tibolone

Last edited 08/2020 and last reviewed 10/2023

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 now also licensed for the prevention of osteoporosis - however, at present, there are no data on whether tibolone prevents fractures (1). The surrogate measure of bone density show increases of the same magnitude as with alendronate (2).

A major advantage is that it is a bleed-free form of hormone replacement therapy.

Tibolone and cardiovascular disease:

• there is evidence that tibolone increased the risk of stroke in patients with osteoporosis (2)
  • the risk of stroke rises exponentially with age: therefore tibolone should generally not be used in elderly women
    • "..Tibolone has been used by women between the ages of 50 and 60 years for menopausal symptoms and the prevention of osteoporosis when the risk of stroke was low, but it should be avoided in women who have strong risk factors for stroke, such as hypertension, smoking, diabetes, and atrial fibrillation.." (2)
• there has been no evidence of an increased risk of thromboembolism with tibolone (2); in contrast to the increased risk that has been seen with hormone therapy and selective estrogen-receptor modulators (SERMs) (2)
• there is no evidence of increased risk of coronary events associated with tibolone use (2)

Tibolone and cancer risk:

• breast cancer risk
  • the Million Women Study (observational study) suggested that tibolone might be associated with an increased risk of breast cancer - however this was smaller when compared with combined oestrogen-progesterone HRT (3,4)
    • however the randomised controlled trial by Cummings SR et al. revealed a reduced breast cancer risk associated with tibolone use (2)
      • tibolone use was associated with a reduction in the risk of invasive breast cancer to a degree that was similar to that observed for treatment with tamoxifen or raloxifene
      • unclear why the results of this trial contrast with the data from the Million Women Study
• tibolone is also associated with a five year risk of endometrial cancer of 6-8 per 1000 (compared with a risk of 3 per 1000 with no use of tibolone or HRT) (4)
• tibolone may be associated with a reduction in risk of colon cancer (2)

Tibolone and osteoporosis:

• study evidence reveals that tibolone was associated with a reduction in the risk of vertebral fracture in older women with osteoporosis (2)
  • absolute reduction was greater (20.8 per 1000 person-years) among women who had already had a vertebral fracture than among those who had not had such a fracture (4.6 per 1000 person-years)
  • magnitude of the reduction in relative risk was similar to those observed for therapy with oestrogen, bisphosphonates, and raloxifene
  • also associated with a reduction in the risk of nonvertebral fracture, an improvement that was also greater in women who had already had a vertebral fracture
    • a similarly decreased risk of nonvertebral fracture has been demonstrated for oestrogen therapy
    • however the risk of non vertebral fractures has not been shown for not for raloxifene and tamoxifen
  • Tibolone may be considered to prevent vertebral and non-vertebral fractures in younger postmenopausal women, particularly those with menopausal symptoms (5)

Summary of results of the Million Women Study

Type of HRT Use at Recruitment

• figures based on use per 1000 never-users of HRT or current users of tibolone or HRT over a 5 year period.
• based on the values observed for never-users of HRT in the MWS and are expressed over a 5 year period
• *results from a meta-analysis of worldwide data suggest a figure of between 6 and 8 per 1000

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 not suitable for premenopausal women - in both cases it may cause unacceptable irregular bleeding (6)

Tibolone is also contraindicated in women with any history of arterial thromboembolic disease, including stroke, TIA, myocardial infarction and angina (7).

Reference:

1. MeReC Bulletin (1999), 10 (7), 25-8.
2. Cummings SR et al.The effects of tibolone in older postmenopausal women. N Engl J Med. 2008 Aug 14;359(7):697-78.
3. Pulse (2003), 63 (41), 104.
4. JAMA. 2002 Jul 17;288(3):321-33.
5. SIGN (June 2020). Management of osteoporosis and the prevention of fragility fractures
6. Current Problems in Pharmacovigilance 2006; 13:1-12.
7. Akzo Nobel (June 19th 2006). Tibolone updated prescribing advice regarding the risk of stroke.