Progestins and their effects on the breast

Nowadays, when the available scientific data on the in vivo effects of progestins on mammary gland tissue remain controversial, it is of utmost importance to establish adequate criteria to evaluate their actions. One of the reasons for this situation is that a variety of progestins have been studied using a number of different study designs. In addition, data relating to the effects of progestins on breast tissue have been interpreted differently from country to country. Recent data indicate that some progestins clearly oppose the favourable effects of estrogens on a number of important metabolic processes, e.g. influencing insulin-like-growth-factor (IGF)-1 serum levels. IGF-1 is a mitogenic and antiapoptotic peptide involved in growth regulation of breast epithelial cells. Circulating IGF-1 exerts endocrine action, it regulates growth hormone secretion by a negative feedback mechanism. In the past few years, both laboratory investigations and epidemiologic studies provided strong evidence that the IGF-1/growth hormone axis is involved in human cancer risk [Maturitas 29 (1998) 61; Horm. Res. 51 (1999) 34; Eur. J. Cancer 36 (2000) 1224; Maturitas 41 (2002) 299] Some progestins also have effects on the enzymes in breast tissue that are responsible for the local synthesis of estradiol. Thus, whilst progestins without androgenic action have been found to markedly inhibit these enzymes, an equivalent degree of inhibition is not achieved with testosterone-derivatives. Therefore, special attention should be paid to the various partial actions of the different progestins and their effects on breast tissue. Furthermore, factors such as the duration of breast tissue exposure to progestin activity, the influence of different regimens on protective apoptotic mechanisms in the breasts, as well as dose levels and the degree of mammary gland tissue differentiation throughout treatment, should also be considered.