Review: Tibolone is as effective as estrogens for postmenopausal symptoms and bone mineral density
ACP J Club. 1999 Sept-Oct;131:44. doi:10.7326/ACPJC-1999-131-2-044
Moore RA. Livial: a review of clinical studies. Br J Obstet Gynaecol. 1999 Mar 19;106(Suppl):1-21.
What is the effect of tibolone (Livial, Organon, Oss, the Netherlands) compared with that of estrogens or placebo on postmenopausal symptoms, bone mineral density, breast cancer, endometrial and vaginal atrophy and bleeding, vaginal dryness, lipid metabolism, and risk factors for coronary heart disease?
Studies were identified by using MEDLINE (to 1997) with the terms Livial, tibolone, and Org OD 14. Personal and company files were also checked.
Clinical trials were selected if they studied postmenopausal women and provided data on symptoms and long-term outcomes.
Data were extracted on population statistics, natural or surgical menopause, study design, drug dose and duration, climacteric symptoms, libido and sexual enjoyment, bone mineral density, endometrial status, vaginal bleeding, carbohydrate and lipid levels, clotting information, and cardiovascular risk factors.
Meta-analysis was not done. 9 randomized controlled trials and 2 clinical trials measured symptoms. In these 11 studies of comparisons with placebo or baseline, 1 study showed an improvement in combined symptom scores with tibolone, 10 of 10 showed an improvement in flushes, 7 of 7 showed an improvement in sweating, 2 of 4 showed an improvement in palpitations, 3 of 5 showed an improvement in irritability, 1 of 3 showed an improvement in tiredness, 3 of 5 showed an improvement in headache, and 2 of 5 showed improvements in insomnia and dizziness. Effects with tibolone were similar to those with estrogen. 7 studies assessed libido and sexual enjoyment; 4 of the 7 showed improvements with tibolone compared with placebo. Effects were similar to those with estrogen. 12 studies assessed bone mineral density or bone biochemistry. All showed improvements that were similar to those seen with estrogen. No clinical data were available to assess the risk for breast cancer or cardiovascular outcomes. 6 studies evaluated the endometrium and found no changes with tibolone; vaginal bleeding was rare and tended to occur early in treatment. 16 studies assessed carbohydrate and lipid levels and clotting outcomes; compared with baseline, improvements with tibolone similar to those with estrogens were shown in most studies. In 7 studies that evaluated vaginal effects (cell maturation, dryness, and pain on intercourse), tibolone was shown to be similar to estrogens.
Tibolone is as effective as estrogen at improving climacteric symptoms, libido, sexual enjoyment, lipid levels, and vaginal effects and at increasing bone mineral density. Data on cardiovascular outcomes and breast cancer are not available.
Source of funding: Not stated.
For correspondence: Dr. R.A. Moore, Pain Research and Nuffield Department of Anaesthetics, University of Oxford, The Churchill, Oxford OX3 7LJ, England, UK. FAX 44-1865-226978.
Hormone replacement therapy has many advantages, but because it is associated with risk for breast cancer, more tissue-selective therapies are being developed. Tibolone, a steroid hormone, has estrogenic effects on climacteric symptoms and bone but not on the breast or endometrium. Its unique action makes it a potential therapy for women concerned about breast cancer who would otherwise benefit from estrogen (1) and women with a history of endometriosis (2).
Moore's comprehensive review outlines the effects of tibolone on climacteric symptoms, bone density, lipid levels, the endometrium, and breast cancer. A clearer presentation of inclusion and exclusion criteria, along with provision of summary effect sizes when feasible (e.g., bone density outcomes), would have been useful. In addition, the results could have been organized according to levels of evidence.
An economic analysis purporting to show the cost-effectiveness of tibolone in alleviating menopausal symptoms is published with this review (3). However, the methods used in the economic study are not clear, making it difficult to meaningfully interpret the results.
This review shows that tibolone may reduce postmenopausal symptoms and low-density lipoprotein cholesterol levels and increase bone density. The effect of tibolone is similar to that of hormone replacement therapy. Therefore, tibolone can be useful for postmenopausal women and may be particularly helpful for women who are at increased risk for breast cancer. However, as noted by Moore, trials with adequate power that evaluate long-term outcomes are required.
Ann Cranney, MD, MSc
Doug Coyle, MScOttawa HospitalLoeb Research UnitOttawa, Ontario, Canada
1. Chetrite GS, Kloosterboer HJ, Philippe JC Parqualini JR. Effect of Org OD14 (LIVIAL) and its metabolites on human estrogen sulphotransferase activity in the hormone-department MCF-7 and T-47D, and the hormone-independent MDA-MB-231, breast cancer cell lines. Anticancer Res. 1999;19:269-75.