausal women. INTERVENTION(S): Participants received daily placebo (n = 22), 2.5 mg of HMR 3339 (n = 25), 10 mg of HMR 3339 (n = 24), 50 mg of HMR 3339 (n = 24), or 60 mg of raloxifene (n = 23) for 12 weeks followed by a 2-week washout period. MAIN OUTCOME MEASURE(S): Blood concentrations of lipids measured at baseline, and after 2, 4, 8, 12, and 14 weeks, and of lipoprotein(a), homocysteine, and endothelin-1 measured at baseline, and after 4 and 12 weeks. RESULT(S): After 12 weeks of treatment with HMR 3339, compared with placebo, serum total cholesterol was reduced (10 mg of HMR 3339: -9.7%; 50 mg of HMR 3339: -15.2%), low-density lipoprotein (LDL)-cholesterol (10 mg of HMR 3339: -10.8%; 50 mg of HMR 3339: -24.2%) and plasma homocysteine concentrations (2.5 mg of HMR 3339: -3.9%; 10 mg of HMR 3339: -10.8%; 50 mg of HMR 3339: -13.8%), suggesting a dose-dependent effect of HMR 3339. These effects were already apparent after 2 weeks of treatment for total cholesterol and LDL-cholesterol, and after 4 weeks of treatment for homocysteine. After 12 weeks, raloxifene, compared with placebo, significantly decreased total cholesterol (-10.5%), LDL-cholesterol (-15.0%), and triglycerides (-16.9%), but not homocysteine. High-density lipoprotein-cholesterol, lipoprotein(a), and endothelin-1 showed no significant changes in any of the active treatment groups. CONCLUSION(S): HMR 3339 reduces total cholesterol, LDL-cholesterol, and homocysteine concentrations in postmenopausal women.     

Lipid effects of hormone replacement therapy with sequential transdermal 17-beta-estradiol and oral dydrogesterone

OBJECTIVE: To assess the effects on lipid and lipoprotein levels of a combination therapy of matrix patch and oral sequential dydrogesterone. METHODS: The lipid effects of transdermal estradiol (E2) (80 microg/day continuously) and oral dydrogesterone (10 mg from days 15-28 of each cycle) were assessed in a multicenter, prospective, open, baseline-controlled study. Subjects were 42 healthy, postmenopausal women who had not had hysterectomies. Fasting blood samples were taken at baseline, day 14 of cycle 3 (estrogen alone), and day 25 of cycle 6 (estrogen and progestogen). The main outcome measures were changes from baseline in total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides after six cycles. RESULTS: Thirty-six subjects completed six cycles and in the 28 with complete data, HDL cholesterol increased by 10.6% from 65.25 to 72.2 mg/dL (95% confidence interval [CI] 2.32, 11.58, P = .005) and LDL cholesterol fell by 5.1% from 130.9 to 124.3 mg/dL (95% CI 13.9, 1.16, P = .07). There was a nonsignificant decrease in LDL cholesterol from 130.9 at baseline to 124.3 mg/dL at 6 months and in triglycerides from 110.6 to 107.1 mg/dL. CONCLUSION: Sequential treatment with transdermal E2 and oral dydrogesterone increased HDL cholesterol, without the accompanying increase in triglycerides that occurs with oral estrogen replacement therapy.     

Correlation of visfatin levels and lipoprotein lipid profiles in women with polycystic ovary syndrome undergoing ovarian stimulation

The aim of this study was to determine serum and follicular fluid (FF) visfatin levels in age and weight-matched women with polycystic ovary syndrome (PCOS) and normally ovulating subjects undergoing controlled ovarian stimulation and correlate them with their lipid and lipoprotein levels. We included 80 PCOS women (40 lean and 40 overweight) and 80 age- and weight-matched controls, enrolled in the IVF program. In PCOS women, we determined significantly increased serum and FF visfatin as well as serum levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, apolipoprotein B, lipoprotein(a) and homocysteine, while high-density lipoprotein cholesterol and apolipoprotein A1 were significantly lower compared to controls. Serum visfatin levels positively correlated with total cholesterol, LDL cholesterol, triglycerides, lipoprotein(a) and homocysteine levels and negatively with apolipoprotein A1. FF visfatin levels positively correlated with triglycerides and homocysteine and negatively with apolipoprotein A1. Dyslipidemia is common in reproductive age women with PCOS exposing them to risk for cardiovascular diseases. However, the detailed role of visfatin on lipoprotein lipid profile awaits further clarification through future investigation.     

