Abstract:
BACKGROUND:Danazol is a synthetic androgen derivative frequently used as prophylaxis in patients with hereditary angioedema (HAE) due to complement-1 esterase inhibitor deficiency. However, danazol has been reported to decrease high-density lipoprotein cholesterol (HDL-C) levels and to adversely affect coagulation parameters, which are considered to be proatherothrombotic. OBJECTIVE:The short- and long-term effects of danazol were evaluated on proatherogenic intermediate end points in healthy volunteers and patients with HAE. METHODS:Short-term effects were evaluated in healthy men randomly assigned to 200 mg/d of danazol or placebo for 4 weeks in a crossover trial with no washout period. Long-term effects of danazol on lipoproteins, coagulation, and carotid intima-media thickness (CIMT) were evaluated in a cross-sectional study in which patients with HAE treated with danazol, a mean dose of 170 mg/d for >or=2 years, were compared with healthy controls matched for age, sex, and body mass index (BMI). Drug tolerability was assessed by questionnaires and adherence was measured by pill count when drug bottles were returned after every study visit. RESULTS:Patients in the short-term study were 15 men with a mean (SD) age of 32.6 (6.9) years and BMI of 24.3 (4.1) kg/m(2). In the long-term study, patients with HAE were 10 women and 7 men with a mean (SD) age of 41.1 (12.9) years and BMI of 25.4 (2.6) kg/m(2); the 17 matched controls had a mean (SD) age of 39.8 (11.8) years and BMI of 25.4 (2.6) kg/m(2). Short-term danazol treatment was associated with a decrease from baseline in apolipoprotein A-I of 21% and in HDL-C of 23%. Flow-mediated dilation and coagulation parameters were unaffected after 4 weeks. Longterm danazol treatment did not adversely affect HDL-C concentration (1.1 [0.5] vs baseline, 1.2 [0.5] pmol/L), HDL-related transfer proteins such as paraoxonase-1 activity (92 [62] vs 80 [40] U/mM), cholesteryl-ester transfer protein mass (1.5 [0.4] vs 2.2 [0.6] microg/mL), lecithin cholesterol acyltransferase activity (21.2 [4.5] vs 32.1 [7.2] nmol CE . mL(-1) . h(-1)), plasma phospholipid transfer protein activity (15.4 [1.5] vs 14.9 [1.2] AU), and apolipoproteins between patients with HAE and controls. The mean (SD) CIMT was similar between patients with HAE and controls (0.62 [0.09] vs 0.59 [0.08] mm; P = NS). However, HAE patients using danazol had increased coagulation activation when compared with controls (prothrombin fragments, 286 [119] vs 164 [57] pmol/L, P = 0.002; thrombinantithrombin complex, 3.9 [1.4] vs 2.6 [1.1] microg/L, P = 0.01). CONCLUSIONS:Short-term danazol treatment in healthy volunteers was associated with a reduction in HDL-C levels without a significant effect on endothelial function or coagulation parameters. In contrast, patients with HAE treated for >2 years with danazol had increased activation of coagulation, but there were no significant differences in HDL-C or CIMT compared with matched healthy controls.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Birjmohun RS,Kees Hovingh G,Stroes ES,Hofstra JJ,Dallinga-Thie GM,Meijers JC,Kastelein JJ,Levi Mdoi
10.1016/j.clinthera.2008.12.021subject
Has Abstractpub_date
2008-12-01 00:00:00pages
2314-23issue
12eissn
0149-2918issn
1879-114Xpii
S0149-2918(08)00456-6journal_volume
30pub_type
杂志文章,随机对照试验abstract:BACKGROUND:Fenofibrate lowers serum total cholesterol and triglyceride levels while it elevates serum high-density lipoprotein cholesterol (HDL-C) level. OBJECTIVE:The aim of this study was to investigate the effects of fenofibrate on the particle size of high-density lipoprotein (HDL). METHODS:Patients with hyperlip...
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pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
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journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
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更新日期:2012-07-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:1994-03-01 00:00:00
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pub_type: 杂志文章
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更新日期:2009-11-01 00:00:00
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更新日期:2005-07-01 00:00:00
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1999-01-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2011-06-01 00:00:00
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更新日期:2014-06-01 00:00:00
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2001-06-01 00:00:00