1. Management of menopause OS Tang Department of Obstetrics and Gynaecology University of Hong Kong

2. Climacteric The phase in the aging process of women marking the transition from the reproductive stage of life to the non- reproductive stage

3. Menopause The final menstrual period and occurs during the climacteric. The average age of menopause is 51.

4. Life expectancy and age of menopause

5. Menopause Premature menopause Surgical menopause Natural menopause

6. Target organs of oestrogen Bone Urogenital Vasomotor Heart Eyes Teeth Breast Colon

7. Consequences of oestrogen loss

8. Menopausal symptoms Vasomotor symptoms: hot flushes, night sweats and palpitation Urogenital atrophy: vaginal dryness, dyspareunia, pruritus vulvae, urinary frequency, urgency, and recurrent cystitis Psychological symptoms: irritability, nervousness, depression, insomnia and anxiety

9. Osteoporosis Oestrogen deficiency Peak bone mass at 30-35 years old Bone loss at a rate of 0.5-1% per year afterward Bone loss at a rate of 2-3% per year for 10 years after menopause Osteoporosis is associated with fracture ( femoral neck, vertebral body and distal radius)

10. Risk factors of osteoporosis Family history Ethnicity Early menopause Hypoestrogenism (excessive exercise, anorexia, bulimia) Hyperthyroidism, excessive thyroxine therapy Cigarette smoking Caffeine High alcohol intake

11. Cardiovascular disease Rapid increase in mortality and morbidity from cardiovascular disease after menopause Epidemiological evidence suggests that HRT is associated with 50% reduction in cardiovascular risk in menopausal women There is no prospective randomised data to show that HRT is effective in the primary prevention of cardiovascular disease.

12. Management of menopause Advise on a healthy life style Psychological support Hormone replacement therapy

13. Management of menopausal symptoms Understand menopause Strengthening of self-image Avoid spicy food, alcohol, strong tea and coffee. Healthy life style Hormone Replacement Therapy

14. Prevention of osteoporosis Change lifestyle risk factors Exercise Adequate calcium / vitamin D intake Hormone Replacement Therapy Alendronate Raloxifene

15. Prevention of cardiovascular disease Healthy life style Diet Avoid smoking Control of hypertension, diabetic and hyperlipidaemia ?Hormone Replacement Therapy (Not effective for secondary prevention. ? Primary prevention)

16. Possible mechanism of cardioprotection by HRT Favourable lipid profile:  HDL,  LDL,  Lipoprotein (a) Other effects:  insulin sensitivity, vascular dilatation,  coagulation factors

17. Hormone replacement therapy Informed choice Risks and benefits of taking HRT Role of doctor: weighing up the pros and cons for individual woman

18. Prescribing HRT

19. Indications for HRT Relief of menopausal symptoms Long term prevention of osteoporosis

20. Absolute contraindications

21. Existing breast cancer Existing endometrial cancer Venous thrombo-embolism Acute liver disease

22. Routes of administration of oestrogen Oral Transdermal Implants Local vaginal preparation

23. Oral therapy Natural occurring oestrogens: includes premarin and various oestradiol preparations. These oestrogens are metabolised in the liver to the weaker metabolite oestrone and then converted to oestradiol in the peripheral circulation and in the target tissue. Tibolone: a steroid hormone that has oestrogenic, progestogenic and androgenic properties. Synthetic oestrogens: such as mestranol or ethinyl oestrodiol are not generally prescribed for older women for HRT.

24. Transdermal therapy Patches (oestrogen only or combined preparation) or oestrogen gels Women’s preference Skin irritation may be a problem but new matrix patches and the gels are usually well tolerated Route of choice for women with risk factors for venous thrombo-embolism, liver disease or gastro-intestinal problems

25. Oestrogen implants Now less widely used Implants should be given no more than every 6 months Not commonly used in HK

26. Local vaginal therapy Useful for local vaginal dryness and symptoms of urgency Contraindication to systemic HRT but require oestrogen for local symptoms

27. HRT regimens Women who have had a hysterectomy only need to take oestrogen Women with an intact uterus must take progestogen for endometrial protection to prevent endometrial cancer or hyperplasia Regular surveillance of endometrium is required for women (extreme intolerance of progestogen) on unopposed oestrogen

28. The Hong Kong College of Obstetricians and Gynaecologists

29. HRT regimens Sequential preparation: progestogen added for 12-14 days each month. Some women will not bleed on sequential preparations and this is not a cause for concern provided that the progestogen is taken correctly. Continuous combined HRT: give oestrogen and progestogen daily. These preparation induces endometrial atrophy. Intermittent bleeding and spotting are common in the first few month of use. More suitable for women who are at least one year since their last spontaneous period.

