Effects on the breast of drugs used in fertility regulation

Some hormones (e.g. gonadotropins and clomiphene) act indirectly on the breast by disturbing the hypothalamopituitary axis while others including estrogens and progestins exert at direct effect. Numerous experimental studies have confirmed that estradiol and progesterone act synergistically in the breast and there are often differential responses of the alveolar and ductal systems. Analysis of fibroadenomas with high epithelial cell density removed from young women at various stages of the menstrual cycle indicated that receptors in both breast and endometrial tissues are under the control of cyclic ovarian function. When breast tumor tissue were exposed to estradiol and progesterone in well-balanced combination a cell distribution of progesterone receptors similar to that observed during a normal luteal phase was observed. On the other hand when estradiol is administered in supraphysiological doses to female rats changes comparable to human fibrocystic disease are noted. The anti-estrogenic mechanisms of action of progesterone and progestins in women includes a reduction of estrogen secretion in systemic circulation inactivation of estradiol by metabolism at the target tissue and a lowering of estrogen receptors in these tissues. The main enzyme involved in the anti-estrogenic activity is the progesterone-dependent 17 beta-hydroxysteroid dehydrogenase. In terms of benign breast disease a context of unopposed estrogen is most likely. Since benign breast disease can be a precursor of breast cancer caution should be exerted in prescribing mini-pills to young women. Estradiol levels in mini-pill users can remain between 50-120 pg/ml given the persistence of some gonadotrophic activity and the consequent partial follicular maturation of the ovary.