A comparative study of breast cell proliferation during hormone replacement therapy: effects of tibolon and continuous combined estrogen-progestogen treatment.
OBJECTIVE
To use the fine-needle aspiration (FNA) biopsy technique to compare the effects of tibolone, conventional hormone replacement therapy (HRT) and placebo on breast cell proliferation in postmenopausal women.


METHODS
A total of 91 women were randomized to receive either estradiol 2 mg plus norethisterone acetate 1 mg (E2/NETA), tibolone 2.5 mg or placebo for 6 months in a prospective double-blind trial. Breast cell proliferation was assessed using the Ki-67/MIB-1 monoclonal antibody.


RESULTS
From the 83 women who completed the study, a total of 166 FNA biopsies were obtained, and 118 of these aspirates (71%) were evaluable for MIB-1 content. Women with assessable biopsies were younger, had a lower body mass index, and had higher levels of sex hormone binding globulin and insulin-like growth factor-I than women in whom the cell yield was insufficient. During treatment with E2/NETA, there was an increase in proliferation (percentage of MIB-1) from a mean value of 2.2 to 6.4% after 6 months (p < 0.01). No significant changes were recorded during treatment with tibolone or placebo. There was a negative association between proliferation and serum levels of total (r(s) = -0.29, p < 0.05) and free (rs = -0.31, p < 0.03) testosterone.


CONCLUSIONS
Tibolone seems to have little influence on breast cell proliferation.
Conner
P
P
Department of Obstetrics and Gynecology, Karolinska Hospital, Stockholm, Sweden.
Christow
A
A
Kersemaekers
W
W
Söderqvist
G
G
Skoog
L
L
Carlström
K
K
Tani
E
E
Mol-Arts
M
M
von Schoultz
B
B
D000368:Aged; D000911:Antibodies, Monoclonal; D001707:Biopsy, Needle; D001940:Breast / Q000166:cytology* / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003280:Contraceptives, Oral, Synthetic / Q000494:pharmacology; D004311:Double-Blind Method; D004958:Estradiol / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen; D008875:Middle Aged; D009640:Norethindrone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077563:Norethindrone Acetate; D009652:Norpregnenes / Q000494:pharmacology*; D011446:Prospective Studies
D000911:Antibodies, Monoclonal; D003280:Contraceptives, Oral, Synthetic; D020847:Estrogen Receptor Modulators; D019394:Ki-67 Antigen; D009652:Norpregnenes; D004958:Estradiol; D000077563:Norethindrone Acetate; C027385:tibolone; D009640:Norethindrone