2.hormonal therapy (final version)
TRANSCRIPT
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Dr Budi Wiweko, SpOG (K)
Tempat/Tgl Lahir : Jakarta, 15 Agustus 1971
Alamat : Vila Jatibening
Jl Villa Cendrawasih III Blok KH No .6 Bekasi
PENDIDIKAN
1. Fakultas Kedokteran Universitas Indonesia (1990-1996)
2. Spesialis Obgin FKUI (2001-2005)
3. Research Student di Hyogo College of Medicine, Japan (2006)
4. Spesialis Konsultan FER di FKUI (2009)
PEKERJAAN
1. Staf Medis Departemen Obstetri Ginekologi FKUI-RSCM (2005-
Sekarang)
2. Asisten Manajer Pendidikan Dokter Spesialis Obgin FKUI (2006-
Sekarang)
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HORMONAL THERAPYWhat should we do after WHI study ?
Division of Reproductive Immunoendocrinology
Department of Obstetrics and Gynecology
Faculty of Medicine University of Indonesia
Dr. Cipto Mangunkusumo General Hospital
Jakarta
Budi Wiweko
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Outline of this talk
1. Background
2. Benefits and risks of hormonal therapy
3. How to choose hormonal therapy ?
4. Take home messages
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An epidemic of fear and distrust has infected women
(and physicians) after publication of the Womens
Health Initiative (WHI)
Background
Benefits and
risk of
hormonal
therapy
How to choose
hormonal
therapy
Take home
messages
Graziottin. Maturitas, 2005
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PROS AND CONS
This is RCT about combination of 0.625 mg Conjugated Equine
Estrogen and 2.5mg Medroxyprogesterone Acetate
on 16.608 post menopausal women between 50-79 years old
JAMA, July 17, 2002 Vol.288, 321-33
Background
Benefits and
risk of
hormonal
therapy
How to choose
hormonal
therapy
Take home
messages
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JAMA, July 17, 2002 Vol.288, 321-33
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JAMA, July 17, 2002 Vol.288, 321-33
Background
Benefits and
risk of
hormonal
therapy
How to choose
hormonal
therapy
Take home
messages
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Background
Benefits and
risk of
hormonal
therapy
How to choose
hormonal
therapy
Take home
messages
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25.000
Speroff L, Glass R, Kase N. Clinical gynecologic endocrinology and infertility, 7th
edition, 2005
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Low level estrogen related symptoms
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EARLY SYMPTOMS- Vasomotor
- Hot flushes
- Night sweat
- Urogenital tract symptoms
- Vaginal dryness and dyspareunia
- Low sexual drive
- Dysfunction of orgasm
- Urinary incontinence
- Psychological symptoms- Mood swings
- Depression
- Anxiety
- Insomnia
Background
Benefits and
risk of
hormonal
therapy
How to choose
hormonal
therapy
Take home
messages
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LONG TERM EFFECT- Osteoporosis
- Pelvic floor laxity
- Cardiovascular disease- Colon cancer
- Alzheimers disease
Background
Benefits and
risk of
hormonal
therapy
How to choose
hormonal
therapy
Take home
messages
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No Terminology Description
1 EPT Combined estrogen-progestogen therapy
2 ET Estrogen therapy
3 HT Hormone therapy (encompassing both ETand EPT)
4 Local therapy Vaginal ET administration
5 Progestogen Encompassing both progesterone and
progestin
6 Systemic therapy HT administration that results in absorptionin the blood
Menopause, 2010
Background
Benefits and
risk of
hormonal
therapy
How to choose
hormonal
therapy
Take home
messages
North American Menopause Society (NAMS)
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Indications for Hormonal Therapy
Relief of menopausal symptoms
Long term prevention of cardiovascular
disease, dementia, and osteoporosis
Background
Benefits and
risk of
hormonal
therapy
How to choose
hormonal
therapy
Take home
messages
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Using validated methods of measuring well-being and quality of life, the
authors showed that, after 1 year, significant improvements wereobserved in the following domains for those taking combined hormone
therapy:
- vasomotor symptoms,
- sexual functioning,
- sleep problems,- aching joints or muscles (p < 0.001 for all)
Health related quality of life after combined hormone replacement therapy:
