Compare Daily Ulipristal Acetate and Combined Oral Contraceptive Effects on Breast Epithelial Cell Proliferation

This will be a randomized controlled parallel group clinical trial with blinded evaluation to be carried out at 2 academic medical centers: Columbia University Medical Center and Weill Cornell Medical College. The investigators will screen healthy women aged 18-39 who meet inclusion/exclusion criteria and will enroll them for the study. After the informed consent process and study enrollment, study participation will begin with a baseline cycle. The main goal of the baseline cycle is to identify the occurrence and the timing of ovulation. Starting at about day 6 of the baseline cycle, participants will undergo blood sampling for progesterone (P4) levels at intervals of every 2-3 days. An increase of P4 to greater than 3 ng/mL, confirmed by a second such value, will indicate ovulation and eligibility to continue in the study. The participant's baseline breast MRI and biopsy (see below) will be scheduled to occur in the mid luteal phase, about 7 days after the first increase (\>3 ng/mL) in P4. The investigators will randomly assign which breast has the first biopsy, and women will return for a post-biopsy visit about 7 days later. At the post-biopsy visit, the investigators will assess acceptability of the MRI and biopsy to the participants using visual analog scales (VAS) as well as interview. At the beginning of the next menstrual period, women will begin the treatment phase of the study. They will receive random assignment to either UPA or COC at the study center and receive their first dose and a 4-week supply of study drug. During cycles 1 and 2 they will return to the study site every 2 weeks for assessment, blood draws and to receive the next cycle of study drug. During the third cycle, they will return to the study site twice weekly for more frequent testing and monitoring. Each cycle will be 28 days, corresponding to usual COC packaging. At day 75-77 of treatment women will undergo the second breast MRI, immediately followed by a biopsy of the contralateral breast to that biopsied at baseline. An end-of-study visit, including checking the incision site and a repeat assessment of acceptability of the MRI and biopsy to the participants, will occur about 7 days later. Participants will also be asked to rate their preference for an MRI versus a biopsy, were it possible to do a study with only one of these procedures. Participants will have up to 24 study visits, and at each visit, participants will be asked about adverse events and use of any concomitant medications. Participants will have a high sensitivity urine pregnancy test at baseline and immediately preceding each MRI and preceding the first dose of study medication. Any participant with a positive pregnancy test will be immediately withdrawn from the study. Breast Biopsies Breast biopsies will take place immediately following each breast MRI. Women will receive 24-hour telephone follow-up, and make a visit within one week following each breast biopsy to ensure that the biopsy site is healing without incident. MRI For each participant, the baseline and follow-up MRI will be done using the same machine. Each MRI study will undergo an immediate wet read to assure adequate quality and to identify any unexpected pathology that would mandate clinical evaluation and withdrawal from the study. A limited report indicating technical adequacy and absence of major clinical abnormalities will be recorded in the patient record. Breast MRI and breast biopsy visits will take place at the Center for Breast Imaging at Columbia University Medical Center.