MENOPOZ GÜNCEL-2011 Prof.Dr.Hakan SEYİSOĞLU

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1 MENOPOZ GÜNCEL-2011 Prof.Dr.Hakan SEYİSOĞLU
İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi Kadın Hastalıkları ve Doğum Anabilim Dalı MORE: Multiple Outcomes of Raloxifene Evaluation The Multiple Outcomes of Raloxifene Evaluation (MORE) trial was a large, multicenter, double-blind, placebo controlled trial of postmenopausal women with osteoporosis, enrolling 7705 women at 180 sites in 25 countries.1,2 The trial consisted of a 3-year core treatment phase with a 1-year extension phase. Women were randomly assigned to receive placebo or raloxifene 60 mg/day (Evista), or raloxifene 120 mg/day. All women also received supplemental calcium (500 mg/day) and vitamin D (400 – 600 IU/day). The primary endpoints of the MORE trial were the incidence of new vertebral fractures and bone mineral density of the lumbar spine and femoral neck. Secondary endpoints included all osteoporotic fractures, serum lipids and other markers of cardiovascular risk, cognitive function, breast cancer, and safety. Major criteria for exclusion from the study included a history of breast or endometrial cancer or the presence of abnormal uterine bleeding. The dose of raloxifene approved for the prevention and treatment of postmenopausal osteoporosis is 60 mg/day, and effects observed with raloxifene 120 mg/day were comparable to those observed with 60 mg/day. Thus, unless noted otherwise, the data in the subsequent slides will focus on the raloxifene 60 mg/day group compared with placebo. 1. Ettinger B et al. JAMA 1999; 282:637-45 2. Cummings SR et al., JAMA 1999;281:

2 HRT-VTE (EMAS Position Statement) HRT-KVH (EMAS Position Statement) OSTEOPOROZ (EMAS Position Statement) TSEC MORE: Multiple Outcomes of Raloxifene Evaluation The Multiple Outcomes of Raloxifene Evaluation (MORE) trial was a large, multicenter, double-blind, placebo controlled trial of postmenopausal women with osteoporosis, enrolling 7705 women at 180 sites in 25 countries.1,2 The trial consisted of a 3-year core treatment phase with a 1-year extension phase. Women were randomly assigned to receive placebo or raloxifene 60 mg/day (Evista), or raloxifene 120 mg/day. All women also received supplemental calcium (500 mg/day) and vitamin D (400 – 600 IU/day). The primary endpoints of the MORE trial were the incidence of new vertebral fractures and bone mineral density of the lumbar spine and femoral neck. Secondary endpoints included all osteoporotic fractures, serum lipids and other markers of cardiovascular risk, cognitive function, breast cancer, and safety. Major criteria for exclusion from the study included a history of breast or endometrial cancer or the presence of abnormal uterine bleeding. The dose of raloxifene approved for the prevention and treatment of postmenopausal osteoporosis is 60 mg/day, and effects observed with raloxifene 120 mg/day were comparable to those observed with 60 mg/day. Thus, unless noted otherwise, the data in the subsequent slides will focus on the raloxifene 60 mg/day group compared with placebo. 1. Ettinger B et al. JAMA 1999; 282:637-45 2. Cummings SR et al., JAMA 1999;281:

3 HRT-VTE Menopozdan sonra artış gösterir HRT (-) :
Premenopozal genel insidens 0,5/1000 60 yaş üzeri genel insidens 2-3/1000 MORE: Multiple Outcomes of Raloxifene Evaluation The Multiple Outcomes of Raloxifene Evaluation (MORE) trial was a large, multicenter, double-blind, placebo controlled trial of postmenopausal women with osteoporosis, enrolling 7705 women at 180 sites in 25 countries.1,2 The trial consisted of a 3-year core treatment phase with a 1-year extension phase. Women were randomly assigned to receive placebo or raloxifene 60 mg/day (Evista), or raloxifene 120 mg/day. All women also received supplemental calcium (500 mg/day) and vitamin D (400 – 600 IU/day). The primary endpoints of the MORE trial were the incidence of new vertebral fractures and bone mineral density of the lumbar spine and femoral neck. Secondary endpoints included all osteoporotic fractures, serum lipids and other markers of cardiovascular risk, cognitive function, breast cancer, and safety. Major criteria for exclusion from the study included a history of breast or endometrial cancer or the presence of abnormal uterine bleeding. The dose of raloxifene approved for the prevention and treatment of postmenopausal osteoporosis is 60 mg/day, and effects observed with raloxifene 120 mg/day were comparable to those observed with 60 mg/day. Thus, unless noted otherwise, the data in the subsequent slides will focus on the raloxifene 60 mg/day group compared with placebo. 1. Ettinger B et al. JAMA 1999; 282:637-45 2. Cummings SR et al., JAMA 1999;281: Grady HERS, 2000 Rossouw WHI, 2007

