Presentation based on malaysia cpg

1. MANAGEMENT OF MENOPAUSE
CPG 2022

2. MENOPAUSE
• Definition: permanent cessation of menstruation resulting from loss of
ovarian follicular activity.
• It marks the end of women fertility.
• A retrospective diagnosis: when no menses for 12 months after the last
menstruation period (LMP) once physiological and pathological causes has
been ruled out
• Menopause subject women to various health problem and morbidity as
estrogen carry protective effect on women organ eg heart, brain, bone, skin
etc.
• Average malaysian women life expectancy in 2021 was 78.3 years old
• Average age of menopause 50.7 years
• 1/3rd or more of women life will be spent in the post menopause, a state of
estrogen deficiency.

3. TERMINOLOGY OF MENOPAUSE
TERMINOLOGY
Perimenopause period immediately before menopause when endocrinological, biological
and clinical features of menopause begin till 1year after LMP.
Natural menopause permanent cessation of menses resulting loss of follicular activity for 12
months after LMP once pathological or physiological causes has been rule out
Menopause
transition
start when there is variability menstrual cycle and last till the LMP
Premenopause refer to 1 or 2 years before menopause. This terminology not encourage.

4. STAGE OF MENOPAUSE

5. PERIMENOPAUSE
• fluctuation estrogen level-->
perimenopause symptom
• Diagnosis: based on clinical sign and
symptom.
• measurement of FSH and estradiol
not necessary at this stage
• ovulation is unpredictable in
perimenopause--> contraception
needed until 1 year after LMP

6. ABNORMAL UTERINE BLEED (AUB)
IN PERIMENOPAUSE
• Abnormal uterine bleeding in perimenopause -->investigated uring FIGO classification system
PALM-COEIN
(polyps, adenomyosis, leiomyoma, malignancy, coagulation disorder, ovulatory disorder,
endometrial causes, iatrogenic causes and not otherwise classified)
• sexually active women with AUB--> VE, pap smear and transvaginal ultrasound TRO cervix,
uterus and ovaries pathology
• Also need to exclude pregnancy
• If VE cannot be done--> pelvic ultrasound on full bladder is sufficient
• Blood ix: FBC, TFT, COAG if necessary
• Other invasive IX eg EUA, endometrial biopsy or hysteroscopy based on above finding
• Treatment AUB: NSAID (eg Ponstan) and antifibrinolytic (eg Tanexamic acid), COCP or
menopause hormonal therapy(estrogen) + levonorgestrel intrauterine system (LNG-IUS) for
endometrial protection

7. PREMATURE OVARIAN INSUFFICIENCY (POI)
• Premature ovarian insufficiency (POI) is
the cessation of ovarian function below
age 40 years old
• Clinical presentation commonly primary
amenorrhea and 10% with secondary
amenorrhea.
• Primary amenorrhea--> no menopausal
symptom
• Secondary amenorrhea--> more severe
menopausal symtom
• women with POI is at higher risk of long
term consequences of estrogen deficiency
--> osteoporosis, premature coronary
artery disease, CVD and dementia.

8. PREMATURE OVARIAN INSUFFICIENCY
• Due to long term complication of POI, hormonal treatment with estrogen and
progestogen (in absence of contraindication required)
• Women with POI would require higher dose of estrogen than dose available in MHT
• Women with POI still have 5-15% chance of pregnancy due to intermittent ovarian
activity.
combine oral contraceptive pill (COCP)
*recommended
Menopausal Hormonal Therapy (MHT)
*alternative
act as hormonal therapy + additional
contraceptive effect
act as hormonal therapy + no additional
contraceptive effect
higher estrogen dose lower estrogen dose
not require additional contraception require additional contraceptive method eg
barrier method
given until natural age of menopause (50years
old) and change to MHT if hormonal therapy still
required
given until natural age of menopause (50years
old) and continued if hormonal therapy still
required

9. SYMPTOMS OF MENOPAUSE
Vasomotor symptoms
(VMS)
• Hot flushes(>50% women) -sudden waves of heat over upper body and
face lasting for 1-2 mins followed by sweating.
• Women with hot flushes has 2 fold risk of CVD in next 14 years.
• Night sweat - leads to poor sleep
• women with hot flushes +night sweat had 2 fold increase risk hip
fracture in the following years
Genitourinary
syndrome of
menopause symptom
(GSM)
• replaces term Vulvovaginal atrophy or atrophic vaginitis
• symptom: vaginal dryness, painful sex, sexual dysfunction, bladder and
urethral symptoms, frequent UTI, vaginal itchiness, burning and
irritation
Mood symptoms • Can range from irritability, palpitations, poor sleep, crying spells,
anxiety and feelings of low mood.
• The intensity of these symptoms may lessen well into post menopause.
Other symptoms • fatigue, lethargy, joint pain, etc.

