Local estrogen metabolism (intracrinology) in endometrial cancer: A systematic review

Endometrial cancer (EC) is the most common malignancy of the female gynaecological tract and increased exposure to estrogens is a risk factor. EC cells are able to produce estrogens locally using precursors like, among others, adrenal steroids present in the serum. This is referred to as local estrogen metabolism (or intracrinology) and consists of a complex network of multiple enzymes. Particular relevant to the final generation of active estrogens in endometrial cells are: steroid sulfatase (STS), estrogen sulfotransferase (SULT1E1), aromatase (CYP19A1), 17β-hydroxysteroid dehydrogenase (HSD17B) type 1 and type 2. During the last decades, a plethora of studies explored the level of these enzymes in EC but contrasting data were reported, which generated vigorous debate and controversies. Several reviews attempted at clarifying some of the debated issues, but published reviews are based on investigator-defined bibliography selection and not on systematic analysis. Therefore, we performed a systematic review of the literature reporting about the level of STS, SULT1E1, CYP19A1, HSD17B1 and HSD17B2 in EC. Additional intracrine enzymes and networks (e.g., HSD17Bs other than types 1 and 2, aldo-keto reductases, progesterone and androgen metabolism) were non-systematically reviewed as well.