Skip Navigation

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Disclaimer
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Palacios, S.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Palacios, S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?


Tibolone: a tissue-specific approach to the menopause

S. Palacios*

Palacios Institute of Women's Health, Madrid, Spain

* Correspondence: Dr S. Palacios, Palacios Institute of Women's Health, Jorge Juan 36, 28001 Madrid, Spain.

Abstract

Tibolone, a synthetic steroid that is used for hormone replacement in menopausal women, is metabolized to three primary active agents: 3-alpha-hydroxy-tibolone; 3-betahydroxy-tibolone; and -tibolone. It can exhibit oestrogenic, progestogenic or androgenic activity, depending primarily on the target tissue involved; for this reason, tibolone is said to have tissue-specific activity. Oestrogenic effects on vasomotor symptoms, the vagina and bone mean that tibolone is effective in the management of climacteric symptoms and bone loss. However, it does not cause oestrogenic stimulation of the endometrium or breast tissue, thus reducing the risk for side effects such as bleeding and breast tenderness.

Key Words: Hormone replacement therapy • menopause • tibolone • tissue-specific activity

References

  1. Markiewicz L, Gurpide E. In vitro evaluation of estrogenic, estrogen antagonistic and progestagenic effects of a steroidal drug (Org OD-14) and its metabolites on human endometrium. J Steroid Biochem Mol Biol. 1990;35:535–541
  2. Ederveen AG, Kloosterboer HJ. Tibolone, a steroid with a tissue-specific hormonal profile, completely prevents ovariectomy-induced bone loss in sexually mature rats. J Bone Miner Res. 1999;14:1963–1970[CrossRef][Medline]
  3. Ederveen AG, Kloosterboer HJ. Tibolone exerts its protective effect on trabecular bone loss through the estrogen receptor. J Bone Miner Res. 2001;: (in press)
  4. Pavlov PW, Ginsburg T, Kicovic PM, et al. Double-blind, placebo-controlled study of the effects of tibolone on bone mineral density in postmenopausal osteoporotic women with and without previous fractures. Gynecol Endocrinol. 1999;13:230–237[Web of Science][Medline]
  5. Berning B, Kuijk CV, Kuiper JW, et al. Effects of two doses of tibolone on trabecular and cortical bone loss in early postmenopausal women: a two-year randomized placebo-controlled study. Bone. 1996;19:395–399[Medline]
  6. Bjarnason NH, Bjarnason K, Haarbo J, et al. Tibolone: prevention of bone loss in late postmenopausal women. J Clin Endocrinol Metab. 1996;81:2419–2422[Abstract]
  7. Lippuner K, Haenggi W, Birkhaüser MH, et al. Prevention of postmenopausal bone loss using tibolone or conventional peroral or transdemal hormone replacement therapy with 17ß-estradiol and dydrogesterone. J Bone Miner Res. 1997;12:806–812[CrossRef][Medline]
  8. Prelevic GM, Bartram C, Wood J, et al. Comparative effects on bone mineral density of tibolone, transdermal estrogen and oral estrogen/progestogen therapy in postmenopausal women. Gynecol Endocrinol. 1996;10:413–420[Medline]
  9. Milner M, Harrison RE, Gilligan E, Kelly A. Bone density changes during two years treatment with tibolone or conjugated estrogens and norgestrel, compared with untreated controls in postmenopausal women. Menopause. 2000;7:327–333[Medline]
  10. Rymer J, Robinson J, Fogelman I. Effects of 8 years' treatment with tibolone 2.5 mg daily on postmenopausal bone loss. Osteoporosis Int. 2001;12:478–483[Medline]
  11. Ross LA, Alder EM. Tibolone and climacteric symptoms. Maturitas. 1995;21:127–136[Medline]
