Postmenopozal Kadınlarda Hormon Tedavisi, Raloksifen ve Tibolonun Osteoporoz ile Meme ve Endometrium Üzerindeki Etkilerinin İncelenmesi

Yıl 2012, Cilt: 4 Sayı: 2, 6 - 14, 01.08.2012

Devran Sencar İ

Öz

Amaç: Postmenopozal osteoporozlu kadınlarda üç farklı ilacın osteoporoz üzerindeki etkinliği ile tedavi sürecinde meme ve endometriyumdaki değişimlerin incelenmesi amaçlanmıştır. Yöntem: Çalışmamıza Dicle Üniversitesi Tıp Fakültesi Aile Hekimliği Polikliniğine 01 Ocak 2006-31 Aralık 2007 tarihleri arasında başvuran postmenopozal dönemde osteoporoz veya osteopenisi bulunan 72 kadından takip sürecini tamamlayan 31 hasta retrospektif kohort olarak incelendi. Çalışmada, açık ve kapalı uçlu sorular ile hazırlanmış anket yüzyüze görüşme tekniği ile uygulandı. Hastaların tedavi modaliteleri Kadın Doğum ve Fizik Tedavi uzman konsültasyonları ile yürütülmüştür. İlk taramadan 12 ay sonra olgular yeniden değerlendirilerek, hastalarda kemik mineral yoğunlukları (KMY) ile endometriyum ve meme dokusundaki değişiklikler incelendi. Bulgular: 31 hastanın beşi (%16) hormon replasman tedavisi (HT), dokuzu (%29) raloksifen (RLX), 17’si (%55) Tibolon (TIB) aldı. Hastaların yaş ortalamaları, 54.7±8.1; ortalama menopoz yaşları 44.2±6.0 yıldır. Tedavi öncesi 31 hastanın 17’si (%55) osteopenik, 14’ü (%45) osteoporotikti. Tedavi sonrası ise altı (%19) hastanın DEXA sonuçları normal sınırlar içine geriledi. Tedavi öncesi ve sonrası L2-4 T skorları karşılaştırıldığında, her üç tedavinin de istatistiksel olarak anlamlı düzeyde etkin iyileşme gösterdiği saptanmıştır (p=0.001). Tedavi öncesi ve sonrasında çalışmamızda endometrium kalınlığı (EK) ve meme dokusunda anlamlı bir farklılık saptanmamıştır (p>0.05). Sonuç: Her üç osteoporoz tedavisi KMY’de istatistiksel olarak anlamlı iyileşme göstermiştir. Her üç ilaç tedavisinin de endometrium ve meme dokusunda anlamlı bir değişiklik oluşturmadığı saptanmıştır. Ancak çalışmamızın sonuçlarının bir yıllık bir periyodu kapsaması nedeniyle, uzun süreli izlem çalışmalarına gereksinim olduğu düşünülmektedir

