THE EFFECT OF RED CLOVER AND BLACK COHOSH COMBINATION IN BONE MINERAL DENSITY Rachman IA Rachman IA Susanti M Rotikan T Tobing A.

THE EFFECT OF RED CLOVER AND THE EFFECT OF RED CLOVER AND BLACK COHOSH COMBINATIONBLACK COHOSH COMBINATION

IN BONE MINERAL DENSITYIN BONE MINERAL DENSITY

Rachman IARachman IASusanti MSusanti MRotikan T Rotikan T Tobing A Tobing A

LOW QOL

NORMAL LOW ESTROGEN LEVEL

OBL low OKL highLIMITED ACTIVITYCHANGE IN SKIN

LOW VIT D RECEPTORLIMITED CALCIUM ASORBTION

LIMITED SUN EXPOSURE LOW UV betaAGING PROCES

ESTROGEN AS HRT ????ESTROGEN AS HRT ????

ESTRADIOL+DROSPIRENONE

TIBOLONE, OVESTIN,PROVERA. .

Disadvantages 0f HRT:Disadvantages 0f HRT:WHI (Women’s Health WHI (Women’s Health Initiative) :Initiative) :

Increase risk of stroke 41 %Increase risk of stroke 41 %Thromboemboli twiceThromboemboli twiceCardiac problem 29%Cardiac problem 29%Ca mammae 26%Ca mammae 26%INCREASE BONE DENSITYINCREASE BONE DENSITYPROTEC OSTEOPOROSIS PROTEC OSTEOPOROSIS FRACTUREFRACTURE

HEPI (Heart and estrogen / HEPI (Heart and estrogen / progestin intervention)progestin intervention)

HipertrigliseridimiaHipertrigliseridimiaEndometrial HiperplasiEndometrial HiperplasiCa mammaeCa mammae

Most of patient –HIGH MIDDLE LOW level refuseMost of patient –HIGH MIDDLE LOW level refuse HRT HRT

Clinician doubt to giveClinician doubt to give HRT, HRT, limitation of HRT for 5-7 limitation of HRT for 5-7 years ?years ?

ECONOMICAL PROBLEM- ONLY 65-70% (Jakarta) can ECONOMICAL PROBLEM- ONLY 65-70% (Jakarta) can buy HRT AND 30% CAN NOT BUY (30-35 US$) - No buy HRT AND 30% CAN NOT BUY (30-35 US$) - No reimbuse from insurancereimbuse from insurance

SO SOME WOMEN IN INDONESIA - NEED CHEAPER SO SOME WOMEN IN INDONESIA - NEED CHEAPER AND GOOD THERAPY FOR AND GOOD THERAPY FOR MS-and osteoporosis MS-and osteoporosis protection -----PHYTOESTROGEN ?protection -----PHYTOESTROGEN ?

PROBLEMS AFTER WHI-HEPIIN INDONESIA -SIMILAR TO OTHERS

PhytoestrogenPhytoestrogen does it work? does it work? Food or drug?Food or drug?

EPIDEMIOLOGICAL STUDYEPIDEMIOLOGICAL STUDY

Diet rich with phytoestrogen Diet rich with phytoestrogen decrease menopause decrease menopause symptoms ,lower symptoms ,lower osteoporosis,low rate of osteoporosis,low rate of malignancy-breast,prostat ,Ca malignancy-breast,prostat ,Ca colon,better quolity of life in colon,better quolity of life in postmenopusepostmenopuseSimilarity between European Similarity between European vegeterian and Asian vegeterian and Asian population lower incidens of population lower incidens of osteoporosis compared with osteoporosis compared with non vegeterian populationnon vegeterian population