Resistance of pelvic arteries and plasma lipids in postmenopausal women: comparative study of tibolone and continuous combined estradiol and norethindrone acetate replacement therapy

OBJECTIVE: We sought to compare vascular resistance and plasma lipids in postmenopausal women assigned to tibolone (a synthetic estrogen replacement steroid) therapy or continuous combined hormone replacement therapy. STUDY DESIGN: Pulsatility and resistance indexes in pelvic arteries (color Doppler transvaginal ultrasonography) and lipids were monitored in this double-blind 1-year trial of 100 women randomized to either 2.5 mg tibolone or 2 mg 17beta-estradiol plus 1 mg norethindrone acetate daily. RESULTS: Both indexes of the arcuate arteries (uterine arteries) were significantly reduced beyond 3 and 6 months (12 months) from baseline, respectively, by the combined regimen compared with tibolone alone. Tibolone increased the resistance index of arcuate arteries but did not affect uterine arteries. There was no effect of either regimen on the internal iliac arteries. The medians of the percentage changes from baseline of high-density lipoprotein cholesterol (triglycerides) were significant between groups after 1 year, as follows: -17% (-16%) in the tibolone group and -4% (+15%) in the combined group, respectively. Both regimens similarly reduced total and low-density lipoprotein cholesterol and lipoprotein Lp(a). CONCLUSION: Hormone replacement therapy may induce different or opposite changes of both vascular resistance and lipids. It is unknown whether these findings may modify cardiovascular risk.     

Effects of conjugated equine estrogen with and without three different progestogens on lipoproteins, high-density lipoprotein subfractions, and apolipoprotein A-I.

The effects of conjugated equine estrogen and subsequent cyclical progestogen supplementation on lipoprotein and apolipoprotein A-I levels were investigated in three groups of postmenopausal women. Unopposed conjugated equine estrogen (0.625 mg) lowered total cholesterol 4-8% and low-density lipoprotein (LDL) cholesterol 12-19% below pre-treatment levels in all three groups. Levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I were increased 9-13 and 9-18%, respectively, with unopposed estrogen. The increase in HDL cholesterol was mainly due to increases in the high-density lipoprotein2 (HDL2) subfraction. Addition of medroxyprogesterone acetate, norethindrone acetate, or d,l-norgestrel at doses shown previously to provide protection against endometrial hyperplasia reversed some of the beneficial estrogen effects, reducing levels of HDL cholesterol 14-17%, HDL2 cholesterol 22-37%, and apolipoprotein A-I 11-15% from those obtained with unopposed estrogen. The LDL cholesterol levels fell 12-19% with unopposed estrogen but remained 7-12% below baseline when progestogens were added. These observations demonstrate that after 3 months of treatment, all three progestogens reversed some of the favorable effects of unopposed estrogen on lipoproteins but permitted a continued modest reduction in LDL cholesterol.     

Effects of postmenopausal hormone replacement therapy on lipid, lipoprotein, and apolipoprotein (a) concentrations: analysis of studies published from 1974-2000

