title: Effects of tibolone and continuous combined hormone replacement therapy on mammographic breast density.
abstract: OBJECTIVE
  Our purpose was to compare the effects of tibolone, continuous combined hormone replacement therapy, and placebo on mammographic breast density.
  
  
  METHODS
  A prospective, randomized, double-blind placebo-controlled study was performed. A total of 166 postmenopausal women were equally randomized to receive tibolone 2.5 mg, estradiol 2 mg/norethisterone acetate 1 mg (E(2)/NETA), or placebo. Mammograms were performed at baseline and after 6 months of treatment. Mammographic density was quantified according to the Wolfe classification and by the percentage area of the breast that had a dense pattern.
  
  
  RESULTS
  An increase in mammographic density was much more common among women receiving continuous combined hormone replacement therapy (46%-50%) than among those receiving tibolone (2%-6%) and placebo (0%) treatment. The difference between E(2)/NETA and placebo was highly significant (P <.001). Treatment with tibolone did not differ from that with placebo. The relative risk of an increase in breast density for E(2)/NETA versus tibolone was found to be 8.3 (95% CI 2.7-25.0).
  
  
  CONCLUSIONS
  An increase in mammographic density should be regarded as an unwanted side effect of hormone replacement therapy. In contrast to estrogen/progestogen treatment, tibolone seems to exert little stimulation of breast tissue.
authors.affiliation: Department of Obstetrics and Gynecology, Karolinska Hospital, Stockholm, Sweden. eva.lundstrom@ks.se
authors.forename: Eva
authors.initials: E
authors.lastname: Lundström
authors.forename: Alexander
authors.initials: A
authors.lastname: Christow
authors.forename: Wendy
authors.initials: W
authors.lastname: Kersemaekers
authors.forename: Gunilla
authors.initials: G
authors.lastname: Svane
authors.forename: Edward
authors.initials: E
authors.lastname: Azavedo
authors.forename: Gunnar
authors.initials: G
authors.lastname: Söderqvist
authors.forename: Mirjam
authors.initials: M
authors.lastname: Mol-Arts
authors.forename: Jan
authors.initials: J
authors.lastname: Barkfeldt
authors.forename: Bo
authors.initials: B
authors.lastname: von Schoultz
mesh_terms: D001707:Biopsy, Needle; D001940:Breast / Q000473:pathology*; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects; D020847:Estrogen Receptor Modulators / Q000009:adverse effects* / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D008327:Mammography; D009640:Norethindrone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077563:Norethindrone Acetate; D009652:Norpregnenes / Q000009:adverse effects* / Q000627:therapeutic use; D010919:Placebos; D017698:Postmenopause; D011446:Prospective Studies
chemical_list: D020847:Estrogen Receptor Modulators; D009652:Norpregnenes; D010919:Placebos; D004958:Estradiol; D000077563:Norethindrone Acetate; C027385:tibolone; D009640:Norethindrone