Tibolone is a synthetic steroid with oestrogenic, progestational and androgenic properties. It was first marketed in April 1991 for post-menopausal vasomotor symptoms. Tibolone is also licensed for the prevention of osteoporosis and it appears the effect of tibolone on preventing bone loss is similar to other types of menopausal hormonal therapy (MHT) (1). The surrogate measure of bone density show increases of the same magnitude as with alendronate (2).
In the LIFT randomised study in older postmenopausal women with low bone mineral density,4538 women age 60-85 years with osteoporosis on the basis of BMD or minimal trauma vertebral fracture, were randomised to 1.25mg tibolone or placebo. After a median of 34 months, there was a significant reduction in the absolute risk of both vertebral and non-vertebral fractures. The reduction in fracture risk was also seen in women with a pre-existing vertebral fracture. (2)
A major advantage is that it is a bleed-free form of hormone replacement therapy.
Tibolone and cardiovascular disease:
Tibolone and cancer risk:
Tibolone and osteoporosis:
Summary of results of the Million Women Study
Type of HRT Use at Recruitment
Never Use (n, 95% CI) | Oestrogen-only (n, 95% CI) | Tibolone(n, 95% CI) | Cyclic combined(n, 95% CI) | Continuous combined (n, 95% CI) | |
Endometrial cancer | 3 (3-3) | 5* (4-8) | 6 (5-8) | 3 (3-4) | 2 (2-3) |
Breast Cancer | 14 (13-14) | 18 (17-20) | 20 (18-23) | 28 (26-30) | 29 (28-31) |
The risk of breakthrough bleeding in the earlier months of therapy is 10-15%.
It is recommended that women within a year of their last natural menstrual period should not receive tibolone.
Tibolone is also contraindicated in women with any history of arterial thromboembolic disease, including stroke, TIA, myocardial infarction and angina (12).
Summary
Tibolone is indicated for the management of vasomotor symptoms associated with the menopause and for the prevention of bone loss. It can be considered an alternative to conventional MHT where improvement in libido is desired. Its effect on lipid metabolism and haemostasis are less certain, while the long-term effects of tibolone on breast cancer and cardiovascular disease remain unknown. It is not recommended for use in women with a history of breast cancer and should be used with caution in women over age 60 because of the increased stroke risk.
Reference:
1. Berning B, Bennink HJ, Fauser BC. Tibolone and its effects on bone: a review. Climacteric. 2001;4(2):120-36
3. Formoso G, Perrone E, Maltoni S, Balduzzi S, Wilkinson J, Basevi V, et al. Short-term and long-term effects of tibolone in postmenopausal women. Cochrane Database Syst Rev. 2016;10(10)
4. Lundstrom E, Christow A, Kersemaekers W, Svane G, Azavedo E, Soderqvist G, et al. Effects of tibolone and continuous combined hormone replacement therapy on mammographic breast density. Am J Obstet Gynecol. 2002;186(4):717-22.
5. Beral V, Reeves G, Bull D, Green J, Million Women Study C. Breast cancer risk in relation to the interval between menopause and starting hormone therapy. J Natl Cancer Inst. 2011;103(4):296-305.
6. Brusselaers N, Tamimi RM, Konings P, Rosner B, Adami HO, Lagergren J. Different menopausal hormone regimens and risk of breast cancer. Ann Oncol. 2018;29(8):1771-6.
7. Kenemans P, Bundred NJ, Foidart JM, Kubista E, von Schoultz B, Sismondi P, et al. Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial. Lancet Oncol. 2009;10(2):135-46.
8. Santen RJ, Stuenkel CA, Davis SR, Pinkerton JV, Gompel A, Lumsden MA. Managing Menopausal Symptoms and Associated Clinical Issues in Breast Cancer Survivors. J Clin Endocrinol Metab. 2017;102(10):3647-61.
9. Lokkegaard ECL, Morch LS. Tibolone and risk of gynecological hormone sensitive cancer. Int J Cancer. 2018;142(12):2435-40.
10. SIGN (June 2020). Management of osteoporosis and the prevention of fragility fractures
11. Electronic Medicines Compendium: Tibolone. 2024.
12. NICE 2024: BNF - Drugs, Tibolone. Contra-indications
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