Both Raloxifene and Estrogen Reduce Major Cardiovascular Risk Factors in Healthy Postmenopausal Women

Roo, G.W. de Valk-de; Stehouwer, C.D.A.; Meijer, Piet; Mijatovic, Velja; Kluft, C.; Kenemans, P.; Cohen, Fredric J.; Watts, Steven; Netelenbos, Coen

doi:10.1161/01.atv.19.12.2993

Cited by 156 publications

(88 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the perspective of DHA and AA, raloxifene seems to be the preferable compound in postmenopausal women when weighed against CEE plus MPA. Raloxifene has beneficial effects on bone density and lipids of raloxifene (de Valk-de Roo et al 1999, Johnston et al 2000, Walsh et al 2000, and in the present study increased DHA levels more strongly than AA (when given in a dosage of 150 mg per day), while n-3 HUFA are relatively deficient compared with n-6 HUFA in the dietary pattern in industrialized countries. The lack of effect on DHA and AA in men, combined with the negative effect on HDL-cholesterol and a significant increase in serum prostate specific antigen (PSA) levels (Duschek et al 2004), would lead us not to recommend raloxifene administration in men.…”

Section: Discussionsupporting

confidence: 57%

“…Linoleic acid is converted into arachidonic acid, and -linolenic acid is converted into eicosapentaenoic acid and docosahexaenoic acid (Sprecher 2000). lowers total and low-density-lipoprotein (LDL) cholesterol (de Valk-de Roo et al 1999, Johnston et al 2000, Walsh et al 2000. Comparing raloxifene, conjugated equine estrogens (CEE) combined with 2·5 mg medroxyprogesterone acetate (MPA), and placebo in healthy early postmenopausal women and healthy elderly men may increase our understanding of their potential effects on the biosynthesis of n-3 and n-6 HUFA.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Raloxifene and hormone replacement therapy increase arachidonic acid and docosahexaenoic acid levels in postmenopausal women

Giltay¹,

Duschek²,

Katan³

et al. 2004

Journal of Endocrinology

View full text Add to dashboard Cite

Estrogens may affect the essential n-6 and n-3 fatty acids arachidonic acid (AA; C20:4n-6) and docosahexaenoic acid (DHA; C22:6n-3). Therefore, we investigated the long-term effects of hormone replacement therapy and raloxifene, a selective estrogen-receptor modulator, in two randomized, double-blind, placebo-controlled studies. In study I, 95 healthy, non-hysterectomized, early postmenopausal women (age range 47-59 years) received one of the following treatments: daily raloxifene 60 mg (n=24), daily raloxifene 150 mg (n=23), 0·625 mg conjugated equine estrogens (CEE) plus 2·5 mg medroxyprogesterone acetate (MPA; n=24), or placebo (n=24). In study II, 30 men (age range 60-69 years) received daily 120 mg raloxifene (n=15) or placebo (n=15). In study I, plasma cholesteryl ester fatty acids were measured at baseline and after 6, 12, and 24 months in 83 (drop out rate 13%), 73 (23%), and 70 (25%) women respectively. In study II, fatty acids were measured at baseline and after 3 months in 29 men (drop out rate 3%). In postmenopausal women, administration of 150 mg raloxifene increased AA by a mean of +6·1% (P=0·055, not significant). Administration of CEE plus MPA increased AA by +14·1% (P<0·0005). Mean changes in DHA were +22·1% (P=0·003) and +14·9% (P=0·047) respectively, as compared with placebo. In men, 120 mg raloxifene for 3 months did not significantly affect AA (-5·2%; P=0·342) or DHA (+4·0%; P=0·755), but it increased testosterone levels by +19·8% (P=0·006). Administration of raloxifene 150 mg/day as well as CEE plus MPA to postmenopausal women increases the proportion of AA and DHA in plasma cholesteryl esters during a follow-up of 2 years. Short term administration of raloxifene in elderly men did not affect AA or DHA. The synthesis of AA and DHA from precursors may be enhanced through an estrogen receptor-dependent pathway.

show abstract

Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Raloxifene and hormone replacement therapy increase arachidonic acid and docosahexaenoic acid levels in postmenopausal women

Giltay¹,

Duschek²,

Katan³

et al. 2004

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Estrogen replacement therapy and the selective estrogen receptor modulator (SERM) raloxifene lower plasma Hcy (Walsh et al, 2000;Yildirir et al, 2002). Estrogen, but not raloxifene, increases circulating CRP concentration (de Valk-de Roo et al, 1999;Walsh et al, 2000;Yildirir et al, 2002) by increasing hepatic production of CRP (Walsh et al, 2001;Skouby et al, 2002). Both estrogen and raloxifene have been reported to decrease vascular adhesion molecules (Koh et al, 1999;Blum et al, 2000) by binding to estrogen receptors on the vascular endothelium and modulating transcription of these adhesion molecules (Caulin-Glaser et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Consumption of isoflavone-rich soy protein does not alter homocysteine or markers of inflammation in postmenopausal women

