Endometrial and endometriotic concentrations of estrone and estradiol are determined by local metabolism rather than circulating levels

Abstract

Context: Aberrant estrogen synthesis and metabolism have been suggested to increase local estradiol (E2) concentration in endometriosis and thus to promote the growth of the lesions. However, tissue estrogen concentrations within the endometrium and different types of endometriosis lesions have not been described.

Objective: The aim of the study was to evaluate local E2 and estrone (E1) concentrations in the endometrium and different types of endometriosis lesions, and to correlate them with the expression of estrogen-metabolizing enzymes.

Patients: Patients with endometriosis (n = 60) and healthy controls (n = 16) participated in the study.

Main outcome measures: We measured serum and tissue concentrations of E2 and E1 as well as mRNA expression of the estrogen-metabolizing enzymes.

Results: Endometrial or endometriotic intratissue E2 concentrations did not reflect the corresponding serum levels. In the proliferative phase, endometrial E2 concentration was five to eight times higher than in the serum, whereas in the secretory phase the E2 concentration was about half of that in the serum. Accordingly, a markedly higher E2/E1 ratio was observed in the endometrium at the proliferative phase compared with the secretory phase. In the endometriosis lesions, E2 levels were predominating over those of E1 throughout the menstrual cycle. Among the hydroxysteroid (17β) dehydrogenase (HSD17B) enzymes analyzed, HSD17B2 negatively correlated with the E2 concentration in the endometrium, and HSD17B6 was strongly expressed, especially in the deep lesions.

Conclusions: Endometrial or endometriotic tissue E2 concentrations are actively regulated by local estrogen metabolism in the tissue. Thus, the inhibition of local E2 synthesis is a valid, novel approach to reduce local E2-dependent growth of endometriotic tissue.

Figures

Fig. 1.

mRNA expression of AKR1C, HSD17B1, -2, -4, -6, -7, -10, -12, and -14, as well as ESR1 and ESR2 in healthy endometrium (CE) and eutopic endometrium of endometriosis patients (PE), and PERIT, OV, and DEEP endometriosis by qRT-PCR analysis in proliferative and secretory phases of the menstrual cycle (median with 25th/75th percentiles). Statistically significant changes compared with CE within the cycle phase are labeled as: *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001. The significant difference between proliferative and secretory phases within each sample group is labeled as: ¤, P ≤ 0.05; ¤¤, P ≤ 0.01; ¤¤¤, P ≤ 0.001 (two-way ANOVA with multiple comparisons with post hoc Tukey-Kramer test on log-transformed data). P, Proliferative; S, secretory.