OBJECTIVE: To establish reference estimates of the effects of different hormone replacement therapy (HRT) regimens on lipid and lipoprotein levels. DESIGN: Review and pooled analysis of prospective studies published up until the year 2000. SETTING: Clinical trials centers, hospitals, menopause clinics. PATIENT(S): Healthy postmenopausal women. INTERVENTION(S): Estrogen alone, estrogen plus progestogen, tibolone, or raloxifene in the treatment of menopausal symptoms. MAIN OUTCOME MEASURE(S): Serum high- and low-density lipoprotein (HDL and LDL) cholesterol, total cholesterol, triglycerides, and lipoprotein (a). RESULT(S): Two-hundred forty-eight studies provided information on the effects of 42 different HRT regimens. All estrogen alone regimens raised HDL cholesterol and lowered LDL and total cholesterol. Oral estrogens raised triglycerides. Transdermal estradiol 17-beta lowered triglycerides. Progestogens had little effect on estrogen-induced reductions in LDL and total cholesterol. Estrogen-induced increases in HDL and triglycerides were opposed according to type of progestogen, in the order from least to greatest effect: dydrogesterone and medrogestone, progesterone, cyproterone acetate, medroxyprogesterone acetate, transdermal norethindrone acetate, norgestrel, and oral norethindrone acetate. Tibolone decreased HDL cholesterol and triglyceride levels. Raloxifene reduced LDL cholesterol levels. In 41 studies of 20 different formulations, HRT generally lowered lipoprotein (a). CONCLUSION(S): Route of estrogen administration and type of progestogen determined differential effects of HRT on lipid and lipoprotein levels. Future work will focus on the interpretation of the clinical significance of these changes.     

Postmenopausal estrogen and androgen replacement and lipoprotein lipid concentrations

The effect of a combined estrogen-androgen drug on the lipoprotein lipid profile of women who received it parenterally as long-term postmenopausal replacement therapy was compared to that of women who had been receiving estrogen alone parenterally and to untreated surgically menopausal women. Plasma estradiol, testosterone, total cholesterol, triglycerides, high-density lipoproteins, and low-density lipoproteins were measured at baseline (55 days after injection) and then on days 2, 4, 8, 15, 21, and 28 after injection. The plasma estradiol levels were greater in the two hormone-treated groups compared with the control group (p less than 0.01), and plasma testosterone levels of the combined group exceeded those of the other two groups (p less than 0.01) and remained above the normal female range for the duration of the study. There were no between-group differences in total cholesterol, triglycerides, high-density lipoprotein, or low-density lipoprotein values. Neither was the low-density/high-density lipoprotein ratio significantly different between groups at any of the test times. Therefore, the addition of testosterone to a long-term parenteral estrogen replacement regimen did not induce an increased atherogenic lipid profile compared with that produced by the parenteral administration of estrogen alone.     

Long-term effects of percutaneous estrogens and oral progesterone on serum lipoproteins in postmenopausal women

Serum lipids and lipoproteins were examined in a group of 45 healthy postmenopausal women who were treated for 2 years with either 3 mg of percutaneous estradiol (n = 20) or placebo (n = 25). Percutaneous estradiol was given alone during the first year of treatment and in combination with oral micronized progesterone (200 mg) for 12 days of each cycle during the second year. The women were examined every 3 months throughout the 2 years. Percutaneous estrogen therapy significantly reduced total serum cholesterol and low-density lipoprotein cholesterol, whereas no significant differences were observed in serum triglycerides and high-density lipoprotein cholesterol. Addition of oral progesterone during the second year of treatment did not produce any significant alterations in serum total cholesterol or low-density lipoprotein cholesterol, both of which remained significantly reduced. Serum triglycerides remained virtually unchanged, whereas a slight but significant increase (p less than 0.05) was observed in high-density lipoprotein cholesterol levels at the end of the study period. We conclude that percutaneous estrogen administration produces changes in total serum cholesterol and low-density lipoprotein cholesterol levels similar to those observed after oral estrogen administration. However, the magnitude and time course of the response seem to be modulated by the route of administration. Addition of oral micronized progesterone does not influence the beneficial estrogenic actions on serum lipids and lipoproteins and seems to be a proper "progestogen" in percutaneous estrogen therapy.     

