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Hormone replacement therapy in healthy postmenopausal women: a randomized, placebo-controlled study of effects on coagulation and fibrinolytic factors

Gottsäter, Anders LU ; Rendell, M; Hulthén, Lennart LU ; Berntorp, Erik LU and Mattiasson, Ingrid LU (2001) In Journal of Internal Medicine1989-01-01+01:00 249(3). p.237-246
Abstract
OBJECTIVES: To evaluate effects of postmenopausal hormone replacement therapy (HRT) on von Willebrand factor, factor (F)VIII, factor (F)VII, fibrinogen, antithrombin (AT) III, prothrombin fragments 1 and 2, protein C, total and free protein S, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and resistance to activated protein C. DESIGN: Part 1: double blind randomized trial for 3 months. Part 2: open study for 9 months. SETTING: Department of Endocrinology, University Hospital, Malmo, Sweden. SUBJECTS: Fifty-one postmenopausal women with a history of amenorrhoea of at least 6 months and body mass index > or = 24 kg m-2 participated in part 1 and 46 participated in part 2. INTERVENTION: Randomization for... (More)
OBJECTIVES: To evaluate effects of postmenopausal hormone replacement therapy (HRT) on von Willebrand factor, factor (F)VIII, factor (F)VII, fibrinogen, antithrombin (AT) III, prothrombin fragments 1 and 2, protein C, total and free protein S, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and resistance to activated protein C. DESIGN: Part 1: double blind randomized trial for 3 months. Part 2: open study for 9 months. SETTING: Department of Endocrinology, University Hospital, Malmo, Sweden. SUBJECTS: Fifty-one postmenopausal women with a history of amenorrhoea of at least 6 months and body mass index > or = 24 kg m-2 participated in part 1 and 46 participated in part 2. INTERVENTION: Randomization for placebo (n=24) or HRT (n=27). HRT was given as 2 mg oestradiol valerate for the first 3 months, with the addition of 10 mg medroxyprogesterone for 10 days every third month thereafter. MEASUREMENTS: At baseline and after 3 and 12 months. RESULTS: During 0-3 months in the HRT group, FVII increased (P < 0.01), whereas fibrinogen, AT III and total protein S all decreased (P < 0.001 for all). Changes in variables were expressed as Delta-values. After 3 months Delta-values differed between groups for fibrinogen (P < 0.05), AT III (P < 0.001), total protein S (P < 0.001), and PAI-1 (P < 0.001). During 0-12 months, fibrinogen, total protein S, tPA (P < 0.01 for all) and AT III (P < 0.05) decreased. In the control group, all variables were unchanged during the study, except for increases (P < 0.05) in total protein S after 3 and 12 months, and a decrease (P < 0.01) in FVIII after 12 months. After 12 months Delta-values differed for fibrinogen (P < 0.05), AT III (P < 0.05) and total protein S (P < 0.001). CONCLUSIONS: Unopposed oestrogen substitution was associated with both potentially beneficial effects, such as decreases in fibrinogen, and potentially thrombogenic effects such as decreasing AT III and protein S and increasing FVII. During prolonged follow-up and addition of progesterone, differences between groups concerning FVII were attenuated. These data suggest that effects of HRT upon coagulation are most pronounced early after institution of unopposed treatment. (Less)
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published
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in
Journal of Internal Medicine1989-01-01+01:00
volume
249
issue
3
pages
237 - 246
publisher
Wiley-Blackwell Publishing Ltd
external identifiers
  • pmid:11285043
  • scopus:0035002657
ISSN
1365-2796
DOI
language
English
LU publication?
yes
id
82ce40ae-6ff8-4e6e-a62e-33db7d6e241c (old id 1120210)
date added to LUP
2008-06-27 15:37:50
date last changed
2018-05-29 12:21:19
@article{82ce40ae-6ff8-4e6e-a62e-33db7d6e241c,
  abstract     = {OBJECTIVES: To evaluate effects of postmenopausal hormone replacement therapy (HRT) on von Willebrand factor, factor (F)VIII, factor (F)VII, fibrinogen, antithrombin (AT) III, prothrombin fragments 1 and 2, protein C, total and free protein S, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and resistance to activated protein C. DESIGN: Part 1: double blind randomized trial for 3 months. Part 2: open study for 9 months. SETTING: Department of Endocrinology, University Hospital, Malmo, Sweden. SUBJECTS: Fifty-one postmenopausal women with a history of amenorrhoea of at least 6 months and body mass index &gt; or = 24 kg m-2 participated in part 1 and 46 participated in part 2. INTERVENTION: Randomization for placebo (n=24) or HRT (n=27). HRT was given as 2 mg oestradiol valerate for the first 3 months, with the addition of 10 mg medroxyprogesterone for 10 days every third month thereafter. MEASUREMENTS: At baseline and after 3 and 12 months. RESULTS: During 0-3 months in the HRT group, FVII increased (P &lt; 0.01), whereas fibrinogen, AT III and total protein S all decreased (P &lt; 0.001 for all). Changes in variables were expressed as Delta-values. After 3 months Delta-values differed between groups for fibrinogen (P &lt; 0.05), AT III (P &lt; 0.001), total protein S (P &lt; 0.001), and PAI-1 (P &lt; 0.001). During 0-12 months, fibrinogen, total protein S, tPA (P &lt; 0.01 for all) and AT III (P &lt; 0.05) decreased. In the control group, all variables were unchanged during the study, except for increases (P &lt; 0.05) in total protein S after 3 and 12 months, and a decrease (P &lt; 0.01) in FVIII after 12 months. After 12 months Delta-values differed for fibrinogen (P &lt; 0.05), AT III (P &lt; 0.05) and total protein S (P &lt; 0.001). CONCLUSIONS: Unopposed oestrogen substitution was associated with both potentially beneficial effects, such as decreases in fibrinogen, and potentially thrombogenic effects such as decreasing AT III and protein S and increasing FVII. During prolonged follow-up and addition of progesterone, differences between groups concerning FVII were attenuated. These data suggest that effects of HRT upon coagulation are most pronounced early after institution of unopposed treatment.},
  author       = {Gottsäter, Anders and Rendell, M and Hulthén, Lennart and Berntorp, Erik and Mattiasson, Ingrid},
  issn         = {1365-2796},
  language     = {eng},
  number       = {3},
  pages        = {237--246},
  publisher    = {Wiley-Blackwell Publishing Ltd},
  series       = {Journal of Internal Medicine1989-01-01+01:00},
  title        = {Hormone replacement therapy in healthy postmenopausal women: a randomized, placebo-controlled study of effects on coagulation and fibrinolytic factors},
  url          = {http://dx.doi.org/},
  volume       = {249},
  year         = {2001},
}