Oral contraceptive use influences resting breast proliferation.

The controversy that surrounds oral contraceptive use and breast cancer risk has arisen from epidemiologic studies, yet the direct effect of such use on breast tissue remains undefined. Breast epithelial proliferation was assessed by 3H-thymidine labeling of normal lobular units dissected from benign biopsies of 347 females aged 14 to 48 years. Factors shown to influence this response included cycle phase, time since menarche (breast age), and parity status. Multivariate analysis allowing for these influences was used to compare activity of natural cycles and those artificially regulated by oral contraceptives (OC). The increased activity in nulliparous OC users was highly significant (P less than .005). Comparing the effect of differences in OC type, whether combined, triphasic, progestin only, or according to estrogen or progestin content, showed a heterogeneity in response that was significant (P less than .01). Examined specifically, the formulation of OC according to progestin content did not have a significant influence, although progestin-only OC was most active, while the influence of increasing estrogen content was significant (P less than .05). However, emphasis is given to acknowledging the multiple factors and interactive processes responsible for breast epithelial stimulation when considering strategies of intervention.