Sixty-three postmenopausal women were assigned to four treatment groups and received either Premarin or percutaneous 17 beta-estradiol (Oestrogel) alone or in combination with micronized progesterone (Utrogentan). The oral administration of estrogen alone to hysterectomized women resulted in: 1) a significant increase in triglyceride levels in plasma and all major lipoprotein fractions, 2) a significant increase in very low density lipoprotein cholesterol, 3) a significant decrease in low density lipoprotein (LDL) cholesterol but not LDL apo B concentration, 4) a significant increase in all the lipid components of high density lipoprotein (HDL) as well as apo AI, 5) and a significant increase in HDL2 cholesterol. In contrast, percutaneous administration of estrogen to hysterectomized women only increased HDL2 cholesterol and the triglyceride and cholesterol content of the whole HDL fraction. These results suggest that the route of estrogen administration is important in determining effects on lipoprotein metabolism. The same two estrogens were given to women with natural menopause, along with utrogestan, a micronized progesterone. The simultaneous administration of Utrogestan reversed the HDL cholesterol elevating effect of percutaneous estrogen alone, but it had no effect on other plasma lipoproteins. On the other hand, utrogestan in combination with oral estrogen had several potential beneficial effects on plasma lipoproteins. This combination did not negate the effects of oral estrogen alone on HDL, rather it further increased the concentrations of HDL cholesterol and apo AI. It also did not negate the LDL cholesterol lowering effect of oral estrogen alone. Furthermore, utrogestan lowered the magnitude of hypertriglyceridemia induced by oral estrogen alone. These results suggest that Utrogestan has lower potency of androgenic action and has desirable effects when given in cyclic combination with estrogen.