title: Different effects of tibolone and continuous combined estrogen plus progestogen hormone therapy on sex hormone binding globulin and free testosterone levels--an association with mammographic density.
abstract: OBJECTIVE
  To compare the effects of tibolone and continuous combined hormone therapy on circulating sex steroids and their binding proteins and their relationship to mammographic density.
  
  
  METHODS
  A prospective, double-blind placebo-controlled study. A total of 166 postmenopausal women were equally randomized to receive tibolone 2.5 mg, estradiol 2 mg/norethisterone acetate 1 mg (E2/NETA) or placebo. Serum analyses of sex steroids, insulin-like growth factor (IGF-I) and binding proteins and assessment of mammographic breast density were performed at baseline and after 6 months of treatment.
  
  
  RESULTS
  Estrogens were markedly increased and androgens decreased by E2/NETA. In contrast, tibolone had only a minor influence on circulating estrogens. Sex hormone binding globulin (SHBG) levels were reduced by 50%, while levels of androgens increased. Baseline values of estrone sulfate (E1S), around 1.0-1.1 nmol/l, were increased to 44.7 nmol/l by E2/NETA and to only 1.7 nmol/l by tibolone (p < 0.001). Mammographic breast density displayed a negative correlation with age and body mass index and a positive association with SHBG. After 6 months there was also a negative correlation with levels of free testosterone. Conclusion We found that tibolone and E2/NETA caused distinct differences in estrogen/androgen status and blood levels of possible breast mitogens. The negative association between free testosterone and mammographic density could be a possible explanation for tibolone having less influence on the breast.
authors.affiliation: Department of Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden. marie.hofling@kbh.ki.se
authors.forename: Marie
authors.initials: M
authors.lastname: Hofling
authors.forename: Kjell
authors.initials: K
authors.lastname: Carlström
authors.forename: Gunilla
authors.initials: G
authors.lastname: Svane
authors.forename: Edward
authors.initials: E
authors.lastname: Azavedo
authors.forename: Helenius
authors.initials: H
authors.lastname: Kloosterboer
authors.forename: Bo
authors.initials: B
authors.lastname: Von Schoultz
mesh_terms: D000368:Aged; D001940:Breast / Q000187:drug effects*; D004958:Estradiol / Q000008:administration & dosage; D015914:Estrogen Replacement Therapy; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D007334:Insulin-Like Growth Factor I; D008327:Mammography; D008593:Menopause / Q000097:blood*; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077563:Norethindrone Acetate; D009652:Norpregnenes / Q000008:administration & dosage; D013739:Testosterone / Q000097:blood
chemical_list: D012739:Gonadal Steroid Hormones; D009652:Norpregnenes; D013739:Testosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D000077563:Norethindrone Acetate; C027385:tibolone; D009640:Norethindrone