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Hum. Reprod. Advance Access published online on May 13, 2004

Human Reproduction, doi:10.1093/humrep/deh282
© 2004 by European Society of Human Reproduction and Embryology
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Received November 19, 2003
Accepted March 31, 2004

Article

Changes in gonadal steroid receptors in the cardinal ligaments of prolapsed uteri: immunohistomorphometric data

Ayman A.A. Ewies 1, John Thompson 1, Farook Al-Azzawi 2*

1 Leicester and Warwick Medical School, Leicester, UK
2 Leicester and Warwick Medical School, Leicester, UK; Gynaecology Research Unit, Department of Cancer Studies and Molecular Medicine, Clinical Sciences Building, Leicester and Warwick Medical School, Leicester LE2 7LX, UK

* To whom correspondence should be addressed. E-mail: fa2{at}le.ac.uk.


   Abstract

BACKGROUND:The precise mechanism of uterine prolapse is poorly understood. This immunohistochemical study was performed on paraffin-embedded sections of the cardinal ligaments in an attempt to evaluate the differential expression of gonadal steroid receptors in human cardinal ligaments of prolapsed uteri compared with non-prolapsed controls. METHODS: Specimens from women with pelvic organ prolapse (POP) stage III (n = 33), together with the appropriate controls (n = 25), were stained for estrogen receptor {alpha} (ER{alpha}), ER{beta}, progesterone receptor (PR), androgen receptor (AR) and Ki-67. The control materials were samples of the cardinal ligaments obtained from pre- and post-menopausal women with no prolapse, who were not using hormonal therapy. RESULTS The prolapsed ligaments expressed 1.5-2.5 times more ER{alpha}-positive cells (statistically significant in post-menopausal women not taking HRT, P < 0.001), a 3-4 times greater percentage of AR-positive cells (P = 0.004 and P = 0.008 in pre-menopausal and post-menopausal women not taking HRT, respectively) and twice the percentage of PR-positive cells (statistically significant in the pre-menopausal group, P = 0.03) compared with the no prolapse group. Expression of ER{beta} was twice as high in the ligaments of pre-menopausal women with no prolapse compared with those with prolapse (P = 0.02), and no significant difference was found in the post-menopausal groups. The use of HRT was significantly associated with low AR and high PR expression. Ki-67 expression was not detected in these specimens. CONCLUSIONS: The clearly discernible levels of expression of ER{alpha}, ER{beta}, AR and PR in the prolapsed cardinal ligaments may suggest a relationship to the process of tissue stretch ‘trauma’, rather than an effect of the menopausal status, HRT use or cell proliferation. The use of HRT in post-menopausal women appears to offset some of the changes observed with the prolapse.

Key words: androgen receptor/cardinal ligament/estrogen receptor/progesterone receptor/prolapse


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