Download Hormone Replacement Therapy

Menopause2
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
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
Unopposed oestrogen therapy
Intact uterus + amenorrhoea < 2 yrs Intact uterus + amenorrhoea > 2 yrs
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 Extra breast cancers in HRT
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 thromboembolism
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