Androgens are 19-carbon steroid rings. Progestagens include both 19-carbon and 21-carbon steroid rings; the 19-carbon progestagens are generally more androgenic than are the 21-carbon compounds. Both androgens and progestagens are physiological regulators of plasma lipids, particularly high-density lipoprotein (HDL) cholesterol. The structure of a particular hormonal preparation, as well as its route of administration, modulates its regulatory effects. Both endogenous and exogenous androgens have a suppressive effect on HDL cholesterol in males, with little effect on other plasma lipoproteins. Oral and nonaromatizable androgens have a greater suppressive effect on HDL cholesterol, particularly on HDL2, than do aromatizable androgens. Cross-sectional studies in males generally show a positive relationship between serum T and plasma HDL levels; data in females suggest an inverse relationship between androgens and HDL cholesterol. Medroxy-progesterone acetate and related progestagens have a mild suppressive effect on plasma HDL levels. The C-19 compounds have a greater suppressive effect on HDL cholesterol and the HDL2 density subfraction.