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.
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.
Hofling
Marie
M
Department of Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden. marie.hofling@kbh.ki.se
Carlström
Kjell
K
Svane
Gunilla
G
Azavedo
Edward
E
Kloosterboer
Helenius
H
Von Schoultz
Bo
B
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
D012739:Gonadal Steroid Hormones; D009652:Norpregnenes; D013739:Testosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D000077563:Norethindrone Acetate; C027385:tibolone; D009640:Norethindrone