randomised controlled trial. BMJ. 2008
Background
Benefits and
risk of
hormonal
therapy
How to choose
hormonal
therapy
Take home
messages
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Vasomotor
ET, with or without a progestogen, is the most
effective treatment for menopause-related
vasomotor symptoms (ie, hot flashes and night
sweats) and their potential consequences (eg,
diminished sleep quality, irritability, and reducedQOL)
Background
Benefits and
risk of
hormonal
therapy
How to choose
hormonal
therapy
Take home
messages
Menopause, 2010
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Urogenital tract
1. Relief of moderate to severe vaginal atrophy with
systemic or local HT can be effective in relieving
dyspareunia, a common cause of intercourse
avoidance2. Local ET may help reduce the risk of recurrent
urinary tract infection (UTI)
Background
Benefits and
risk of
hormonal
therapy
How to choose
hormonal
therapy
Take home
messages
Menopause, 2010
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Cardiovasvular
1. HT is currently not recommended as a sole or
primary indication for coronary protection inwomen of any age
2. Initiation of HT by women ages 50 to 59 years or by
those within 10 years of menopause to treat typicalmenopause symptoms (eg, vasomotor, vaginal)
does not seem to increase the risk of CHD events
Background
Benefits and
risk of
hormonal
therapy
How to choose
hormonal
therapy
Take home
messages
Menopause, 2010
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Drive J. Curr Op Obste Gynecol, 2005
Background
Benefits and
risk of
hormonal
therapy
How to choose
hormonal
therapy
Take home
messages
10 years Estrogen +MPA
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HORMONAL THERAPY
ESTROGEN1. Oral (tablet)
2. Transdermal
Patch
Gel
3. Vaginal
Vaginal ring
Vaginal cream
PROGESTIN Tablet Levonorgestrel intrauterine system
(LNG-IUS)
Background
Benefits and
risk of
hormonal
therapy
How to choose
hormonal
therapy
Take home
messages
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Resistensi Insulin
Increase PAI-I
Increase VLDL
Decrease HDLHyperinsulinemiaLow estrogen
will improved
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Increasing HDL
Lowering VLDL
Increase NO and prostacyclin
Sitruk et al. Maturitas, 2007
Bonasi. Contraception, 2010
Antagonis
Background
Benefits and
risk of
hormonal
therapy
How to choose
hormonal
therapy
Take home
messages
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Negative Effects of Progestin
Cardiovascular
a. Decreasing HDL and increasing VLDL
b. Decreasing NO intravascular
Lopez et al. Maturitas, 2008
Water retention
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Medroxyprogesteroneacetate (MPA)
Medrogestone
Chlormadinone acetate
Cyproterone acetate
Trimegestone
Nestorone
Nomegestrol Acetate
Promegestone Norethindrone(Estranes)
Norethindroneacetate (NETA)
Norethynodrel
Lynestrenol
Ethynodiol diacetate
Levonorgestrel(gonanes)
Desogestrel
Norgestimate
Gestodene
Norgestrel
Natural Synthetic
Progesterone
17-hydroxyprogesterone 19-nortestosterone19-norprogesterone
Spirolactone
Drospirenone
Retroprogesterone
Dydrogesterone
PROGESTERONE AND PROGESTINS
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Anti-aldosterone action of drospirenone
Adrenal gland
Angiotensinogen
Angiotensin I
Angiotensin II
Aldosterone
Receptor level-Increased plasma volume
-Rise of blood pressure in susceptibles
-Water retention -related symptoms
(edema,bloating ,weight gain )
Sodium -and
water retention
Estrogens
DRSP
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Endogenous estrogens seem to play a protective role on cardiovascular
cells, including endothelial, smooth muscle cells and cardiomyocytes,
explaining part of the gender-related differences in coronary heart
disease (CHD)
This study assess the effects of DRSP on eNOS activity and expression inhuman endothelial cells and compare it with P and the synthetic
progestogen MPA
Drospirenone increases endothelial nitric oxide
synthesis via a combined action on progesterone and
mineralocorticoid receptorsT. Simoncini, X-D. Fu, A. Caruso, S. Garibaldi, C. Baldacci, M.S. Giretti, P. Mannella,
M.I. Flamini, A.M. Sanchez and A.R. Genazzani
Hum Reprod, 2007
Background
Benefits and
risk of
hormonal
therapy
How to choose
hormonal
therapy
Take home
messages
