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

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 (ERalpha), ERbeta, 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 ERalpha-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 ERbeta 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 ERalpha, ERbeta, 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.