Percent mammographic density (PMD) is a strong marker of breast cancer risk. It may be a correlate of the rate of breast tissue aging, as proposed by Pike to explain breast cancer age-incidence. We examined longitudinal changes in PMD in 645 breast screening attendees in London, UK, in which each had between 2 and 5 screens spanning 3-12 years at ages 50-65 years and compare these to Pike's model. Within-woman PMD declined during these ages, with a slowing rate of decline. Annual rates of decline were 1.4% (95% confidence interval: 1.2-1.6), 0.7% (0.6-0.9) and 0.1% (-0.2 to 0.4) at ages 50, 57 and 64. Dense area declined similarly, but the absolute magnitude of the rate of increase of nondense area was almost double that of dense area. PMD dropped by 2.4% (1.4-3.4) on menopausal transition and increased by 2.4% (1.4-3.5) with the use of hormone therapy. Higher body mass index, greater parity and being Afro-Caribbean or South Asian ethnicities were associated with lower PMD, but did not affect rate of change of PMD at these ages. Within-woman rank correlation of PMD was 0.80 for readings taken 9 years apart. Effects of menopause and parity and the lack of effect of menarche on age-specific PMD at these ages are consistent with the predicted determinants in Pike's model. A high degree of tracking of PMD indicates that at ages 50-65 years high-risk women could be identified by a single early screen at age older than 50.