4 HRT-VTE (VERİLİŞ YOLU - TROMBİN)
Oral yol (östrojen) Karaciğer üzerinden E1 potensi ile trombin üretimi Protrombin Aktivasyon Peptid (F1+2) plazma konsantrasyonu Trombin jenerasyonu Antitrombin konsantrasyonu Transdermal yol bu trombotik etkileri göstermez MORE: Multiple Outcomes of Raloxifene Evaluation The Multiple Outcomes of Raloxifene Evaluation (MORE) trial was a large, multicenter, double-blind, placebo controlled trial of postmenopausal women with osteoporosis, enrolling 7705 women at 180 sites in 25 countries.1,2 The trial consisted of a 3-year core treatment phase with a 1-year extension phase. Women were randomly assigned to receive placebo or raloxifene 60 mg/day (Evista), or raloxifene 120 mg/day. All women also received supplemental calcium (500 mg/day) and vitamin D (400 – 600 IU/day). The primary endpoints of the MORE trial were the incidence of new vertebral fractures and bone mineral density of the lumbar spine and femoral neck. Secondary endpoints included all osteoporotic fractures, serum lipids and other markers of cardiovascular risk, cognitive function, breast cancer, and safety. Major criteria for exclusion from the study included a history of breast or endometrial cancer or the presence of abnormal uterine bleeding. The dose of raloxifene approved for the prevention and treatment of postmenopausal osteoporosis is 60 mg/day, and effects observed with raloxifene 120 mg/day were comparable to those observed with 60 mg/day. Thus, unless noted otherwise, the data in the subsequent slides will focus on the raloxifene 60 mg/day group compared with placebo. 1. Ettinger B et al. JAMA 1999; 282:637-45 2. Cummings SR et al., JAMA 1999;281: Lowe GD, Thromb Haemost, 2001 Scarabin PY, Arterioscler Thromb Vasc Biol, 1997 Oger E, Arterioscler Thromb Vasc Biol, 2003 Bagot CN, J Thromb Haemost, 2010

5 HRT-VTE (VERİLİŞ YOLU - APC)
Oral yol (östrojen) Aktive Protein C (APC) Rezistansını arttırır APC, naturel antikoagulandır Faktör V Leiden APC yi aktive eder Mutasyon durumunda APC aktive edilemez ve koagulasyon artar Transdermal yol APC aktivitesini bozmaz MORE: Multiple Outcomes of Raloxifene Evaluation The Multiple Outcomes of Raloxifene Evaluation (MORE) trial was a large, multicenter, double-blind, placebo controlled trial of postmenopausal women with osteoporosis, enrolling 7705 women at 180 sites in 25 countries.1,2 The trial consisted of a 3-year core treatment phase with a 1-year extension phase. Women were randomly assigned to receive placebo or raloxifene 60 mg/day (Evista), or raloxifene 120 mg/day. All women also received supplemental calcium (500 mg/day) and vitamin D (400 – 600 IU/day). The primary endpoints of the MORE trial were the incidence of new vertebral fractures and bone mineral density of the lumbar spine and femoral neck. Secondary endpoints included all osteoporotic fractures, serum lipids and other markers of cardiovascular risk, cognitive function, breast cancer, and safety. Major criteria for exclusion from the study included a history of breast or endometrial cancer or the presence of abnormal uterine bleeding. The dose of raloxifene approved for the prevention and treatment of postmenopausal osteoporosis is 60 mg/day, and effects observed with raloxifene 120 mg/day were comparable to those observed with 60 mg/day. Thus, unless noted otherwise, the data in the subsequent slides will focus on the raloxifene 60 mg/day group compared with placebo. 1. Ettinger B et al. JAMA 1999; 282:637-45 2. Cummings SR et al., JAMA 1999;281: Hoibraaten E, Br J Haematol 2001 Post MS, Arterioscler Thromb Vasc Biol 2003 Canonico M, Menopause 2010

6 Transdermal HRT , VTE riskini arttırmaz
Renoux C et al, J Thromb Haemost 2010

7 Ε3Ν Study: HRT kullanım yolu ve progestin tipi,
VTE riskini etkiler Canonico M et al, Arterioscler Thromb Vasc Biol. 2010;30:340-45