30. Progestogen Oral or transdermal form Levo-norgestrel releasing intra-uterine system

31. Oral progestogens C21 progesterone derivatives : dydrogesterone or medroxyprogesterone acetate C19 nor-testosterone derivatives: norethisterone acetate or levonorgestrel

32. Side effects of HRT Nausea breast pain heavy or painful withdrawal period premenstrual syndrome type of side effects weight gain

33. Risk of HRT Breast cancer Thrombo-embolism

34. HRT and breast cancer

35. Breast cancer is a hormone dependent cancer and its relationship with HRT is a complex one. The chance of a woman developing breast cancer is 1 in 24 in HK

36. HRT and breast cancer No data from randomised trial of any significant size The Collaborative Group on Hormonal Factors in Breast Cancer reported in Lancet in 1997 is now widely accepted to represent the present situation.

37. Findings of the Collaborative Group on Hormonal Factors in breast cancer Collaborative Group on Hormone Factors in Breast Cancer Lancet 1997;350:1047-59

38. For women aged 50-70 years not using HRT, about 45 in every 1000 will have breast cancer diagnosed over the next 20 years. Collaborative Group on Hormone Factors in Breast Cancer Lancet 1997;350:1047-59

39. The extra risk of developing breast cancer on HRT does not persist beyond about 5 years after stopping treatment. Women taking HRT diagnosed with breast cancer are less likely to have tumours with metastatic spread and therefore have an improved prognosis. Regular mammography is indicated for women on HRT after 50 years old. There is no indication to arrange mammography routinely for women commencing HRT under the age of 50 years.

40. HRT and venous thrombo-embolism

41. Natural oestrogens Women taking HRT have a 2-4 fold increase in risk of venous thrombo-embolism (VTE). Overall risk remain small: 1 in 5000 and mortality from VTE is around 1-2%. Women with significant past history of VTE should have a thrombophilia screen before commercing HRT

42. Duration of treatment

43. Indication of HRT

44. Menopausal symptoms Duration of treatment will depend upon the women’s preference and the presence of risk factors In the absence of risk factors, HRT can be stopped after 2 years

45. Prevention of Osteoporosis 10 years after HRT has been stopped, bone density and fracture risk are similar in women who had used HRT and those have not Long term treatment (>10-15 years) is required to prevent osteoporosis Constant reassessment (general health, risk factors and life expectancy) is required.

46. Monitoring of women on HRT Compliance of treatment, symptoms control, side effects and bleeding pattern Cervical smear

47. Monitoring of women on HRT Recommendation by the Hong Kong College of Obstetricians and Gynaecologists

48. Bleeding pattern

49. Management of irregular bleeding Sequential regimen: bleeding should occur at around the time of progestogen withdrawal (on or after day 11). Bleeding occurs at other time or persistent irregular bleeding should be investigated. Continuous combined regimen: amenorrhoea should be achieved 4 months after start of treatment. Spotting during the first few months is common. Spotting which occurs after a period of amenorrhoea should be investigated.

50. Other options for management of menopausal symptoms and prevention of osteoporosis

51. Tibolone Steriod hormone The parent compound and its metabolites can all bind to steroid receptos Oestrogenic, progestogenic and androgenic properties Different hormonal effects predominate in different tissues. Oestrogenic: climacteric symptoms, bone and lipid Progestogenic: endometrium Androgenic: libido Breast: less breast pain and no change in breast density on mammography

52. Other options for prevention of osteoporosis

53. Bisphosphates Etidronate and Alendronate Inhibitors of bone turnover and slow down or prevent bone loss Both need to be taken on an empty stomach Non-hormonal agents Treatment of choice for older women and those with contra-indications to HRT

54. Raloxifene Selective oestrogen receptor modulators (SERMs) Agonist and antagonist properties Bone protective and reduce cholesterol No effect on the endometrium Evidence to suggest that it is protective against breast cancer Does not help menopausal symptoms and may worsen them

55. Summary Menopause provides an excellent opportunity for the woman to see a doctor and discuss about her own health Health education Promotion of healthy life style Update on the various options for long term health benefit