1. MENAPOUSE

2. Natural Surgical premature

4. RETROSPECTIVE Cessation of menstruation for 12 months In the absence of other physiological or psychological cause STRAW staging

7. SYMPTOMS Acute Hot flashes Sleep Disturbance Mood SWINGS Joint pain Sexual dysfunction (loss of libido.Vaginal Dryness. Loss of elasticity)

8. LONG TERM Bone loss : Osteoporosis Needs separate lecture !

9. Cardiovascular: Change in lipid profile ↑LDL 6% No change in HDL but reduced protective effect

10. DEMENTIA There is limited epidemiologic support for the hypothesis that estrogen preserves overall cognitive function in non-demented women. Preliminary data suggest that estrogen may be important in preventing amyloid deposition, in addition to any role it plays in cognitive function

11. OTHER SKIN: reduced cutaneous collagen elasticity Joints: Degenerative Osteoarthritis Body composition :↑ fat mass >lean mass Balance

14. WHI STUDY 27000 women Age mean 63y Placebo Vs Unopposed Estrogens and continuous combined estrogens and progesterone

15. Regarding the WHI trial: Demographics of women in trial Relative risk of hip and total fracture with HRT Relative risk of breast and total cancer with HRT Relative risk of AMI and CVS problems with HRT What is the problem with general application of these findings? What are the risk factors for breast cancer

16. Demographics of women in WHI trial 16,600 women in combined HRT treatment arm Age 50-79 (mean age 63) with intact uterus (only 33% were in 50s and 20% were > 70) 60% were overweight or obese 50% were previous or current smokers 35% were hypertensive 12% had hypercholesterolaemia 5% had previous coronary artery disease Randomised to 0.625mg of equine oestrogen with 2.5 mg MPA or placebo Primary outcome measures were CHD and breast cancer, and global index of risks and benefits

17. Relative risk of hip and total fracture with HRT Hip fracture HR 0.66 Total fracture HR 0.76 Relative risk of breast and total cancer with HRT Breast cancer HR 1.26 – this lead to premature cessation of the trial Total cancer HR 1.03 (not significant) Note colorectal cancers HR 0.63

18. Relative risk of AMI and CVS problems with HRT Coronary heart disease HR 1.29 Stroke HR 1.41 Total cardiovascular disease (including stoke & venous thromboembolism) HR 1.22

19. WHAT IS THE PROBLEM WITH GENERAL APPLICATION OF THESE FINDINGS? WHI was designed as a primary prevention RCT – not a trial of adverse outcomes of 51 yo taking HRT for menopausal symptoms (which is the main reason women take HRT) Wide inclusion criteria (not really healthy women) – average age 63 (only 33% were in 50s and 20% were > 70), half were past or current smokers, 2/3 were overweight or obese, 1/3 had HT, 12% had  chol, 7.7% had CVS disease Counted events not people – hip #, DVT, PE could all occur in the same person and therefore are not independent HR for beast cancer was 1.26 but CI was 1.00 – 1.59, so result is actually not significant ! Furthermore 25% had already used HRT – there was no increase in the hormone naïve subjects (HR 1.06) Subgroup analysis in women < 10 yrs postmenopausal indicated no increased coronary heart risk Absolute risk of harm to an individual women is very small

20. Only one drug regime tested – cyclic progesterone may have had less adverse outcomes and is commonly used ¼ had used HRT before Does not address the short term risks & benefits of HRT for treatment of menopausal symptoms High discontinuation rate in treatment group 47% and 10% cross-over from placebo to treatment arm Short term follow-up – only 5.2 years – can conclusions really be made re long term prevention