Tibolone and Endometrial Cancer
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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.
- 2.Office for National Statistics. Cancer registration statistics. England, 1992-2001 [online]. Available from URL: http://www.statistics.gov.uk/statbase/Product.asp?vlnk=8843 [Accessed 2004 Sep 30]Google Scholar
- 3.Parsons AK, Londono JL. Detection and surveillance of endometrial hyperplasia and carcinoma. In: Lobo RA, editor. Treatment of the postmenopausal woman: basic and clinical aspects. 2nd ed. Philadelphia (PA): Lippincott Williams & Wilkins, 1999Google Scholar
- 4.Herbst AL. Neoplastic diseases of the uterus. In: Mishell DR, Stenchever MA, Droegemueller W, et al., editors. Comprehensive gynecology. 3rd ed. St Louis (MO): Mosby-Year Book Inc., 1997Google Scholar
- 5.Collins JA, Schlesselman JJ. Hormone replacement therapy and endometrial cancer. In: Lobo RA, editor. Treatment of the postmenopausal woman: basic and clinical aspects. 2nd ed. Philadelphia (PA): Lippincott Williams & Wilkins, 1999Google Scholar
- 7.The Writing Group for the PEPI Trial. Effects of hormone replacement therapy on endometrial histology in postmenopausal women: the postmenopausal estrogen/progestin interventions (PEPI) trial. JAMA 1996; 275: 370–5Google Scholar
- 14.García Rodriguez LA, Perez-Gutthann S, Jick S. The UK General Practice Research Database. In: Strom BL, editor. Pharmacoepidemiology. 3rd ed. Chichester: John Wiley & Sons Ltd, 2000Google Scholar
- 17.StataCorp. Stata Statistical Software: Release 8.0. College Station (TX): StataCorp LP, 2001Google Scholar
- 22.De Vries CS, Bromley SE, Williams TJ, et al. Risk factors associated with endometrial cancer [abstract]. Pharmacoepidemiol Drug Saf 2001; 10: S84Google Scholar
- 23.Burger CW, Van Unnik GA, Kenemans P. Hormone replacement therapy and endometrial cancer. In: Genazzani AR, editor. Hormone replacement therapy and cancer: the current status of research and practice. London: The Parthenon Publishing Group, 2002Google Scholar