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.

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.

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

• Inclusion criteria:
  • 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
• Exclusion criteria:
  • 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.