Atherosclerosis and oral contraceptive use. Serum from oral contraceptive users stimulates growth of arterial smooth muscle cells

Pooled serum from women taking a combined estrogen-progestin oral contraceptive preparation caused significantly greater cell proliferation and incorporation of 3H-thymidine into DNA in both human arterial smooth muscle cells and dermal fibroblasts in tissue culture than did serum from controls. A portion of this mitogenic effect appears to be related to the presence of a factor(s) that is heat stable, nondialyzable, and contained in the lipoprotein-deficient serum fraction. In vitro addition of varying concentrations of mestranol and norethindrone, the two constituents of the oral contraceptive preparation taken by participants in the study, to control serum did not enhance its mitogenicity, suggesting that the effect observed with intact serum was due either to a metabolite of these compounds or to the production of other growth-promoting substances during oral contraceptive treatment. Since smooth muscle cell proliferation is an integral feature of all atherosclerotic lesions, these findings provide some insights applicable to understanding the pathogenesis of vascular disease associated with oral contraceptive use.