ฮอร์ โมนสำคัญอย่ ำงไรในวัยทอง
Siraya K.
Clinical Practice Guideline
Evidence-Based Medicine
Strength of
Recommendation
A
B
C
D
I
Level of Evidence
I
II
III
Guideline & Recommendations
International Menopause Society (Climacteric)
http://www.imsociety.org/index.php
(2007)
North American Menopause Society (Menopause)
http://www.menopause.org/
(2010)
Asia Pacific Menopause Federation
http://www.apmf.net/ (2008)
American Association of Clinical Endocrinologists Medical Guideline for
Clinical Practice for the Diagnosis and the Treatment of Menopause
(2006)
The Endocine Society. The Journal of Clinical Endocrinology & Metabolism, July
2010, Vol 95, Suppl 1. No 07
HRT – Benefits
Symptomatic
Vasomotor
Mood
Vaginal Atrophy
Insomnia
HRT – RISK
Preventative:
Osteoporosis
Coronary Heart Dz
Alzheimer’s
Genitourinary Health
Colon Cancer
Atrophic Vaginitis
General Sense of Well Being
Sexual Functioning
Breast Ca
Deep Vein Thrombosis (DVT)
Pulmonary Emboli (PE)
Endometrial Ca
Gallbladder Dz
Principles
-> Overall strategy
- lifestyle recommendations: diet, exercise,
smoking and alcohol
- Hormone therapy
-> HT must be individualized (symptoms and need
for prevention)
-> The risks and benefits of HT differ
- Age of menopause woman
- hormonal products and routes of administration
Climacteric 2007;10:181–94
Principles
- Spontaneous or iatrogenic menopause before the
age of 45 and particularly before 40 are at higher
risk for cardiovascular disease and osteoporosis
-> benefit from hormone replacement (should be
given at least until the normal age of menopause
- Counseling should convey the benefits and risks
Climacteric 2007;10:181–94
Principles
- Dosage should be titrated to the lowest effective
dose
- Progestogen should be added to systemic estrogen
for all women with a uterus to prevent endometrial
hyperplasia and cancer
Climacteric 2007;10:181–94
Guideline & Recommendation
Indication
Contraindication
Indication
One
Moderate to
severe vasomotor
symptoms
associated with
menopause
Two
Three
Moderate to
Prevention of
severe symptoms postmenopausal
of vulvar and
osteoporosis
vaginal atrophy
LOE 1, Grade A
SYSTEMATIC REVIEW & META-ANALYSIS
HRT VS placebo
Hot flushes frequency/week
Study
HRT
N
Placebo Mean Difference Weight Mean difference
Mean (SD)
N Mean (SD)
95% CI
95% CI
Less with HRT
Less with placebo
Cochrane Database of Systematic Reviews 2004, Issue 4. Art
HRT VS placebo
Hot flush severity
Study
HRT
N
Placebo Mean Difference Weight Mean difference
Mean (SD)
N Mean (SD)
95% CI
95% CI
Less with HRT
Less with placebo
Cochrane Database of Systematic Reviews 2004, Issue 4. Art
Indication
One
Moderate to
severe vasomotor
symptoms
associated with
menopause
Two
Three
Moderate to
Prevention of
severe symptoms postmenopausal
of vulvar and
osteoporosis
vaginal atrophy
LOE 1, Grade A
SYSTEMATIC REVIEW & META-ANALYSIS
Rings
Pessaries
Tablets
equally effective
for vaginal
Creams
atrophy
Suckling JA, Kennedy R, Lethaby A, Roberts H. Local oestrogen for vaginal atrophy
in postmenopausal women. Cochrane Database of Systematic Reviews 2006, Issue 4.
Systematic
forwith
Vaginal
Atrophy
The
CEE cream isReview
associated
significant
adverse
effects when compared to E2 tablets
(OR 0.18, 95% CI 0.07 to 0.50)
Uterine bleeding
Breast pain
Perineal pain
Suckling JA, Kennedy R, Lethaby A, Roberts H. Local oestrogen for vaginal atrophy
in postmenopausal women. Cochrane Database of Systematic Reviews 2006, Issue 4.
Systematic Review for Vaginal Atrophy
Significant endometrial overstimulation with the CEE
cream group when compared to the ring (OR 0.29,
95% CI 0.11 to 0.78)
2% incidence of simple hyperplasia in the ring group
when compared to the CEE cream
4% incidence of hyperplasia in the CEE cream group
when compared to the tablet (E2).
Suckling JA, Kennedy R, Lethaby A, Roberts H. Local oestrogen for vaginal atrophy
in postmenopausal women. Cochrane Database of Systematic Reviews 2006, Issue 4.