  12. Egarter C, Huber J, Leikermoser R, et al. Tibolone versus conjugated estrogens and sequential progestogen in the treatment of climacteric complaints. Maturitas. 1996;23:55–62[CrossRef][Web of Science][Medline]
  13. Volpe A, Facchinetti F, Grasso A, et al. Benefits and risks of different hormonal replacement therapies in postmenopausal women. Maturitas. 1986;8:327–334[Medline]
  14. Hammar M, Christgau S, Nathorst-Boos J, et al. A double-blind, randomized trial comparing the effects of tibolone and continuous combined hormone replacement therapy in post menopausal women with menopausal symptoms. Br J Obstet Gynaecol. 1998;105:904–911[Web of Science][Medline]
  15. Morris EP, Wilson POG, Robinson J, Rymer JM. Long-term effects of tibolone on the genital tract in postmenopausal women. Br J Obstet Gynaecol. 1999;106:954–959[Web of Science][Medline]
  16. Genazzani AR, Facchinetti F, Ricci-Danero M, et al. ß-lipo-protein and ß-endorphin in physiological and surgical menopause. J Endocrinol Invest. 1981;4:375–378[Medline]
  17. Taskin O, Gokdeniz R, Yalcinoglu A, et al. Placebo controlled cross-over study of the effects of tibolone on premenstrual symptoms and peripheral beta-endorphin concentrations in premenstrual syndrome. Hum Reprod. 1998;13:2402–2405[Abstract/Free Full Text]
  18. Palacios S, Menéndez C, Jurado AR, et al. Changes in sex behaviour after menopause: effects of tibolone. Maturitas. 1995;22:155–161[Medline]
  19. Nathorst-Boos J, Hammar M. Effect on sexual life: a comparison between tibolone and a continuous estradiol-norethisterone acetate regimen. Maturitas. 1997;26:15–20[CrossRef][Web of Science][Medline]
  20. Albertazzi P, Natale V, Barbolini C, et al. The effect of tibolone versus continuous combined norethisterone acetate and oestradiol on memory, libido and mood of postmenopausal women: a pilot study. Maturitas. 2000;36:223–229[Medline]
  21. Tang B, Markiewicz L, Kloosterboer HJ, Gurpide E. Human endometrial 3ß-hydroxystereroid dehydrogenase/isomerase can locally reduce intrinsic estrogenic/progestagenic activity ratios of a steroidal drug (Org OD 14). J Steroid Biochem Mol Biol. 1993;45:345–351[CrossRef][Web of Science][Medline]
  22. Meuwissen JH, Wiegerinck MA, Haverkorn MJ. Regression of endometrial thickness in combination with reduced withdrawal bleeding as a progestational effect of tibolone in post menopausal women on oestrogen replacement therapy. Maturitas. 1995;21:121–125[Medline]
  23. Ginsburg J, Prelevic GM. Cause of vaginal bleeding in postmenopausal women taking tibolone. Maturitas. 1996;24:107–110[Medline]
  24. Genazzani AR, Benedek-Jaszmann LJ, Hart DM, et al. Org OD14 and the endometrium. Maturitas. 1991;13:243–251[CrossRef][Medline]
  25. Bergeron C. Microscopic evaluation of the effect of hormone replacement therapy on the endometrium in women who bled. Gynecol Endocrinol. 1997;11(suppl 2):11–16[Web of Science][Medline]
  26. Colditz G, Hankinson SE, Hunter DJ, et al. The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N Engl J Med. 1995;332:1589–1593[Abstract/Free Full Text]
  27. Gompel A, Kandouz M, Siromachkova M, et al. The effect of tibolone on proliferation, differentation and apoptosis in normal breast cells. Gynecol Endocrinol. 1997;11(suppl 1):77–79
  28. Gompel A, Siromachkova M, Lombet A, et al. Tibolone actions on normal and breast cancer cells. Eur J Cancer. 2000;36(suppl 4):S76–S77
  29. Kloosterboer HJ, Schoonen WG, Deckers GH, Klijn JG. Effects of progestagens and Org OD14 in in vitro and in vivo tumor models. J Steroid Biochem Mol Biol. 1994;49:311–318[CrossRef][Medline]
  30. Kloosterboer HJ, Deckers GIL. Effects of tibolone (Livial®) and its metabolites on the growth of DMBA induced tumors in rats. [abstract]Acta Obstet Gynaecol Scand. 1997;76(suppl 167:5):59
