The effect of medroxyprogesterone acetate and norethisterone on the estradiol stimulated proliferation in MCF-7 cells: comparison of continuous combined versus sequential combined estradiol/progestin treatment.
OBJECTIVE
Little is known on the type of progestin and regimen type in relation to breast cancer risk. We have compared the effect of medroxyprogesterone acetate (MPA) and norethisterone (NET) on the estradiol stimulated proliferation in MCF-7 cells with respect to different regimens used in combined hormone replacement therapy (HRT).


METHODS
To approximate the in vivo conditions in HRT, MCF-7 cultures were pretreated with estradiol followed by estradiol/progestin treatment to represent the sequential combined model and compared with non pretreated cultures followed by estradiol/progestin treatment for the continuous combined model.


RESULTS
When using progestins in the continuous combined form with estradiol (10(-10) M) both progestins showed a significant reduction in the estradiol stimulated proliferation of the MCF-7 cells. In the sequential combined model the addition of MPA led to a stronger significant reduction of MCF-7 proliferation but in a narrower concentration range (from 10(-8) to 10(-6) M) compared to the continuous treatment. NET did not show any significant effect on proliferation in the SC model.


CONCLUSIONS
Different regimen types and different progestins do lead to significantly different effects on the proliferation of a breast cancer cell line. These findings might be useful in the elucidation of potential mechanisms involved in the clinical situation.
Lippert
C
C
Centre for Endocrinology and Menopause, Department of Obstetrics and Gynaecology, University of Tuebingen, Tuebingen, Germany.
Seeger
H
H
Wallwiener
D
D
Mueck
A O
AO
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002277:Carcinoma / Q000188:drug therapy; D004958:Estradiol / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy / Q000379:methods*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D009640:Norethindrone / Q000494:pharmacology*; D045167:Progesterone Congeners / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D045167:Progesterone Congeners; D011372:Progestins; D004958:Estradiol; D017258:Medroxyprogesterone Acetate; D009640:Norethindrone