title: Effect of vaginal or systemic estrogen on dynamics of collagen assembly in the rat vaginal wall.
abstract: The objective of this study was to compare the effects of systemic and local estrogen treatment on collagen assembly and biomechanical properties of the vaginal wall. Ovariectomized nulliparous rats were treated with estradiol or conjugated equine estrogens (CEEs) either systemically, vaginal CEE, or vaginal placebo cream for 4 wk. Low-dose local CEE treatment resulted in increased vaginal epithelial thickness and significant vaginal growth without uterine hyperplasia. Furthermore, vaginal wall distensibility increased without compromise of maximal force at failure. Systemic estradiol resulted in modest increases in collagen type I with no change in collagen type III mRNA. Low-dose vaginal treatment, however, resulted in dramatic increases in both collagen subtypes whereas moderate and high dose local therapies were less effective. Consistent with the mRNA results, low-dose vaginal estrogen resulted in increased total and cross-linked collagen content. The inverse relationship between vaginal dose and collagen expression may be explained in part by progressive downregulation of estrogen receptor-alpha mRNA with increasing estrogen dose. We conclude that, in this menopausal rat model, local estrogen treatment increased total and cross-linked collagen content and markedly stimulated collagen mRNA expression in an inverse dose-effect relationship. High-dose vaginal estrogen resulted in downregulation of estrogen receptor-alpha and loss of estrogen-induced increases in vaginal collagen. These results may have important clinical implications regarding the use of local vaginal estrogen therapy and its role as an adjunctive treatment in women with loss of vaginal support.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Female Pelvic Medicine and Reconstructive Surgery, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: T Ignacio
authors.initials: TI
authors.lastname: Montoya
authors.affiliation: Department of Obstetrics and Gynecology, Division of Female Pelvic Medicine and Reconstructive Surgery, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: P Antonio
authors.initials: PA
authors.lastname: Maldonado
authors.affiliation: Department of Obstetrics and Gynecology, Division of Female Pelvic Medicine and Reconstructive Surgery, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Jesus F
authors.initials: JF
authors.lastname: Acevedo
authors.affiliation: Department of Obstetrics and Gynecology, Division of Female Pelvic Medicine and Reconstructive Surgery, University of Texas Southwestern Medical Center, Dallas, Texas ruth.word@UTSouthwestern.edu.
authors.forename: R Ann
authors.initials: RA
authors.lastname: Word
mesh_terms: D000282:Administration, Intravaginal; D000284:Administration, Oral; D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D003094:Collagen / Q000378:metabolism*; D004958:Estradiol / Q000008:administration & dosage*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage*; D005260:Female; D051381:Rats; D014599:Uterus / Q000187:drug effects / Q000378:metabolism; D014621:Vagina / Q000187:drug effects* / Q000378:metabolism; D014622:Vaginal Creams, Foams, and Jellies
chemical_list: D004966:Estrogens, Conjugated (USP); D014622:Vaginal Creams, Foams, and Jellies; D004958:Estradiol; D003094:Collagen
keywords: collagen; conjugated equine estrogen; estradiol; lysyl oxidase; pelvic organ prolapse