Influence of oral contraceptives on normal human breast epithelial proliferation

Abstract

Researchers studied the influence of different formulations of oral contraceptives (OC) on breast tissue response and resting breast proliferation in response to menstrual cycles. They accepted only benign lesions mostly fibroadenomas of breast tissue from women less than 35 years old already undergoing biopsy. In order to have a good yield of parenchymal elements pathologists applied stereomicroscopic dissection techniques of vitally stained fresh tissue slices (from adjacent normal tissue). The tissues were then incubated with 3H-thymidine under hyperbaric oxygen situations for 1 hour and subsequently processed for autoradiography. Interviewers questioned patients the day of surgery to determine menstrual and obstetric history and details of OC use. Interviewers recorded the date of onset of the last menstrual period and gave the women a card to mark the date of the next menses. Researchers only accepted cycles of 26-30 days and averaged the data to a 28 day cycle for graphic plotting. TLI values for the 127 women with natural cycles ranged form .01-11.66 with a significant difference between the and phases. TLI values for the 144 women with artificial (OC) cycles spanned from .05-10.43 also with a significant difference between the phases. Researchers noted a significant difference in the level of response in the 8-13 day period of the proliferative phase of the artificial cycle and the natural cycle. Additionally maximal response in the late secretory phase of the artificial cycle was significantly higher than the equivalent phases of the natural cycle. Researchers also compared proliferation according to progestin content of the OC using 4 groups: low dose combined; high dose combine; sequential combined; and continuous progestin alone. ALL comparisons of the different types of OCs within either proliferative or secretory phases of the cycle proved to be not significantly different. When researchers studied the effect of parity however major differences appeared. Nulliparous women who used OCs had a higher response in the secretory phase than did nulliparous natural cycles. Conversely parous OC users did not respond in the secretory phase. When comparing between phases in nulliparous and parous women OC users researchers found a highly significant difference (p=.0036). The influence of parity on breast response in OC users is of major relevance yet researchers and health practitioners must exercise caution in its interpretation because of the possibility of confounding factors. It is not yet known whether the factors regulating these responses are a direct or indirect consequence with regard to parity and OC use. Evidence supports both and therefore further research is necessary.