Management of menopause

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 Hot flushes
(early) Insomnia
Irritability
Mood disturbances

Physical changes Vaginal atrophy

(intermediate) Stress (urinary) incontinence
Skin atrophy

Diseases Osteoporosis
(late) 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
 A n a lg o r it h m f o r t h e a d m in i s t r a t io n o f H R T

D e c is io n m a d e t o u s e r H R T

A b s o lu t e c o n t r a - in d ic a t io n ?

Yes N o

N o HR T B a s e lin e in v e s t ig a t io n s c o m p le t e d

C om m ence H R T

P r e v io u s h y s te r e c o m y In ta c t u te ru s + a m e n o rrh o e a < 2 y rs In ta c t u te ru s + a m e n o rrh o e a > 2 y rs

U n o p p o s e d o e s tro g e n th e ra p y C y c lic a l / s e q u e n t ia l H R T C o n tin u o u s c o m b in e d 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

 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 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