Drug Safety

, Volume 28, Issue 3, pp 241–249 | Cite as

Tibolone and Endometrial Cancer

A Cohort and Nested Case-Control Study in the UK
  • Corinne S. de Vries
  • Susan E. Bromley
  • Hilary Thomas
  • Richard D.T. Farmer
Original Research Article


Objective: Case series and spontaneous reports of endometrial cancer have raised the question as to whether the use of tibolone (introduced into the UK in 1991) is associated with an increased risk of endometrial cancer. This study set out to evaluate whether tibolone use is associated with an increased risk of endometrial cancer.

Methods: Age-adjusted incidence rate ratios (IRRs) of endometrial cancer were calculated for tibolone use compared with the use of other hormone replacement therapy (HRT). Separate sets of controls, matched for age and general practice, were compared with cases, all nested within a cohort of HRT users identified from the UK General Practice Research Database (GPRD). Conditional logistic regression analysis, adjusted for potential confounders, was used to study the association between tibolone use and the risk of endometrial cancer.

Results: 4995 women used tibolone as their first HRT product; 10 783 (4.3%) of the users of combined HRT had changed to tibolone at some time during the study period. Amongst women whose HRT began with tibolone, the age-adjusted IRR relative to those who started with combined sequential HRT was 1.83 (95% CI 1.19, 2.82). The nested case-control study comprised 162 cases, each matched to two sets of 972 controls. There were 43 tibolone-exposed subjects, 28 of whom had used other HRT before or after tibolone. The adjusted odds ratio of the risk of endometrial cancer in women who had ever used tibolone, compared with users of combined sequential HRT, was 1.54 (95% CI 1.03, 2.32) in the age-matched set and 1.58 (95% CI 1.01, 2.47) in the practice-matched set. Sensitivity analyses did not decrease the risk estimates found.

Discussion: Tibolone may be associated with an increased risk of endometrial cancer compared with conventional forms of HRT, but our data are fragile. Residual bias and uncontrolled confounding cannot be excluded, and follow-up time is insufficient to draw any firm conclusions with respect to the endometrial safety of tibolone.



We are indebted to the members of the independent scientific advisory board for overseeing this study. They advised on methodological issues, provided essential background information, advised on interpretation of the results and commented on a draft of this manuscript. Dr Tim Williams extracted controls for the study from the GPRD and carried out part of the mapping of HRT products in an attempt to establish duration of use. The study was funded through an unconditional research grant from Organon NV, The Netherlands.

The study was overseen by an independent scientific advisory board comprising experts in gynaecological oncology, pathology, (pharmaco)epidemiology and statistics and the study was carried out in accordance with their recommendations. The funding organisation was not present at the meetings of the scientific advisory board and had no say in the way in which the study was carried out. The research contract was unconditional and the authors have the right to publish without consulting the funding organisation.


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Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Corinne S. de Vries
    • 1
  • Susan E. Bromley
    • 1
  • Hilary Thomas
    • 2
  • Richard D.T. Farmer
    • 1
  1. 1.Department of Pharmacoepidemiology, Postgraduate Medical SchoolUniversity of SurreyGuildfordUK
  2. 2.Department of Oncology, Postgraduate Medical SchoolUniversity of SurreyGuildfordUK

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