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DRSPblocks the reduction of eNOS expression associated with
aldosterone through its anti-mineralocorticoid activity
This action might result in beneficial cardiovascular actions in women,
particularly in the presence of endothelial dysfunction, such as in
hypertension
Hum Reprod, 2007
Background
Benefits and
risk of
hormonal
therapy
How to choose
hormonal
therapy
Take home
messages
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No Estrogen
1 Estradiol valerate 1 dan 2 mg
2 Conjugated equine estrogen 0.625 mg
No Progestin
1 Norethisterone 5 mg
2 Medroxyprogesterone acetate 5 mg, 10 mg
3 Nomegestrol acetate 5 mg
No Estrogen Progestin Nama Paten
1 Estradiol valerate 1 mg Drospirenone 2 mg Angeliq
2 Estradiol valerate 2 mg Norgestrel 500 g Cyclo progynova
3 Estradiol valerate 2 mg Cyproterone
Acetate 1mg
Climen
Background
Benefits and
risk of
hormonal
therapy
How to choose
hormonal
therapy
Take home
messages
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HT Regimens
Women who have had a hysterectomy only
need to take estrogen
Women with an intact uterus must take
progestogen for endometrial protection to
prevent endometrial cancer or hyperplasia
Background
Benefits and
risk of
hormonal
therapy
How to choose
hormonal
therapy
Take home
messages
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Continu
Sequential
Estrogen and progestin were given since day 1st
Progestin was given on last 10 days
HORMONAL THERAPY
NO PERIODS
PERIODS
Background
Benefits and
risk of
hormonal
therapy
How to choose
hormonal
therapy
Take home
messages
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Clinical efficacy: Amenorrhea rates after 1 year
Angeliq: 88% cycle control after 1 year 64% of bleedings confined in 12 pill cycles
In most cases spottings
Mean number of bleeding days: 0.9 days
%p
atientswith
nobleeding
Cycle number
Archer DF et al. Menopause 2005; 12 (6): 716-727
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Angeliq: Number of hot flushes
BL, baselineSchrmann R et al. Climacteric 2004;7:189-196
Me
annumberofhotflushes/week
Treatment week
*P>0.001
*
0
10
20
30
40
50
60
70
80
BL 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Placebo (n=46)
Angeliq (n=38)
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Angeliq: Incidence of menopausal CNS symptoms
Sweating episodes
Sleep problems
Depression
Patients(%)
Baseline
Week 16
Baseline
Week 16
Placebo (n=61)
Angeliq (n=52)
CNS, central nervous system
Schrmann R et al. Climacteric 2004;7:189-196
0
25
50
75
100
Placebo Angeliq Placebo Angeliq Placebo Angeliq
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BL: baseline; BMD: bone mineral density
Schering AG, data on file
Placebo (n=18)
Angeliq (n=18)
-2
-1
0
1
2
3
4
5
6
BL 3 6 12 18 24
Osteopenic women
Change frombaseline in
lumbar spineBMD (%)
Months
of treatment
Effect on vertebral BMD in osteopenic patients
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Angeliq: Change in lipid levels
Archer D et al. Menopause 2005;12:716-27
0,6
-6,7
4,2
17,5
0,1
-12,8 -12,7
-0,2
1,40,1
-15
-10
-5
0
5
10
15
20
Total C LDL-C HDL-C TG HDL/LDL
Angeliq
Estradiol 1 mg
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1. The best candidates for HT are early postmenopausal
symptomatic women
2. Those who should not be treated with HT include
obese women (BMI of 30 or more) and women with
high cardiovascular risk or previous coronary events
3. Drospirenone is the progestogen of choice, given its
anti mineralcorticoid and anti androgenic activity that
prevent cardiovascular risk
4. The benefits of reduction in bone fractures and
reduction ofcolon cancer risk , constantly found in
observational studies, are confirmed by WHI as well
Background
Benefits and
risk of
hormonal
therapy
How to choose
hormonal
therapy
Take home
messages
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Menopausal women
Hormonal therapy
Anamnesis and physical examination
Intact uterus No uterus
Periods No periods
E + P
EP Sequential EP Continu
E: D1-D21
P: D11-D21
Starting lowest dosage
Estradiol valerate 1 mgCEE 0.375 mg
Norethisterone 2.5 mg
Nomegestrol acetate 2.5 mg
Estrogen
ANGELIQ
Combination
Climacteric symptoms
History of breast cancer
USG
Mammography
Pap smear
Liver function, lipid profile
BMD
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