Tibolone versus 17beta-estradiol/norethisterone: effects on the proliferation of human breast cancer cells.
Tibolone is a synthetic progestin with estrogenic and progestogenic properties, widely used for alleviation of menopausal syndromes and for osteoporosis prophylaxis in postmenopausal women. Since only little data are available on tibolone and breast cancer risk the present study investigates the effect of tibolone on the growth of the human breast cancer cell line, MCF-7. Tibolone is clinically comparable to an estradiol/norethisterone combination, therefore we included this hormone combination in our experiments. Tibolone was examined alone and in the presence of 0.1 nM estradiol in the concentration range from 0.001 microM to 1 microM. Norethisterone was studied using the same concentration range in combination with 0.1 nM estradiol. Tibolone led to significant cell growth in the concentration range of 0.01 to 1 microM and was able to significantly stimulate estradiol-induced proliferation at the concentrations 0.01 and 0.1 microM. In contrast, the estradiol/norethisterone combination elicited significant inhibition of cell growth at the concentrations 0.001 and 0.01 microM. These data suggest that tibolone does have tumor cell-growth promoting effects in vitro whereas the estradiol/norethisterone combination partially inhibits cell growth. Therefore no differences in risk profile are to be expected between conventional hormone substitution using estradiol and norethisterone acetate and tibolone. Drawing a clinical consequence from our experiments would result in not recommending the use of tibolone in postmenopausal women at high risk for breast cancer development until long-term controlled clinical studies have been performed on the effect of tibolone administration and breast cancer risk.
Lippert
C
C
Department of Obstetrics and Gynecology, University of Tuebingen, Germany.
Seeger
H
H
Wallwiener
D
D
Mueck
A O
AO
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D009640:Norethindrone / Q000494:pharmacology*; D009652:Norpregnenes / Q000494:pharmacology*; D045167:Progesterone Congeners / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D018931:Antineoplastic Agents, Hormonal; D009652:Norpregnenes; D045167:Progesterone Congeners; D004958:Estradiol; C027385:tibolone; D009640:Norethindrone