OE Iversen KK, Haukeland Universitetssykehus ” HRT – og cancer/hjerte- karsykdommer ” Emnekurs i Gynekologi 2010

Lipidendringer (%) etter menopause

LDL hos menn og kvinner etter alder

ØSTROGEN - KORONARSYKD. METAANALYSER ØSTROGEN - KORONARSYKD. METAANALYSER RREndep. l Stampfer M –910,56 (0,5-0,6)Ins.+ død l Grady D -920,65 (0,6-0,7)Insidens 0,63 (0,6-0,7)Død l Barrrett-Connor -980,70 (0,6-0,8)Insidens

RCT of HRT RISK of Coronary disease Cases RR (95 % CI) l HERS179/1820,99(0,8-2,3) l WHI HRT164/1221,29 (1,02-1,6) l WEST 14/121,20 (0,5-2,5) l TOTAL357/3161,11 (0,96-1,3) l WHI ERT177/1990,91 (0,8-1,1) Beral et al. Lancet Sept. -02

RCT of HRT RISK of Stroke Cases RR (95 % CI) l HERS 82/671,23(0,9-1,7) l WHI HRT*127/851,41 (1,07-1,9) l WEST 63/561,10 (0,8-1,6) l TOTAL272/2081,27 (1,06-1,5) l WHI ERT 158/1181,39 (0,97-2,0) Beral et al. Lancet Sept. -02

RCT of HRT RISK of Pulmonary embolus/VT Cases RR (95 % CI) l EVTET 3/12,90 (0,3-27) l HERS 11/42,78(0,9-8,7) l WHI HRT* 70/312,13 (1,4-3,3) l WEST 2/21,00 (0,1-7,1) l TOTAL 86/382,16 (1,5-3,2) l WHI ERT* 101/781,33 (0,9-2,1) Beral et al. Lancet Sept. -02

Effect of HT on CHD in Postmenopausal Women: Timing of Initiation WHI (CEE+MPA-arm) Manson JE, et al. N Engl J Med. 2003;349: Years Since Menopause < > Hazard Ratio for CHD

HORMONAL TREATMENT AND RISK OF CANCER HORMONAL TREATMENT AND RISK OF CANCER l IS IT INCREASED (RR >1) ? l DO PROGESTINS MODIFY RISK? l IS MORBIDITY AFFECTED? IS IT THE SAME DISEASE? (STAGE, SIZE, GRADE) l IS MORTALITY AFFECTED? l CAN IT BE GIVEN TO CANCER PATIENTS? l Epidemiology: Associations or causations ?

RELATIV OG ABSOLUTT RISIKO (eks. ENDOMETRIECANCER) l KVINNER ÅR: 0,5/1000 pr.år l ØSTROGENBRUK (- G): RR = 2 l ØSTROGENBRUK:ABS.R.= 1/1000 Stor eller liten økning?

ERT/HRT – Colon cancer Metaanalyse av 18 studier*. (Grodstein F, -99) RR (95 % CI) l Colon0,80 (0,7-0,9) l Rectum0,81 (0,7-0,9) l Colorect ”current”0,66 (0,6-0,7) l *13 av 18 viste beskyttelse l 3 med E+G !

RCT of HRT RISK of Colorectal cancer Cases RR (95 % CI) l HERS 11/160,69(0,3-1,5) l WHI HRT 45/670,63 (0,4-0,9) l WHI ERT 61/581,08 (0,8-1,6) l TOTAL 56/830,64 (0,5-0,9) Beral et al. Lancet Sept. -02 / JAMA april -04

HRT - CANCER COLI MORTALITET RR (95 % CI) l Calle 1995 ”ever”: 0,71 (0,61-0,82) ”current” :0,55 (0,4-0,76) l Persson 1996: 0,70 (0,5-0,9) l Slattery 1999: 0,60 (0,4-0,9) l Paganini-Hill 1999:0,82 (0,4-1,5) l Nanda 1999:0.72 (0,6-0,8)* *Meta-analyse Oei 01

Hva har skjedd etter ”collborative study” 1997 (51 studier)? Hva har skjedd etter ”collborative study” 1997 (51 studier)? nye obs studier (MWS) Fokus på gestagener 1-2 RCT (WHI, HERS) Lavere doser

WHI: Cancer Risk and Mortality ERT (n=10.739) HRT (n=16.608) ERT(n) HRT(n) Incidence l Breast0, ,26290 l Colon1, ,63*112 l Endometrium - - 0,83 47 l All cancer0,93 (0,8-1,1) 1,03 (0,9-1,2) l Mortality1,04 (0,9-1,2) 0,98 (0,8-1,2)

WHI – ERT 2004

HRT AND CANCER RISK + = INCREASED; - = REDUCED; 0 = NEUTRAL; * UNOPPOSED

Mortality Rates in Women Coronary Artery Disease Stroke Lung Cancer Breast Cancer Colon Cancer Endometrial Cancer Age (years) Mortality Rate per 100, National Center for Health Statistics. 1999: Klin. WHI HERS Terapistart: