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This version published online on May 29, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-2719
A more recent version of this article appeared on August 1, 2007
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Right arrow Female Endocrinology

Submitted on December 8, 2006
Accepted on May 23, 2007

Lower Levels of Urinary 2-Hydroxyestrogens in Polycystic Ovary Syndrome

Sana Salih, Xia Xu, Timothy D. Veenstra, Antoni J. Duleba, Hala Fouad, Manubai Nagamani, and Ayman Al-Hendy*

Department of Obstetrics & Gynecology, University of Texas Medical Branch, Galveston, Texas 77555; Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick, Inc., Frederick, Maryland; and Department of Obstetrics and Gynecology, Yale University, New Haven, Connecticut 06511

* To whom correspondence should be addressed. E-mail: ayalhend{at}utmb.edu.

Context: Women with polycystic ovary syndrome (PCOS) have anovulation due to arrested follicular maturation. The substrate (2-hydroxyestrogen) and the product (2-methoxyestrogen) of catechol-O-methyl transferase (COMT) have been shown to modulate proliferation and angiogenesis of granulosa cells.

Objective: To evaluate COMT ovarian expression, as well as the production of estrogen metabolites (2-hydroxyestrogen and 2-methoxyestrogen) in subjects with PCOS.

Design: Immunohistochemistry was used to assess COMT expression in ovarian tissues. Urinary levels of 10 different estrogens and estrogen metabolites were measured using enzyme-labeled immunoassays and/or liquid chromatography with tandem mass spectrometry.

Setting: Tertiary University Referral Center

Patients and Other Participants: Ovarian tissues were obtained from 6 control subjects and 6 subjects with PCOS. Fasting first-void urinary samples were collected from 49 subjects with PCOS and 36 healthy control subjects.

Main Outcome Measure(s): COMT protein expression in ovarian tissues. Urinary levels of 2-hydroxyestrogen and 2-methoxyestrogen levels in PCOS patients.

Results: While immunohistochemistry showed that COMT was expressed in ovaries from control and PCOS subjects, its expression was significantly higher in ovaries from subjects with PCOS, both in the follicular structures and in the ovarian stroma. The urinary 2-hydroxyestrogen level was significantly lower in subjects with PCOS, compared with normal controls (P = .009). Additionally, urinary 2-hydroxyestrogen levels negatively correlated with serum insulin levels in subjects with PCOS (r = -0.333, P = .031).

Conclusions: Urinary 2-hydroxyestrogen is decreased in subjects with PCOS, which could be due in part to increased ovarian expression of COMT. Further studies are needed to ascertain the role of estrogen metabolism in PCOS before this information can be used in clinical settings.


Key words: Polycystic ovary syndrome • catechol-O-methyl transferase • 2-hydroxyestrogen • granulosa cell atresia • anovulation




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