8 HRT-VTE (PROGESTERON SEÇİMİ) (E3N Study)
Transdermal E2 + Mikronize Progesteron Transdermal E2 + Didrogesteron Kombinasyonlarında risk artışı olmadığı bildirilmekte APC Rezistansını ve Prothrombin Activation Peptid (F1+2) konsant. arttırmazlar Canonico M, et al. Arterioscler Thromb Vasc Biol, 2010 ve Menopause 2010 MORE: Multiple Outcomes of Raloxifene Evaluation The Multiple Outcomes of Raloxifene Evaluation (MORE) trial was a large, multicenter, double-blind, placebo controlled trial of postmenopausal women with osteoporosis, enrolling 7705 women at 180 sites in 25 countries.1,2 The trial consisted of a 3-year core treatment phase with a 1-year extension phase. Women were randomly assigned to receive placebo or raloxifene 60 mg/day (Evista), or raloxifene 120 mg/day. All women also received supplemental calcium (500 mg/day) and vitamin D (400 – 600 IU/day). The primary endpoints of the MORE trial were the incidence of new vertebral fractures and bone mineral density of the lumbar spine and femoral neck. Secondary endpoints included all osteoporotic fractures, serum lipids and other markers of cardiovascular risk, cognitive function, breast cancer, and safety. Major criteria for exclusion from the study included a history of breast or endometrial cancer or the presence of abnormal uterine bleeding. The dose of raloxifene approved for the prevention and treatment of postmenopausal osteoporosis is 60 mg/day, and effects observed with raloxifene 120 mg/day were comparable to those observed with 60 mg/day. Thus, unless noted otherwise, the data in the subsequent slides will focus on the raloxifene 60 mg/day group compared with placebo. 1. Ettinger B et al. JAMA 1999; 282:637-45 2. Cummings SR et al., JAMA 1999;281:

9 HRT-VTE YÜKSEK RİSKLİ GRUPLAR VE ÖNERİLER
VTE öyküsü bulunan kişiler Oral yol kontrendike Transdermal sistemler kullanılabilir MEVE (Menopause, Estrogen and Venous Events) Çalışması Protrombotik mutasyonu olanlar Kesinlikle kontrendike Obezite Zayıflara göre risk 2,9 kat Düşük doz transdermal uygundur MORE: Multiple Outcomes of Raloxifene Evaluation The Multiple Outcomes of Raloxifene Evaluation (MORE) trial was a large, multicenter, double-blind, placebo controlled trial of postmenopausal women with osteoporosis, enrolling 7705 women at 180 sites in 25 countries.1,2 The trial consisted of a 3-year core treatment phase with a 1-year extension phase. Women were randomly assigned to receive placebo or raloxifene 60 mg/day (Evista), or raloxifene 120 mg/day. All women also received supplemental calcium (500 mg/day) and vitamin D (400 – 600 IU/day). The primary endpoints of the MORE trial were the incidence of new vertebral fractures and bone mineral density of the lumbar spine and femoral neck. Secondary endpoints included all osteoporotic fractures, serum lipids and other markers of cardiovascular risk, cognitive function, breast cancer, and safety. Major criteria for exclusion from the study included a history of breast or endometrial cancer or the presence of abnormal uterine bleeding. The dose of raloxifene approved for the prevention and treatment of postmenopausal osteoporosis is 60 mg/day, and effects observed with raloxifene 120 mg/day were comparable to those observed with 60 mg/day. Thus, unless noted otherwise, the data in the subsequent slides will focus on the raloxifene 60 mg/day group compared with placebo. 1. Ettinger B et al. JAMA 1999; 282:637-45 2. Cummings SR et al., JAMA 1999;281: Olive V, et al. Menopause, 2010

10 EMAS Position Statement (07.March.2011)
Managing menopausal women with personal or family history of VTE Menopoz sonrası ilerleyen yaş ile birlikte VTE riski artar Trombojenik mutasyon ve obezite risk faktörleridir Genel olarak oral CE ya da kombinasyonları, VTE riskini arttırır Transdermal sistemler VTE açısından daha güvenlidir Obezitede transdermal sistemler bu nedenle tercih edilmelidir Özgeçmiş ve soygeçmişte VTE ya da özellikle protrombotik mutasyon varsa oral yol kesinlikle kontrendikedir, transdermal sistemler ise çok gerekirse yarar&zarar durumuna göre verilebilir Mikronize Progesteron ya da Didrogesteron emin progesteronlardır Maturitas, June 2011

