Comparison of the effect of progesterone, medroxyprogesterone acetate and norethisterone on the proliferation of human breast cancer cells.

Abstract

To investigate in vitro the influence of the three most used progestogens in continuous combined HRT on cell proliferation of the human breast cancer cell line MCF-7. Progesterone (P), medroxyprogesterone acetate (MPA) and norethisterone (NET) were investigated in the range of 0.01 nM to 10 microM alone and in combination with 10 nM oestradiol. Cell proliferation was measured after seven days using the ATP-chemosensitivity test. P alone reduced cell proliferation by 20 and 40% at 10(-7) and 10(-5) M. MPA and NET displayed a significant inhibition of cell proliferation between 20 and 25% for MPA and 23 and 41% for NET over the whole concentration range tested. The effect was greatest at 10(-7) M for MPA and at 10(-9) M for NET. In combination with oestradiol, P still significantly reduced cell proliferation, the values being between 12 and 61%. For MPA too an inhibitory effect between 20 and 40% was found, whereas for NET the values were between 23 and 38%. Our in vitro results indicate that the influence on breast cancer risk using HRT in postmenopausal women may depend on the type of progestogen used as well as on the regimen applied. However, the inhibitory in vitro net effect of the progestogens at clinically relevant dosages is rather minimal and it remains uncertain as to whether progestogens generally may reduce breast cancer risk in long-term treatment. Further clinical trials are urgently required to determine the appropriate choice - if any - of progestogen to complement HRT.