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 non-reproductive stage

Menopause

The final menstrual period and occurs during the climacteric. The average age

of menopause is 51.

Life expectancy and age of menopause

0

10

20

30

40

50

60

70

80

90

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 flushesInsomniaIrritabilityMood disturbances

Physical changes(intermediate)

Vaginal atrophyStress (urinary) incontinenceSkin atrophy

Diseases(late)

OsteoporosisCardiovascular diseaseDementia of the Alzheimer’s typeCancers

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 afterw

ard• Bone loss at a rate of 2-3% per year for 10 ye

ars after menopause• Osteoporosis is associated with fracture ( fem

oral 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 hyp

erlipidaemia• ?Hormone Replacement Therapy (Not eff

ective 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 matri

x 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 adm inistration of H R T

N o H R T

Y es

U nopposed oestrogen therapy

P revious hysterecom y

C yclical / sequen tial H R T

In tact u terus + am enorrhoea < 2 yrs

C on tinuous com bined H R T

In tact u terus + am enorrhoea > 2 yrs

C om m ence H R T

B aseline investigations com pleted

N o

A bsolu te con tra-indication?

D ecis ion m ade to user H R T

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

Length of time onHRT

Extra breast cancers in HRTusers, above the 45

occurring in Non-users, over20 years

5 years use 2 per 1000

10 years use 6 per 1000

15 years use 12 per 1000

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

• 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 i

n risk of venous thrombo-embolism (VTE).• Overall risk remain small: 1 in 5000 and mort

ality from VTE is around 1-2%.• Women with significant past history of VTE sh

ould 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 HRTVisits Tests

First History and physical examination,Blood pressure, FSH/LH, lipid profile,liver function test, bone biochemistry,mammography and urinanalysis

At each visit Blood pressureUrinanalysis

Every 2 years Physical examination, lipid profile,liver function test, determination offasting 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 t

o steroid receptos• Oestrogenic, progestogenic and androgenic properties• Different hormonal effects predominate in different tiss

ues.• Oestrogenic: climacteric symptoms, bone and lipid• Progestogenic: endometrium• Androgenic: libido • Breast: less breast pain and no change in breast densit

y 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 tho

se 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