10. EFFECT AND COMPLICATION OF MENOPAUSE
Cardiovascular
disease
• risk of cardiovascular disease due to increase age, loss of estrogen, changes of
fat distribution, decrease physical activity and increase in BP, lipid and
glucose level
• incidence of CVD 2-3 times more in post menopause compared to
premenopause
• reduction of modifiable risk factor such as DM, HTN, abdominal obesity,
smoking, psychosocial stress is the most effective strategy
Stroke • more stroke event occur in women due to longer life expectancy
• risk of stroke doubles in women after 10years of menopause
• estradiol shown to have protective effect in premenopausal women
• Other risk factor: DM,HTN,dyslpidemia, obesity, smoking
Venous
thromboembolism
(VTE)
• incidence of VTE is 1 in 1000 among post menopausal women with fatality
rate 10%
• women with early menopause have lesser risk of VTE compared to women
menopause late (each delay year of menopause increase risk of VTE by 7%)
• combination late menopause with high parity (>2child) confers 3fold risk of
VTE

11. EFFECT AND COMPLICATION OF MENOPAUSE
Osteoporosis • women loss 50% their trabecular bone and 30% cortical bone during the
course of their lifetime, about half of which is lost during first 10 years of
menopause
• Estimated 7-10% decline in spine bone mineral density (BMD) and 5-7% in the
hip BMD after 5 years menopause then increase risk of fracture by 50-100%
Sarcopenia • age-related involuntary loss of skeletal muscle mass and strength
• up to 50% muscle mass can be lost by 80 years of age
• causes: age related hormonal changes, low level physical activity, reduce
protein and calorie intake
• with aging, loss of type 2 muscle causes disability and problems with certain
movement such as regain posture after diturbed balance, rising from chair
Metabolic
syndrome
• consist of abdominal obesity, insulin resistance/glucose dysregulation,
dyslipidemia and hypertension
• average weight gain 2.0-2.5kg over 3years after menopause
• increase visceral fat especially around abdomen as early 3-4 years before
menopause

12. EFFECT AND COMPLICATION OF MENOPAUSE
Cognition • estrogen has positive effect on long term cognition
• women who menopause early/ POI has poor long term effect of congintive
function compared to women who menopause late
Skin • 30% skin collagen lost withing first 5 years menopause
• skin changes associated with loss estrogen are:
• Oily skin due to increase sebum production
• sagging skin and wrinkles due to change in fat distribution
• elastrosis due to lesser collagen and elastion
• thinning of epidermis lead to skin dryness and itchiness
• hyperpigmentation due to increase melanin result from hormonal imbalance
Hair • lesser and thinner scalp hair, male pattern baldness along with darker hair over
chin, upper lip and chest
• due to change in androgen:estrogen ratio (high androgen, low estrogen)
Taste • change of taste and neural function
• caused by reduction in saliva production, dysesthesia and atrophic gingivitis

13. EFFECT AND COMPLICATION OF MENOPAUSE
Dentition • increase risk of gum disease
• bone loss at the jaw lead to loosening of teeth and mandibular dysfunction
• mouth dryness due to lesser saliva secretion
• others: gingival atrophy, oral ulcer, oral candidiasis, sensation of painful mouth
and burning mouth syndrome
Vision • dry eyes (common) due to inflammatory process within lacrimal gland
• cataract more prevalent post menopause (estrogen confers an anti-oxidative
protection against cataractogenesis)
Voice • more throat clearing episode and mouth dryness
• hoarseness of voice due to higher androgen level (androgen:estrogen
imbalance)
Hearing • estrogen have positive influence on hearing
• higher decline of hearing occur during menopause
Smells • ageing is accompanied by olfactory loss and hyposmia or anosmia
• women affected strongly than man

14. HISTORY AND PHYSICAL EXAMINATION
*Vaginal examination only carried out in women
who sexually active.

16. INVESTIGATION
• *pap smears are carried out
only in women who are
have been sexually active.
• Blood tests for FSH
(Follicular Stimulating
Hormone) should not be
routinely considered when
diagnosing menopause in
women aged over 45 years.