11 HRT ve KVH Erken yaşta başlama kuralı halen geçerliliğini korumaktadır
Düşük doz ve erken kullanım konusunda yarar çalışmaları devam etmektedir Şu anda HRT nin kardioprotektif amaçlı endikasyonu yoktur

12 WHI : Evolution of Messages From the Investigators
2002 : WHI Study stopped : ‘Risk exceed benefits’. The only fundamentally new finding : ‘Substantial risks for CVD’ 2003 : Re-analysis : HRT may increase the risk of CHD 2007 : Further re-analysis : Woman who initiated HRT closer to menopause tended to have reduced CHD risk

13 Kardiovasküler riskin belirlenmesi
Yaş Menopozdan sonra geçen süre VKİ Kan basıncı Lipidler Sigara Diabetes mellitus İlave risk faktörleri Am J Cardiol 2009:103:1174 Klinik koroner arter hastalığı Kronik böbrek hastalığı Atrial fibrilasyon Sol ventrikül hipertrofisi

14 Düşük KVH riski Orta KVH riski HRT kullanılabilir
HRT kullanılabilir, şu öneriler doğrultusunda : Transdermal yol Mümkün olabilen düşük doz Düşük riskli progestin Diğer risk faktörlerini de düzelterek

15 Yüksek KVH Riski KVS riskleri nedeni ile HRT önerilmemelidir. AYRICA,
Klinik KVH olanlar Kronik böbrek hastalığı olanlar Kontrolsüz Diabetes Mellitus olanlar USG de unstabil aterosklerotik plak tespit edilenler KVS riskleri nedeni ile HRT önerilmemelidir.

16 EMAS Position Statement (14.October.2010)
Managing the menopause in the context of coronary heart disease (1) KVH, kadınlarda önemli ölüm nedenleri arasındadır. Menopoz, koroner kalb hastalıklarının prevalansında artış nedenidir Randomize kontrollü çalışmalar 50 yaş üzeri kadınlarda HT nin koroner kalb hastalığı açısından primer korumada rolü olmadığını bildirmektedir. Fakat verilerin çok büyük bölümü CEE+MPA kombinasyonu ile sınırlıdır HT nin koroner kalb hastalığı açısından sekonder korumada rolü yoktur. Fakat bu konudaki randomize kontrollü çalışmalarda olgu sayısı düşüktür Maturitas, January 2011

17 EMAS Position Statement (14.October.2010)
Managing the menopause in the context of coronary heart disease (2) Postmenopozal semptomların giderilmesinde düşük doz östrojen kullanılmalıdır (17 beta E2 (oral)= 0.5-1mg ; 17 beta E2 (transdermal)=25-50 mikrogr ; CEE= mg ) Artmış KVH riski olanlarda ya da geçirilmiş hastalığı olanlarda kullanmak gerekirse, koagulasyon üzerinde etkisinin çok az olması nedeni ile transdermal sistemler tercih edilmelidir Tedavi altındaki kadını düzenli kontrol ve takip edebilecek bölümlerin bulunması tercih sebebidir Maturitas, January 2011

18 KEMİK HRTnin osteoporoz üzerine olumlu etkisi kesindir (A sınıfı)
İleri yaşta KMY belirleyicilik oranı yükselmektedir. Bu nedenle tarama başlangıç yaşının ileriye alınması görüşü hakimdir 50 yaş KMY taramasında pozitif belirleyicilik %11 65 yaş KMY taramasında pozitif belirleyicilik %24 KMY sensitivitesi %18 dir. Yani her 100 kırıktan 82 tanesinin KMY değeri normal ya da osteopenidedir Bu nedenle ‘Kemik Gücü’nün tespiti daha anlamlıdır. Ancak bu konuda rutin yöntem yoktur FRAX algoritması Dünya Sağlık Örgütü tarafından geliştirilmiş, popülasyon tabanlı bilgiye dayanan, klinik risk faktörleri ve femur boynu KMY ölçümüne göre hesaplanabilen, yaklaşık 10 yıllık fraktür öngörüsü veren sistemdir. Kanis JA, et al Osteoporos Int, ; Brincat M, et al Maturitas,2011

19 EMAS Position Statement (22.September.2010)
Boen densitometry screening for osteoporosis Kemik mineral yoğunluk ölçümü, postmenopozal dönem osteoporoz taramasında halen geçerli yöntemdir İleri yaş taramalarında bu yöntemin belirleyiciliği, sensitivite ve spesifisitesi daha yüksektir FRAX algoritması fraktür riski açısından ilave bilgi verir Maturitas, January 2011

