Mechanisms
Long-term danazol use lowers CETP mass without significantly affecting HDL cholesterol or atherosclerosis markers (Clin Ther 2008)
Original title: Effects of short-term and long-term danazol treatment on lipoproteins, coagulation, and progression of atherosclerosis: two clinical trials in healthy volunteers and patients with hereditary angioedema
Danazol, a synthetic androgen used prophylactically in hereditary angioedema, is known to lower HDL cholesterol short-term, so its short- and long-term effects on proatherogenic intermediate endpoints were evaluated in healthy volunteers and hereditary angioedema patients. Short-term danazol (200 mg per day, 4 weeks) reduced apolipoprotein A-I by 21% and HDL cholesterol by 23%, without affecting flow-mediated dilation or coagulation. In hereditary angioedema patients on long-term danazol (mean 170 mg per day, 2 years or more), HDL cholesterol, paraoxonase-1 activity, lecithin cholesterol acyltransferase activity and phospholipid transfer protein activity were unchanged versus matched controls, while CETP mass was lower (1.5 versus 2.2 microgram per mL) and carotid intima-media thickness was similar, though coagulation activation markers were increased.
Original 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.