title: Digitized assessment of mammographic breast density--effects of continuous combined hormone therapy, tibolone and black cohosh compared to placebo.
abstract: OBJECTIVE
  To determine the effects of continuous combined hormone therapy, tibolone, black cohosh, and placebo on digitized mammographic breast density in postmenopausal women.
  
  
  METHODS
  A prospective, double-blind, placebo-controlled study of 154 postmenopausal women randomized to estradiol 2 mg/norethisterone acetate 1 mg (E2/NETA), tibolone 2.5 mg or placebo and a prospective, open, uncontrolled drug safety study, of which 65 postmenopausal women were treated with black cohosh. Mammograms, at baseline and after six months of treatment, were previously classified according to visual quantification scales.
  
  
  METHODS
  Reanalysis of assessable mammograms by digitized quantification of breast density.
  
  
  RESULTS
  Treatment groups were comparable at baseline. During treatment, both E2/NETA and tibolone significantly increased breast density (mean increase 14.3%, p<0.001 and 2.3%, p<0.001, respectively), while black cohosh and placebo did not. Twenty-four out of the 43 women on E2/NETA had an increase in density exceeding 10% and 6 women had an increase of 30% or more. In the tibolone group, only one woman had an increase in density of more than 10%. The difference in increase in breast density between E2/NETA on the one hand and tibolone, black cohosh and placebo on the other was highly significant (p<0.0001).
  
  
  CONCLUSIONS
  Digitized mammographic breast density is a highly sensitive method confirming significant increase in density by standard E2/NETA treatment and to a lesser extent by tibolone, whereas black cohosh does not influence mammographic breast density during six months treatment. Digitized assessment also yields data on individual variation and small increases left undetectable by visual classification.
authors.affiliation: Department of Women's and Children's Health, Karolinska Institutet and University Hospital, Stockholm, Sweden. eva.lundstrom@karolinska.se
authors.forename: E
authors.initials: E
authors.lastname: Lundström
authors.forename: A L
authors.initials: AL
authors.lastname: Hirschberg
authors.forename: G
authors.initials: G
authors.lastname: Söderqvist
mesh_terms: D001940:Breast / Q000187:drug effects* / Q000473:pathology; D031885:Cimicifuga; D003280:Contraceptives, Oral, Synthetic / Q000494:pharmacology; D003720:Densitometry; D004311:Double-Blind Method; D004958:Estradiol / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D008327:Mammography; D008875:Middle Aged; D009640:Norethindrone / Q000031:analogs & derivatives / Q000494:pharmacology; D000077563:Norethindrone Acetate; D009652:Norpregnenes / Q000494:pharmacology*; D028321:Plant Preparations / Q000494:pharmacology*; D017698:Postmenopause; D011857:Radiographic Image Interpretation, Computer-Assisted; D018709:Statistics, Nonparametric
chemical_list: D003280:Contraceptives, Oral, Synthetic; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D009652:Norpregnenes; D028321:Plant Preparations; D004958:Estradiol; D000077563:Norethindrone Acetate; C027385:tibolone; D009640:Norethindrone