Post menopausal hormone replacement therapy. Benefits and risks. Cancer inducing potential.

1. Prof. Shad Salim Akhtar
MBBS, MD, MRCP(UK), FRCP(Edin), FACP(USA)
Consultant Medical Oncologist & Director
Hakim Sanaullah Cancer Centre
Sopore, Kashmir, J & K

2.  Women value different health outcomes
differently
 The decision to use HRT should be taken
jointly
 All possible benefits and risks mentioned
 Assess the women’s health history
 Outline the possible goals
 Accommodate the personal point of view
Greendale GA et al. The Menopause. Lancet 1999;353:571

3. Symptoms Syndromes
Vasomotor changes
Urogenital complications
Others Coronary artery disease
Osteoporosis
Others
Poster M. Br J Obst Gynecol 1996;103:1025
75% asymptomatic

4.  Since 40s
 Millions on HRT
 Why?

5.  Beneficial effects
 Cardio protection
 Osteoporosis prevention
 Improved general quality of life
 Risks
 Cancer
 GB disease
 Thromboembolism
!!!HRT!!!!!!HRT!!!

6. Does HRT prevent osteoporosis??
 Observational studies—yes
 One clinical trial—yes
 30%-50% decrease in fracture risk
 Useful in pts prone to osteoporosis
 Must be continued indefinitely
Fitzpatrick LA et al. Mayo Clin Proced 2000;75:559

7. Meta-analysis of Randomized Trials
 Decreased incidence of
 Non vertebral fractures—27%
 Overall fractures in younger women—33%
 No significant effect in older (>60 yrs)
FDA has removed osteoporosis as an indication for treatment
by conjugated equine oestrogen
Fitzpatrick LA et al. Mayo Clin Proced 2000;75:559

8.  Other FDA approved agents are more
effective
 10 yrs therapy is reqd to decrease risk of
fracture substantially
 ERT has risks
 Treatment other than ERT should be the first
chioce for osteoporsois
Grady D et al. JAMA 2001;285:2909
Grant from Organaon dgrady@itsa.ucsf.edu

9.  Favourable observational studies
 Effect of estrogens on lipids
 Is it true???Is it true???

10.  Randomized, controlled, blinded trial
 2763 women with CHD <80 yrs
 1383 placebo and 1380 CHRT
 Average follow up 4 yrs
 Outcome
 Non fatal MI
 CHD death
 Secondary outcomes

11. Results
 No significant difference between 2 gps
 More CHD events during Ist yr in HRT gp
 <CHD events in yrs 4-5 in HRT gp
 >Thromboembolic and GB disease in HRT gp.
Hulley S et al. JAMA 1998;280:605

12.  ERA study (Estrogen replacement and
atherosclerosis trial)
 Randomized double blind controlled trial
 309 women
 Coronary artery diameter measurement
 No difference in three gps (ERT, CHRT,
Placebo)
 Conclusion:
 HRT should not be used with an expectation of
cardiovascular benefit
Harrington DM et al. NEJM 2000;343:522

13. Breast Cancer
 Collaborative group study
 52705 women with breast cancer
 108411 controls
 51 studies in 21 countries
 53865 postmenopausal women
 17830 on HRT
 Median age at first use 48yrs

14. Incidence in 50-70 yrs age
 Never users-----45/1000
 5 yr users--------47/1000
 10 yr users-------51/1000
 15 yr users-------57/1000
Collaborative Group. Lancet 1997;350:1047-59

15.  46355 post menopausal women
 Cohort study
 2082 cases of Breast Ca diagnosed
 Risk increased by
 1% with each yr of use of estrogen
 8% with each yr of use of CHRT
Schraiar C et al. JAMA 2000;283:485

16.  1897 Post menopausal women on HRT
 1637 controls
 HRT associated with 10 % increase in breast
cancer risk for each 5 year use
 CHRT higher risk than ERT
Ross RK et al. J Natl Cancer Inst 2000;92:328-32

17.  211581 post menopausal women form Am
Cancer Society Cancer Prevention Study
 944 Ovarian cancer deaths
 Users 1.55 RR
 Former users 1.16 RR
 >10 yrs use 2.20 RR
 Breast ca risk declines after stoppage of HRT
 Increased mortality due to ovarian ca
persists even after29 yrs of use.

18.  WE DO NOT KNOW
 WISDOM trial
 WHI trial
 ??? Early results positive against the useagainst the use??

19.  “The idea of an anti-ageing pill in the form of ERT is
certainly attractive, but it is unlikely to be the
solution to healthy ageing in women. The huge
international variations and secular trends in
chronic disease indicate that many of these
conditions are potentially preventable and not due
to menopause per se. Japanese women who have
lowest endogenous estrogen levels, also have
greatest longevity, the lowest rates of CHD and a
low prevalence of menopausal symptoms. We
already have a good understanding of some existing
dietary and other measures we can take to improve
health. The valuable clinical uses of estrogens
should not divert attention form identifying and
acting on the major determinants of health in
women.”
BMJ editorial 1998;316:1842