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Management of menopause OS Tang Department of Obstetrics and Gynaecology University of Hong Kong Climacteric The phase in the aging process of women marking the transition from the reproductive stage of life to the nonreproductive stage Menopause The final menstrual period and occurs during the climacteric. The average age of menopause is 51. Life expectancy and age of menopause 90 80 70 60 50 40 30 20 10 0 1850 1900 1950 2000 Menopause • Premature menopause • Surgical menopause • Natural menopause Target organs of oestrogen • • • • • • • • Bone Urogenital Vasomotor Heart Eyes Teeth Breast Colon Consequences of oestrogen loss Symptoms (early) Hot flushes Insomnia Irritability Mood disturbances Physical changes (intermediate) Vaginal atrophy Stress (urinary) incontinence Skin atrophy Diseases (late) Osteoporosis Cardiovascular disease Dementia of the Alzheimer’s type Cancers 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 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) Risk factors of osteoporosis • • • • • • • • Family history Ethnicity Early menopause Hypoestrogenism (excessive exercise, anorexia, bulimia) Hyperthyroidism, excessive thyroxine therapy Cigarette smoking Caffeine High alcohol intake 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. Management of menopause • Advise on a healthy life style • Psychological support • Hormone replacement therapy Management of menopausal symptoms • Understand menopause • Strengthening of self-image • Avoid spicy food, alcohol, strong tea and coffee. • Healthy life style • Hormone Replacement Therapy Prevention of osteoporosis • • • • • • Change lifestyle risk factors Exercise Adequate calcium / vitamin D intake Hormone Replacement Therapy Alendronate Raloxifene 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) Possible mechanism of cardioprotection by HRT • Favourable lipid profile: HDL, LDL, Lipoprotein (a) • Other effects: insulin sensitivity, vascular dilatation, coagulation factors Hormone replacement therapy • Informed choice • Risks and benefits of taking HRT • Role of doctor: weighing up the pros and cons for individual woman Prescribing HRT Indications for HRT • Relief of menopausal symptoms • Long term prevention of osteoporosis Absolute contraindications Absolute contraindications • Existing breast cancer • Existing endometrial cancer • Venous thrombo-embolism • Acute liver disease Routes of administration of oestrogen • Oral • Transdermal • Implants • Local vaginal preparation 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. 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 Oestrogen implants • Now less widely used • Implants should be given no more than every 6 months • Not commonly used in HK Local vaginal therapy • Useful for local vaginal dryness and symptoms of urgency • Contraindication to systemic HRT but require oestrogen for local symptoms 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 An algorithm for the administration of HRT Decision made to user HRT Absolute contra-indication? Yes No No HRT Baseline investigations completed Commence HRT Previous hysterecomy Intact uterus + amenorrhoea < 2 yrs Intact uterus + amenorrhoea > 2 yrs Unopposed oestrogen therapy Cyclical / sequential HRT Continuous combined HRT The Hong Kong College of Obstetricians and Gynaecologists 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. Progestogen • Oral or transdermal form • Levo-norgestrel releasing intra-uterine system Oral progestogens • C21 progesterone derivatives : dydrogesterone or medroxyprogesterone acetate • C19 nor-testosterone derivatives: norethisterone acetate or levonorgestrel Side effects of HRT • • • • Nausea breast pain heavy or painful withdrawal period premenstrual syndrome type of side effects • weight gain Risk of HRT • Breast cancer • Thrombo-embolism HRT and breast cancer HRT and breast cancer • 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 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. Findings of the Collaborative Group on Hormonal Factors in breast cancer HRT Use Risk Ratio Each year of HRT use 1.023 (1.011-1.036) >5 years of HRT use 1.35 (1.210-1.400) Collaborative Group on Hormone Factors in Breast Cancer Lancet 1997;350:1047-59 For women aged 50-70 years not using HRT, about 45 in every 1000 will have breast cancer diagnosed over the next 20 years. Length of time on HRT Extra breast cancers in HRT users, above the 45 occurring in Non-users, over 20 years 5 years use 2 per 1000 10 years use 6 per 1000 15 years use 12 per 1000 Collaborative Group on Hormone Factors in Breast Cancer Lancet 1997;350:1047-59 • 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. HRT and venous thrombo-embolism HRT and venous thrombo-embolism • 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 Duration of treatment Indication of HRT 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 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. Monitoring of women on HRT • Compliance of treatment, symptoms control, side effects and bleeding pattern • Cervical smear Monitoring of women on HRT Visits Tests First History and physical examination, Blood pressure, FSH/LH, lipid profile, liver function test, bone biochemistry, mammography and urinanalysis At each visit Blood pressure Urinanalysis Every 2 years Physical examination, lipid profile, liver function test, determination of fasting glucose level, mammography As indicated Bone mineral density Recommendation by the Hong Kong College of Obstetricians and Gynaecologists Bleeding pattern 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. Other options for management of menopausal symptoms and prevention of osteoporosis 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 Other options for prevention of osteoporosis 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 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 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