title: Proliferative effects of different hormone regimens on mammary glands in ovariectomized rats.
abstract: OBJECTIVE
  To compare the proliferative effect of different hormone regimens and estrogen receptor modulation on mammary glands in a rat model of surgical menopause.
  
  
  METHODS
  Experimental animal study.
  
  
  METHODS
  University Hospital.
  
  
  METHODS
  In a rat model of surgical menopause, 78 adult Sprague Dawley female rats were ovariectomized and treated with estrogen, estrogen combined with continuous or intermittent progesterone or the estrogen receptor modulator raloxifene and their respective vehicle controls. Following intraperitoneal drug administration for 20 days, rats were perfused, mammary glands were removed, tissues were processed for immunohistochemical (Ki-67) and hematoxylin-eosin staining, and investigated under light microscope.
  
  
  METHODS
  Histopathological examination of mammary glands and Ki-67 positive cells (proliferation index).
  
  
  RESULTS
  Histological examination showed dilatation in the duct cysts and vacuolization in the epithelial cells in groups receiving progestin, either intermittent or continuous. Histological findings in the raloxifene group were no different from the control group, and the atrophic terminal ductal lobular unit in adipose tissue rich stroma was similar to postmenopausal breast. In animals with a proliferative response, increased proliferation started and dominated in the terminal ductal lobular unit epithelium. Comparison of Ki-67 proliferation indices between groups revealed that estrogen alone or combined with intermittent progesterone yielded significantly higher Ki-67 indices compared to controls; estrogen combined with continuous progesterone also resulted in increasing the probability of proliferation, but the effect was not as pronounced as the other two groups. Raloxifene treatment, on the other hand, did not cause proliferation.
  
  
  CONCLUSIONS
  Estrogen alone or combined with progesterone may increase the risk of breast cancer by enhancing proliferation in the TDLU; raloxifen does not induce proliferation and may be a safe estrogen receptor modulator regarding its effects on mammary glands during menopause.
authors.affiliation: Department of Obstetrics and Gynecology, Ege University Faculty of Medicine, Izmir, Turkey.
authors.forename: T
authors.initials: T
authors.lastname: Cirpan
authors.forename: O
authors.initials: O
authors.lastname: Iscan
authors.forename: M C
authors.initials: MC
authors.lastname: Terek
authors.forename: S
authors.initials: S
authors.lastname: Ozsener
authors.forename: L
authors.initials: L
authors.lastname: Kanit
authors.forename: S
authors.initials: S
authors.lastname: Pogun
authors.forename: O
authors.initials: O
authors.lastname: Zekioglu
authors.forename: S
authors.initials: S
authors.lastname: Yucebilgin
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D020249:Hormone Replacement Therapy; D019394:Ki-67 Antigen / Q000032:analysis; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects*; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology; D020849:Raloxifene Hydrochloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology
chemical_list: D004965:Estrogen Antagonists; D004967:Estrogens; D019394:Ki-67 Antigen; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D011374:Progesterone