Background: We investigated the associations of oral contraceptives (OC) with percent breast density (PD), absolute dense area (DA), nondense area (NDA), and a novel image intensity variation (V) measure in premenopausal women.

Methods: This study included 1,233 controls from a nested case-control study within Nurses' Health Study II cohort. Information on OCs was collected in 1989 and updated biennially. OC use was defined from the questionnaire closest to the mammogram date. PD, DA, and NDA were measured from digitized film mammograms using a computer-assisted thresholding technique; the V measure was obtained with a previously developed algorithm measuring the SD of pixel values in the eroded breast region. Generalized linear regression was used to assess associations between OCs and density measures (square root-transformed PD, DA, and NDA, and -untransformed V).

Results: OC use was not associated with PD [current vs. never: β = -0.06; 95% confidence interval (CI), -0.37-0.24; past vs. never: β = 0.10; 95% CI, -0.09-0.29], DA (current vs. never: β = -0.20; 95% CI -0.59-0.18; past vs. never: β = 0.13; 95% CI, -0.12-0.39), and NDA (current vs. never: β = -0.19; 95% CI, -0.56-0.18; past vs. never: β = -0.01; 95% CI, -0.28-0.25). Women with younger age at initiation had significantly greater V-measure (<20 years vs. never: β = 26.88; 95% CI, 3.18-50.58; 20-24 years vs. never: β = 20.23; 95% CI, -4.24-44.71; 25-29 years vs. never: β = 2.61; 95% CI -29.00-34.23; ≥30 years vs. never: β = 0.28; 95% CI, -34.16-34.72, P _trend = 0.03).

Conclusions: Our findings suggest that an earlier age at first OC use was associated with significantly greater V.

Impact: These findings could guide decisions about the age for OC initiation.