Urinary Disorders
Urinary incontinence
Systemic estrogen + progestin  worsen incontinence
RR 1.32, 95% CI 1.17 -1.48
Local estrogens use  improve incontinence
RR 0.74, 95%CI 0.64-0.86
Cody JD et al. Cochrane Database of Systematic Reviews 2009, Issue 4.
Urinary Disorders
Urinary tract infection
- Oral estrogens did not reduce UTI
- Vaginal estrogens versus placebo reduced the
number of women with UTIs
Perrotta C et al. Cochrane Database of Systematic Reviews 2008, Issue 2. Art
Indication
One
Moderate to
severe vasomotor
symptoms
associated with
menopause
Two
Three
Moderate to
Prevention of
severe symptoms postmenopausal
of vulvar and
osteoporosis
vaginal atrophy
LOE 1, Grade A
SYSTEMATIC REVIEW & META-ANALYSIS
Farquhar C, et al . Long term hormone therapy for perimenopausal
and postmenopausal women. Cochrane Database of Systematic Reviews 2009, Issue 2
WHEN TO USE HRT FOR OSTEOPOROTIC
PREVENTION?
When to use HRT for osteoporotic
prevention?
Established reduction in bone mass, regardless
of menopause symptoms
when alternate therapies are not appropriate or
cause side effects
when the benefits of extended use are expected to
exceed the risks.
2010 The North American Menopause Society
Additional indication
AACE & IMS
Mood disorders (depression)
Sexual dysfunction
Cognitive disruption
Comment
Need to exclude other causes
IMS, NAM & APMF
Sleep disturbances associated with vasomotor symptom
Sexual function
HRT can be effective in relieving dyspareunia.
Lubrication
Blood flow
Sensation in vaginal tissue
HRT is not the sole treatment for diminished sexual function.
NAMS 2010
Guideline & Recommendation
Indication
Contraindication
Contraindication
1) Current, past, or
suspected breast
cancer
2) Known or suspected
estrogen-sensitive
malignant conditions
3) Undiagnosed genital
bleeding
4) Untreated EH
5) Known
hypersensitivity to
the active
substances of HT
6) Active liver disease
7) Previous idiopathic
or current venous
thromboembolism
7) Active or recent
arterial
thromboembolic
disease
8) Untreated
hypertension
9) Porphyria cutanea
tarda
History taking & PE
• Assessment of risk factors for stroke, CHD, VTE,
osteoporosis, Breast cancer
Mammogram
• Should be performed according to national
guidelines and age
• preferably within the 12 months before initiation
of therapy
Bone mineral density measurement
• May be considered on a case-by-case basis.
Other
• Lipid profile
• Blood sugar
2010 The North American Menopause Society
Mammogram & Breast Cancer Screening
Systematic Review & Meta-analysis
Reduction of Death from Mammogram
Women > 50
Women 40-50
yrs
RR 0.84
RR 0.85
(95% CI, 0.77,
0.91)
(95% CI, 0.73 ,
0.99)
NNT 1224
NNT 1792
(95% CI, 665,
2564)
(95%CI, 764, 10
540)
Ann Intern Med. 2002;137:347-360.
Breast Cancer Mortality
& Screening Mammogram
Mortality 
Mortality 
Screened Women
Mortality 
Mortality 
Unscreened Women
Cancer Epidemiol Biomarkers Prev 2006;15(1):45–51
HRT IN BREAST CANCER
Randomized Controlled trials
Estrogen + Progestin , RR per 5 years of use
Observational trials
Tips
Endometrial & breast cancer remain contraindications
Ovarian cancer, cervical cancer, are not
contraindication
HT is not a contraindication.
Women at different levels of CV risk with either
optimal BP or with HT
Progestogens with antimineralocorticoid activity preferred
Routes Estrogen treatment
ORAL
TOPICAL
TRANSDERMAL
INJECTABLE
VAGINAL
Progestogen
Estrogen
Cyclic sequential regimen
Continued estrogen everyday
Estradiol gel 1 mg/day
Estradiol oral 1 mg/day
Progestogen in last 14 days of cycle
MPA 5 mg/day
Dydrogesterone 10 mg/day
Cycloprogynova
- Schering, Germany.
- Pills N=21 calendaristic packing.
Composition:
- Estradiol Valerate 2 mg (11 white Pills)
- Estradiol Valerate 2 mg and
Norgestrel 0.5 mg (10 light-brown Pills)
Continuous combined regimen
E+P everyday
Estrogen
Estradiol gel 1 mg/day
Estradiol oral 1 mg/day
Progestogen
MPA 1.5 or 2.5 mg/day
Dydrogesterone 5 mg/day
Levonorgestrel IUD
Femoston conti.
- Solvay Pharmaceuticals
- Containing
5 mg dydrogesterone
1 mg estradiol
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No
Contraindication
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E+P
E
Contraindication
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Advise
THANK YOU FOR YOUR
ATTENTION