Effects of the selective estrogen receptor modulator, raloxifene, on carotid artery pulsatility index in postmenopausal women

OBJECTIVE: Estrogen replacement therapy after menopause reduces the incidence of arterial disease and cerebrovascular events. The reduced incidence also seems to be due to a positive effect of estrogens on brain blood flow as shown by a decrease in the carotid artery pulsatility index. Raloxifene, a second-generation selective estrogen receptor modulator, has aroused considerable interest because of its tissue-specific agonist-antagonist effect on estrogen receptors. However, there have been no studies on the effect of raloxifene on carotid blood flow after menopause. METHODS: A total of 66 healthy women in postmenopause for more than a year were divided randomly into 2 groups: the first group (n = 33; mean age +/- SD, 53.3 +/- 5.2 years) was treated with raloxifene (one 60-mg capsule per day) for 6 months, and the other group (n = 33; mean age +/- SD, 51.9 +/- 4 years) was untreated. Doppler ultrasonography was used to measure carotid artery pulsatility index (PI) at the beginning of the study and at 2-month intervals. RESULTS: A reduction in carotid artery PI was observed in all patients receiving raloxifene. No significant changes were observed in the control group. The reduction with respect to baseline values was 6.1%(P <.05) after 2 months, 11.2% (P <.05) after 4 months, and 13.2% (P <.05) after 6 months of therapy.The higher the baseline PI, the greater was its reduction after therapy. CONCLUSIONS: After 6 months of therapy, raloxifene induced a reduction in PI similar to that reported after estrogen therapy. The present results further our understanding of the mechanisms by which raloxifene might reduce the incidence of cardiovascular disease in postmenopausal women.     

Effects of third-generation oral contraceptives on high-sensitivity C-reactive protein and homocysteine in young women

OBJECTIVE: To evaluate the effect of third-generation oral contraceptives on high-sensitivity C-reactive protein (CRP), homocysteine, and lipids levels in a population of young, fertile, nonobese women. METHODS: Blood markers were evaluated in 277 healthy white women (mean age 23 years and mean body-mass index 21 kg/m(2)). Seventy-seven oral contraceptive users were compared with 200 non-oral contraceptive users. Progressive cutoffs of high-sensitivity CRP and homocysteine levels were examined. RESULTS: Levels of high-sensitivity CRP posing a high risk of cardiovascular disease (3.0 to less than 10.0 mg/L) were found in 27.3% of oral contraceptive users and in 8.5% of non-oral contraceptive users (odds ratio 4.04; 95% confidence interval [CI] 1.99-8.18). Levels of high-sensitivity CRP at intermediate risk (1.0 to less than 3.0 mg/L) were found in 32.5% of oral contraceptive users and in 11.0% of non-oral contraceptive users (odds ratio 3.89; 95% CI 2.03-7.46). Notably, non-oral contraceptive users were 8.65 (95% CI 4.39-17.1) times as likely to demonstrate a protective level of high-sensitivity CRP (less than 0.5 mg/L) compared with oral contraceptive users. Oral contraceptive use increased serum triglycerides (P<.001) and total cholesterol P=.001); however, high-density lipoprotein, not low-density lipoprotein, contributed to this increase. A decreased ratio of low-density lipoprotein to high-density lipoprotein cholesterol was observed in oral contraceptive users compared with nonusers (P=.016). Oral contraceptive use did not affect homocysteine levels. CONCLUSION: Third-generation oral contraceptive use increases low-grade inflammatory status measured by high-sensitivity CRP concentrations. Alteration of inflammatory status in oral contraceptive users could affect the risk of venous thromboembolism, cardiovascular disease, and other oral contraceptive-associated adverse conditions in young women.     

Effect of hormone replacement therapy, tibolone and raloxifene on serum lipids, apolipoprotein A1, apolipoprotein B and lipoprotein(a) in Greek postmenopausal women.

