Effect of large doses of the oral contraceptive Enovid on cholesterol metabolism in the rat.

Short-term effects of the oral contraceptive drug, Enovid, a mixture of estrogenic and progesterone compounds, have been determined in experiments on male and female rats. Oral administration of large doses for 7 days resulted in marked decreases of cholesteryl esters in plasma accompanied by only slight elevations of hepatic cholesterol content. Cholesteryl esters were also much lower in adrenals and ovaries, organs which are usually responsible for steroid hormone biosynthesis. At the same time, cholesterol-esterifying activity in plasma was substantially increased. Enovid administration was shown also to affect the fatty acid composition of sterol esters remaining in plasma, adrenals, and ovaries. The concentration of linoleate and arachidonate was significantly decreased in plasma sterol esters, whereas the concentrations of arachidonate and docosatetraenoate in adrenals and of docosatetraenoate in ovaries were significantly lowered. All of the changes reported were more pronounced in the female than in the male rat. It is hypothesized that the decreased levels of cholesteryl ester found in the organs investigated, together with the increase in plasma cholesterol-esterifying activity, are probably associated either with changes in cholesterol biosynthesis and(or) transport or with an increase in cholesterol transformation to other steroids and excretion. These possibilities are now under investigation.