Phytoestrogen scientific Phytoestrogen scientific reaserch areareaserch area

FOOD DRUGSPhytoE

Bioactivecompound

PHYTOESTROGEN reaserch since 1950PHYTOESTROGEN reaserch since 1950

Bacciottini I etall 2006Geneistein has Geneistein has 33% potency of estradiol33% potency of estradiol when interacts with when interacts with

estrogen receptor estrogen receptor ββ and and 0,1%the potency of estradiol when 0,1%the potency of estradiol when intereact with estrogen receptor intereact with estrogen receptor αα

Markiewicz et allMarkiewicz et all,, compare biologic potential of isoflavones with compare biologic potential of isoflavones with estradiol at human cells of mammae carcinoma cultured, found that estradiol at human cells of mammae carcinoma cultured, found that

biologic potentialbiologic potential of isoflavon compare to estradiol : 0.13-0.84% of isoflavon compare to estradiol : 0.13-0.84%

Kuiper,Carrison etall 1997Kuiper,Carrison etall 1997Bind estrogen receptor Bind estrogen receptor αα - 5% - 5% and estrogen and estrogen receptor receptor ββ - 36% - 36% compare to compare to estradiol bindingestradiol bindingAffinity of isoflavon to estrogen receptorAffinity of isoflavon to estrogen receptor αα 7 times than afinity to receptor 7 times than afinity to receptor estrogen estrogen ββ Bone have more estrogen receptorBone have more estrogen receptor ββ than estrogen receptor estrogen receptor αα

BEFORE----PHYTOESTROGEN-----BEFORE----PHYTOESTROGEN-----PLACEBOPLACEBO

SINCE 2 YEAR AGO SINCE 2 YEAR AGO PHYTOESTROGEN NOT PHYTOESTROGEN NOT PLACEBO – DO A STUDY FOR PLACEBO – DO A STUDY FOR PHYTOESTROGENPHYTOESTROGEN

IOF World Congresson Osteoporosis2-6 June 2006, Toronto, Canada

Volume 17 Supplement 2 2006 ISSN 0937-941X

Rachman IA et allRachman IA et all

After one-year administration of therapy, clinical complaint of estrogen After one-year administration of therapy, clinical complaint of estrogen deficiency (MS) of 2-11% was still observeddeficiency (MS) of 2-11% was still observedcombined therapy of red clover and black cohosh and calcium and combined therapy of red clover and black cohosh and calcium and weight bearing, a mean bone density of 2.4 – 4.9%, was found in weight bearing, a mean bone density of 2.4 – 4.9%, was found in premenopausal osteoporo sis, and 2.3 – 4.6% in postmenopausal premenopausal osteoporo sis, and 2.3 – 4.6% in postmenopausal osteoporosis.osteoporosis.

Baseline - Day 0

iCR-extractTibolone

Hot flush Insomnia Depressive mood

Weaknessfatigue

Headache

Profusesweating

Nervous-ness

Vertigo Jointpain

Palpitation

none

slight

moderate

severe

none

slight

moderate

severeiCR-extractTibolone week 12

Profusesweating

Nervous-ness

Vertigo Jointpain

Palpitation

Hot flush Insomnia Depressive mood

Weaknessfatigue

Headache

Pr Santiago Palacios, Instituto Palacios, Madrid, SPAINIMS WORLD CONGCRESS 2008

30 center in French, 1 center in Belgium , 2 center in Spain and1 center in Australia

3 years study wiyh PHYTOSOYA save for breast and endometrium

Recommended for menopausal women who Recommended for menopausal women who don’t want to take HRTdon’t want to take HRT

For this reason:For this reason:

we must know the effect of we must know the effect of PHYTOESTROGEN(PHYTOESTROGEN( Red Red Clover+ Black Cohosh )Clover+ Black Cohosh ) + Calcium+Vit D + WBE to the + Calcium+Vit D + WBE to the

perimenopause osteoporosis Indonesia women compare to perimenopause osteoporosis Indonesia women compare to Low Low dose HRTdose HRT +Cal+VITD+WBE and +Cal+VITD+WBE and to to PALCEBOPALCEBO(only(only Calcium+Vit D +WBE) for bone density increaseCalcium+Vit D +WBE) for bone density increase