The aim of this study was to assess the effect of estrogen, two regimens of continuous combined hormone replacement therapy (HRT), tibolone and raloxffene on serum lipid, apolipoprotein A1 and B and lipoprotein(a) levels in Greek postmenopausal women. A total of 350 postmenopausal women were studied in a prospective open design. Women were assigned to one of the following regimens depending on the presence of risk factors for osteoporosis, dimacteric symptoms and an intact uterus: conjugated equine estrogen 0.625 mg (CEE, n = 34), continuous combined CEE 0.625 mg plus medroxyprogesterone acetate (MPA) 5 mg, (n = 80), continuous combined 17beta-estradiol 2 mg plus norethisterone acetate (NETA) 1 mg (n = 58), tibolone 2.5 mg (n = 83) and raloxifene HCl 60 mg (n = 50). Forty-five postmenopausal women with no indications for HRT served as controls. Total cholesterol (TC), low-density lipoprotein (LDL) cholestrol and high-density lipoprotein (HDL) cholesterol, triglyceride (TG), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and lipoprotein(a) (Lp(a)) levels were assessed in each subject at baseline, and at 6 and 12 months of therapy. All therapy regimens lowered TC levels compared to baseline (4.2-8.0% decrease). This effect was more prominent in the subgoup of women with high baseline TC levels (9.1-20.4% decrease). LDL cholesterol decreased significantly in CEE, CEE/MPA and raloxifene groups (-11.2%, -11.9% and -11.0%, respectively). Hypercholesterolemic women exhibited a steeper decrease in LDL cholesterol (10.6-27.8% in all therapy groups). TG levels increased significantly in the CEE and CEE/MPA groups (23.7% and 21.8%, respectively), while estradiol/NETA had no effect on TG levels. Tibolone decreased TG levels markedly, by 20.6%, while raloxifene had no TG-lowering effect. HDL cholesterol and ApoA1 were increased by CEE and CEE/MPA (HDL cholesterol, 7.4% and 11.8%, respectively; ApoA1, 17.8% and 7.9%, respectively) and decreased by tibolone (HDL cholesterol, -13.6%; and ApoA1, -9.9%). All therapy regimens except raloxifene lowered Lp(a) levels, with tibolone having the more pronounced effect (-13.2 to -29.0%). In conclusion, each therapy regimen had a diferent effect on lipid-lipoprotein levels, exerting favorable and unfavorable modifications. Hypercholesterolemic women seemed to benefit more from the cholesterol-lowering effect of estrogen replacement therapy/HRT. The choice for a particular regimen should be based on individual needs, indications and lipid-lipoprotein profile.     

Effect of hormone replacement therapy,tibolone and raloxifene on serum lipids,apolipoprotein A1, apolipoprotein B and lipoprotein(a) in Greek postmenopausal women

The aim of this study was to assess the effect of estrogen, two regimens of continuous combined hormone replacement therapy (HRT), tibolone and raloxifene on serum lipid, apolipoprotein A1 and B and lipoprotein(a) levels in Greek postmenopausal women. A total of 350 postmenopausal women were studied in a prospective open design. Women were assigned to one of the following regimens depending on the presence of risk factors for osteoporosis, climacteric symptoms and an intact uterus: conjugated equine estrogen 0.625 mg (CEE, n=34), continuous combined CEE 0.625 mg plus medroxyprogesterone acetate (MPA) 5 mg, (n=80), continuous combined 17β-estradiol 2 mg plus norethisterone acetate (NETA) 1 mg (n=58), tibolone 2.5 mg (n=83) and raloxifene HCl 60 mg (n=50). Forty-five postmenopausal women with no indications for HRT served as controls. Total cholesterol (TC), low-density lipoprotein (LDL) cholestrol and high-density lipoprotein (HDL) cholesterol, triglyceride (TG), apolipoprotein A1 (ApoA₁), apolipoprotein B (ApoB) and lipoprotein(a) (Lp(a)) levels were assessed in each subject at baseline, and at 6 and 12 months of therapy. All therapy regimens lowered TC levels compared to baseline (4.2-8.0% decrease). This effect was more prominent in the subgoup of women with high baseline TC levels (9.1-20.4% decrease). LDL cholesterol decreased significantly in CEE, CEE/MPA and raloxifene groups (?11.2%, ?11.9% and ?11.0%, respectively). Hypercholesterolemic women exhibited a steeper decrease in LDL cholesterol (10.6-27.8% in all therapy groups). TG levels increased significantly in the CEE and CEE/MPA groups (23.7% and 21.8%, respectively), while estradiol/NETA had no effect on TG levels. Tibolone decreased TG levels markedly, by 20.6%, while raloxifene had no TG-lowering effect. HDL cholesterol and ApoA₁ were increased by CEE and CEE/MPA (HDL cholesterol, 7.4% and 11.8%, respectively; ApoA₁, 17.8% and 7.9%, respectively) and decreased by tibolone (HDL cholesterol, ?13.6%; and ApoA₁, ?9.9%). All therapy regimens except raloxifene lowered Lp(a) levels, with tibolone having the more pronounced effect (?13.2 to ?29.0%). In conclusion, each therapy regimen had a different effect on lipid-lipoprotein levels, exerting favorable and unfavorable modifications. Hypercholesterolemic women seemed to benefit more from the cholesterol-lowering effect of estrogen replacement therapy/HRT. The choice for a particular regimen should be based on individual needs, indications and lipid-lipoprotein profile.     

