Action of danazol on plasma lipids and lipoprotein metabolism

Danazol, a weakly androgenic, heterocyclic compound with anabolic properties, is used primarily in the treatment of endometriosis and other gynecological complaints. Early reports indicated that the drug had little effect on plasma lipid (cholesterol and triglyceride) levels but recently concern has been expressed over more subtle changes reported in plasma lipid and lipoprotein metabolism after danazol treatment. Therapy produces a rapid reduction in high density lipoprotein (HDL) cholesterol (particularly in the putatively cardioprotective HDL2 subfraction) coupled with a rise in the pro-atherogenic low density lipoprotein (LDL). These apparently unwanted actions are balanced against a possibly beneficial reduction in the atherogenic lipoprotein(a) fraction. The mechanism of these changes induced by danazol is unknown but probably relates to effects on hepatic lipase, LDL receptor and lecithin cholesterol acyl transferase activity. While it is prudent to recognize the potential detriment that may follow these perturbations, concern is only warranted where therapy is prolonged (> 12 months) or given to subjects with a high background risk of ischemic heart disease.