Anahtar Kelimeler

Menopoz, osteoporoz, meme, endometriyum

Kaynakça

• Speroff L. Menopause and Postmenapausal Hormone therapy. In: Glass RH, Kasa NG, Speroff L (Eds). Clinical Gynecologic Endocrinology and Infertility. 5th ed. Baltimore; Williams and Wilkins, 1996:583- 649.
• Hassa H, Ünlü C, Yakın K, ve ark. Hormon replasman tedavisi, İçinde: Ertüngealp E, Seyisoğlu H. (ed) Menopoz ve osteoporoz. İstanbul; Menopoz ve Osteoporoz Derneği, 2000:142-300.
• Osteoporosis Prevention, Diagnosis, and Therapy. NIH Consens Statement 2000;17(1):1-36.
• Kara IH, Aydın S, Gemalmaz A, et al. Habitual Tea Drinking and Bone Mineral Density in Postmenopausal Turkish Women: Investigation of Prevalence of Postmenopausal Osteoporosis in Turkey (IPPOT Study). Int J Vitam Nutr Res 2007;77(6):389-397.
• Kanis JA. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int 1994;4(6):368-81.
• Pitkin J, Smetnik VP, Vadász P, Mustonen M, Salminen K, Ylikangas S; Indivina 321 Study Group. Continuous combined hormone replacement therapy relieves climacteric symptoms and improves health- related quality of life in early postmenopausal women. Menopause Int. 2007 Sep;13(3):116-23.
• Rubinacci A, Peruzzi E, Modena AB, et al. Effect of low-dose transdermal E2/NETA on the reduction of postmenopausal bone loss in women. Menopause 2003;10(3):241-9.
• Seidman H, Mushinski M, Gelb S, Silverberg E. Probabilities of eventually developing or dying of cancer– United States. CA Cancer J Clin 1985;35(1):36-56.
• Beral V; Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the million women study. Lancet. 2003;362(9382):419-427.
• Warner E, Plewes DB, Shumak RS, et al. Comparison of breast magnetic resonance imaging, mammography, and ultrasonography for surveillance of women at high risk for hereditary breast cancer. J Clin Oncol,2001; 19(15):3524-3531.
• Houssamı N, Ciatto S, Irwig L, Simpson JM, Macaskill P. The comparative sensitivity of mammography and ultrasound in women with breast symptoms: an age-specific analysis. The Breast, 2002;11(2):125-130.
• Ohta T, Okamoto K, Kanemaki Y, et al. Use of ultrasonography as an alternative modality for first-line examination in detecting breast cancer in selected patients. Clin Breast Cancer 2007;7(8):624-6.
• Ziel HK, Finkle WD. Increased risk of endometrial carcinoma among users of conjugadet esrogens. N Engl J Med 1975;293(23):1167-70.
• Grady D, Gebretsadik T, Kerlikowski K, et al. Hormone replacement therapy and Endometrial cancer risk, A Meta-analysis. Obstet Gynecol 1995;85(2):304-13.
• Finkle WD, Greerland S, Miettinen OS, Ziel HK. Endometrial cancer risk after discontinuing use of unopposed conjugated estrogens. Cancer Causes Control 1995;6(2):99-102.
• Delmas PD, Bjarnason NH, Mitlak BH, et al. The effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 1997;337(23):1641-1647.
• Azevedo GD, Prado MF, Ferriani RA, et al. Raloxifene therapy does not affect uterine blood flow in postmenopausal women: a transvajinal Doppler study. Maturitas 2004;47(3):195-200.
• Archer DF, Hendrix S, Gallagher JC, et al. Helmond for the Tibolone Histology of the Endometrium and Breast Endpoints (THEBES) Study Group. Endometrial Effects of Tibolone. J Clin Endocrinol Metabol 2007;92(3):911-918.
• Margaret ME, Chester HF, Stephen BE, Cathleen AC, Martin CM. BI-RADS Classification for Management of Abnormal Mammograms. J Am Board Fam Med 2006;19(2):161- 4.
• World Health Organization. Guidelines for Preclinical Evaluation and Clinical Trials in Osteoporosis. Geneva: World Health Organization; 1998.p.1-68.
• World Health Organization. Obesity: preventing and managing the global epidemic: report of a WHO Consultation on Obesity, Geneva, 3-5 June 1997. Geneva: World Health Organization; 1998. p. 9 (document WHO/NUT/NCD/98.1).
• Writing Group for the Women’s Health Initiative Investigators. Risk and benefits of estrogen plus progestin in healthy postmenopausal women: principle results from the Women’s Health Initiative randomized controlled trial. JAMA 2002;288(3):321-333.
• Arrenbrecht S, Boermans AJ. Effects of transdermal östradiol delivered by a matrix patch on bone density in hysterectomized, postmenopausal women: a 2-year placebo-controlled trial. Osteoporosis Int 2002;13(2):176-83.
• Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. JAMA 1999;282(7):637-45.
• Zheng S, Wu Y, Zhang Z, et al. Effects of raloxifene on bone mineral density, bone metabolism and serum lipids in postmenopausal women: a randomized clinical trial in Bejing. Chin Med J 2003;116(8):1127-33.