17. NON PHARMACOLOGICAL MANAGEMENT OF
MENOPAUSE

18. MENOPAUSAL HORMONAL THERAPHY (MHT)
• Replaces old term “ Hormonal Replacement Theraphy (MHT)”
• Effective for GSM, VSM and prevent bone loss and reduces fracture.
• Benefit outweight risk when given to healthy symptoms who are less
than 60 years or within 10 years of onset of menopause.
• MHT should be individualized taking into account:
womans personal health risk and preferences
signs and symptoms and its effect on her quality of life
age and duration of menopause in relation to initiation or continuation of MHT
balance of potential benefit and risk of MHT versus Non hormonal therapies or
other option.

19. INDICATION OF MHT
1. Vasomotor symptom(VMS):
 reduces hot flushes and night sweat.
MHT recommended as first line therapy for moderate and severe
VMS
2. Genitourinary syndrome of menopause (GSM):
 Low dose vaginal ET (estrogen therapy) recommended over
systemic therapy as first line therapy.
MHT has been shown to effectively restore genitourinary tract
anatomy, increase superficial vaginal cells, reduces vaginal PH and
treat symptoms of Vulvovaginal atrophy (VVA).

20. INDICATION OF MHT
3. Prevention of bone loss:
MHT reduce bone loss and reduces fractures (include hip/vertebra)
in post menopause women.
4. Hypoestrogenism:
 caused by hypogonadism, POI, premature surgical menopause.
 Hormonal therapy such as low dose COC or MHT recommended at
least until median age of menopause (50years ) and can be
continued after 50years with annual benefit and risk assessment.
 Hormonal therapy relieves VMS, prevent bone loss, improve
cognition, mood and improve lipid profile.

21. CONTRAINDICATION OF MHT
• women with past or present history of following:
Hormonal related
cancer such as
breast or
endometrial cancer
Blood clots
particularly in the
lungs, eyes or deep
vein
Heart attack, stroke
or transient
ischemic attac (TIA)
liver disease or liver
problem
Inadequately
controlled arterial
hypertension
Pregnancy
Undiagnosed uterine
or vaginal bleeed
Hypertriglyceridemia Porphyria

22. TYPES OF MHT
Hysterectomised women
• Estrogen therapy only (ET)
Non-hysterectomised women (intact uterus)
• Estrogen and progesterone therapy(EPT)
• Can be given as cyclical therapy or continuos
combined therapy

23. Estrogen and Progesterone Therapy (EPT)
Cyclical Therapy
• Estrogen taken daily while progestrone taken at least for 12-14 days of cycle to provide endometrial
protection.
• women would experience regular monthly bleeds.
• For women in the perimenopause and up to 1 year from LMP.
Continuous combined therapy
• Estrogen and progesterone taken daily without break
• Called “non bleed therapy”
• Initial spotting or staining (breakthrough bleeding) is common up to 6 month.
• For women 1 year or more from LMP.
• Not recommended for perimenopause due to increase risk of irregular bleeding.
• Unscheduled bleeding > 6months should be investigated after rule out missing pills or non compliance.

25. ESTROGEN -ORAL ROUTE

26. ESTROGEN - TRANSDERMAL CREAM

27. ESTROGEN - TRANSDERMAL CREAM/SPRAY

28. ESTROGEN- TRANSVAGINAL ROUTE

29. CYCLICAL ESTROGEN/PROGESTERONE
PREPARATION

30. CYCLICAL ESTROGEN/PROGESTERONE
PREPARATION

31. CONTINUOUS COMBINE PREPARATION

32. PROGESTERONE PREPARATION

33. BENEFIT AND RISK OF MHT
• In healthy symptomatic women who are less than 60years old or
within 10 years of menopause and with no contraindication, the
benefit risk rato is favourable towards VMS, GSM and bone health.
• For maximum cardio protective efficacy, a women should initiate
MHT as soon as VMS symptoms occur, preferebly within 10years of
menopause
• For women who initiate MHT after 60years old of age or 10years
after menopause, the benefit risk ratio may associate with greater
absolute risk toward CHD, stroke, VTE and dementia.
• Younger women who undergo surgical menopause are advised ET (in
absence of contraindication), to prevent immediate and long term
problems of menopause especially to bone, brain and heart.

