Tibolone is an anabolic steroid. Tibolone has been examined in the treatment of hot flashes.
Not Recommended for Practice
Research Evidence Summaries
Kroiss, R., Fentiman, I.S., Helmond, F.A., Rymer, J., Foidart, J.M., Bundred, N., … Kubista, E. (2005). The effect of tibolone in postmenopausal women receiving tamoxifen after surgery for breast cancer: A randomised, double-blind, placebo-controlled trial. BJOG, 112, 228–233.doi:10.1111/j.1471-0528.2004.00309.x
The study assessed the effects of tibolone versus placebo in postmenopausal women receiving tamoxifen, measuring effects on hot flashes, endometrium, and serum lipid and lipoproteins.
Intervention Characteristics/Basic Study Process:
Women were randomized to receive 20 mg/day tamoxifen plus 2.5 mg/day tibolone or placebo.
Seventy (70) post-menopausal women less than or equal to 75 years of age (mean age: 58. I years) with Stage IIB or less started on tamoxifen postoperatively. Sixty-seven (67) patients completed the study. I
- Post-menopausal women less than or equal to 75 years of age with newly diagnosed Stage Ilb or lower breast cancer
- Surgical treatment with conservative therapy or modified radical mastectomy
- Receiving tamoxifen therapy
- Last menstrual period one year or more before the diagnosis of breast cancer
- Serum estradiol concentration of less than or equal to 30 pg/mL
- Other malignancies; prior hysterectomy or bilateral oophorectomy; endometrial hyperplasia/adenocarcinoma; cervical smear result showing moderate dysplasia or worse
- Cardiovascular, cerebrovascular, or thromboembolic disorders
- Uterine bleeding of unknown cause; severe liver disorders
- Drug or alcohol abuse in the previous 12 months
- Requirement for cancer therapy (other than tamoxifen therapy and radiotherapy)
- Nedication that may affect the metabolism of tibolone
- Use of steroids or tamoxifen in the six weeks prior to the study
- Hormonal implants at any time
This was an outpatient, multicenter trial.
The trial was a double-blind, randomized, placebo-controlled, multicenter, pilot study.
The trial's primary end point was frequency and severity of hot flashes at three months. Daily hot flash diaries were used to assess frequency and severity of hot flashes. The Landgren scale assessed intensity of hot flashes and sweats. Patients completed a questionnaire to assess interference of hot flashes and sweats with everyday life. Endometrial biopsies were taken at 6 and 12 months. Monthly diaries assessed the incidence of bleeding or spotting throughout the study. Serum lipid profiles were assessed.
Daily diaries showed no change in the daily number of hot flashes with either tibolone or placebo (p = 0.219) after three months. There was a significant reduction in the severity of hot flashes with tibolone verses placebo (-0.4 versus 0.2, p = 0.031). The Landgren scale showed a mean change in the number of hot flashes of –0.6 with tibolone and +1.1 with placebo after 12 months (p = 0.022). Endometrial biopsies were normal and vaginal bleeding similar in both groups. Significant decrease in triglycerides ( 23% versus 1.4%) and HDL (12% versus 19%) with tibolone versus placebo after 12 months were noted.
The study was limited by its small sample size with less than 100 participants.
The effect of tibolone on recurrence of breast cancer is unknown.
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.doi:10.1016/j.maturitas.2011.09.003
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.
Intervention Characteristics/Basic Study Process:
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 and Clinical Applications:
- 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:
- Number of hot flashes per day at 12 and 104 weeks of treatment (p’s < 0.0001)weeks
- Mean composite hot flash severity at week 12 (p < .0006)
- Mean vaginal dryness score at week 104 (p < 0.0001)
- WHQ scores in vasomotor, sexual and sleep at weeks 28, 52, 78, and 104 (p < .05)
- 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.