• Lufkin EG, Whitaker MD, Nickelsen T. Treatment of established postmenopausal osteoporosis with raloxifene: a randomized trial. J Bone Miner Res 1998;13(11):1747-54.
• Johnston CC Jr, Bjarnason NH, Cohen FJ, et al. Long-term effects of raloxifene on bone mineral density, bone turnover, and serum lipid levels in early postmenopausal women: three-year data from 2 doubleblind, randomized, placebo-controlled trials. Arch Intern Med 2000;160(22):3444-50.
• Liu JL, Zhu HM, Huang QR, et al. Effect of raloxifene hydrochloride on bone mineral density, bone metabolism and serum lipids in Chinese postmenopausal women with osteoporosis. Zhonghua Yi Xue Za Zhi. 2004;84(4):269-73.
• Prestwood KM, Gunnes M, Muchmore DB, Lu Y, Wong M, Raisz LG. A comparison of raloxifene and estrogen on bone in postmenopausal women. J Clin Endocrinol Metab 2000;85(6):2197-2202.
• Meunier PJ, Vignot E, Garnero P, et al. Treatment of postmenopausal women with osteoporosis or low bone density with raloxifene. Osteoporosis Int 1999;10(4):330-336.
• Ederveen AGH, Spanjers CPM, Quaıjtaal JHM, Kloosterboer HJ. Effect of 16 Months of Treatment with TIBolone on Bone Mass, Turnover, and Biomechanical Quality in Mature Ovariectomized Rats. J Bone Mineral Res 2001;16(9):1674-81.
• Gallagher JC, Baylink DJ, Freeman R, Mcclung M. Prevention of Bone Loss with TIBolone in Postmenopausal Women: Results of Two Randomized, Double-Blind, Placebo Controlled, Dose-Finding Studies. J Clin Endocrinol & Metabol 2001;86(10):4717-4726.
• Rymer J, Robinson J, Fogelman GI. Ten years of treatment with tibolone 2,5 mg daily: effects on bone loss in postmenopausal women. Climacteric 2002;5(4):390-398.
• Dören M., Nilsson J, Johnell O. Effects of specific post-menopausal hormone therapies on bone mineral density in post-menopausal women: a metaanalysis. Human Reproduct 2003;18(8):1737-1746.
• Boyd NF, Martin LJ, Stone J, Greenberg C, Minkin S, Yaffe MJ. Mammographic densities as a marker of human breast cancer risk and their use in chemoprevention. Curr Oncol Rep 2001;3(4):314-321.
• Byrne C, Schairer C, Brinton LA, et al. Effects of mammographic density and benign breast disease on breast cancer risk. Cancer Causes Control 2001;12(2):103-110.
• Jackson VP, San Martin JA, Secrest RJ, et al. Comparison of the effect of raloxifene and continuous combined hormone therapy on mammographic breast density and breast tenderness in postmenopausal women. Am J Obstet Gynecol 2003;188(2):389-94.
• Cirpan T, Akercan F, Itil IM, Gundem G, Bilgen I, Yucebilgin MS. Does raloxifene therapy affect mammographic breast cancer screening in postmenopausal patients? Eur J Gynaecol Oncol 2006;27(2):177- 178.
• Lundström E, Christow A, Kersemaekers W, et al. Effects of Tibolone and continuous combined hormone replacement therapy on mammographic breast density. Am J Obstet Gynecol 2002;186(4):717-722.
• Pantidou A, Kaplanis K, Chrissogonidis I, Destouni C. Mammographic changes during postmenopausal hormonal replacement therapy with TIBolone. Eur J Gynaecol Oncol 2004;25(4):493-494.
• Kutlu T, Fiçicioğlu C, Başaran T, et al. Mammographic breast density changes after 1 year of Tibolone use. Maturitas 2004;48(2):133-6.
• Lundström E, Wilczek B, von Palffy Z, et al. Mammografhic breast density during hormone replacement therapy. Am J Obstet Gynecol 1999;181(2):348-52.
• Rutter CM, Mandelson MT, Laya MB, et al. Changes in breast density associated with initiation, discontinuation and continuing use of hormone replacement therapy. JAMA 2001;285(2):171-6.
• Jackson VP, San Martin JA, Secrest RJ, et al. Comparison of the effect of raloxifene and continuous combined hormone therapy on mammographic breast density and breast tenderness in postmenopausal women. Am J Obstet Gynecol 2003;188(2):389-94.
• Freedman M, San Martin J, O'Gorman J, et al. Digitized mammography. A clinical trial of postmenopausal women randomly assigned to receive raloxifene, estrogen or placebo. J Natl Cancer Inst 2001;93(1):51-56.
• Bush TL, Whiteman M, Flaws JA. Hormone Replacement Therapy and breast cancer: a gualitative review. Obstet Gynecol 2001;98(3):498-508.
• Marchesoni D, Driul L, Ianni A, et al. Postmenopausal hormone Therapy and mammographic breast density. Maturitas 2006;53(1):59-64.
• Boutet G, Boisserie-Lacroix M, Trillaud H. Menopausal hormonal therapies: impact on mammographic breast density. J Radiol. 2004;85 (10 Pt 1):1673-86.