The effects of transdermal estradiol in combination with oral norethisterone on lipoproteins, coagulation, and endothelial markers in postmenopausal women with type 2 diabetes: A randomized, placebo-controlled study

被引:48
作者
Perera, M
Sattar, N
Petrie, JR
Hillier, C
Small, M
Connell, JMC
Lowe, GDO
Lumsden, MA
机构
[1] W Glasgow Hosp Natl Hlth Serv Trust, Ctr Diabet, Glasgow G31 2ER, Lanark, Scotland
[2] Univ Glasgow, Dept Med & Therapeut, Glasgow G31 2ER, Lanark, Scotland
[3] Univ Glasgow, Dept Pathol Biochem, Glasgow G31 2ER, Lanark, Scotland
[4] Univ Glasgow, Dept Med, Glasgow G31 2ER, Lanark, Scotland
[5] Univ Glasgow, Dept Obstet & Gynecol, Glasgow G31 2ER, Lanark, Scotland
关键词
D O I
10.1210/jc.86.3.1140
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
People with type 2 diabetes have a substantially increased risk of coronary heart disease (CHD). Short-term studies with unopposed oral estradiol in women with diabetes have suggested potentially beneficial effects on lipids, thrombotic factors, and insulin sensitivity. However, most (nonhysterectomized) postmenopausal women require combined estrogen-progesterone preparations. We randomized 43 women with type 2 diabetes either to continuous transdermal estradiol (80-mug patches) in combination with oral norethisterone (1 mg daily) or to identical placebos. Blood samples were taken before and after 6 months for measurement of lipoproteins, coagulation factors, and endothelial markers. Total cholesterol and triglyceride concentrations decreased by 8% and 22%, respectively, in those receiving hormone replacement therapy (P < 0.05 relative to change in placebo group after adjustment for baseline concentrations). There was a trend toward a reduction in high density lipoprotein cholesterol concentration (P = 0.06). Factor VII activity decreased by 16% (P < 0.001), and von Willebrand factor antigen decreased by 7% (P = 0.014) with active treatment. Levels of fibrinogen, tissue plasminogen activator, fibrin D dimer, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, lipoprotein(a), and leptin were not significantly altered. No change in glycemic control was detected. Overall, lipid changes may be considered slightly beneficial with respect to CHD risk. The significant decrease in factor VII activity in this study is notable, because elevated factor VII activity has been associated with an increased risk of coronary thrombosis and normally increases with administration of oral estrogen-containing preparations. In addition, a reduction in von Willebrand factor antigen is consistent with an improvement in endothelial function. We suggest that the regimen used in this study may have the potential to reduce CHD risk in women with type 2 diabetes.
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页码:1140 / 1143
页数:4
相关论文
共 27 条
  • [1] Estrogen replacement therapy decreases hyperandrogenicity and improves glucose homeostasis and plasma lipids in postmenopausal women with noninsulin-dependent diabetes mellitus
    Andersson, B
    Mattsson, LA
    Hahn, L
    Marin, P
    Lapidus, L
    Holm, G
    Bengtsson, BA
    Bjorntorp, P
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1997, 82 (02) : 638 - 643
  • [2] Short-term oestrogen replacement therapy improves insulin resistance, lipids and fibrinolysis in postmenopausal women with NIDDM
    Brussaard, HE
    Leuven, JAG
    Frolich, M
    Kluft, C
    Krans, HMJ
    [J]. DIABETOLOGIA, 1997, 40 (07) : 843 - 849
  • [3] Effect of 17 beta-estradiol on plasma lipids and LDL oxidation in postmenopausal women with type II diabetes mellitus
    Brussaard, HE
    Leuven, JAG
    Kluft, C
    Krans, HMJ
    vanDuyvenvoorde, W
    Buytenhek, R
    vanderLaarse, A
    Princen, HMG
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1997, 17 (02) : 324 - 330
  • [4] Triglyceride-rich lipoproteins: are links with atherosclerosis mediated by a procoagulant and proinflammatory phenotype?
    Byrne, CD
    [J]. ATHEROSCLEROSIS, 1999, 145 (01) : 1 - 15
  • [5] Effect of postmenopausal hormones on inflammation-sensitive proteins - The Postmenopausal Estrogen/Progestin Interventions (PEPI) Study
    Cushman, M
    Legault, C
    Barrett-Connor, E
    Stefanick, ML
    Kessler, C
    Judd, HL
    Sakkinen, PA
    Tracy, RP
    [J]. CIRCULATION, 1999, 100 (07) : 717 - 722
  • [6] Association of hormone replacement therapy and carotid wall thickness in women with and without diabetes
    Dubuisson, JT
    Wagenknecht, LE
    D'Agostino, RB
    Haffner, SM
    Rewers, M
    Saad, MF
    Laws, A
    Herrington, DM
    [J]. DIABETES CARE, 1998, 21 (11) : 1790 - 1796
  • [7] Feher MD, 1996, BRIT J CLIN PRACT, V50, P431
  • [8] Postmenopausal estrogen and progestin use and the risk of cardiovascular disease
    Grodstein, F
    Stampfer, MJ
    Manson, JE
    Colditz, GA
    Willett, WC
    Rosner, B
    Speizer, FE
    Hennekens, CH
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1996, 335 (07) : 453 - 461
  • [9] Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction
    Haffner, SM
    Lehto, S
    Rönnemaa, T
    Pyörälä, K
    Laakso, M
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1998, 339 (04) : 229 - 234
  • [10] Hokanson J E, 1996, J Cardiovasc Risk, V3, P213, DOI 10.1097/00043798-199604000-00014