Advertisement

Effects of tibolone and continuous combined hormone replacement therapy on mammographic breast density

      Abstract

      Objective: Our purpose was to compare the effects of tibolone, continuous combined hormone replacement therapy, and placebo on mammographic breast density. Study design: 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 (E2/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 E2/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 E2/NETA versus tibolone was found to be 8.3 (95% CI 2.7-25.0). Conclusion: 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. (Am J Obstet Gynecol 2002;186:717-22.)

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Collaborative Group on Hormonal Factors in Breast Cancer
        Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 without breast cancer.
        Lancet. 1997; 350: 1047-1059
        • Söderqvist G
        Effects of sex steroids on proliferation in normal mammary tissue.
        Ann Med. 1998; 30: 511-524
        • Greendale GA
        • Reboussin BA
        • Sie A
        • Singh R
        • Olson L
        • Gatewood O
        • et al.
        Effects of estrogen and estrogen-progestin on mammographic parenchymal density.
        Ann Intern Med. 1999; 130: 262-269
        • Lundström E
        • Wilczek B
        • von Palffy Z
        • Söderqvist G
        • von Schoultz B
        Mammographic breast density during hormone replacement therapy: differences according to treatment.
        Am J Obstet Gynecol. 1999; 181: 348-352
        • Boyd NF
        • Lockwood GA
        • Byng JW
        • Tritchler DL
        • Yaffe MJ
        Mammographic densities and breast cancer risk.
        Cancer Epidemiol Biomark Prev. 1998; 7: 1133-1144
        • Moore RA
        Livial: a review of clinical studies.
        Br J Obstet Gynaecol. 1999; 106: 1-21
        • Rymer JM
        The effects of tibolone.
        Gynecol Endocrinol. 1998; 12: 213-220
        • Valdivia I
        • Ortega D
        Mammographic density in postmensopausal women treated with tibolone, estriol or conventional hormone replacement therapy.
        Clin Drug Invest. 2000; 20: 101-107
        • Pasqualini JR
        • Chetrie GS
        Estrone sulfatase versus estrone sulfotransferase in human breast cancer: potential clinical applications.
        J Steroid Biochem Mol Biol. 1999; 69: 287-292
        • Gompel A
        • Kanduz M
        • Siromachkova M
        • Lombet A
        • Thevenin D
        • Mimoun M
        • et al.
        The effect of tibolone on proliferation, differentiation and apoptosis in normal breast cells.
        Gynecol Endocrinol. 1997; 11: 77-79
        • Wolfe JN
        Breast patterns as an index of risk for developing breast cancer.
        AJR Am J Roentgenol. 1976; 26: 1130-1139
        • Wolfe JN
        Risk for breast cancer development determined by mammographic parenchymal pattern.
        Cancer. 1976; 37: 2486-2492
        • Lundström E
        • Wilczek B
        • von Palffy Z
        • Söderqvist G
        • von Schoultz B
        Mammographic breast density during HRT-effects of continuous combination, unopposed transdermal and low-potency oestrogen regimens.
        Climacteric. 2001; 4: 42-48
        • Erel CT
        • Elter K
        • Akman C
        • Ersavasti G
        • Altug A
        • Seyisoglu H
        • et al.
        Mammographic changes in women receiving tibolone therapy.
        Fertil Steril. 1998; 69: 870-875
        • Magnusson C
        • Baron JA
        • Correia N
        • Bergström R
        • Adami HO
        • Persson I
        Breast-cancer risk following long-term oestrogen- and oestrogen-progestin replacement therapy.
        Int J Cancer. 1999; 81: 339-344
        • Schairer C
        • Lubin J
        • Troisi R
        • Sturgeon S
        • Brinton L
        • Hoover R
        Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk.
        JAMA. 2000; 283: 485-491
        • Ross RK
        • Paganini-Hill A
        • Wan PC
        • Pike MC
        Effect of hormone replacement therapy on breast cancer risk: estrogen versus estrogen plus progestin.
        J Natl Cancer Inst. 2000; 92: 328-332
        • Hesch RD
        • Kenemans P
        Hormonal prevention of breast cancer: proposal for a change in paradigm.
        Br J Obstet Gynaecol. 1999; 106: 1006-1018
        • Cline M
        • Söderqvist G
        • von Schoultz E
        • Skoog L
        • von Schoultz B
        Effects of hormone replacement therapy on the mammary gland of surgically postmenopausal macaques.
        Am J Obstet Gynecol. 1996; 174: 93-100
        • Hofseth L
        • Raafat A
        • Osuch J
        • Pathak D
        • Slomski C
        • Haslam S
        Hormone replacement therapy with estrogen plus medroxyprogesteroneacetate is associated with increased eptihelial proliferation in the normal postmenopausal breast.
        J Clin Endocrinol Metab. 1999; 84: 4559-4565
        • Kloosterboer HJ
        • Schoonen WG
        • Deckers GH
        • Klijn G
        Effects of progestagens and Org OD14 in in vitro and in vivo tumor models.
        J Steroid Biochem Mol Biol. 1994; 49: 311-318
        • McNicholas MMJ
        • Heneghan JP
        • Milner MH
        • Tunney T
        • Hourihane JB
        • MacErlaine DP
        Pain and increased mammographic density in women receiving hormone replacement therapy: A prospective study.
        AJR Am J Roentgenol. 1994; 163: 311-315
        • Hammar M
        • Christau S
        • Nathorst-Böös J
        • Rud T
        • Garre K
        A double blind, randomized trial comparing the effects of tibolone and continuous combined hormone replacement therapy in postmenopausal women with menopausal symptoms.
        Br J Obstet Gynaecol. 1998; 45: 345-351
        • Rutter C
        • Mandelson M
        • Laya M
        • Taplin S
        Changes in breast density associated with initiation, discontinuation and continuing use of hormone replacement therapy.
        JAMA. 2001; 285: 171-176
        • Spicer DV
        • Ursin G
        • Parisky YR
        • Pearce JG
        • Shoupe D
        • Pike A
        • et al.
        Changes in mammographic densities induced by a hormonal contraceptive designed to reduce breast cancer risk.
        J Natl Cancer Inst. 1994; 86: 431-436