* * Low costLow cost * Most Indonesian women know about herb* Most Indonesian women know about herb

Material - MethodsMaterial - Methods

All women from high level ,age > 45-65 came to 2 menopause and All women from high level ,age > 45-65 came to 2 menopause and postmenopause osteoporosis clinic and avaible for 2 years follow-postmenopause osteoporosis clinic and avaible for 2 years follow-upup

Symptoms of estrogen deficiency (menopausal symptoms)Symptoms of estrogen deficiency (menopausal symptoms)

Normal routine laboratory findingNormal routine laboratory finding

Lunar densitometer examination we found osteoporosis in one Lunar densitometer examination we found osteoporosis in one side ; lumbal, femur or radiusside ; lumbal, femur or radius

No hormonal treatment during last 3 monthNo hormonal treatment during last 3 month

Patient or family understanding about treatment and fill the research Patient or family understanding about treatment and fill the research form modification of Kuppermant index for several menopause form modification of Kuppermant index for several menopause complain(clinical complain form)complain(clinical complain form)

The patient get one “clinical complain form” that she can fill every week The patient get one “clinical complain form” that she can fill every week weather the complain disappeared or reduceweather the complain disappeared or reduce

The patient must control every month for the 6The patient must control every month for the 6 thth month and after that month and after that every 3 month and after 1 and 2 years treatment we do densitometer every 3 month and after 1 and 2 years treatment we do densitometer examination and laboratory (HDL,LDL,Estradiol and FSH)examination and laboratory (HDL,LDL,Estradiol and FSH)

All cases we devide 3 group :All cases we devide 3 group : GROUP A we givre low dose of estradiol 0,3 mg+Calc+VitD +WBEGROUP A we givre low dose of estradiol 0,3 mg+Calc+VitD +WBE GROUP B we give red clover 225mg + Black Cohosh 40 mg + GROUP B we give red clover 225mg + Black Cohosh 40 mg +

Calcium 1516 mg + vit D 200 IU daily and WBECalcium 1516 mg + vit D 200 IU daily and WBE GROUP C only Calc+VitD + WBEGROUP C only Calc+VitD + WBE

All data from the patient we write on the research status form. After one All data from the patient we write on the research status form. After one and two years we collect the clinical complain form from patientand two years we collect the clinical complain form from patient

Red clover ( Red clover ( Trifolium pratense Trifolium pratense )) Red cloverRed clover,has a variety of isoflavones ,has a variety of isoflavones

genistein ,daidzein , genistein ,daidzein , formononetin formononetin and biochaninand biochanin. Red clover also . Red clover also contains flavonoid compounds called contains flavonoid compounds called coumestans,coumestans, which some studies which some studies suggest have suggest have six times more six times more estrogenlike activityestrogenlike activity than most than most isoflavonesisoflavones. .

Bind to RE than RE

Black CohoshBlack Cohosh

Extracts of black cohosh are standardized Extracts of black cohosh are standardized to to 26-deoxyactein26-deoxyactein content (erroneously content (erroneously reported in the scientific literature as 27-reported in the scientific literature as 27-deoxyactein, a member of a group of deoxyactein, a member of a group of chemicals known as chemicals known as saponinssaponins. . Commercially available preparations of Commercially available preparations of black cohosh usually contain 1 mg of total black cohosh usually contain 1 mg of total triterpene saponinstriterpene saponins (expressed as 26- (expressed as 26-deoxyactein) in each 20-mg dose of extract.deoxyactein) in each 20-mg dose of extract.

Bind to RE and to RE

PEROSI-PERWATUSI OSTEOPOROSIS WEIGHT BEARING EXERSISE

Found Found 435435 cases perimenopausal women, 46-55 years old, divided 3 group. cases perimenopausal women, 46-55 years old, divided 3 group.

