2. How to diagnose Menopause?
In a woman > 45 years of age, diagnose
• Perimenopause
• If she is having vasomotor symptoms and irregular periods
• Menopause (with uterus)
• If her last menstrual period was >12 months ago and she is not
using hormonal contraception
• Menopause (without uterus)
• If she has climacteric symptoms
NICE guideline : Menopause: diagnosis and management, 2015
3. FSH measurement
Consider using FSH to diagnose menopause only in:
• Women aged 40-45 years with menopausal symptoms +
change in menstrual cycle
• Women aged <40 years in whom menopause is suspected
• FSH > 35miu/ml in 2 separate occasions 6 weeks apart
NICE guideline : Menopause: diagnosis and management, 2015
4.
5. Average age of Menopause
• Mean age of menopause in Malaysia = 50.7 years
• Average life expectancy of Malaysian women = 74 years
First Consensus Meeting on Menopause in the East Asian Region – Menopause
and HRT in Malaysia
6. Physiology of Menopause
• Menopause occurs when the ovary runs out of eggs
• This results in reduced estradiol (E2) and increased FSH
• Therefore, symptoms of menopause relate to estrogen
deficiency
During perimenopause,
• There can be wide variation in hormone levels
• Women can present with a mixture of both estrogen excess
and estrogen deficiency symptoms
• Symptoms of estrogen excess include breast tenderness,
menorrhagia, migraine, nausea, shorter cycle length, shorter
follicular phase
7. Climacteric Symptoms
MUM’S Vagina
• Musculoskeletal symptoms
• Joint and muscle pain
• Urogenital symptoms
• Vaginal dryness / itching, dyspareunia, urinary frequency/urgency
• Mood changes
• Irritability, depressive sx, sleep disturbance, reduced
concentration
• Sexual difficulties
• Loss of libido
• Vasomotor symptoms
• Hot flushes, night sweats
8. Symptom Prevalence
In the US
• African-American > Caucasian > Chinese > Japanese
In the UK
• 1 in 4 experience severe VMS
• 1 in 3 experience severe psychological symptoms (anxiety,
depression)
• 1 in 2 experience moderate to severe symptoms of sleep
disturbance, joint pain or headache
• 1 in 4 have sexual problems
F. M. Jane & S.R. Davis (2014) A Practitioner’s Toolkit for Managing the
Menopause, Climacteric 17:5, 564-579, DOI: 10.3109/13697137.2014.929651
9. Symptom Prevalence
In Malaysia
• 52% felt that symptoms affected their quality of life
• Only 2.7% reported severe symptoms
Bahiyah Abdullah et al, Prevalence of menopausal symptoms, its effect to quality of life
among Malaysian women and their treatment seeking behaviour, Med J Malaysia Vol 72
Symptom Prevalence
Joint pains / Muscular discomfort 24%
Fatigue / Irritabiliry 60%
VSM symptoms 55%
Depression / Anxiety 45%
Vaginal dryness 41%
Sexual problems 35%
10. Symptom Duration
• There is no age limit at which menopausal symptoms cease
• 10% of women have VMS 10 years after menopause
• 16% of 85 year olds continue to experience VMS
F. M. Jane & S.R. Davis (2014) A Practitioner’s Toolkit for Managing the
Menopause, Climacteric 17:5, 564-579, DOI: 10.3109/13697137.2014.929651
11. Other Health Consequences of
Menopause
Metabolic
• Central abdominal fat deposition
• Insulin resistance / T2DM
Cardiovascular
• Impaired endothelial function
• Increased cholesterol
Skeletal
• Accelerated bone loss
• Increased fracture risk
12. Neurological
• ? Cognitive performance decline
Urogenital
• Atrophic vaginitis
• Urinary tract – frequency, cystitis, urge incontinence, dysuria
Cancer
• Breast / cervical / colon
Other Health Consequences of
Menopause
13. Indications for starting HRT
• Management of menopausal symptoms
• VSM symptoms
• Mood disorders
• Altered sexual function
• Urogenital atrophy
• Prevention of Osteoporosis
14. Indications for Treatment
Complaint 1st line treatment 2nd line treatment
Vasomotor symptoms HRT SSRI, SNRI, Clonidine
Black cohosh
Low mood HRT CBT
SNRI/SSRI only for
diagnosed depression
Reduced libido HRT / Tibolone Add on Testosterone
Urogenital atrophy Vaginal estrogen Add on moisturisers,
lubricants
High risk of osteoporosis HRT ( <60 yo) Bisphosphonates,
Denosumab, SERM
NICE guideline : Menopause: diagnosis and management, 2015
15. Treatment options
HRT
• Estrogen only – ERT (Only to be used in women w/out uterus)
• Oral / Patch / Vaginal
• Estrogen + Progestogen – E+P
• Oral / Patch
• Continuous HRT or Sequential HRT
Other options
• Tibolone
• TSEC (Tissue-selective estrogen complex therapy)
• Estrogen + SERM
• SSRI / SNRI
16. Contraindication for HRT
• History of breast cancer
• History of VTE / stroke
• Undiagnosed uterine bleeding
• Significant cardiovascular disease
• Hypersensitivity to estrogen
• Active liver disease
• Fibroids / endometriosis (Relative contraindications)
17. Timing of Initiation
• Best to start within 10 years of menopause
• Should NOT start HRT above 60 yo without STRONG indication
• In premature menopause, HRT is recommended until at least
age of ‘natural’ menopause ie 50yo
18. Dosages
Use the LOWEST EFFECTIVE dose
of estrogen consistent with
TREATMENT GOALS
• All women with an intact uterus will require progestogen.
