title: Effects of short-term estradiol and norethindrone acetate treatment on the breasts of normal postmenopausal women.
abstract: OBJECTIVE
  The aim of this study was to evaluate among postmenopausal women the effects of a 3-month treatment with estradiol (E2) alone or in combination with norethindrone acetate (NA) on expression of hormone receptors and proliferation in the breast as well as on lipids and climacteric symptoms.
  
  
  METHODS
  Sixty healthy postmenopausal women were computer-randomized into two groups, with one group receiving 1 mg of E2 and the other group receiving 1 mg of E2 and 0.5 mg of NA daily for 12 weeks. Before and after treatment, middle-needle biopsies were obtained for histology and investigation of the expression levels of estrogen receptors (ERs; ER-α and ER-β), progesterone receptors (PRs; PR-A and PR-B), androgen receptor (AR), the proliferation marker Ki67, and collagen. Climacteric symptoms were recorded, and serum was collected to measure lipoprotein levels.
  
  
  RESULTS
  Fifty-six women finished the 12-week study. Proliferating cells (Ki67-positive) were very rare in all but a few of the untreated women. There were proliferating cells in both E2- and E2/NA-treated groups; however, these were not widespread and limited to nests of cells that amounted to 2% of the total epithelial cells. Some of these nests were positive for human epithelial growth factor receptor 2. Treatments caused no marked changes in the expression of ER-α, ER-β, or AR. However, both treatments resulted in an increase in PR-A and PR-B expressions. The presence of collagen was clearly associated with a mammographic diagnosis of dense breasts, but neither hormone treatment affected breast density. Both E2 and E2/NA treatments were effective in relieving hot flashes and sweating without adverse effects on blood pressure, weight, and liver, kidney, and thyroid functions. A decrease in cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was induced by E2/NA but not by E2.
  
  
  CONCLUSIONS
  This short-term prospective study shows that E2 and estrogen-progestogen treatment can up-regulate PRs but do not significantly affect ERs, AR, proliferation, or breast density.
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Novum, Sweden. guojun.cheng@ki.se
authors.forename: Guojun
authors.initials: G
authors.lastname: Cheng
authors.forename: Ryan
authors.initials: R
authors.lastname: Butler
authors.forename: Margaret
authors.initials: M
authors.lastname: Warner
authors.forename: Jan-Åke
authors.initials: JÅ
authors.lastname: Gustafsson
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wilczek
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Landgren
mesh_terms: D000368:Aged; D001940:Breast / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003094:Collagen / Q000378:metabolism; D003280:Contraceptives, Oral, Synthetic / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D019584:Hot Flashes / Q000188:drug therapy; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008327:Mammography; D008875:Middle Aged; D009640:Norethindrone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077563:Norethindrone Acetate; D017698:Postmenopause / Q000097:blood / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013546:Sweating / Q000187:drug effects
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D003280:Contraceptives, Oral, Synthetic; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D019394:Ki-67 Antigen; D011944:Receptors, Androgen; D011980:Receptors, Progesterone; C101118:progesterone receptor A; C097314:progesterone receptor B; D004958:Estradiol; D003094:Collagen; D000077563:Norethindrone Acetate; D009640:Norethindrone