Effects of tibolone and conventional HRT on the expression of estrogen and progesterone receptors in the breast

Abstract 

Objective

There is evidence that long-term hormone replacement therapy (HRT) is associated with an increased breast cancer risk. The aim of this study was to assess the effects of tibolone on estrogen and progesterone receptors in comparison to the effects of conventional HRT in the breast of surgically postmenopausal macaques.

Method

Sixty macaques were bilaterally ovariectomized 3 months before hormonal treatment was initiated. The animals were randomized into four treatment groups, including tibolone (TIB), conjugated equine estrogens (CEE), conjugated equine estrogens+medroxyprogesterone acetate (CEE+MPA) and control animals (C). After 2 years treatment, breast tissues were collected, fixed and paraffin embedded. Immunohistochemistry assays with monoclonal antibodies for estrogen receptors (ERα and ERβ) and progesterone receptors (PRA and PRB) were performed.

Results

The expression of ERα was markedly decreased in the CEE+MPA group as compared to C and TIB groups. The TIB group was not different from the C and CEE groups. No significant differences were found for ERβ immunostaining. The expression of PRA was strongly increased in the TIB group as compared to the C and CEE+MPA groups. Immunostaining of PRB was increased in the CEE and TIB treated animals as compared to both C and CEE+MPA groups.

Conclusions

Tibolone increased the expression of both PRA and PRB, without affecting ERα and ERβ expression in the macaque breast. These findings indicate that the effects of tibolone in breast tissue could be mediated via differential regulation of PRA and PRB isoforms and therefore distinct from those observed with conventional HRT.

Keywords: Tibolone, Hormone replacement therapy, ERα, ERβ, PRA, PRB, Breast, Cynomolgus macaques