34. BENEFIT AND RISK OF MHT

35. DURATION OF MHT
• There is no mandatory limitation to duration of MHT use
• Post menopausal women can continue MHT as long as annual review which
includes a benefit-risk assessment and relevant investigation are carried out.
• When long term MHT (beyond 10 years) is considered, a low dose hormonal
regime is advised.
• Stopping MHT may cause recurrence in VSM (50%), GSM and further bone loss
with increase risk of fracture.
• Continue use of MHT (beyond 10 years) recommended in post-menopausal
women with persistent VSM, to improve GSM, to increase bone density and to
reduce fracture at all sites.
• women with POI or early menopause (natural, induced, surgical), early
initiation of COC or MHT till natural age of menopause (50years old) is
recommended and MHT can be continued after age 50 years if benefit
outweight risk.

36. SIDE EFFECT OF MHT
• Side effect--> usually transient and may resolve spontaneously with
continue used.
• encouraged to continue particular hormone for at least 3months
before swithching or stopping as to allow the initial side effect to
settle
• Side effect likely to occur or be problematic when women further into
their menopause (further away from LMP)

37. • Estrogen is taken daily. Its side
effect likely to occur randomly
or continuously throughout the
cycle.
• Progesterone related side effect
are more problematic and
usually depend on the type,
duration and dose of estrogen
• In cyclic theraphy,progesterone
side effect present during
progestogenic phase of the
cycle
• In continuous combined
theraphy, progesterone side
effect can occur randomly
through the cycle.

38. MANAGEMENT OF MHT SIDE EFFECT
SIDE EFFECT EXPLAINATION AND MANAGEMENT
Breast Pain -due to stimulation of breast gland and discomfort may be settle within 4-6weeks
-Mx: reduce MHT dose and with time, increase to normal dose.
-Alternative: change of progestogen or complete switch to tibolone
Irregular
bleeding
-Cyclical preparation may produces regular and predictable bleeding pattern.
-Non compliance to meds or GI upset (reduce absorption) may alter the pattern.
-Continues combine preparation may cause breakthrough bleeding (BTB) up to 6 months.
- BTB more than 6 months (despite good compliance) should be investigated TRO pelvic
pathology
Abdominal
bloating
-progestrogen inhibit smooth muscle peristalsis resulting in bloating and distension
-symptoms may settle with time.

39. MANAGEMENT OF MHT SIDE EFFECT
SIDE EFFECT EXPLAINATION AND MANAGEMENT
Weight gain -Weight gain in menopause are due to low estrogen level, lifestyle changes and lack of
exercise.
-MHT not associated with weight gain and has been shown to redistribute the fat away
from abdominal area
-MX: appropriate dietary and lifestyle measures.
Leg Cramps not common. Exercise and stretching movement may help reduce the incidence
Nausea and
dyspepsia
-MX: altering the time of intake oral MHT --> taken at night, nausea may not be
experienced.
-or oral MHT taken with food to reduce gastric issue
Alternative: switch oral to transdermal MHT
Headaches -MX : change oral MHT to transdermal MHT in women with persistent headache.
Tansdermal estrogen produces stable estradiol which may cut down frequency of headache
Mood swing
and
Depression
-women with combined theraphy may experience mood changes
-symptoms usually disappear with prolong used.

40. MANAGEMENT OF BREAKTHROUGH BLEEDING
(BTB)
• BTB is common in the first 6
month of continous combine
MHT.
• Noncompliance / GI disturbance
(reduce absorption) also lead to
BTB.
• persistent bleed (6months) or
new onset of bleed need furter
investigation using the FIGO
classification using PALM-COEIN
polyps, adenomyosis, leiomyoma,
malignancy, coagulation disorder,
ovulatory disorder, endometrial
causes, iatrogenic cause and not
otherwise classified

41. CYCLICAL THERAPY WITH ABSENCE SCHEDULED
BLEEDING
• women on cyclical therapy usually may experience regular monthly
bleeding
• 5% of women who compliant on cyclical therapy may not experience
any bleeding due to presence of atrophic endometrium.
• Pregnancy should be ruled out !

