Abstract
Conventional oestrogen-based hormone therapy (HT) increases the incidence of breast
pain and tenderness, mammographic density and the risk of breast cancer. Combined
oestrogen plus progestogen therapy (EPT) increases the risk of breast cancer to a
greater degree than oestrogen alone (ET). Attention must therefore be focused on identifying
women at risk of breast cancer or on producing a HT that has fewer breast side effects.
Randomised controlled trials have shown that while EPT induces breast tenderness or
pain in up to 50% of women and increases mammographic density in up to 70% during
the first year of treatment, only about as many as one-tenth women report breast tenderness
or pain with tibolone and increases in mammographic density are rare, occurring with
a similar incidence as seen in untreated controls. Many women with breast cancer suffer
vasomotor symptoms rather than risk recurrence with conventional HT. However, in a
small randomised controlled trial in women with early breast cancer undergoing adjuvant
tamoxifen treatment, tibolone reduced hot flushes, night sweats and improved quality
of life compared with placebo.
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 accessOne-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 MaturitasAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Effect of age, breast density and family history on the sensitivity of first screening mammography.JAMA. 1996; 276: 33-38
- Effects of estrogen and estrogen-progestin on mammographic parenchymal density: postmenopausal estrogen-progestin interventions (PEPI) investigators.Ann. Int. Med. 1999; 130: 262-269
- The effect of hormone replacement therapy on the sensitivity of screening mammograms.Clin. Radiol. 1999; 54: 285-288
- Tibolone: a steroid with a tissue-selective mode of action.J. Steroid. Biochem. Mol. Biol. 2001; 76: 231-238
- Tibolone: what does tissue specific activity mean?.Maturitas. 2001; 37: 159-165
- In vitro evaluation of estrogenic, estrogen antagonistic and progestogenic effects of a steroidal drug (Org OD14) and its metabolites on human endometrium.J. Steroid. Biochem. 1990; 35: 535-541
- Tibolone does not stimulate the endometrium or breast in Cynomolgus monkeys.FASEB J. 2001; 15: A594
- Effects of progestagens and Org OD14 in in vitro and in vivo tumor models.J. Steroid. Biochem. Mol. Biol. 1994; 49: 311-318
- Effects of tibolone (Livial®) and its metabolites on the growth of DMBA induced tumors in rats.Acta. Obstet. Gynaecol. Scand. 1997; 76: 59
- Tibolone does not stimulate epithelial proliferation in the breast. Abstract 461.San Antonio Breast Cancer Conf. 2001; 69: 292
- A double-blind randomised trial comparing the effects of tibolone and continuous combined hormone replacement therapy in postmenopausal women with menopausal symptoms.Br. J. Obstet. Gynaecol. 1998; 105: 904-911
- Effects of tibolone and a continuous combined HRT regimen on mammographic breast density.Am. J. Obstet. Gynecol. 2002; 186: 717-722
- Impact on uterine bleeding and endometrial thickness: tibolone compared with continuous combined estradiol and norethisterone acetate replacement therapy.Menopause. 1999; 6: 299-306
- Effect of tibolone and continuous combined hormone replacement therapy on parameters in the clotting cascade: a multicenter, double-blind, randomized study.Fertil. Steril. 2000; 74: 10-19
- The effect of tibolone compared with conjugated equine oestrogens continuously combined with medroxyprogesterone acetate on bleeding rates, quality of life and tolerability in postmenopausal women.Br. J. Obstet. Gynaecol. 2002; 109: 886-893
- Clinical experience with tibolone (Livial) over 8 years.Maturitas. 1995; 21: 71-76
- Effect of tibolone on breast symptoms resulting from postmenopausal hormone replacement therapy.Maturitas. 2003; 45: 267-273
- Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer.Lancet. 1997; 350: 1047-1059
- Risks and benefits of estrogen plus progestin in healthy postmenopausal women. Principle results from WHI RCT.JAMA. 2002; 288: 321-333
- Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial.JAMA. 2004; 291: 1701-1712
- Evidence from randomised trials on the long term effect of hormone replacement therapy.Lancet. 2002; 360: 942-944
- Menopausal oestrogen and estrogen-progestin replacement therapy and breast cancer risk.JAMA. 2000; 283: 485-491
- Effect of hormone replacement therapy on breast cancer risk: estrogen versus estrogen plus progestin.J. Natl. Cancer Inst. 2000; 92: 328-332
- Use of estrogens plus progestin is associated with greater increase in breast cancer risk than estrogen alone.Am. J. Epidemiol. 1998; 147: 64S
