The Role of Hydroxysteroid Dehydrogenases in the Regulation of Estrogen and Progestagen Activity: a Case of Endometrial Cancer and Endometriosis

Endometrial cancer and endometriosis are very common estrogen-dependent diseases. Endometrial cancer is the third most common cancer in women, while endometriosis affects around 15–20% of women of reproductive age and leads to infertility in 30–50% of patients. The current hypoth­esis postulates that exposure to estrogens unopposed by progestagens increases the mitotic activity of endometrial cells and the number of errors during DNA replication that can lead to hyper­plasia or a malignant phenotype. The activity of estrogens and progestagens is regulated at the receptor and pre-receptor levels, by interconversions between the active forms (estradiol, progesterone) and inactive forms (estrone, 20α-hydroxyprogesterone). The enzymes which are responsible for these interconversions are 17β-hydroxysteroid dehydrogenase and 20α-hydroxysteroid dehydrogenase. The difference in the expression of these enzymes in endometrial cancer and endometriosis may lead to high estrogen concentrations and low progestagen concentrations, which could result in the development of endometrial cancer or endometriosis.