20 Doku Selektif Östrojen Kompleksi TSEC (Tissue Selective Estrogen Complex)
MORE: Multiple Outcomes of Raloxifene Evaluation The Multiple Outcomes of Raloxifene Evaluation (MORE) trial was a large, multicenter, double-blind, placebo controlled trial of postmenopausal women with osteoporosis, enrolling 7705 women at 180 sites in 25 countries.1,2 The trial consisted of a 3-year core treatment phase with a 1-year extension phase. Women were randomly assigned to receive placebo or raloxifene 60 mg/day (Evista), or raloxifene 120 mg/day. All women also received supplemental calcium (500 mg/day) and vitamin D (400 – 600 IU/day). The primary endpoints of the MORE trial were the incidence of new vertebral fractures and bone mineral density of the lumbar spine and femoral neck. Secondary endpoints included all osteoporotic fractures, serum lipids and other markers of cardiovascular risk, cognitive function, breast cancer, and safety. Major criteria for exclusion from the study included a history of breast or endometrial cancer or the presence of abnormal uterine bleeding. The dose of raloxifene approved for the prevention and treatment of postmenopausal osteoporosis is 60 mg/day, and effects observed with raloxifene 120 mg/day were comparable to those observed with 60 mg/day. Thus, unless noted otherwise, the data in the subsequent slides will focus on the raloxifene 60 mg/day group compared with placebo. 1. Ettinger B et al. JAMA 1999; 282:637-45 2. Cummings SR et al., JAMA 1999;281:

21 TSEC AMAÇ Yaşam kalitesi parametreleri üzerine olumlu etki sağlamak ve SERM in bu yöndeki etkisini önlemek SERM olumlu etkilerini potansiyalize etmek SERM lerin yetersizliği olan nonvertebral kırıklarda etkinliği arttırmak Meme üzerinde proliferasyona antagonist etki sağlamak Endometrium güvenliğini sağlamak ve progestin kullanımını devreden çıkarmak Hem temel hormon Östrojeni vermek ve hem de bunun olası yan etkilerini en aza indirgemek.

22 BAZ+CE nin diğer SERM+CE kombinasyonlarına üstünlüğü
Östrojenin Meme üzerindeki proliferatif etkisini baskılamada Uterustaki etkisini baskılamada Kemik volümünü (konnektivite+kalınlık) arttırmada en güçlü etki CE nin meme MCF-7 hücre proliferasyon ölçümleri ile yapılan çalışmalarda, Bazedoksifenin CE nin memedeki etkisini antagonize eden en güçlü SERM olduğu gösterilmiştir. Kharode Y et al. Endocrinology 2008 Peano BJ et al. Endocrinology 2009

23 BAZ + CE klinik faz III çalışmaları
SMART (Selective estrogen, Menopause, And Response to Therapy) Trial PROTOKOL SMART-1 SMART-2 SMART-3 SMART-4 SÜRE 2 yıl 12 hf OLGULAR Postmenopozal kadın (n=3397) Postmenopozal kadın vazomotor yakınma (n=318) Postmenopozal kadın vajinal atrofi (n=652) (n=1083) PROTOKOL BAZ 10, 20, 40 mg + CE 0.45, mg vs. RAL 60mg vs. plasebo BAZ 20mg + CE 0.45, mg vs. plasebo BAZ 20mg + CE 0.45, vs. BAZ 20mg vs. plasebo BAZ 20mg + CE 0.45, vs. CE MPA 1.5mg vs. plasebo PRİMER AMAÇ Bir yılda endometrial hiperplazi 4 – 12 hafta orta ve şiddetli vazomotor yakınma Vajinal atrofi (superfisyel ve parabazal hücreler hiperplazi ve KMY değişimi SEK. AMAÇ 2 yılda endometrial hiperplazi ; meme ağrısı ; KMY değişimi Meme hassasiyeti ; uyku kalitesi Seksüel fonksiyon ; menopozda yaşam kalitesi Uterus kanaması/ spotting ; memede ağrı Effects on Bone Gallagher et al; Lindsay et al; Bergmann Koury; Pinkerton et al; Kagan et al 2007 (Gennari et al Ther Clin Risk Manag. 2008)