- More about: effect of hormone replacement therapy on breast cancer risk: risk; estrogen versus estrogen plus progestin.J. Natl. Cancer Inst. 2000; 92: 1183-1184
- Postmenopausal estrogen and progestin use in relation to breast cancer risk.Cancer Epidemiol. Biomarkers Prev. 2002; 11: 593-600
- Effect of estrogen and estrogen-progestin replacement regimes on mammographic breast parenchymal density.J. Clin. Oncol. 1997; 15: 3201-3207
- Breast cancer and hormone replacement therapy in the Million Women Study.Lancet. 2003; 362: 419-422
- Increased risk of breast cancer following different regimens of hormone replacement therapy frequently used in Europe.Int. J. Cancer. 2004; 109: 721-727
- HABITS (hormonal replacement therapy after breast cancer – is it safe?) a randomised comparison: trial stopped.Lancet. 2004; 363: 453-455
- Cancer recurrence and mortality in women using hormone replacement therapy.J. Fam. Practice. 2002; 51: 1056-1062
- Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women.Lancet. 1998; 352: 93-97
- Prospective evaluation of Vitamin E for hot flashes in breast cancer survivors.J. Clin. Oncol. 1998; 16: 495-500
- Oral clonidine in postmenopausal patients with breast cancer experiencing tamoxifen-induced hot flashes: a University of Rochester Cancer Center Community Clinical Oncology Program study.Ann. Int. Med. 2000; 132: 788-793
- Phase III controlled trial of venlafaxine in the management of hot flashes.Lancet. 2000; 356: 2059-2063
- Pilot evaluation of venlafaxine hydrochloride for the therapy of hot flashes in cancer survivors.J. Clin. Oncol. 1998; 16: 2377-2381
- Megestrol acetate for the prevention of hot flashes.New Engl. J. Med. 1994; 331: 347-352
Kroiss R, Fentiman IS, Helmond FA, Rymer J, Foidart J-M, Bundred N, et al. The effect of tibolone in postmenopausal women receiving tamoxifen after surgery for breast cancer: a randomised, double-blind placebo-controlled trial. BJOG 2004 (in press).
- The effects of soy supplementation on hot flushes.Obstet. Gynecol. 1998; 91: 6-11
- Vasomotor symptom relief by soy isoflavone extract tablets in postmenopausal women: a multicentre, double-blind, randomised, placebo-controlled study.Menopause. 2000; 7: 236-242
- Clinical effects of a standardized soy extract in postmenopausal women: a pilot study.Menopause. 2000; 7: 105-111
- Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, controlled clinical trial.J. Clin. Oncol. 2002; 20: 1449-1455
- Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial.Lancet. 2000; 356: 2059-2063
- Preliminary data from a randomised evaluation of fluoxetine (Prozac) for treating hot flashes in breast cancer survivors.Breast Cancer Res. Treat. 1999; 57: 34
- Megestrol acetate for the prevention of hot flashes.N. Eng. J. Med. 1994; 331: 347-352
- Chemical castration induced by adjuvant cyclophosphamide, methotrexate and fluorouracil chemotherapy causes rapid bone loss that is reduced by clodronate: a randomized study in premenopausal breast cancer patients.J. Clin. Oncol. 1997; 15: 1341-1347
- Long-term adjuvant tamoxifen in early breast cancer: effect on bone mineral density in postmenopausal women.J. Clin. Oncol. 1990; 8: 1019-1024
- A controlled trial of raloxifene HCL: impact on bone turnover and serum lipid profile in healthy postmenopausal women.J. Bone Miner. Res. 1996; 11: 835-842
- A pilot trial assessing the efficiency of paroxetine hydrochloride in controlling hot flashes in breast cancer survivors.Annal. Oncol. 2000; 11: 17-22
- Influence of nomogestrel acetate on the improvement of the quality of life induced by oestrogen therapy in menopausal women.Contracept. Fertil. Sex. 1996; 24: 847-851
- Long-term use of megestrol acetate for treatment of hot flashes in cancer survivors.Cancer. 1998; 82: 1784-1788
- Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: an NCCTG trial.J. Clin. Oncol. 2000; 18: 1068-1074
- Soy isoflavones: are they useful in menopause?.Mayo Clin. Proc. 2000; 75: 1174-1184
- Isoflavone-rich or isoflavone-poor protein does not reduce menopausal symptoms during 24 weeks of treatment.Menopause. 2001; 8: 17-26
- Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: an NCCTG trial.J. Clin. Oncol. 2000; 18: 1068-1074
- Randomised placebo-controlled trial of an isoflavone supplement and menopausal symptom in women.Climacteric. 1999; 2: 85-92
- The effects of Promensil an isoflavone extract on menopausal symptoms.Climacteric. 1999; 2: 79-84
Article info
Publication history
Accepted:
June 10,
2004
Received in revised form:
May 21,
2004
Received:
January 12,
2004
Identification
Copyright
© 2004 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
