Evaluation of aromatase expression in endometrioid heterotopias and endometria in patients with external genital endometriosis

In: Journal of obstetrics and women's diseases · 2023 · vol. 72(5) , pp. 39–47 · doi:10.17816/jowd568877 · W4388936715
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This study found increased aromatase expression in endometriosis foci and, on average, in the eutopic endometrium of endometriosis patients compared to controls, but noted significant heterogeneity.

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This original study evaluated CYP19A1 (aromatase) gene expression in eutopic endometrium and in endometrioid heterotopies from 55 patients with external genital endometriosis, compared with eutopic endometrium from 24 women without endometriosis, using reverse transcription real-time PCR on endometrial biopsy samples obtained during surgery. The authors found generally high aromatase expression in endometriosis foci and increased average aromatase expression in the eutopic endometrium of patients with endometriosis versus controls, but with notable heterogeneity, as some patients showed low endometrial aromatase expression. No association was detected between increased aromatase expression and clinical/anamnestic characteristics including infertility, pain syndrome, prevalence of disease, or relapses, which the authors frame as a potential explanation for variable effectiveness of hormone-modulating therapy such as aromatase inhibitors. The paper does not explicitly discuss adenomyosis, but it is centrally about endometriosis—specifically aromatase (CYP19A1) expression heterogeneity in endometrioid heterotopias and eutopic endometrium in patients with external genital endometriosis.

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Abstract

BACKGROUND:External genital endometriosis is a multifactorial estrogen-dependent disease. Local estrogen production due to aromatase activity can play an important role in its pathogenesis, so aromatase inhibitors are considered promising drugs for the treatment of the disease. However, the data on their effectiveness are contradictory. AIM:The aim of this study was to evaluate the expression level of the aromatase-encodingCYP19A1gene in the eutopic endometrium and endometrioid heterotopies of patients with endometriosis and in the eutopic endometrium of women from the comparison group. MATERIALS AND METHODS:This study included 79 women. The main group consisted of 55 patients with endometriosis, and 24 patients without endometriosis formed a comparison group. All of the patients underwent an endometrial biopsy during surgery, with excision of endometriotic lesions performed in patients with endometriosis.CYP19A1gene expression was studied using reverse transcription real-time polymerase chain reaction. RESULTS:The data obtained confirm a high level of aromatase expression in endometriosis foci. On average, aromatase expression is increased in the eutopic endometrium of patients with endometriosis when compared to the endometrium of women in the comparison group. However, in a significant number of patients with endometriosis, aromatase is expressed in the endometrium at a low level. We did not find an association of increased aromatase expression with any clinical and anamnestic features of the studied group of women, in particular, with infertility, pain syndrome, prevalence of endometriosis, or relapses of the disease. CONCLUSIONS:Our findings highlight the heterogeneity of endometriosis and may account for the variable effectiveness of hormone-modulating therapy, in particular aromatase inhibitors.
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Abstract

BACKGROUND: External genital endometriosis is a multifactorial estrogen-dependent disease. Local estrogen production due to aromatase activity can play an important role in its pathogenesis, so aromatase inhibitors are considered promising drugs for the treatment of the disease. However, the data on their effectiveness are contradictory. AIM: The aim of this study was to evaluate the expression level of the aromatase-encoding CYP19A1 gene in the eutopic endometrium and endometrioid heterotopies of patients with endometriosis and in the eutopic endometrium of women from the comparison group.

Materials and methods

This study included 79 women. The main group consisted of 55 patients with endometriosis, and 24 patients without endometriosis formed a comparison group. All of the patients underwent an endometrial biopsy during surgery, with excision of endometriotic lesions performed in patients with endometriosis. CYP19A1 gene expression was studied using reverse transcription real-time polymerase chain reaction.

Results

The data obtained confirm a high level of aromatase expression in endometriosis foci. On average, aromatase expression is increased in the eutopic endometrium of patients with endometriosis when compared to the endometrium of women in the comparison group. However, in a significant number of patients with endometriosis, aromatase is expressed in the endometrium at a low level. We did not find an association of increased aromatase expression with any clinical and anamnestic features of the studied group of women, in particular, with infertility, pain syndrome, prevalence of endometriosis, or relapses of the disease.

Conclusions

Our findings highlight the heterogeneity of endometriosis and may account for the variable effectiveness of hormone-modulating therapy, in particular aromatase inhibitors. Full Text About the authors Olga V. Malysheva The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Email: [email protected] ORCID iD: 0000-0002-8626-5071 SPIN-code: 1740-2691 Cand. Sci. (Biol.) Russian Federation, Saint PetersburgArsenii S. Molotkov The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Email: [email protected] ORCID iD: 0000-0003-3433-3092 SPIN-code: 6359-6472 MD, Cand. Sci. (Med.) Russian Federation, Saint PetersburgNatalia Yu. Shved The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Email: [email protected] ORCID iD: 0000-0001-6354-9226 SPIN-code: 8276-1720 Cand. Sci. (Biol.) Russian Federation, Saint PetersburgMarina A. Mikhailova The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Email: [email protected] ORCID iD: 0009-0001-5828-2245 Russian Federation, Saint Petersburg Maria I. Yarmolinskaya The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Author for correspondence. Email: [email protected] ORCID iD: 0000-0002-6551-4147 SPIN-code: 3686-3605 MD, Dr. Sci. (Med.), Professor, Professor of the Russian Academy of Sciences Russian Federation, Saint PetersburgReferences - Bulun SE, Yilmaz BD, Sison C, et al. Endometriosis. Endocr Rev. 2019;40(4):1048–1079. doi: 10.1210/er.2018-00242 - Shafrir AL, Martel E, Missmer SA, et al. Pelvic floor, abdominal and uterine tenderness in relation to pressure pain sensitivity among women with endometriosis and chronic pelvic pain. Eur J Obstet Gynecol Reprod Biol. 2021;264:247–253. doi: 10.1016/j.ejogrb.2021.07.029 - Vsemirnaya organizatsiya zdravookhraneniya [Internet]. Endometrioz. (In Russ.) 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