2.Hormonal Therapy (Final Version)

7/29/2019 2.Hormonal Therapy (Final Version)

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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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2.Hormonal Therapy (Final Version)

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