42. FOLLOW UP MHT
• TCA 3 month after start
MHT to review side
effect and
effectiveness.
• Upon satisfactory
evaluation, annual
consultation is advised
.

44. STOPPING MHT
• if stopping MHT --> risk of recurrent
VSM (rebound VSM is more severe),
recurrent GSM, risk of fracture.
• Gradual taper down MHT dose over 3-6
months to minimize rebound
symptoms.
• In severe rebound symptoms, continue
low dose MHT for longer time
(preferably 3-6months) prior trying to
stop again.
• succesful stopping MHT --> if women
had none or minimal symptoms after 2-
3 month of hormone cessation

45. MHT IN PERIMENOPAUSE
• fluctuation in estrogen level during perimenopause --> irregular bleeding,
perimenopause symptoms eg hot flushes, night sweat, mood swing,
disturbed sleep pattern, anxiety, depression, myalgia.
• Estrogen is the most effective treatment for perimenopausal symptoms.
• contraception is important in perimenopause as risk of pregnancy 2-3%
between ages 45-50years and 1% after 50years if still not menopause.
• MHT--> only adequate to treat perimenopause symptom, but inadequate as
contraceptive (estrogen and dose in MHT less than in the low dose COCP)
• Low dose COCP (in women without contraindication) can be used until
50years old and change to MHT (if menopause and if hormonal therapy still
required).
• LNG-IUS can be used to control irregular bleeds and as contraception with
added oral/transdermal estrogen to treat perimenopause symptoms

46. EFFECT OF MHT
Vasomotor symptoms -MHT is first line theraphy for VMS
-low dose MHT can be taken 6-8weeks to relieve vasomotor symptoms
-micronised progestrogen when taken at night was effective in treating VSM and improving
sleeps
Mood disorder -MHT not act as antidepressant but augment the effect of SSRI-->improve mood
-oral estrogen improve mood significantly compared to transdermal preparation
Genitourinary syndrome
of menopause (GSM)
-topical vaginal estrogen --> effective to treat GSM +minimal side effect (added
progesterone not required for endometrial protection)
-regular topical vagina estrogen for 2 years not associated with endometrial hypertrophy
-non ablative laser theraphy may be used to treat vulvovaginal symptoms (eg vaginal
dryness, burning, itching, dysparenuia, dysuria) and as short term basis (need to be
repeated at regular interval)
Cardiovascular disease -estrogen improve lipid profile (primarily oral estrogen), improve insulin sensitivity
-estrogen increase serum triglyceride (oral estrogen), increase risk of blood clot
-MHT not recommend for primary and secondary prevention CHD in menopause women
- risk of CVD is higher when starting MHT in women age >60years and >10years from
menopause
-Transdermal estrogen has low risk to CVD, less thrombotic and low risk VTE compared to
oral

47. Stroke -MHT in women <60years old or <10 years of menopause --> minimal risk of stroke
-MHT in women >60years old or > 10 years of menopause --> high risk of stroke
-cardiovascular risk factor: DM/HTN/Dyslipidemia --> increase risk of stroke (oral
therapy)
Venous
thromboembolism
(VTE)
-MHT in women <60years old or <10 years of menopause --> minimal risk of VTE
-Transdermal preparation has lower risk of VTE compared to oral
-obesity increase risk of VTE in MHT
-transdermal estrogen not increase risk of VTE in obese women
Osteoporosis -MHT is first line treatment for osteoporosis prevention for women below 60years
-MHT slows bone turnover, increase bone mineral density (BMD) and decrease
fracture
-in women >60 years old and >10years menopause--> other non hormonal bone-
active therapy require to prevent osteoporosis/fracture.
Sarcopenia -no recommendation use of MHT for prevention or treatment of sarcopenia
Cognition -MHT should not be used solely for cognition or for reduction of alzheimer disease
Skin -collagen loss within 5years of menopause
-estrogen may reverse collagen loss, elastin content, skin moisture and wrinkle
-MHT not advised as first line treatment for aging skin
Hair -MHT not decrease menopause related hair loss or improve hair density

