RCT of HRT RISK of Coronary disease Cases RR 95

							 ” HRT – og cancer/hjerte-
     karsykdommer ”
Emnekurs i Gynekologi 2010




               OE Iversen
    KK, Haukeland Universitetssykehus
     Lipidendringer (%) etter
           menopause

10                        10
               8
8
        6
6
4                                         Kolesterol
2                                         LDL
0                                         HDL
                                          TG
-2
-4
-6                  -6
            Endring i %        "Alt ugunstig!"
LDL hos menn og kvinner etter alder
           ØSTROGEN - KORONARSYKD.
                METAANALYSER

                             RR            Endep.
   Stampfer M –91        0,56 (0,5-0,6)   Ins.+ død
   Grady D -92           0,65 (0,6-0,7)   Insidens

                          0,63 (0,6-0,7)   Død
   Barrrett-Connor -98   0,70 (0,6-0,8)   Insidens
                    RCT of HRT
              RISK of Coronary disease

                Cases     RR (95 % CI)
   HERS        179/182   0,99 (0,8-2,3)
   WHI HRT     164/122   1,29 (1,02-1,6)
   WEST         14/12    1,20 (0,5-2,5)
   TOTAL       357/316   1,11 (0,96-1,3)

   WHI ERT     177/199   0,91 (0,8-1,1)

                               Beral et al. Lancet Sept. -02
                   RCT of HRT
                  RISK of Stroke

               Cases     RR (95 % CI)
   HERS        82/67    1,23 (0,9-1,7)
   WHI HRT*   127/85    1,41 (1,07-1,9)
   WEST        63/56    1,10 (0,8-1,6)
   TOTAL      272/208   1,27 (1,06-1,5)

   WHI ERT    158/118   1,39 (0,97-2,0)
                     RCT of HRT
            RISK of Pulmonary embolus/VT
                Cases     RR (95 % CI)
   EVTET         3/1     2,90 (0,3-27)
   HERS         11/4     2,78 (0,9-8,7)
   WHI HRT*     70/31    2,13 (1,4-3,3)
   WEST          2/2     1,00 (0,1-7,1)
   TOTAL        86/38    2,16 (1,5-3,2)

   WHI ERT*     101/78   1,33 (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)

                                           Hazard Ratio for CHD
                           0.00   0.5   1.0    1.5    2.0   2.5   3.0   3.5   4.0
Years Since Menopause
                                    0.89
    < 10
                                              1.22
    10 - 19
                                                     1.71
    > 20


              Manson JE, et al. N Engl J Med. 2003;349:523-534.
    HORMONAL TREATMENT AND
        RISK OF CANCER
   IS IT INCREASED (RR >1) ?
   DO PROGESTINS MODIFY RISK?
   IS MORBIDITY AFFECTED?   IS IT THE
    SAME DISEASE? (STAGE, SIZE, GRADE)
   IS MORTALITY AFFECTED?
   CAN IT BE GIVEN TO CANCER PATIENTS?



   Epidemiology: Associations or causations ?
      RELATIV OG ABSOLUTT RISIKO
       (eks. ENDOMETRIECANCER)

 KVINNER 50-59   ÅR:         0,5/1000 pr.år

 ØSTROGENBRUK (-       G):   RR = 2

 ØSTROGENBRUK:               ABS.R.= 1/1000

         Stor eller liten økning?
                                            ERT/HRT – Colon cancer
                                           Metaanalyse av 18 studier*.
                                               (Grodstein F, -99)
                                                             RR (95 % CI)
                                 Colon                      0,80 (0,7-0,9)
                                 Rectum                     0,81 (0,7-0,9)
                                 Colorect       ”current”   0,66 (0,6-0,7)

                                 *13    av 18 viste beskyttelse
                                   3 med E+G!


       ØSTROGENSUBSTITUSJON -
            CANCERRISIKO

   ENDOMETRIECANCER
   MAMMACANCER
   OVARIALCANCER
   CERVIXCANCER
   COLONCANCER
   ANDRE
                    RCT of HRT
              RISK of Colorectal cancer

                Cases           RR (95 % CI)
   HERS         11/16         0,69 (0,3-1,5)
   WHI HRT      45/67         0,63 (0,4-0,9)
   WHI ERT      61/58         1,08 (0,8-1,6)
   TOTAL        56/83         0,64 (0,5-0,9)


                         Beral et al. Lancet Sept. -02 / JAMA april -04
HRT - CANCER COLI MORTALITET

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



                              Oei 01
                        Hva har skjedd etter ”collborative
                           study” 1997 (51 studier)?


CASES PR 1000
   80
   80
   70
           NO HRT
             HRT 5 Y                                •10-15 nye obs studier
   60        HRT 10 Y

   50
                                                    (MWS)
   40                                               •Fokus på gestagener
   30
   20
                                                    •1-2 RCT (WHI, HERS)
   10                                               •Lavere doser
   0
        50       55        60        65           70 AGE

                                LANCET OCT 1997
                WHI: Cancer Risk and Mortality
                ERT (n=10.739) HRT (n=16.608)
                   ERT         (n)   HRT       (n)

                   Incidence
 Breast     0,77        218         1,26      290
 Colon      1,08         61         0,63*     112
 Endometrium -           -          0,83       47
 All cancer 0,93 (0,8-1,1)          1,03 (0,9-1,2)

   Mortality      1,04 (0,9-1,2)    0,98 (0,8-1,2)
WHI – ERT 2004
WHI – ERT 2004
                         HRT AND CANCER RISK

                                   INCIDENCE           MORTALITY
  BREAST                                +                    -
  CORPUS                            0 (+/-)*                 0
  COLON                                -                     -
  CERVIX                               0                     0
  OVARIAN                            0 (?)                 0 (?)
  OTHERS                               0                     0
 * Ø UTEN G/Cont.comb.

+ = INCREASED;           - = REDUCED; 0 = NEUTRAL; * UNOPPOSED
                                     Mortality Rates in Women

                             6500                                                                           Coronary Artery Disease
                                                                                                            Stroke
                             4500                                                                           Lung Cancer
Mortality Rate per 100,000




                             2500                                                                           Breast Cancer
                                                                                                            Colon Cancer
                             1600                                                                           Endometrial Cancer
                                        Terapistart:
                             1200
                                     Klin.             WHI HERS

                              800


                              400


                                0
                                    45-49   50-54 55-59 60-64   65-69 70-74   75-79   80-84   85+

                                                        Age (years)
                                                                                        National Center for Health Statistics. 1999:164-167.