Lipoprotein metabolism during normal pregnancy.

OBJECTIVE: We sought to investigate the changes in circulating serum lipids and lipoproteins, including lipoprotein (a), and low-density lipoprotein size in women during normal pregnancy. STUDY DESIGN: Twenty-two women (mean age, 31 +/- 5 years; 13 primiparous subjects) were studied during uncomplicated pregnancy with normal outcome. Twenty-four nulliparous women of similar age (31 +/- 4 years) were studied as control subjects. RESULTS: Serum triglycerides and total and low-density lipoprotein cholesterol increased significantly during pregnancy in all women. Women with changes in low-density lipoprotein during the second and third trimesters showed a more marked increase in serum triglycerides, and this effect was slightly more evident in the multiparous subjects. No other differences were evident between primiparous and multiparous women apart from high-density lipoprotein cholesterol levels, which were slightly decreased in the latter subjects. CONCLUSIONS: Our results show that during normal pregnancy, the increase in plasma triglycerides may lead to the appearance of the atherogenic dense low-density lipoproteins in a subgroup of women. We suggest that the observed changes in low-density lipoprotein patterns during pregnancy might be used to identify those women who later in life will have these atherogenic small and dense low-density lipoproteins.     

Effects of raloxifene, hormone therapy, and soy isoflavone on serum high-sensitive C-reactive protein in postmenopausal women.

OBJECTIVE: To compare the effects of raloxifene, estradiol valerate plus dienogest, and soy isoflavones (genistein) on serum concentrations of high-sensitive C-reactive protein in healthy postmenopausal women. METHODS: The 80 healthy postmenopausal women enrolled in the study were randomly allocated to receive 60 mg of raloxifene, 2 mg of estradiol valerate plus dienogest, 40 mg of genistein, or placebo (n=20 in each group). Blood samples were collected at the start of the study and at 3 and 6 months. Lipid profile was also determined. RESULTS: Only the group receiving estradiol valerate plus dienogest showed an increase in serum levels of high-sensitive C-reactive protein compared with baseline values and values in the control and other groups. All 3 treatments resulted in an increase in high-density lipoprotein cholesterol levels and a decrease in total, low-density, and very-low-density lipoprotein cholesterol levels. CONCLUSIONS: Estradiol valerate plus dienogest, but not raloxifene and genistein, increase serum high-sensitive C-reactive protein levels. All 3 treatments, however, have an estrogen-like effect on serum lipid profile.     

Randomized, double-blind, placebo-controlled study of the effects of raloxifene and conjugated equine estrogen on plasma homocysteine levels in healthy postmenopausal women

Objective: To investigate the long-term effects of raloxifene on fasting plasma homocysteine levels in postmenopausal women compared with conjugated equine estrogen (CEE).

Design: Randomized, double-blind, placebo-controlled study.

Setting: Outpatient department of a university hospital.

Patient(s): Fifty-two hysterectomized, healthy postmenopausal women.

Intervention(s): Oral raloxifene in two dosages (60 mg/d [n = 13] and 150 mg/d [n = 13]), oral CEE (0.625 mg/d [n = 13], and placebo (n = 13) were given for 24 months.

Main Outcome Measure(s): Fasting plasma homocysteine concentrations.

Result(s): Plasma homocysteine levels were not altered in the placebo group. After 12 months, a significant reduction versus baseline in the mean plasma homocysteine level (−16%) was found only in the raloxifene 150-mg group. The mean change in plasma homocysteine levels within this group also was significantly different from the changes versus baseline found in the placebo group (+2%) and the raloxifene 60-mg group (−2%), but not different from those found in the CEE group (−8%). After 24 months, plasma homocysteine levels were decreased significantly in the raloxifene 150-mg and CEE groups compared with both baseline (−13% and −10%, respectively) and placebo values (−15% and −11%, respectively). No significant change in plasma homocysteine levels was observed in the raloxifene 60-mg group.

Conclusion(s): Raloxifene has a favorable, dose-related effect on plasma homocysteine levels in postmenopausal women.     

雷洛昔芬对绝经后妇女骨密度、骨代谢生化指标和血脂影响的随机对照研究

目的　确定盐酸雷洛昔芬 (RLX)对中国绝经后妇女骨密度、骨代谢生化指标及血脂的影响。方法　将来自 3所医院的 2 0 4例绝经后妇女 [平均年龄 (6 0± 5 )岁 ,平均体重 (6 3± 9)kg]随机分组 ,进行双盲安慰剂对照的临床研究 ,受试者每天接受RLX 6 0mg(n =10 2 ,RLX组 )或安慰剂 (n =10 2 ,安慰剂组 )治疗 12个月 ,并于服药前及服药 12个月后各进行一次骨密度、骨代谢生化指标及血脂的测定。结果　与安慰剂相比 ,RLX使腰椎和髋部骨密度显著升高 ,RLX组腰椎的骨密度增加2 30 % ,而安慰剂组降低 0 0 8% ,两组比较 ,差异有极显著性 (P <0 0 0 1) ;RLX组髋部骨密度增加2 4 6 % ,安慰剂组增加 1 0 7% ,两组比较 ,差异有显著性 (P <0 0 5 )。RLX组骨代谢生化指标血清骨钙素和血清C端交联肽分别降低 2 7 6 %和 2 4 0 % ,而安慰剂组则分别降低 10 6 %和升高 15 8% ,两组比较 ,差异有极显著性 (P <0 0 0 1)。RLX组总胆固醇和低密度脂蛋白胆固醇分别降低 6 4 %和34 6 % ,而安慰剂组则分别升高 1 4 %和降低 19 1% ,两组比较 ,差异有极显著性 (P <0 0 0 1)。两组间高密度脂蛋白胆固醇和甘油三酯水平未见差异。仅有 5例因不良事件而提前退出研究 (RLX组 3例 ,安慰剂组 2例 )。结论　RLX能增加绝经后中国妇女     

Effects of estrogen dose and smoking on lipid and lipoprotein levels in postmenopausal women

The joint effects of conjugated estrogen use, age, body mass index, and smoking on plasma lipid and lipoprotein levels were assessed in 585 women who used oral estrogen and 1093 women who did not who participated in the Walnut Creek Contraceptive Drug Study. Whether administered daily or cyclically, conjugated estrogen was associated with reductions in low-density lipoprotein cholesterol levels and increases in high-density lipoprotein cholesterol and triglyceride levels. The adjusted mean low-density lipoprotein cholesterol concentration was 132 mg/dl for women who used conjugated estrogen in a dose ≥ 1.25 mg/day; the adjusted corresponding mean concentration was 147 mg/dl for postmenopausal women who did not use estrogen. A dose-response pattern was demonstrated between conjugated estrogen and low- and high-density lipoprotein cholesterol levels. A maximum low-density lipoprotein cholesterol level reduction was reached at a dose of 1.25 mg, suggesting a saturation phenomenon. Stepwise dose-response increases in high-density lipoprotein cholesterol levels were also found with estrogen therapy, with a maximum increase of 8 to 10 mg/dl observed with the 1.25 mg dose. Estrogen-related rises in low-density lipoprotein cholesterol levels and decreases in high-density lipoprotein cholesterol levels were offset by 2 to 3 mg/dl in women who smoked. It may be concluded, therefore, that among postmenopausal women, low-risk lipoprotein profiles as assessed by low- and high-density lipoprotein cholesterol levels are found in nonsmokers whose postmenopausal hormone therapy includes the equivalent of a conjugated estrogen dose of 1.25 mg.