• Younger women generally require higher doses than older
women
20. Which is better?
• CEE and Micronised Estradiol found to have lowest risk of
increase in VTE
• Micronised progesterone and Dydrogesterone found to have
lower risk of breast cancer
21. Pre-treatment evaluation
General examination
• Medical history
• Family history
• Weight/Height/BMI
• Blood pressure
• Breast examination
• Bimanual
examination
• Papsmear
Optional Investigations
• Lipid profile
• FBS
• FBC
• Buse/Cr
• LFT
• TFT
• BMD
• Mammogram
Mammography screening should be done 2 yearly from 50-74 yo – US
Preventive Task Force (USPTF) 2009
22. Duration of use
• NO MANDATORY duration
• HRT can be given for AS LONG AS THE WOMAN WANTS IT
• Ensure adequate supervision – annual risk-benefit assessment
• Ensure woman aware of risks and benefits
23. Clinical Side Effects of HRT
Estrogen excess
• Nausea, headache, breast tenderness
• May be reduced by transdermal estrogen
• Try changing to a different preparation
E+P HT
• Heavy bleeding, low mood
• Micronised progesterone may have less mood side effects
24. Long Term Effects of HRT
• VTE
• Stroke
• Cardiovascular disease
• Breast cancer
• Type 2 diabetes
• Osteoporosis
NICE guideline : Menopause: diagnosis and management, 2015
25. VTE and HRT
• Micronised progesterone has lower risk of CTE compared to
other types of progesterone
• Estradiol may have lower risk of VTE compared to other types
of estrogen
• E only – 4 additional cases per 10 000 woman years
• E+P – 6 additional cases per 10 000 woman years
• Transdermal estrogen patch is NOT SHOWN to increase VTE
• Patch should be used in women with increased risk of VTE
R. J. Baber, N. Panay & A. Fenton the IMS Writing Group (2016) 2016 IMS Recommendations on women’s
midlife health and menopause hormone therapy, Climacteris, 19:2, 109-150, DOI: 10.3109-
13697137.2015.1129166
26. Stroke and HRT
• HRT in women <60 years of age and <10 years since
menopause is not shown to increase risk in stroke
• WHI study
• Small increased risk of stroke in women taking oral estrogen
>60 yo (but not transdermal estrogen!)
