Estrogens in the causation of breast, endometrial and ovarian cancers - evidence and hypotheses from epidemiological findings

Estrogens along with progesterone/progestins, and other hormones, are important determinants of cancer in the breast, endometrium and ovary. Estrogens may increase the risk of breast cancer through various mechanisms and at various phases of life, with a possible synergistic effect of progesterone/progestins. Exposure to high doses of placental hormones, such as estrogens and/or progesterone, during pregnancy may play a pivotal role in reducing subsequent breast cancer susceptibility. Estrogens cause endometrial cancer, an effect that can be reduced, prevented or reversed by progesterone/progestin — if allowed to act for a sufficiently long period of each cycle. The role of sex hormones seems important for ovarian carcinogenesis. Intake of combined oral contraceptives has a substantial and well-documented protective effect on endometrial and ovarian cancer risks. Epidemiological observations and experimental data from an animal model indicate that estrogens may have an adverse effect, while progesterone/progestins have a risk reducing effect directly on the ovarian epithelium. Thus, estrogens and other sex hormones have potential effects on the three most important female cancers. Research has yet to define how some of the risk factors can be modified or treatment regimens can be improved to reduce these cancer risks.