Increased production of 17β-estradiol in endometriosis lesions is the result of impaired metabolism

Context: substantial evidence suggests that the expression of steroid metabolizing enzymes in endometriosis is altered, turning the ectopic endometrium into a source of 17β-estradiol. However, whether these differences result in a net increase in local 17β-estradiol production/activity has not been shown. Subjects and Methods: The activities of the most important steroidogenic enzymes synthesizing and inactivating 17β-estradiol were determined by HPLC in matched eutopic and ectopic tissue from patients with endometriosis (n = 14) and in endometrium from controls (n = 20). Results: Aromatase activity is negligible in the ectopic endometrium, whereas the activity of estrogen sulfatase is high though not different between ectopic, eutopic and control endometrium. The activity of 17β- hydroxysteroid dehydrogenases (17β-HSDs) converting estrone into 17β-estradiol is higher in the ectopic compared to the eutopic endometrium in patients. The activity of 17β-HSDs converting 17β-estradiol backto estrone is significantly lower in the ectopic compared to the eutopic endometrium of both patients and controls. To evaluate the net metabolic capacity of tissues to synthesize 17β-estradiol, we calculated the activity ratio between 17β-HSDs synthesizing versus 17β-HSDs inactivating 17β-estradiol. This ratio is significantly higher in the ectopic compared to the eutopic endometrium of patients and controls, indicating a high synthesis of 17β-estradiol in the ectopic locations. This is further supported by the elevated mRNA levels of the estrogen-responsive gene TFF1 in all ectopic compared to eutopic endometria. Conclusion: Endometriotic lesions have higher production of 17β-estradiol than the eutopic endometrium of patients and controls. This is mostly the result of impaired metabolism.