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 Vaginal atrophy Stress (urinary) incontinence Skin atrophy Osteoporosis Cardiovascular disease Dementia of the Alzheimers type Cancers

Physical changes (intermediate)

Diseases (late)

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 Womens 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 HRT No Baseline investigations completed

Commence HRT
Previous hysterecomy Unopposed oestrogen therapy Intact uterus + amenorrhoea < 2 yrs Cyclical / sequential HRT Intact uterus + amenorrhoea > 2 yrs 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 2 per 1000 6 per 1000 12 per 1000

5 years use 10 years use 15 years use

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 womens 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 First Tests History and physical examination, Blood pressure, FSH/LH, lipid profile, liver function test, bone biochemistry, mammography and urinanalysis Blood pressure Urinanalysis Physical examination, lipid profile, liver function test, determination of fasting glucose level, mammography Bone mineral density

At each visit

Every 2 years

As indicated

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