  31. Pasqualini JR, Kloosterboer HJ. Estrone sulfatase and 17ß-hydroxysteroid dehydrogenase activities in human breast cancer. Inhibitory effect by tibolone and its metabolites. Acta Obstet Gynaecol Scand. 1997;76(suppl 167:3):35
  32. Pasqualini JR, Paris J, Sitruk-Ware R, et al. Progestins and breast cancer. J Steroid Biochem Mol Biol. 1998;65:225–235[CrossRef][Web of Science][Medline]
  33. Pasqualini JR, Chetrite GS. Estrone sulfatase versus estrone sulfotransferase in human breast cancer: potential clinical implications. J Steroid Biochem Mol Biol. 1999;69:287–292[CrossRef][Medline]
  34. Chetrite G, Kloosterboer HJ, Pasqualini JR. Effect of tibolone (Org OD14) and its metabolites on estrone sulfatase activity in MCF-7 and T-47D mammary cancer cells. Anticancer Res. 1997;17:135–140[Web of Science][Medline]
  35. Mol-Arts M, Engelen S, Stathopoulos V. Endometrial safety summary of Livial. Climacteric. 1999;2(suppl 1):319
  36. Ginsburg J, Prelevic G, Butler D, Okolo S. Clinical experience with tibolone (Livial®) over 8 years. Maturitas. 1995;21:71–76[Medline]
  37. Erel CT, Elter K, Akman C, et al. Mammographic changes in women receiving tibolone therapy. Fertil Steril. 1998;69:870–875[CrossRef][Medline]
  38. Valdivia I, Ortega D. Mammographic density in postmenopausal women treated with tibolone, estriol or conventional hormone replacement therapy. Clin Drug Invest. 2000;20:101–107[CrossRef]
  39. Haenggi W, Lippuner K, Riesen W, et al. Long-term influence of different postmenopausal hormone replacement regimens on serum lipids and lipoprotein(a): a randomised study. Br J Obstet Gynaecol. 1997;104:708–717[Web of Science][Medline]
  40. Bjamason NH, Bjamason K, Haarbo J, et al. Tibolone: influence on markers of cardiovascular disease. J Clin Endocrinol Metab. 1997;82:1752–1756[Abstract/Free Full Text]
  41. Castelo-Branco C, Casals E, Figueras E, et al. Two-year prospective and comparative study on the effects of tibolone on lipid pattern, behaviour of apolipoproteins AI and B. Menopause. 1999;6:92–97[Medline]
  42. Lloyd GWL, McGing E, Cooper A, et al. A randomised controlled trial of the effects of tibolone on blood pressure and lipids in hypertensive women. J Hum Hypertens. 2000;14:99–104[CrossRef][Medline]
  43. Lip G, Beevers M, Churchill D, Beevers DG. Hormone replacement therapy and blood pressure in hypertensive women. J Hum Hypertens. 1994;8:491–494[Web of Science][Medline]
  44. Lloyd GWL, Patel NR, McGing EA, et al. Acute effects of hormone replacement therapy with tibolone on myocardial ischaemia in women with angina. Int J Clin Pract. 1998;52:155–157[Medline]
  45. Prelevic GM, Beljic T, Ginsburg J. The effect of tibolone on cardiac flow in postmenopausal women with non-insulin dependent diabetes mellitus. Maturitas. 1997;27:85–90[Medline]
  46. Hardiman P, Nihoyannopoulos P, Kicovic P, et al. Cardiovascular effects of Org OD14: a new steroidal therapy for climacteric symptoms. Maturitas. 1991;13:235–242[CrossRef][Medline]
  47. Haenggi W, Linder HR, Birkhäuser MIL, Schneider H. Microscopic findings of the nail-fold capillaries: dependence on menopausal status and hormone replacement therapy. Maturitas. 1998;22:37–46
  48. Walker ID, Davidson JF, Richards A, et al. The effect of the synthetic steroid Org OD 14 on flbrinolysis and blood lipids in postmenopausal women. Thromb Haemost. 1985;53:303–305[Web of Science][Medline]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?



This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Disclaimer
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Palacios, S.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Palacios, S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?