The Effectiveness of Tibolone Versus Intranasal Oestrogen Replacement Therapy on Serum Lipid Profile in Postmenopausal Women

Öz

Objective: To compare tibolone therapy with intranasal estrogen replacement therapy protocols on their effects on serum lipid profiles. Material Method: 84 post-menopausal women were included in the study. They were given either oral daily treatment with tibolone (2.5 mg) (Group I; n= 35); or intranasal administration of estrogen (Group II; n = 49 ). The duration of the treatment was 6 months. At the beginning and at the end of the therapy, lipid levels were measured in each of the group and then these two different groups were compared. Student-t test was used for statistical analysis. Results: No statistical difference was observed at baseline levels between two groups. Total cholosterol levels were increased significantly from baseline levels in both groups. However, at the end of the 6 months no statistical difference was found between two groups. LDL-cholesterol (LDL-C) levels were not changed from the baseline levels in both of the groups. In intranasal estrogen group, while HDL-C levels were decreased, it has increased in tibolone group. While triglycerides (TAG) levels were significantly decreased in intranasal 17β-E2 group, no significant change has been found in tibolone group. Lp(a) levels were not changed with therapy in both group. Conclusion: Short-term treatment with tibolone showed a good clinical-laboratory safety profile in postmenopausal women. Also it may be a good alternative to other HRT protocols in postmenopausal women. Key words: Tibolone, İntranasal estrogen, Lipids

Anahtar Kelimeler

• Tibolone, İntranasal estrogen, Lipids

Postmenopozal Kadınlarda Tibolon ve İntranasal Östradiol’ün Kan Lipid Parametreleri Üzerine Olan Etkileri

Öz

Amaç: Tibolon ve intranasal östrojen replasman tedavisi'nin serum lipid seviyeleri üzerine etkilerinin karşılaştırılması Gereç ve Yöntem: Çalışmaya toplam 84 postmenopozal kadın dahil edildi. Hastalara günlük tibolon (2,5 mg)(Grup I; n= 35) ve intranasal östrojen (Grup II; n= 49) verildi. Tedavi süresi 6 aydı. Tedavinin başlangıcı ve sonu lipid seviyeleri her grup için ölçüldü ve farklı iki grubun değerleri karşılaştırıldı. İstatistiksel analiz için Student-t testi kullanıldı. Sonuç: Her iki grup değişkenlerin basal seviyeleri arasında istatistiksel olarak anlamlı fark saptanmadı. Her iki grupta total kolesterol seviyeleri başlangıç seviyelerine göre belirgin artmıştı. Fakat 6 aylık tedavi sonrasında iki grup arasında istatistiksel fark saptanamadı. LDL kolesterol (LDL-C) seviyelerinde her iki grupta da tedavi öncesine göre değişim saptanamadı. HDL kolesterol (HDL-C) seviyeleri intranasal 17β-E2 grubunda belirgin olarak azalırken, tibolon grubunda belirgin olarak artmıştır. Trigliserid (TAG) seviyeleri intranasal 17β-E2 grubunda belirgin azalırken tibolon grubunda belirgin değişiklik saptanmadı. Her iki grup Lipoprotein (a) (Lp(a)) seviyeleri her iki tedavide de değişim saptanmadı. Tartışma: Postmenopozal kadınlarda, tibolon ile kısa süreli tedavinin iyi klinik-laboratuar güvenlilik profili gösterdiği saptandı.. Ayrıca postmenopozal kadınlarda diğer HRT protokollerine iyi bir alternatif olabilir. Anahtar kelimeler: Tibolon, İntranasal östrojen, Lipidler.

Anahtar Kelimeler

• Tibolon, İntranasal östrojen, Lipidler.

Kaynakça

1. Walsh BW, Schiff I, Rosner B, Greenberg L, Raunikar V, Sacks FM. Effects of postmenopausal estrogen replacement on the concentrations and metabolism of lipoproteins. New Engl J Med 1991;325:1196 –204.
2. Wild RA. Estrogens: effects on the cardiovascular tree. Obstet Gynecol 1996;87:27 – 35.
3. The writing group for the PEPI trial. Effects of estrogen or estrogenyprogestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal EstrogenyProgestin Interventions (PEPI) Trial. J Am Med Assoc 1995;273:199 –208.
4. Williams C. High level of high-density Lipoprotein cholesterol (HDL-C) does not attenuate increased risk of elevated triglycerides. Arch Intern Med 2001;161(19):2385.
5. Sposito AC, Mansur AP, Maranhao RC, Martinez TR, Aldrighi JM, Ramires JA. Triglyceride and Lipoprotein (a) are markers of coronary artery disease severity among postmenopausal women. Maturitas 2001;39(3):203 –8.
6. Sprecher DL. Triglycerides as a risk factor for coronary artery disease. Am J Cardiol 1998;82(12A):49U–56U (discussion 85U–86U).
7. Watts NB, Notelovitz M, Timmons MC, Addison A, Wiita B, Downey LJ. Comparisons of oral estrogens plus androgen on bone mineral density, menopausal
8. N. Mendoza , A.M. Sua´rez, F. A´ lamo, E. Bartual, F. Vergara, A. Herruzo. Lipid effects, effectiveness and acceptability of tibolone versus transdermic 17b-estradiol for hormonal replacement therapy in women with surgical menopause. Maturitas 37 (2000) 37–43

