Estradiol Synthesis and Metabolism and Risk of Ovarian Cancer in Older Women Taking Prescribed or Plant-derived Estrogen Supplementation

Estradiol, the most potent of the biological estrogens, is implicated in the genesis of ovarian epithelial cancer, a heterogeneous cancer affecting mainly older women. The postmenopausal ovary traditionally has not been viewed as contributing significantly to estradiol synthesis, since this is thought to occur almost exclusively as the result of peripheral aromatization of adrenal androgens. Recent evidence supports a role for both normal and malignant ovarian tissue in de novo synthesis of estradiol using inactive biological precursors and available enzymatic pathways. The process is termed “intracrinology”. The present paper reviews available evidence for the intracrinological synthesis of estradiol in ovarian surface epithelium. It further proposes how exogenous supplementation with synthetic hormone replacement may act to augment this process by increasing the risk of developing ovarian epithelial cancer in older women. Phytoestrogens are also examined for their role in regulating levels of estradiol metabolites with potent estrogenic and carcinogenic potential.