27. Cardiovascular disease & HRT
• HRT does NOT increase cardiovascular disease risk when
started in women <60 yo
• Risk of cardiovascular disease depends largely on other factors
• HRT with estrogen alone is associated with no, or REDUCED
risk of coronary heart disease
• HRT with E+P is associated with little or no increase in the risk
of coronary heart disease (up to 5 more women per 1000
women)
• DOPs study – reduction in risk of CVD present up to 16 years
later
NICE guideline : Menopause: diagnosis and management, 2015
28. Breast cancer & HRT
• Estrogen ALONE is associated with little or NO CHANGE in the
risk of breast cancer
• E+P is associated with a small increase in risk of breast cancer
• Up to 5 more cases per 1000 women
• Any increase in risk will reduce after stopping HRT
• Micronised progesterone may have lower risk
NICE guideline : Menopause: diagnosis and management, 2015
29. Type 2 diabetes & HRT
• No contraindication for HRT
• Not shown to have any impact on DM
30. Osteoporosis and HRT
• T-score
• Osteopenia -1 to -2.4
• Osteoporosis -2.5 or lower
• Osteoporosis depends on multiple factors including genetics
and lifestyle
• HRT significantly reduces the risk of fragility fracture but the
benefits decrease once treatment is stopped
• 23 fewer fractures per 1000 women
NICE guideline : Menopause: diagnosis and management, 2015
31. Summary of Long Term Effects
of HRT
E only E+P
VTE
Baseline risk 1:1000
+4 per 10 000 women
No increase in transdermal
+6 per 10 000 women
Stroke
Baseline risk 11:1000
No increase in transdermal +6 per 1000 women
CHD
Baseline risk 26:1000
-6 per 1000 women +5 per 1000 women
Breast cancer
Baseline risk 22:1000
-4 per 1000 women +5 per 1000 women
Osteoporosis
Baseline : variable
-23 per 1000 women -23 per 1000 women
NICE guideline : Menopause: diagnosis and management, 2015
32. Summary of Long Term Effects
of HRT
E only E+P
VTE
Baseline risk 1:1000
+ / = +
Stroke
Baseline risk 11:1000
+ / = +
CHD
Baseline risk 26:1000
+
Breast cancer
Baseline risk 22:1000
+
Osteoporosis
Baseline : variable
33. Perimenopausal Women
GOALS – Cycle control, Contraception, Symptom control
• OCP
• Rule out CI eg smoking, hypertension, dyslipidaemia, migraine,
thrombosis risk, CVS risk
• Consider switching to estradiol containing OCP rather than EE
• Progestogen only contraception
• Oral progestogens may be helpful in cycle control but not
symptoms
• LNG-IUS can be combined with oral estrogen for symptom control
• Cyclical MHT
• MHT does not suppress ovulation hence there may be symptoms
of estrogen excess eg mastalgia, erratic bleeding
36. Tibolone
• Estrogenic, progestogenic and androgenic action
• Contraindicated for breast cancer patients
Improvement Increased Risk
Libido /
Osteoporosis /
Stroke >60yo – 2x risk
Breast cancer Reduced risk
Colon cancer Reduced risk
Endometrial
hyperplasia
No impact
F. M. Jane & S.R. Davis (2014) A Practitioner’s Toolkit for Managing the
Menopause, Climacteric 17:5, 564-579, DOI: 10.3109/13697137.2014.929651
37. TSEC – Tissue-selectiveestrogencomplextherapy
• SERM + Estrogen
• CEE 0.45mg/day + Bazedoxifene 20mg /day
• Reduces VMS
• Improves urogenital atrophy
• Preserves bone mass
• Does not stimulate the endometrium
• No evidence to increase VTE
• No increase in breast cancer
F. M. Jane & S.R. Davis (2014) A Practitioner’s Toolkit for Managing the
Menopause, Climacteric 17:5, 564-579, DOI: 10.3109/13697137.2014.929651
38. SSRI / SNRI
• Second line treatment for VMS
• May also improve mood and well-being
• Not indicated for low mood without clinical depression
39. HRT available in Malaysia
Brand name Hormonal content Dosage
Angeliq Estradiol hemihydrate
+ Drosperinone
1.0mg
2.0mg
Climen - 16 pills
- 12 pills
Estradiol valerate
Estradiol valerate
+ cyproterone acetate
2.0mg
2.0mg
1.0mg
Divigel gel
(28 sachets)
Estradiol 1mg/g
41. HRT available in Malaysia
Brand name Hormonal content Dosage
Oestrogel gel 17ẞ estradiol 1.5mg/2.5g gel
Permarin Conjugated equine
estrogen
0.3mg, 0.625mg
Premarin vaginal cream Conjugated equine
estrogen
0.3mg/0.625mg/42.5g
Premelle 2.5 CEE
+ MPA
0.625mg
2.5mg
Premelle 5.0 CEE
+ MPA
0.625mg
5mg
42. HRT available in Malaysia
Brand Name Hormonal content Dosage
Progynova Estradiol valerate 1.0mg or 2.0mg
Progyluton - 11 pills
- 10 pills
Estradiol valerate
Estradiol valerate
+ norgestrel
2.0mg
2.0mg
500mcg
43.
44.
45.
46.
47.
48.
49. Summary
• Current evidence indicates that HRT BENEFITS OUTWEIGHS
HARM
• HRT should be given to symptomatic women / women at high
risk of osteoporotic fractures
• Clinicians have an important role to offer HRT after
appropriate counselling and ruling out any contraindications
• The lowest dose of estrogen consistent with treatment goals
should be used
• HRT can be given for as long as the woman wants
• Review women on HRT 6-12 monthly TRO any new
contraindications
• All menopausal women should be given advice on healthy
lifestyle and ideal weight.