48. Metabolic
disease,
weight & DM
-MHT has beneficial effect on metabolic system but not
recommend as first line to prevent metabolic disease
-in women without DM: increase lean body mass, reduce waist
circumference, reduce abdominal fat, reduction fasting glucose
level, reduction insulin resistance, 30-40% reduction new onset
DM
-in women with DM: reduction insulin resistance, fasting glucose
and fasting insulin
-MHT increase HDL, reduce LDL and mean BP
-oral estrogen increase TG level
Dentition,
vision, voice
changes,
hearing, smell
&taste
-MHT decrease gum disease and tooth loss, improve eyesight,
hearing, smell, taste, decrease hoarseness of voice
-However MHT is not recommend as first line to treat this
problem

49. MHT AND CANCER
Type of cancer Effect of MHT use
Cervical cancer -MHT not increase risk of cervical ca recurrence post hysterectomy
-post hysterectomy cervical ca women--> can use MHT (estrogen therapy) to treat
menopausal symptom
Endometrial cancer -MHT not recommend even after surgery due to fears of stimulating remnant
cancer cells
Lung cancer -MHT not increase risk of lung cancer
-MHT can be use to treat menopause symptom in women completed lung cancer
treatment
Ovarian cancer - risk of ovarian ca with long term MHT use has remained inconclusive
-MHT can be used for treatment of menopause symptom in women completed
ovarian ca treatment

50. MHT IN WOMEN WITH SPECIAL PROBLEM
• endometriosis is an estrogen dependant disease
• MHT should be used with caution -> fear of reactivation endometriotic foci
• women who had surgical menopause due to endometriosis-->estrogen
progesterone treatment is preferred over estrogen therapy only
ENDOMETRIOSIS
• MHT is not contraindicated in fibroids, but volume and size of fibroid may
increase
• Tibolone may be used as alternative to MHT
UTERINE FIBROID
• MHT not contraindicated in women with well controlled BP
HYPERTENSION

51. TIBOLONE (STEAR)
1. Selective estrogenic activity regulator (STEAR) - activates hormonal receptor in a tissue specific manner.
estrogenic effect- relieve vasomotor symptom
progestrogenic effect- prevent endometrial activity and hyperplasia
androgenic effect- increase libido and sexual activity
Decrease bone turnover, increase BMD
2. Tibolone used as follows:
women with intact uterus with no period for 1 year (started early may cause unscheduled bleeding)
transition from continuous combine MHT to tibolone
hysterectomised women if various estrogen preparation not suites them
women with special problem eg endometriosis, fibroid
3. tibolone above women >60years old --> risk of stroke
4. Not recommend in breast ca --> increase risk of recurrence

52. Selective Estrogen Receptor Modulator (SERMs)
• compound that exhibit tissue specific estrogen receptor (ER) agonist or antagonist
• works either stimulate or negate the effect of estrogen
• Usage: treat post menopausal osteoporosis, adjunct therapy by estrogen positive breast
ca due antagonistic action
• Side effect: exacerbate vasomotor symptoms
Tamoxifen -taken in breast cancer survivor to reduce recurrence (estrogen antagonist
activity)
-improve bone mineral density in post menopause women
-may stimulate endometrium (estrogen agonist activity)--> risk of
endometrial hyperplasia
Raloxifen
hydrochloride
- 2nd generation SERMs , alternative to tamoxifen for treatment and
prevention breast ca
-recommended in post menopausal osteoporosis women with higher risk of
breast ca
-cause 55% reduction vertebral fracture

53. NON HORMONAL MANAGEMENT OF MENOPAUSE
(PHARMACOTHERAPHY)
• used as alternative to MHT eg women with breast ca, other medical disorder such as CAD, liver
disease, previous VTE
• Data is limited and inconclusive in treating post menopause symptoms
(a2 adrenergic agonist)
Clonidine
- an antihypertensive and the only licensed non hormonal therapy in UK
-use for vasomotor symptoms
SNRI
(venlafaxine,desvenlafaxine)
-use for vasomotor symptoms
SSRIs
(paroxetine,fluoxetine,citalopram,
escitalopram
-use for vasomotor symptoms
Antiepileptic
(Gabapentin, pregabalin)
-use for vasomotor symptoms

54. NON HORMONAL MANAGEMENT OF MENOPAUSE
(SUPPLEMENT AND HERBS)

55. ALTERNATIVE THERAPY

56. perimenopause/POI

57. THANK YOU