9. Gordon T, Castelli WP, Hjortland MC, Kannel WE, Dawber TR. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med. 1977; 62:707–14.
10. The Expert Panel. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). J Am Med Assoc. 2001; 285: 2486–97.
11. Robins SJ, Collins D, Wittes JT, Papademetriou V, Deedwania PC, Schaefer EJ, McNamara JR, Kashyap ML, Hershman JM, Wexler LF, Rubins EB. Relation of gemfibrozil treatment and lipid levels with major coronary events. VA-HIT: a randomized controlled trial. J Am Med Assoc. 2001;285:1585–91
12. Nabulsi AA, Folsom AR, White A, Patsch W, Heiss G, Wu KK, Szklo M: Association of hormone-replacement therapy with various cardiovascular risk factors in postmenopausal women: the Atherosclerosis Risk in Communities Study Investigators. N Engl J Med 1993; 328:1069–75,
13. Godsland IF, Gangar K, Walton C, Cust MP, Whitehead MI, Wynn V, Stevenson JC: Insulin resistance, secretion, and elimination in postmenopausal women receiving oral or transdermal hormone replacement therapy. Metabolism 1993; 42: 846–53,
14. Wild RA. Estrogens: effects on the cardiovascular tree. Obstet Gynecol 1996;87:27 – 35.
15. The writing group for the PEPI trial. Effects of estrogen or estrogenyprogestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogeny Progestin Interventions (PEPI) Trial. J Am Med Assoc 1995;273:199 –208
16. Lamon-Fava S, Postfai B, Diffenderfer M, DeLuca , O’Connor J J. Francine K. Welty, Gregory G. Dolnikowski, P. Hugh R. Barrett, Ernst J. Schaefer Role of the Estrogen and Progestin in Hormonal Replacement Therapy on Apolipoprotein A-I Kinetics in Postmenopausal Women. Arterioscler. Thromb. Vasc. Biol. 2006;26;385- 91
17. De Aloysio D, Fabiani AG, Mauloni M, Bottiglioni F. Use of Org OD14 for the treatment of climacteric complaints. Maturitas 1987;1:49 –65.
18. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA 2002;288(3):321–33. Jul 17.
19. Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/ progestin Replacement Study (HERS) Research Group.JAMA 1998; 280(7):605–13.
20. Lapidus L, Lindstedt G, Lundberg PA, Bengtsson C, Gredmark T. Concentrations of sex-hormone binding globulin and corticosteroid binding globulin in serum in relation to cardiovascular risk factors and to 12-year incidence of cardiovascular disease and overall mortality in postmenopausal women. Clin Chem 1986; 32(1):146– 52. Pt 1.
21. Milner MH, Sinnott MM, Cooke TM, Kelly A, McGill T, Harrison RF. A 2 years study of lipid and Lipoprotein changes in postmenopausal women with tibolone and estrogen and progestogen. Obstet Gynecol 1996;87:593–9.
22. Crona N, Silverstolpe G, Samsioe G. A double blind cross-over study on the effects of ORG OD 14 compared to oestradiol valerate and placebo on lipids and carbohydrate metabolism in oophorectomised women. Acta Endocrinol (Copenh) 1983;102:451–5.
23. Farish E, Barnes JF, Rolton HA, Spowart K, Fletcher CD, Hart DM. Effect of tibolone on lipoprotein (a) and HDL subfractions. Maturitas 1995;20: 215–9.
24. Hanggi W, Lippuner K, Riesen W, Jaeger P, Birkhauser MH. Long term influence of different postmenopasual hormone replacement regimens on serum lipids and lipoprotein (a): a randomised study. Br J Obstet Gynaecol 1997;104:708–17.
25. Cagnacci A, Mallus E, Tuveri F, Cirillo R, Setteneri AM, Melis GB. The effect of tibolone on glucose and lipid metabolism in postmenopausal women. J Clin Endocrinol Metab 1997;82:251–3.
26. Rosati D, Pinto S, Fedi S, et al. Changes in lipid and haemodinamic parameters induced by tibolone treatment. Thrombosis Res 1997;85:273–8.
27. Kloosterboer HJ, Benedek-Jazmann LJ, Kicovic PM. Long term effects of Org OD 14 on lipids metabolism in postmenopausal women. Maturitas 1990;12:37–42.
28. Campos H, Roeder GO, Lussier Cacan S, Davignon J, Krauss RM. Predominance of large LDL and reduced HDL 2 cholesterol in normolipidemic men with coronary artery disease. Arterioscler Thromb Vasc Biol 1995;15:1043–8.
29. Stampfer MJ, Sacks FM, Simonetta S, Willett WC, Hennkens CH. A prospective study of cholesterol, apolipoproteins and the risk of myocardial infarction. New Engl J Med 1991;325:373–81.
30. Lobo RA, Speroff L. International consensus conference on postmenopausal hormone therapy and the cardiovascular system. Fertil Steril 1994;61:592–5
31. E. C. Baracat, I. C. Barbosa, M. G. Giordano, M. A. Haidar, R. M. Marinho, J. C. Menegocci, K. M. Morais, G. Tomaz and S. Wehba et al. A randomized, open-label study of conjugated equine estrogens plus medroxyprogesterone acetate versus tibolone: effects on symptom control, bleeding pattern, lipid profile and tolerability. Clımacterıc 2002;5:60–9
32. R. Rontu, T Solakivi, K Teisala, T Lehtima, R Punnonen, H Jokela.Impact of Long- term Hormone Replacement Therapy on In vivo and In vitro Markers of Lipid Oxidation. Free Radical Research, Volume 38 Number 2 (February 2004), pp. 129–37
33. A. Bayrak, D A Aldemir, T Bayrak, A Corakcı, P Dursun. The effect of hormone replacement therapy on the levels of serum lipids, apolipoprotein AI, apolipoprotein B and lipoprotein (a) in Turkish postmenopausal women. Arch Gynecol Obstet (2006) 274:289–96