Sismondi, P., Kimmig, R., Kubista, E., Biglia, N., Egberts, J., Mulder, R., ... Kenemans, P. (2011). Effects of tibolone on climacteric symptoms and quality of life in breast cancer patients--data from LIBERATE trial. Maturitas, 70(4), 365-372.

The study reported the effects of tibolone 2.5mg daily on climacteric symptoms, vaginal dryness, and health-related quality of life in breast cancer survivors.

Patients were randomized one-to-one to tibolone 2.5 mg by mouth daily or 1 placebo pill by mouth daily, with mean duration of treatment of 2.75 years.

The study enrolled 3098 women, with 1556 on tibolone and 1542 on placebo. Combined treatment and placebo groups mean age was 52.7 (SD=7.3), range = 28-75.
    

• KEY DISEASE CHARACTERISTICS:  Non-metastatic breast cancer T1-3, N0-2, M0
• INCLUSION CRITERIA: Postmenopausal, younger than age 75 and treated in past 5 years.  At entry to study 6.5%were taking aromatase inhibitors, 66.6% taking tamoxifen, 4.3% taking GnRH analogues, 16.7% post oophorectomy.  Race and ethnicity are not reported.

This was a multi-site, multi-national study conducted in at least eight countries: Austria, Belgium, Germany, Spain, France, United Kingdom, Italy, The Netherlands.
 

• PHASE OF CARE: Long term followup
• APPLICATIONS: Late effects & survivorship

The study was a multinational, multicenter, randomized, double-blind, parallel group, placebo-controlled trial.

Measurements and instruments included:

• Daily hot flash diary - frequency and severity - with calculated composite score    
• Climacteric symptoms form - hot flash frequency per day, change from baseline, maximum intensity of hot flashes, sweats, interference of flushes/sweats with normal life, palpitations, joint pain, vaginal dryness, incontinence
• Women’s Health Questionnaire - health-related quality of life,  subset of participants
   

Compared to placebo, tibolone resulted in a significantly greater reduction in:

1. Number of hot flashes per day at 12 and 104 weeks of treatment (p’s < 0.0001)weeks
2. Mean composite hot flash severity at week 12 (p < .0006)
3. Mean vaginal dryness score at week 104 (p < 0.0001)
4. WHQ scores in vasomotor, sexual and sleep at weeks 28, 52, 78, and 104 (p < .05)
5. WHQ scores of attraction at week 78 and mood at weeks 26, 52, and 78 (p’s < 0.05). 

There were interaction effects of tamoxifen and AI such that those using those therapies obtained less relief in hot flashes and climacteric symptoms with tibolone. 

Tibolone 2.5 mg orally daily was effective in alleviating menopausal symptoms in breast cancer survivors overall, but was less effective in tamoxifen users.

 A very small percentage of participants were on AIs or GnRH analogues at study entry.

Despite efficacy, the main trial report published in another journal indicated that tibolone increased the risk of breast cancer recurrence and is therefore contraindicated as a menopausal symptom therapy in breast cancer survivors.   Also, placebo effect was evident and persistent.