Download Management of menopause - University of Hong Kong

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
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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
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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
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Change lifestyle risk factors
Exercise
Adequate calcium / vitamin D intake
Hormone Replacement Therapy
Alendronate
Raloxifene
Prevention of cardiovascular disease
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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
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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