Testosterone inhibits estrogen/progestogen-induced breast cell proliferation in postmenopausal women.
OBJECTIVE
During the past few years serious concern has been raised about the safety of combined estrogen/progestogen hormone therapy, in particular about its effects on the breast. Several observations suggest that androgens may counteract the proliferative effects of estrogen and progestogen in the mammary gland. Thus, we aimed to study the effects of testosterone addition on breast cell proliferation during postmenopausal estrogen/progestogen therapy.


METHODS
We conducted a 6-month prospective, randomized, double-blind, placebo-controlled study. A total of 99 postmenopausal women were given continuous combined estradiol 2 mg/norethisterone acetate 1 mg and were equally randomly assigned to receive additional treatment with either a testosterone patch releasing 300 microg/24 hours or a placebo patch. Breast cells were collected by fine needle aspiration biopsy at baseline and after 6 months, and the main outcome measure was the percentage of proliferating breast cells positively stained by the Ki-67/MIB-1 antibody.


RESULTS
A total of 88 women, 47 receiving active treatment and 41 in the placebo group, completed the study. In the placebo group there was a more than fivefold increase (P<0.001) in total breast cell proliferation from baseline (median 1.1%) to 6 months (median 6.2%). During testosterone addition, no significant increase was recorded (1.6% vs 2.0%). The different effects of the two treatments were apparent in both epithelial and stromal cells.


CONCLUSIONS
Addition of testosterone may counteract breast cell proliferation as induced by estrogen/progestogen therapy in postmenopausal women.
Hofling
Marie
M
Department of Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden. marie.hofling@ki.se
Hirschberg
Angelica Lindén
AL
Skoog
Lambert
L
Tani
Edneia
E
Hägerström
Torsten
T
von Schoultz
Bo
B
D000279:Administration, Cutaneous; D000368:Aged; D001707:Biopsy, Needle; D001940:Breast / Q000187:drug effects* / Q000473:pathology; D001943:Breast Neoplasms / Q000473:pathology / Q000517:prevention & control; D049109:Cell Proliferation / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000097:blood; D017698:Postmenopause; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone / Q000008:administration & dosage* / Q000097:blood; D016896:Treatment Outcome
D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D009640:Norethindrone