Changes in extracellular matrix proteins in the cardinal ligaments of post-menopausal women with or without prolapse: a computerized immunohistomorphometric analysis

BACKGROUND: The precise mechanism of uterine prolapse is poorly understood. There is evidence to suggest that abnormalities of connective tissue structure or its repair mechanism may predispose women to prolapse. METHODS and RESULTS: This immunohistochemical study was performed on paraffin‐embedded sections of the cardinal ligaments in an attempt to evaluate differences in the expression of extracellular matrix (ECM) proteins: collagen I, collagen III, elastin and tenascin, in the cardinal ligaments of prolapsed compared to non‐prolapsed uteri. There appear to be discernable differences in the level of expression of ECM proteins in prolapsed compared to non‐prolapsed cardinal ligaments. We found that the ligaments of the prolapsed uteri are characterized by a higher expression of collagen III and tenascin, and lower quantities of elastin. It appears that the use of HRT in post‐menopausal women reverses some of the changes observed in cases of prolapse. Collagen I expression is directly related to the age and menopausal status rather than to prolapse. CONCLUSIONS: In contrast to collagen I, our findings clearly indicate that collagen III expression is directly related to the presence of prolapse rather than age or menopausal status and is suppressed with the use of HRT. The pattern of change may fit a picture of healing phase of traumatized tissue as evidenced by the raised tenascin expression. The trauma itself may have been initiated by events such as childbirth, and that the lack of estrogen following the menopause results in decompensation. In spite of ameliorating some of the changes such as suppression of collagen III expression, treatment with estrogen falls short of rectifying the expression of other necessary proteins. If these mechanisms can be elucidated, a supplementary drug therapy may help along with estrogens to rebuild these ligaments.