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.

Study design: 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.