24 QoL Parametreleri ve TSEC
* * Olgu yüzdesi Bazale göre değişim * * * Genel Hasta Memnuniyeti * * * * * * * * * * * * * Olgu yüzdesi 12 hafta süreli Utian ve Pickar ın ortak Faz 3 çalışması. Yaşam kalitesi parametreleri açısından yapılan araştırmada sorgulama şeklinde çalışılmış ve elde edilen sonuçlar belirlenmiştir. Utian W, Pickar J. et al. Maturitas, 2009

25 BAZ+CE vs. Raloksifen : KMY değişimi
BAZ+CE her dozda bazal değer ve plaseboya göre anlamlı 40 mg BAZ dozları hariç diğer tüm dozlarda RAL e göre anlamlı BAZ dozu artınca, CE etkisini attenüe ediyor. Bu nedenle kombinasyonlarda BAZ dozu 20 mg da tutuluyor MORE: Multiple Outcomes of Raloxifene Evaluation The Multiple Outcomes of Raloxifene Evaluation (MORE) trial was a large, multicenter, double-blind, placebo controlled trial of postmenopausal women with osteoporosis, enrolling 7705 women at 180 sites in 25 countries.1,2 The trial consisted of a 3-year core treatment phase with a 1-year extension phase. Women were randomly assigned to receive placebo or raloxifene 60 mg/day (Evista), or raloxifene 120 mg/day. All women also received supplemental calcium (500 mg/day) and vitamin D (400 – 600 IU/day). The primary endpoints of the MORE trial were the incidence of new vertebral fractures and bone mineral density of the lumbar spine and femoral neck. Secondary endpoints included all osteoporotic fractures, serum lipids and other markers of cardiovascular risk, cognitive function, breast cancer, and safety. Major criteria for exclusion from the study included a history of breast or endometrial cancer or the presence of abnormal uterine bleeding. The dose of raloxifene approved for the prevention and treatment of postmenopausal osteoporosis is 60 mg/day, and effects observed with raloxifene 120 mg/day were comparable to those observed with 60 mg/day. Thus, unless noted otherwise, the data in the subsequent slides will focus on the raloxifene 60 mg/day group compared with placebo. 1. Ettinger B et al. JAMA 1999; 282:637-45 2. Cummings SR et al., JAMA 1999;281: Lindsay R, Gallagher JC, et al. Fertil Steril,2009

26 Bazedoksifen + CE (Endometrium güvenilirliği) (SMART-1)
Kümülatif Amenore oranları: (13 ay) 0-13 ay %83 10-13 ay %93 (Archer DF, Pickar JH, et al. Fertil Steril, 2009) Endometrial güvenilirlik: (n=3.397 – 2 yıl) Hiperplazi oranı < %1 ns vs. plasebo (Pickar JH, Speroff L, et al. Fertil Steril, 2009) ** PROGESTIN-FREE MENOPAUSAL THERAPY**

27 HRT den optimal etkiyi alabilmemiz için şu kurallara dikkat etmeliyiz :
Uygun tedavi başlama zamanı Uygun hasta seçimi Uygun hormon tipi ve dozu

28 MENOPOZ GÜNCEL-2011 Prof.Dr.Hakan SEYİSOĞLU
İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi Kadın Hastalıkları ve Doğum Anabilim Dalı MORE: Multiple Outcomes of Raloxifene Evaluation The Multiple Outcomes of Raloxifene Evaluation (MORE) trial was a large, multicenter, double-blind, placebo controlled trial of postmenopausal women with osteoporosis, enrolling 7705 women at 180 sites in 25 countries.1,2 The trial consisted of a 3-year core treatment phase with a 1-year extension phase. Women were randomly assigned to receive placebo or raloxifene 60 mg/day (Evista), or raloxifene 120 mg/day. All women also received supplemental calcium (500 mg/day) and vitamin D (400 – 600 IU/day). The primary endpoints of the MORE trial were the incidence of new vertebral fractures and bone mineral density of the lumbar spine and femoral neck. Secondary endpoints included all osteoporotic fractures, serum lipids and other markers of cardiovascular risk, cognitive function, breast cancer, and safety. Major criteria for exclusion from the study included a history of breast or endometrial cancer or the presence of abnormal uterine bleeding. The dose of raloxifene approved for the prevention and treatment of postmenopausal osteoporosis is 60 mg/day, and effects observed with raloxifene 120 mg/day were comparable to those observed with 60 mg/day. Thus, unless noted otherwise, the data in the subsequent slides will focus on the raloxifene 60 mg/day group compared with placebo. 1. Ettinger B et al. JAMA 1999; 282:637-45 2. Cummings SR et al., JAMA 1999;281: