PENYAKIT KARDIO VASKULER DENGAN HORMON TERAPI
Noor Pramono Noerpramana
Kongres Obstetri Ginekologi Indonesia Ke-XIII Manado 7-12 Juli 2006
RABU, 12 JULI 2006. PKL 11.30 – 12.30
SKEMA MEKANISME KERJA AKSIS HIPOTALAMUS- HIPOFISIS-OVARIUM PADA MASA REPRODUKSI
SKEMA PERUBAHAN AKSIS HIPOTALAMUS- HIPOFISIS-OVARIUM PADA MENOPAUSE
DEFISIENSI ESTROGEN
• SINTESIS SEROTONIN ↓ • KATABOLISME SEROTONIN ↑
PREKURSOR ESTROGENKATEKOLAMIN ↓
KENDALI SIMPATOHIPOTALAMIK ↓ SISTEM LIMBIK • TERMOREGULASI • SISTEM KARDIOVASKULER • • • • •
MOOD ↓ AFEK ↓ MEMORI ↓ LIBIDO ↓ MOTIVASI ↓
• • •
HOT FLUSHES KERINGAT MALAM PALPITASI
GEJALA DAN TANDA MENOPAUSE
TERAPI HORMON IDEAL
FAKTOR RISIKO PENYAKIT KARDIO VASKULER Potentially modifiable risk factors l High total cholesterol (>240mg/dl =>6.2mm0l/dl) l Low serum high density lipoprotein cholesterol (<35mg/dl=<0.9mmol/L) l Hypertension (>140/>90 mm Hg) l Obesity (> 130% normal body weight) l Physical inactivity l Smoking l Alcohol abuse l Diabetes mellitus
Unmodifiable risk factors l Premature menopause (<45 years) l Family history of premature CVD l Male sex l Male age (> 45 Years)
FAKTOR RISIKO PENYAKIT KARDIO VASKULER DYSLIPIDEMIA HYPERTENSION & ATHEROSCLEROSIS OBESITY DIABETES MELLITUS HEMOSTASIS SYSTEM PHYSICAL INACTIVITY SMOKING AND ALCOHOL ABUSE OTHER
DYSLIPIDEMIA DIWASPADAI PENYAKIT KARDIO VASKULER q Total Kolesterol Serum > 240 mg/dl (>= 62 mmol/L ) q LDL Kolesterol Serum > 160 mg/dl q HDL Kolesterol Serum < 35 mg/dl ( =< 0.9 mmol/L) q HDL-2 Kolesterol Serum < 30 mg/dl
HYPERTENSION & ATHEROSCELORIS DIWASPADAI PENYAKIT KARDIO VASKULER q Tekanan Darah >140 / > 90 mm Hg q Atherosclerosis
ATHEROSCLEROSIS MERUPAKAN PENYEBAB UTAMA PENYAKIT KARDIO VASKULER
MEKANISME TERJADINYA ATHEROSCLEROSIS
SEL ENDOTEL VASKULER l
Sel endotel vaskuler menghasilkan prostasklin ( Vasodilator) dan Endotelin (Muscle relaxant) à Stabilisator tekanan diastolik
l
Post menopause à Produksi prostasiklin dan endotelin ?, Transport kalsium pada otot vaskuler ?à Tekanan darah tak stabil dan kejadian atheroma ?à PKV
OBESITY DIWASPADAI PENYAKIT KARDIO VASKULER q Obesity ( >= 130 % normal body weight) q Obesitas Androgenik ( ANDROID FAT ?) à PKV ? q Post Menopause à Proporsi Android FAT/GYNECOID FAT ?à RESISTENSI INSULIN ? à HIPERGLIKEMIA à PKV
DIAGNOSIS PKV
• ANAMNESIS • PEMERIKSAAN FISIK
PEMERIKSAAN PENUNJANG
• • • •
ELEKTROKARDIOGRAFI EKHOKARDIOGRAFI ANGIOGRAFI KORONER THALLIUM EXERCISE MYOCARDIAL IMAGING • LABORATORIUM (CKMB, LDH, AST)
DIABETES MELLITUS • Diwaspadai penyakit kardio vaskuler oleh karena komplikasinya • Post menopause à Sekresi insulin ? & sensitivitas jaringan terhadap insulin ? à Resistensi insulin ?à Hiperglikemia
HEMOSTASIS SYSTEM • Pada gangguan hemostasis sebagai akibat dari peningkatan PAI-1 (Plasminogen activator inhibitor-1) à Hipofungsi Fibrinolitik à PKV • Post Menopause à Estrogen ? Produksi Prostasiklin ? à Adhesi Trombocit ?, Faktor Koagulasi VII Dan Fibrinogen ,?Faktor Anti Koagulan Antitrombin III ? dan Inhibitor Fibrinolisis PAI-1 ?à PKV
The Role of Estrogen & Progestin in Hormone Therapy
Estrogen Positive Effect
Negative Effect
Hot Flushes Skin Dyslipidemia (HDL ?, LDL?) Hemostasis syst Cardio Vascular Endothel Vasc Metabolism Advantage
Proliferation: Endometrium Breast, mitosis ?
Bone Turn Over
Body Weight ? Blood Pressure
CNS, etc
Progestin
RAAS Adverse :
Aldosterone ? ? ?
Positive Effect
Negative Effect
Anti Estrogen
Androgen, Proliferation, Metabolism
Proliferation ?
Acne SHBG ? ? Proliferation of Breast Gland Metabolism Adverse
& ?
Aldosterone ?
RAAS = Renin Angiotensin Aldosterone System
PENGARUH ESTROGEN PADA METABOLISME LIPOPROTEIN
PENGARUH ESTROGEN PADA PEMBULUH DARAH (Estrogen Menghambat Atherosclerosis) q
Menghambat Oksidasi LDL Kolesterol
q
Meningkatkan reseptor LDL Hepatik
q
Meningkatkan produksi EDRF ( Endothelium-Dependent Relaxing Factor)
PENGARUH ESTROGEN PADA SISTEM HEMOSTASIS l
Pemberian Estrogen à Produksi Prostasiklin ? à Adhesi Trombocit? , Faktor Koagulasi VII & Fibrinogen ? , Faktor Anti Koagulan Antitrombin III ?& Inhibitor Fibrinolisis PAI-1 ? à Proteksi PKV
PENGARUH ESTROGEN PADA ENDOTEL VASKULAR l
Pemberian Estrogen à produksi Prostasiklin dan Endotelin ?, Transport Kalsium pada otot Vaskuler? à Tekanan darah stabil dan kejadian Atheroma? à cegah PKV
METABOLISM ADVANTAGE OF ESTROGEN • Pemberian Estrogenà Sekresi Insulin & Sensitivitas jaringan terhadap insulin ?à Resistensi Insulin ? à cegah Hiperglikemia
NEGATIVE EFFECT OF ESTROGEN PENGARUH ESTROGEN PADA RAAS l
Aldosterone ?
l l
Body Weight ? Blood Pressure ?
POSITIVE EFFECT OF PROGESTIN PENGARUH PROGESTIN (Anti Estrogen)
l
Aldosterone ?
Aldosterone ? ( BW ?, BP ?)
NEGATIVE EFFECT OF PROGESTIN PENGARUH PROGESTIN (Metabolism Adverse) l
Progestin à sekresi insulin pankreas ?& resistensi insulin ?à hiperglikemia à PKV
PENELITIAN TERAPI HORMON PADA MENOPAUSE 1. PEPI 2. NHLBI 3. HERS 4. WHI 5. NURSES’ HEALTH STUDY ( NHS) 6. PROSPECTIVE EPIDEMIOLOGICAL RISK FACTORS ( PERF STUDY)
Relative and absolute risks (hazard ratio,HR) for preventable postmenopausal diseases. * An estrogen monotherapy study, randomized and controlled against placebo: hysterectomized women; mean age at start of treatment 63.8 years (50-79 years); mean duration of treatment 6.8 years; 0.625 mg conjugated estrogens treatment and in part not healthy Disease
Relative risk againts placebo (HR); nominal 95% confidence limits
Absolute risk no.of probands/ 10,000 women years Conjugated estrogen
Risk ERT 1
Benefit ERT 1
Placebo
Breast cancer
0.77 (0.59-1.01)
26
33
-
7
Coronary infarction
0.91 (0.75-1.12)
49
54
-
5
Stroke
1.39(1.01-1.77)2
44
32
12
-
Thromboembolism
1.33 (0.99-1.79)
28
21
7
-
Colorectal cancer
1.08(0.75-1.55)
17
16
1
-
Osteoporotic fractures
0.70 (0.63-0.79)3
139
195
-
56
-
-
20
68
-
-
-
-
Sum of events Mortality
0.98
* Source; WHI Steering Committee. JAMA 2004; 291:1701291:1701 -12
Relative and absolute risks (hazard ratio,HR) for preventable postmenopausal po stmenopausal diseases. * An estrogen + MPA study, randomized and controlled against placebo: mean age at start of treatment 63.2; mean age at end of treatment 69.4 years; mean duration duration of treatment 5.2 years with correction in 2003;0.625 mg conjugated estrogens + 2.5 2.5 mg MPA given combined and continuosly; n=8506 estrogen +MPA, n 8102 placebo Disease
Relative risk againts placebo (HR); nominal 95% confidence limits
Absolute risk no.of probands/ 10,000 women years
Risk EPRT 1
Conjugated Estrogens + MPA
Placebo
Benefit EPRT 1
Breast cancer
1.24 (1.01-1.54)2
41
33
8
0
Coronary infarction
1.24 (1.00-154)3
37
30
7
0
Stroke
1.41(1.07-1.85)4
29
21
8
0
Thromboembolism
2.11 (1.58-2.82)
34
16
18
0
Colon cancer
0.63(0.43 -0.92)5
10
16
-
6
Osteoporotic fractures
0.76 (0.69-0.83)
152
199
-
47
Diabetes
0.79
20
15
-
5
-
-
41
59
52
53
-
1
Sum of events Mortality
0.98
* Source; WHI Steering Committee. JAMA 2004; 291:1701291:1701 -12
Influence of age on the hazard ratio (HR) of preventable postmenopausal postmenopausal disease with the intervention of conjugated estrogen. * An estrogen monotherapy study, study, randomized and controlled against placebo: mean duration of treatment 6.8 years; years; 0.625 mg conjugated estrogen given continously Disease
Age (years)
Total HR for all ages
50-571
60-69
70-79
Total of probands population (%)
33.4
45.3
27.3
-
Coronary heart disease
0.56
0.92
1.04
0.91
Stroke
1.08
1.652
1.25
1.29
Venous Thromboembolism
1.22
1.31
1.44
1.33
Mammary cancer
0.72
0.72
0.94
0.77
Colorectal cancer
0.59
0.88
2.09
1.03
-
0.333
0.62
0.703
0.73
1.01
1.20
1.08
Hip fractures Mortality
* Source; WHI Steering Committee. JAMA 2004; 291:1701291:1701 -12
Data for manifold prepre -existing disease, anomalies and medicaments of probands of the WHI W HI study.* An estrogen monotherapy study, randomized and controlled againts placebo; placebo; mean duration of treatment 6.8 years; 0.625 mg conjugated estrogens given continuously; n = 5310 5310 estrogen, n=5429 placebo. A high percentage of probands exhibited contraindications of estrogen medication medication and relevant risk factors were present, as evidenced by the use of specific medicaments. Probands Probands were mostly too old for oral estrogen administration and no indication for replacement was existent in the majority of cases. No proof of estrogen deficiency was performed. Therefore the study was not one of replacement replacement but of experimental medication, embedded in a worstworst-case scenario Anamnestic data Hypertension Cholesterol increase Medication of statins Medication of acetyl salicyclic acid History of myocardial infarction Angina pectoris History of stroke Bypass operation (angioplasty) History of thromboembolism Diabetes mellitus Smokes Overweight (BMI>30) ERT before study Nulliparae First child 30 years of age Breast cancer in family
No. of probands 2308 694 394 1030 165 308 76 120 87 410 2529 2376 2540 489 210 836
Probands (%) 48 14.5 7.4 19.4 3.11 5.81 1.41 2.31 1.61 7.7 47.62 45.02 47.8 9.32 4.92 18.02
* Source; WHI Steering Committee. JAMA 2004; 291:1701291:1701 -12
Ispection of the year by year analysis of incidence of coronary heart disease (CHD) in the treatment and placebo groups of the women’s Health Initiative (WHI) study Hazard rate ( risk ratio) No. of CHD events Treatment
Placebo
Year 1
43
23
1.781
Year 2
36
30
1.15
Year 3
20
18
1.06
Year 4
25
24
0.99
Year 5
23
09
2.381
Year 6
17
18
0.78
* Source; WHI Steering Committee. Effects of conjugated equine estrogen e strogen in postmenopausal women with hysterectomy . JAMA 2004; 291:1701291:1701 -12
l The
timing of the initiation of HT may well
be critical for the effects on the coronary arteries à estrogen is now beneficial if started at the right time ( the pendulum swings back), table below
Number of cases of selected coronary events over 7 year’s treatm ent with either conjugated equine estrogens (CEE) or placebo in wom en aged 50-59 years at baseline (from WHI)
CEE (n=1673)
Placebo (n=1637)
(95 % confidence interval)
Coronary heart disease (MI or coronary death)
23
34
0.63 (0.36-1.08)
CABG or PCI MI, coronary death,
29 42
52 65
0.55 ( 0.35- 0.86) 0.66 (0.44-0.97)
46
70
0.66 ( 0.45 – 0.96)
Coronary event
Hazard ratio
CABG and PCI
MI, coronary death,CABG, PCI and angina
MI myocardial infraction; CABG, coronary artery bypass grafting; grafting; PCI, percutaneous coronary intervention
Adapted from Hisa et.al Arch intern Med 2006;3572006;357-65.
A META-ANALYSIS OF CARDIAC EVENTS IN 23 RANDOMIZED, CONTROLLED TRIALS ON HT lA
significant reduction in younger women OR 0.68 ; CI 0.48-0.96. l When RCT are divided into the initiation of HT before or after age 60 years, a significant reduction in all-cause mortality is seen in younger users, compared to placebo HR 0.61; CI 0.39-0.95 Adapted from Salpeter SR, et.al J.gent Intern Med 2004;19: 791791-804.
MORE DATA ON HT & CORONARY HEART DISEASE (CHD): COMMENTS ON RECENT PUBLICATIONS FROM THE WHI & NHS l
EP & E WHI Study Actually à HT does not ? the risk of CHD in the PERI & Early Menopause, à may carry beneficial effect
l
NHS : Starting HT near the Menopause à reduced risk of CHD RR 0.66, CI 0.54 - 0.80 for ET; RR 0.72, CI 0.56 – 0.92 for EPT
MORE DATA ON HT & CORONARY HEART DISEASE (CHD): COMMENTS ON RECENT PUBLICATIONS FROM THE WHI & NHS l
Sub group WHI study: no relation between HT & CHD among women who initiated therapy at least 10 years after the menopause RR 0.87, CI 0.68 – 1.10 FOR ET; RR 0.90, CI 0.62 – 1.29 FOR EPT.
l
Initiating HT in older women with established atherosclerosis is not likely to produce any cardiac or neuro protection à not to be recommended for those indication; for younger age groups of WHI & NHS study are in line with the ‘Window of opportunity’ theory, Based on the assumption that estrogen is cardio protective when the arterial endothelium is still intact
THE LONG-TERM IMPACT OF 2-3 YEARS OF HT ON CARDIOVASCULAR MORTALITY & ATHEROSCLEROSIS IN HEALTHY WOMEN (PERF STUDY) l
In 2000 &2001, Subjects of the original randomized control trial were invited to partipate in a follow-up examination at research institute PERF study
l
The subjects show in table below
PERF Study Tahun 2000 dan 2001 Penelitian di PERF StTUDY (Prospective Epidemiological Risk Factors) Factors) Hormone replacement therapies used in randomized, placeboplacebo-controlled, clinical trials for the present analysis Age range Study
n
(years)
Estrogen
.A
226
44-70
17ß-estradiol, estradiol valerate
B
154
44-54
Years of
Years of
Progestin
treatment
follow-up
Reference
norethisterone acetate,
1977-79
2000
16
1983-85
2000
17,18
cyproterone acetate
17ß-estradiol,
norethisterone acetate,
*17ß-estradiol,
cyproterone acetate progesterone
C
11
45-53
17ß-estradiol,
norethisterone acetate,
1983-84
2000
17
D
160
45-55
17ß-estradiol,
cyproterone acetate
1987-90
2000
19
estradiol valerate
levonorgestrel, desogestrel, Medroxyprogesterone Acetate
E
338
44-62
17ß-estradiol,
gestodene
1993-95
2000
20
F
70
56-75
17ß-estradiol,
norethisterone acetate,
1985-86
2000
21
G
314
49-68
17ß-estradiol,
norethisterone acetate,
1993-94
2000
22
norethisterone acetate,
1994-95
2000
23
piperazine estrone sulfate H
185
56-71
17ß-estradiol,
All hormone regimens were oral, except for the 17ß-estradiol, indicated by asterisk (8) which as transdermal
PERF Study
Baseline characteristic for women who received a few years of HR T (HRT+) or no HRT (HRT(HRT-). Data are mean ± 1SD
Age at baseline (years) Body mass index (kg/m2) Serum total cholesterol (mmol//) Serum triglycerides (mmol/l) Fasting serum glucose (mmol/l) White blood cell count (X109/l) Current smokers (%)
HRT + (n=553)
HRT – (n=727)
55.3 ± 5.6 24.9 ± 3.9 6.2 ± 1.6 1.1 ± 0.6 5.3 ± 0.6 5.4 ± 1.6 50.3
55.9 ± 6.4 25.6 ± 4.5 5.9 ± 2.2 1.2 ± 0.6 5.4 ± 1.3 5.5 ± 1.5 54.5
PERF Study
Incidence of all-cause mortality due to cardiovascular disease (CVD) and coronary heart disease (CHD) in postmenopausal women stratified according to use of hormone replacement therapy (HRT) Cases
All-cause mortality
HRT+
HRT-
p Value
174
51 (29.3%)
123 (70.7%)
0.024
CVD mortality
61
14 (23.0%)
47 (77.0%)
0.024
CHD mortality
39
8 (20.5%)
31 (79.5%)
0.025
PERF Study
The impact of hormone replacement therapy on mortality rate of post menopausal women as a function of the follow-up period Cases
HRT+
HRT-
pValue
All cause mortality
45
17
28
0.637
CVD mortality
138
4
9
0.521
CHD mortality
8
3
5
0.901
All cause mortality
38
9
29
0.843
CVD mortality
13
4
9
0.521
CHD mortality
8
3
5
0.901
All cause mortality
91
25
66
0.004
CVD mortality
32
9
23
0.042
CHD mortality
20
5
15
0.305
Follow-up = 5 years
Follow up > 5 years and = 10 years
Follow up > 10 years
CVD, cardiovascular disease: CHD, coronary heart disease HRT + designates users of HRT, and HRT - designates non-users of HRT
SUMMARY OF PERF STUDY l
Short term use of HT in healthy postmenopausal women provides longterm cardiovascular benefits as indicated by a decreased all cause and cardiovascular mortality rate and decelerated atherogenesis compared with non-users of HRT
ESTROGEN & PROGESTIN YANG DIPAKAI PADA HT l
l
l
Estrogen : - CEE - 17 ß-estradiol - Estradiol Valerate - Piperazine - Estrone sulfate Hasil penelitian mempunyai efek cukup baik Progestin : - pada tabel dibawah Progestin baru diperlukan untuk pengganti progestin lama yang mempunyai banyak efek samping Tibolone (bersifat progestogenik, estrogenik & androgenik) à penelitian telah dilakukan
Comparison of Drospirenone With Other Progestins Progestins
C-21 progestins
19-nortestosterone
Pregnanes
Estranes
Gonanes
• Medroxyprogesterone acetate • Megestrol acetate • Cyproterone acetate
• Norethindrone • Noreth. acetate • Ethynodiol diacetate • Lynestrenol • Norethynodrel
• Norgestrel • Levonorgestrel • Norgestimate • Desogestrel • Gestodene
Spirolactone
Drospirenone
Klasifikasi Progestin (Progesteron sintetik) Related to progesterone l Dydrogesterone l
Related to testosterone l Estranes – Norethisterone
17-OH Progesterone – Medroxyprogesterone – – – –
Acetate Cyproterone Acetate Chlormadinone Acetate Megestrol Acetate Drospirenone
l
Estrane/Pregnane – Dienogest
l
Gonanes – Norgestrel – Desogestrel
l
19-nor progesterone – Nomegestrol Acetate – Trimegestone
– Gestodene – Norgestimate
– Promegestone Pharmacological profile of progestins, R. Struck-Ware. Maturitas 47 (2004) 278
DIPERLUKAN PROGESTIN BARU YANG LEBIH BAIK l
17-OH Progesterone – Medroxyprogesterone Acetate – Cyproterone Acetate – Chlormadinone Acetate – Megestrol Acetate – Drospirenone (PARA = Progestogen with Aldosterone Receptor Antagonismà mempengaruh RAAS)
l
Tibolone ( bersifat progestogenik, estrogenik dan androgenik)
Comparison of Drospirenone With Other Progestins Progestogenic Androgenic Antiandrogenic activity activity activity
Antialdosterone Glucocortiactivity coid activity
Progesterone
+
–
(+)
+
–
Drospirenone
+
–
+
+
–
CPA
+ +
– (+)
+ –
– –
(+) –
+ + +
– (+) (+)
+ – –
– (+) –
– – –
+ +
(+) (+)
– –
– –
(+) –
+ +
(+) +
– –
– –
– –
Desogestrel Dienogest Gestodene Levonorgestrel MPA Norethisterone Norgestimate Tibolone
+ relevant activity; (+) activity not clinically relevant; – no activity CPA: cyproterone acetate ; MPA: medroxy progesterone acetate Schindler AE et al. Maturitas. 2003;46(suppl 1):S7-S16; Rübig A. Climacteric. 2003;6(suppl 3):49-54.
Renin – Angiotensin - Aldosteron System
Effect of Drospirenone on the ReninAngiotensin -Aldosterone System (RAAS)
Estrogens Angiotensinogen Angiotensin I Angiotensin II
Adrenal gland
Aldosterone
Sodium- and water retention
- Increased plasma volume - Rise of blood pressure in susceptibles - Water retention-related symptoms (edema, bloating, weight gain)
Receptor level
DRSP
Pharmacological and Clinical Effects of Aldosterone and Anti-Aldosterone Action of DRSP
GLOMERULUS
RBF JGA RENIN
+ ANGIOTENSINOGEN
ANGIOTENSIN I
LIVER CONVERTING ENZYM ADRENAL CORTEX
LUNG
ANGIOTENSIN II
BRAIN
ALDOSTERON
S retensi Na & H2O
ARTERI
Intake H2O Blood Vol
VASOKONSTRIKSI HEART SV
RENIN-ANGIOTENSIN CONTROL”BP”
COP
HR “BP”
x
R
DROSPIRENONE & CARDIOVASCULAR DISEASE l The
beneficial effect on the cardiovascular
system of drospirenon as demonstrated by control of blood pressure, and the prevention of estrogen induced sodium and water retention and body weight gain
THE POSSIBLE CARDIOVASCULAR BENEFITS ASSOCIATED WITH ALDOSTERONE ANTAGONISM INCLUDE: INCREASED SODIUM EXCRETION AND PREVENTION OF EDEMA AND WEIGHT GAIN LEADING TO: l l l l
Decreased systolic and diastolic blood pressure Improved baroreceptor function Prevention of vascular and myocardial fibrosis Improved vascular compliance (elasticity/thickening)
THE POSSIBLE CARDIOVASCULAR……. l Improved
diastolic function l Improved endothelial function and nitric oxide availability l Improved myocardial norepinephirine uptake l Decreased ventricular ectopic activity l Decreased levels of plasminogen activator inhibator (PAI-1) l Reduced mortality and morbidity in patients with severe heart failure
Pharmacological and Clinical Effects of Aldosterone and Anti-Aldosterone Action of DRSP
Penelitian Drospirenon terhadap metabolisme karbohidrat l Drospirenon
shows :
– No glucocorticoid or antiglucocorticoid activity – No relevant impairment of fasting glucose levels
or oral glucose tolerance
EFFECTS OF TIBOLONE ON BLOOD FLOW RESISTANCE AND INTIMA-MEDIA THICKNESS OF THE CAROTID ARTERIES: EFFECT OF TIME SINCE MENOPAUSE l
No significant effects of tibolone on either intima-media thickness or blood flow resistance in the carotid arteries in postmenopausal women . However, the results suggest that tibolone may have a positive effect on the vascular system if commenced within 18 months since menopause; this warrants further investigation.
A.Somunkiran, B.Yazici,F.Demirci, Berdogmus and I.Ozdemir. Climacteric 2006;9:59-65
SIMPULAN l Patofisiologi: – Pengaruh positif estrogen l l l l l
Metabolisme lipoprotein Menghambat atherosklerosis Sistem hemostasis Endotel vaskular Metabolisme karbohidrat à cegah hiperglikemia
– Pengaruh negatif Estrogen l
RAAS à Aldosterone ?àBB ?&TD ?
– Pengaruh positif Progestin tertentu l
RAAS à Aldosterone ? àBB ? &TD ?
– Pengaruh negatif Progestin l
Metabolisme karbohidrat à hiperglikemia
SIMPULAN l Penelitian – Estrogen mempunyai pengaruh positif pada PKV apabila –
–
– –
dimulai pada saat yang tepat ( umur 50- 59 th) Estrogen-progestin mempunyai pengaruh posistif pada PKV apabila pemberiannya sebelum umur 60 th dimana umumnya endotel arteri masih utuh Pemakaian Terapi Hormon jangka pendek (5 th atau kurang) pada wanita postmenopause sehat berdampak positif jangka panjang terhadap Kardio Vaskuler Pemakaian Progestin baru yang berpengaruh positif terhadap PKV, sangat bermanfaat, masih perlu penelitian lanjut. Pengaruh negatif Terapi Hormon diluar Kardio Vaskular perlu ditelaah lebih teliti
