Effects of continuous estrogen and estrogen-progestin replacement regimens on cardiovascular risk markers in postmenopausal women

被引:80
作者
Davidson, MH
Maki, KC
Marx, P
Maki, AC
Cyrowski, MS
Nanavati, N
Arce, JC
机构
[1] Chicago Ctr Clin Res, Nutr & Metab Res Unit, Chicago, IL 60610 USA
[2] Novo Nordisk Pharmaceut Inc, Princeton, NJ USA
关键词
D O I
10.1001/archinte.160.21.3315
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: To evaluate the influence of 2 continuous combined estrogen-progestin replacement products, compared with unopposed estrogen and placebo, on cardiovascular risk markers in postmenopausal women in a randomized, double-blind, placebo-controlled trial. Methods: Two hundred seventy healthy postmenopausal women were randomly assigned to 1 of 4 treatment groups: placebo, unopposed 17-beta estradiol(1 mg), 1 mg of 17-beta estradiol with 0.25 mg of norethindrone acetate, or 1 mg of 17-beta estradiol with 0.5 mg of norethindrone acetate. The primary outcome variable was change from baseline in low-density lipoprotein cholesterol concentration. Additional outcome variables included changes in other serum lipid levels, hemostatic variables, and indicators of carbohydrate metabolism. Results: The low-density lipoprotein cholesterol level was reduced to a similar degree in all groups receiving active treatment (10%-14% from baseline; P=.001 for 17-beta estradiol with 0.5 mg of norethindrone acetate, P=.004 for 17-beta estradiol with 0.25 mg of norethindrone acetate, and P=.001 for 1 mg of 17-beta estradiol vs placebo). Compared with unopposed 17-beta estradiol, 17-beta estradiol with 0.5 mg of norethindrone acetate enhanced the reductions in total cholesterol and apolipoprotein B levels (P<.01 vs 17-<beta> estradiol). 17-beta Estradiol plus norethindrone blunted or reversed the increases in levels of high-density lipoprotein cholesterol, apolipoprotein A-I, and triglycerides produced by 17-beta estradiol alone. Effects of 17-beta estradiol plus norethindrone on hemostatic variables were similar to those of 17-beta estradiol except for factor VII activity, which was significantly reduced with 17-beta estradiol combined with 0.25 mg (P<.01) and 0.5 mg (P<.05) of norethindrone acetate. 17-beta Estradiol plus norethindrone appeared to blunt reductions in C-peptide and insulin levels produced by unopposed 17-beta estradiol but did not elevate these values compared with placebo. Conclusions: 17-beta Estradiol plus norethindrone produced favorable changes in most cardiovascular risk markers evaluated and has a profile distinct from that of unopposed 17-beta estradiol. The impact of these differences on cardiovascular events warrants investigation.
引用
收藏
页码:3315 / 3325
页数:11
相关论文
共 36 条
[1]   INHIBITION OF CORONARY-ARTERY ATHEROSCLEROSIS BY 17-BETA ESTRADIOL IN OVARIECTOMIZED MONKEYS - LACK OF AN EFFECT OF ADDED PROGESTERONE [J].
ADAMS, MR ;
KAPLAN, JR ;
MANUCK, SB ;
KORITNIK, DR ;
PARKS, JS ;
WOLFE, MS ;
CLARKSON, TB .
ARTERIOSCLEROSIS, 1990, 10 (06) :1051-1057
[2]   Norethindrone acetate enhances the antiatherogenic effect of 17β-estradiol -: A secondary prevention study of aortic atherosclerosis in ovariectomized cholesterol-fed rabbits [J].
Alexandersen, P ;
Haarbo, J ;
Sandholdt, I ;
Shalmi, M ;
Lawaetz, H ;
Christiansen, C .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1998, 18 (06) :902-907
[3]   Risk of venous thromboembolism in users of hormone replacement therapy [J].
Daly, E ;
Vessey, MP ;
Hawkins, MN ;
Carson, JL ;
Gough, P ;
Marsh, S .
LANCET, 1996, 348 (9033) :977-980
[4]   CARBOHYDRATE-METABOLISM DURING HORMONAL SUBSTITUTION THERAPY [J].
DECLEYN, K ;
BUYTAERT, P ;
COPPENS, M .
MATURITAS, 1989, 11 (03) :235-242
[5]   Effect of postmenopausal hormone therapy on glucose and insulin concentrations [J].
Espeland, MA ;
Hogan, PE ;
Fineberg, SE ;
Howard, G ;
Schrott, H ;
Waclawiw, MA ;
Bush, TL .
DIABETES CARE, 1998, 21 (10) :1589-1595
[6]  
FRIEDEWALD WT, 1972, CLIN CHEM, V18, P499
[7]   Seasonal variations of rheological and hemostatic parameters and acute-phase reactants in young, healthy subjects [J].
Frohlich, M ;
Sund, M ;
Russ, S ;
Hoffmeister, A ;
Fischer, HG ;
Hombach, V ;
Koenig, W .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1997, 17 (11) :2692-2697
[8]   Low-dose esterified estrogen therapy - Effects on bone, plasma estradiol concentrations, endometrium, and lipid levels [J].
Genant, HK ;
Lucas, J ;
Weiss, S ;
Akin, M ;
Emkey, R ;
McNaneyFlint, H ;
Downs, R ;
Mortola, J ;
Watts, N ;
Yang, HM ;
Banav, N ;
Brennan, JJ ;
Nolan, JC .
ARCHIVES OF INTERNAL MEDICINE, 1997, 157 (22) :2609-2615
[9]   HORMONE-THERAPY TO PREVENT DISEASE AND PROLONG LIFE IN POSTMENOPAUSAL WOMEN [J].
GRADY, D ;
RUBIN, SM ;
PETITTI, DB ;
FOX, CS ;
BLACK, D ;
ETTINGER, B ;
ERNSTER, VL ;
CUMMINGS, SR .
ANNALS OF INTERNAL MEDICINE, 1992, 117 (12) :1016-1037
[10]   Postmenopausal hormone therapy and mortality [J].
Grodstein, F ;
Stampfer, MJ ;
Colditz, GA ;
Willett, WC ;
Manson, JE ;
Joffe, M ;
Rosner, B ;
Fuchs, C ;
Hankinson, SE ;
Hunter, DJ ;
Hennekens, CH ;
Speizer, FE .
NEW ENGLAND JOURNAL OF MEDICINE, 1997, 336 (25) :1769-1775