Effects of tibolone and continuous combined hormone replacement therapy on mammographic breast density.
OBJECTIVE
Our purpose was to compare the effects of tibolone, continuous combined hormone replacement therapy, and placebo on mammographic breast density.


METHODS
A prospective, randomized, double-blind placebo-controlled study was performed. A total of 166 postmenopausal women were equally randomized to receive tibolone 2.5 mg, estradiol 2 mg/norethisterone acetate 1 mg (E(2)/NETA), or placebo. Mammograms were performed at baseline and after 6 months of treatment. Mammographic density was quantified according to the Wolfe classification and by the percentage area of the breast that had a dense pattern.


RESULTS
An increase in mammographic density was much more common among women receiving continuous combined hormone replacement therapy (46%-50%) than among those receiving tibolone (2%-6%) and placebo (0%) treatment. The difference between E(2)/NETA and placebo was highly significant (P <.001). Treatment with tibolone did not differ from that with placebo. The relative risk of an increase in breast density for E(2)/NETA versus tibolone was found to be 8.3 (95% CI 2.7-25.0).


CONCLUSIONS
An increase in mammographic density should be regarded as an unwanted side effect of hormone replacement therapy. In contrast to estrogen/progestogen treatment, tibolone seems to exert little stimulation of breast tissue.
Lundström
Eva
E
Department of Obstetrics and Gynecology, Karolinska Hospital, Stockholm, Sweden. eva.lundstrom@ks.se
Christow
Alexander
A
Kersemaekers
Wendy
W
Svane
Gunilla
G
Azavedo
Edward
E
Söderqvist
Gunnar
G
Mol-Arts
Mirjam
M
Barkfeldt
Jan
J
von Schoultz
Bo
B
D001707:Biopsy, Needle; D001940:Breast / Q000473:pathology*; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects; D020847:Estrogen Receptor Modulators / Q000009:adverse effects* / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D008327:Mammography; D009640:Norethindrone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077563:Norethindrone Acetate; D009652:Norpregnenes / Q000009:adverse effects* / Q000627:therapeutic use; D010919:Placebos; D017698:Postmenopause; D011446:Prospective Studies
D020847:Estrogen Receptor Modulators; D009652:Norpregnenes; D010919:Placebos; D004958:Estradiol; D000077563:Norethindrone Acetate; C027385:tibolone; D009640:Norethindrone