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

      Abstract

      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. (Am J Obstet Gynecol 2002;186:832-5.)

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      References

        • Grimes DA
        Prevention of cardiovascular disease in women: role of the obstetrician-gynecologist.
        Am J Obstet Gynecol. 1988; 158: 1662-1668
        • Stampfer MJ
        • Colditz GA
        • Willett WC
        • Manson JE
        • Rosner B
        • Speizer FE
        • et al.
        Postmenopausal estrogen therapy and cardiovascular disease.
        N Engl J Med. 1991; 325: 756-762
        • Hulley S
        • Grady D
        • Bush T
        • Furberg C
        • Herrington D
        • Riggs B
        • et al.
        Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group.
        JAMA. 1998; 280: 605-613
        • de Valk-de Roo GW
        • Stehouwer CDA
        • Meijer P
        • Mijatovic V
        • Kluft C
        • Kenemans P
        • et al.
        Both raloxifene and estrogen reduce major cardiovascular risk factor in healthy postmenopausal women.
        Arterioscler Thromb Vasc Biol. 1999; 19: 2993-3000
        • Jackson S
        • Vyas S
        A double-blind, placebo controlled study of postmenopausal oestrogen replacement therapy and carotid artery pulsatility index.
        Br J Obstet Gynecol. 1998; 105: 408-412
        • Cacciatore B
        • Paakkari I
        • Toivonen J
        • Tikkanen MJ
        • Ylikorkala O
        Randomized comparison of oral and transdermal hormone replacement on carotid and uterine artery resistance to blood flow.
        Obstet Gynecol. 1998; 92: 563-568
        • Gangar KF
        • Vyas S
        • Whitehead M
        • Crook D
        • Meire H
        • Campbell S.
        Pulsatility index in internal carotid artery in relation to transdermal oestradiol and time since menopause.
        Lancet. 1991; 338: 839-842
        • Penotti M
        • Nencioni T
        • Gabrielli L
        • Farina M
        • Castiglioni E
        • Polvani F
        Blood flow variations in internal carotid and middle cerebral arteries induced by postmenopausal hormone replacement therapy.
        Am J Obstet Gynecol. 1993; 169: 1226-1232
        • Gustafsson J
        Raloxifene: magic bullet for heart and bone?.
        Nat Med. 1998; 4: 152-153
        • De Leo V
        • la Marca A
        • Morgante G
        • Lanzetta D
        • Setacci C
        Randomized control study of the effects of raloxifene on serum lipids and homocysteine in older women.
        Am J Obstet Gynecol. 2001; 184: 350-353
        • Penotti M
        • Farina M
        • Castiglioni E
        • Gaffuri B
        • Barletta L
        • Gabrielli L
        • et al.
        Alteration in the pulsatility index values of the internal carotid and middle cerebral arteries after suspension of postmenopausal hormone replacement therapy: a randomized crossover study.
        Am J Obstet Gynecol. 1996; 175: 606-611
        • Rosenfeld CR
        • Killam AP
        • Battaglia FC
        • Makowski EL
        • Meschia G
        Effect of estradiol-17beta on the magnitude and distribution of uterine blood flow in nonpregnant, oophorectomized ewes.
        Pediatr Res. 1973; 7: 139-148
        • Lang U
        • Baker S
        • Clark KE
        Estrogen induced increases in coronary blood flow are antagonized by inhibitors of nitric oxide synthesis.
        Eur J Obstet Gynecol Reprod Biol. 1997; 74: 229-235
        • Barrett-Connor E
        • Wenger NK
        • Grady D
        • Mosca L
        • Collins P
        • Korn- itzer M
        • et al.
        Coronary heart disease in women, randomized clinical trials, HERS and RUTH.
        Maturitas. 1998; 31: 1-7
        • Delmas PD
        • Bjarnason NH
        • Mitlak BH
        • Ravoux AC
        • Shah AS
        • Huster WJ
        • et al.
        Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women.
        N Engl J Med. 1997; 337: 1641-1647
        • Greene RA
        Cerebral blood flow [letter].
        Fertil Steril. 2000; 73: 143
        • Shaywitz SE
        • Shaywitz BA
        • Pugh KR
        • Fulbright RK
        • Skudlarski P
        • Mencl WE
        • et al.
        Effect of estrogen on brain activation patterns in postmenopausal women during working memory tasks.
        JAMA. 1999; 281: 1197-1202
        • Yaffe K
        • Krueger K
        • Sarkar S
        • Grady D
        • Barrett-Connor E
        • Cox DA
        • et al.
        Cognitive function in postmenopausal women treated with raloxifene.
        N Engl J Med. 2001; 344: 1207-1213