et al. 2007

View full text Add to dashboard Cite

Background/Objective: To investigate the effect of soy protein containing isoflavones on homocysteine (Hcy), C-reactive protein (CRP), soluble E-selectin (sE-selectin), soluble vascular adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1). Subject/Methods: In a randomized crossover design, 34 postmenopausal women consumed soy protein isolate (2675 g protein containing 4478 mg isoflavones per day) or milk protein isolate (2675 g protein per day) for 6 weeks each. Fasting blood samples were collected at the end of each diet period and end points analyzed by enzyme-linked immunosorbent assay. Results: Concentrations of Hcy, CRP, sE-selectin, sVCAM-1 and sICAM-1 were not different between soy and milk diet treatments. Results did not differ by equol production status or by baseline lipid concentration. Adjustment for intake of folate and methionine did not alter the Hcy results. Conclusions: These data suggest that decreasing vascular inflammation and Hcy concentration are not likely mechanisms by which soy consumption reduces coronary heart disease risk.

show abstract

“…No significant alterations associated to raloxifene were detected in F1ϩ2, fibrinopeptide A, and plasminogen activator inhibitor-1 levels. In another study involving more extensive assessment of the hemostatic system, De Valk-de Roo et al (15) also observed a fibrinogen reduction associated with raloxifene use but without significant alter- ations in other coagulation parameters assessed. In relation to fibrinolysis assessment, no significant modifications were detected in any of the parameters considered, in groups which received raloxifene.…”

Section: Discussionmentioning

confidence: 92%

Procoagulant state after raloxifene therapy in postmenopausal women

Azevedo

Franco

Baggio

et al. 2005

Fertility and Sterility

View full text Add to dashboard Cite

Objective: To investigate the effects of raloxifene on the hemostatic system in postmenopausal women. Design: A prospective longitudinal study. Setting: Outpatient clinic of the Faculty of Medicine of Ribeirão Preto, Brazil. Patient(s): Sixteen postmenopausal women aged 56.8 Ϯ 5.9 years (mean Ϯ SD). Intervention(s): Raloxifene hydrochloride (60 mg once daily) was administered orally for a period of 6 months. Main Outcome Measure(s): Plasma activities of coagulation factors (II, V, VII, VIII, IX, X, XI, XII, and fibrinogen), prothrombin-derived fragment 1ϩ2, and activated protein C (APC) sensitivity ratio were measured at baseline and after 1, 3, and 6 months of treatment. Result(s): Factor VIII activity increased by 17.1% and 26.9% at 3 and 6 months of treatment, respectively, compared with baseline. Factor XI and FXII activities significantly increased by 10.9% and 43.1%, respectively, after 6 months compared with baseline. A significant reduction of APC sensitivity ratio also was observed after 6 months of treatment. Conclusion(s):A procoagulant state characterized by increased factor VIII, XI, and XII plasma levels and by reduced APC sensitivity was observed after raloxifene therapy in post-menopausal women. (Fertil Steril 2005; 84:1680 -4. ©2005 by American Society for Reproductive Medicine.)Key Words: Climacteric, hemostatic system, raloxifene, SERMs Raloxifene is a selective estrogen receptor modulator and exerts tissue-selective effects similar to those of estrogen (E) on bone and serum lipids, without any apparent stimulatory effect on mammary and uterine tissues (1-5). The effect of raloxifene on the cardiovascular system in postmenopausal women has been studied, and the favorable results have been explained mainly by its effects on metabolic changes in lipoproteins, homocysteine, and improved endothelium-dependent vasomotricity, preventing arteriosclerosis and acting as a vasodilating agent (6 -9).Despite these benefits, raloxifene therapy increases the risk of venous thromboembolism (VTE) by approximately threefold, a similar effect to that observed with hormone therapy (HT) (4). Although a large body of data supports a procoagulant state related to E administration, there are few published data on the effect of raloxifene on hemostatic parameters in postmenopausal women. In an article published elsewhere (10), we reported that raloxifene therapy is associated with a significant reduction in plasma antithrombin activity, suggesting that this effect may contribute to a procoagulant state and partly explain the increased risk of VTE in raloxifene users. Here, we report the results of a longitudinal study assessing the effects of raloxifene on other hemostatic parameters in healthy postmenopausal women. MATERIALS AND METHODS Study SubjectsSixteen postmenopausal women were enrolled in a prospective longitudinal study. General characteristics of the subjects were as follows (values given as mean Ϯ SD): age, 56.8 Ϯ 5.9 years; duration of menopause, 9.3 Ϯ 5.5 years; and body mass index, 25.8 Ϯ 3.7 kg/m 2 . ...

show abstract

Both Raloxifene and Estrogen Reduce Major Cardiovascular Risk Factors in Healthy Postmenopausal Women

Cited by 156 publications

References 69 publications

Raloxifene and hormone replacement therapy increase arachidonic acid and docosahexaenoic acid levels in postmenopausal women

Raloxifene and hormone replacement therapy increase arachidonic acid and docosahexaenoic acid levels in postmenopausal women

Consumption of isoflavone-rich soy protein does not alter homocysteine or markers of inflammation in postmenopausal women

Procoagulant state after raloxifene therapy in postmenopausal women

Contact Info

Product

Resources

About