The effect of estradiol metabolites and progestogens on the proliferation of human ovarian cancer cells.

The etiology of ovarian cancer appears to be associated with a long-term influence of estrogens. However, evidence is accumulating that certain estradiol metabolites may play a decisive role in the carcinogenesis of estrogen-dependent diseases. As yet little data are available on the association of estradiol metabolites and ovarian cancer. In vitro experiments revealed a potent stimulatory effect of certain metabolites on the proliferation of ovarian cancer cells, which is similar to or even stronger than the effect of their parent substance 17beta-estradiol. Therefore, the pattern of endogenous estradiol metabolism may play a role in defining ovarian cancer risk. This may be of importance in certain predisposed women who are treated with hormone therapy in the postmenopause. The role of progestogens in the genesis of ovarian cancer still remains unclear, rather a protective behaviour is suggested. Epidemiological studies indicate a possible increase in the risk for combined estrogen/progestin as compared to estrogen alone. It is ambigious whether a difference exists within the various progestogens. Apart from sex steroids growth factors play a crucial role in the genesis of ovarian cancer, although as yet little investigated. In vitro experiments indicate that progestogens do not have a protective role on the growth of pre-existing ovarian cancer cells, at least in the presence of growth factors. Further investigations are worthwile to evaluate possible differences between the effect of the various progestogens.