Endometrial and endometriotic concentrations of estrone and estradiol are determined by local metabolism rather than circulating levels
Open accessAbstract
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.
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Higher gene expression levels of HSD17B1, CYP19A1, and ESR2 in OE lesions than DE lesions and comparable HSD17B1 expression in DE to normal endometrium have been reported.
“For example, higher gene expression levels of HSD17B1, CYP19A1, and ESR2 in OE lesions than DE lesions and the comparable HSD17B1 expression in DE to normal endometrium have been reported (Huhtinen et al., 2012).”
From Progressively diminished estrogen signaling concordant with increased fibrosis in ectopic endometrium (2025) · cites this paper as Huhtinen et al., 2012
The same study reported a 6-fold higher E2 concentration in OE lesions compared with normal endometrium, but practically comparable E2 concentration in DE lesions.
“In fact, the same study also reported a 6-fold higher E2 concentration in OE lesions as compared with normal endometrium, but practically comparable E2 concentration in DE lesions (Huhtinen et al., 2012).”
From Progressively diminished estrogen signaling concordant with increased fibrosis in ectopic endometrium (2025) · cites this paper as Huhtinen et al., 2012
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- Authors
- Huhtinen, K., Desai, R., Ståhle, M., Salminen, A., Handelsman, D. J., Perheentupa, A., & Poutanen, M.
- Affiliations
- University of Turku (FI)
- The University of Sydney (AU)
- Corresponding author
- Poutanen, Matti
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2012-11
- Volume
- 97
- Issue
- 11
- Pages
- 4228-4235
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC3485603
- OpenAlex
- W2065528753
- Cited by
- 195
- References
- 10
- Citations by year
- 2026: 9 · 2025: 20 · 2024: 14 · 2023: 18 · 2022: 14 · 2021: 15 · 2020: 16 · 2019: 15 · 2018: 15 · 2017: 9 · 2016: 22 · 2015: 13 · 2014: 11 · 2013: 4
- FWCI
- 10.46
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
- Keywords
- endometriosis, endometrium, estradiol, estrone, menstrual cycle, HSD17B2, HSD17B6, hydroxysteroid dehydrogenase
- MeSH terms
- Adult, Endometriosis, Endometrium, Estradiol, Estrone, Female, Humans, Ovarian Diseases, Peritoneal Diseases
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