Group A (156 cases)Group A (156 cases) HDL (Low) 69,9% HDL (Low) 69,9% LDL (High) 62,5% LDL (High) 62,5%

E2(Low) 92,7% FSH (High) 100%E2(Low) 92,7% FSH (High) 100% Osteoporosis: L1-4: 65,4% ; NF: 45,7% ; R: 86,4%Osteoporosis: L1-4: 65,4% ; NF: 45,7% ; R: 86,4%

Group B (153 cases)Group B (153 cases) HDL(low) 65,1% LDL(high)59,8%HDL(low) 65,1% LDL(high)59,8% E2 (low) 96,4% FSH(HIGH) 100%E2 (low) 96,4% FSH(HIGH) 100% Osteoporosis L1-4 57,4% NF 51,8% R:88,4%Osteoporosis L1-4 57,4% NF 51,8% R:88,4%

GROUP (126 cases)GROUP (126 cases) HDL (Low) 58,3%HDL (Low) 58,3% LDL (high) 52,1%LDL (high) 52,1% E2 (Low) 93,4% FSH (High) 100%E2 (Low) 93,4% FSH (High) 100% Osteoporosis : L1-4: 55,7% ; NF: 52,4% ; R: 85,9%Osteoporosis : L1-4: 55,7% ; NF: 52,4% ; R: 85,9%

RESULT

0%

20%

40%

60%

80%

100%

120%

Group A (Cee+P+Ca+WBE) Group B (RC+BC+Ca+WBE) Group C (Ca+WBE)

Menopause Symptom

99.799.298.2

83.280.1

48.736.8

78.4

9.720.7 19.1

12.8

0

20

40

60

80

100

120

Periode

Prec

enta

ge

Sup A

Sup B

Sup C

6 Month 12 Month 24 Month3 Month

Lumbal Bone Density

0

5.7

9.7

0

3.1

4.6

1.3 1.6

00

2

4

6

8

10

12

Periode

Prec

enta

ge

Sup A

Sup B

Sup C

1 Year 2 Year

Femur Bone Density

0

4.1

6.7

0

1.92.3

00.8 1.1

0

1

2

3

4

5

6

7

8

Periode

Prec

enta

ge

Sup A

Sup B

Sup C

1 Year 2 Year

Radius Bone Density

0

3.2

4.6

0

1.41.7

0

0.7 0.9

0

1

2

3

4

5

Periode

Prec

enta

ge

Sup A

Sup B

Sup C

1 Year 2 Year

Bone densityBone density After one years therapy we found a After one years therapy we found a

significant bone density increase for HRT significant bone density increase for HRT treatment but for RC+BC we found treatment but for RC+BC we found slightly increase still significant of bone slightly increase still significant of bone density from before treatment but not in density from before treatment but not in Placebo only (very slightly increase)Placebo only (very slightly increase)

After 2 years therapy we found a After 2 years therapy we found a significant bone density increase for HRT significant bone density increase for HRT treatment also for RC +BC and for treatment also for RC +BC and for placebo we found very slightly increase of placebo we found very slightly increase of bone density but not significantbone density but not significant

CONCLUSIONCONCLUSION LOW HRTLOW HRT is a is a BEST TREATMENTBEST TREATMENT for for

recovery MS symptom and significantly recovery MS symptom and significantly increase bone density increase bone density

RC+BCRC+BC G00D for recovery MS(70-75% from G00D for recovery MS(70-75% from HRT)HRT) and and significantly increase bone significantly increase bone density(36-53% from HRT)density(36-53% from HRT) after 1 and 2 after 1 and 2 year treatment , compare to placebo and year treatment , compare to placebo and before treatment before treatment

PLACEBOPLACEBO slightly recovery MS(12% from slightly recovery MS(12% from RC+BC) and very slightly increase bone RC+BC) and very slightly increase bone density(40-51% from RC+BC)density(40-51% from RC+BC) after 1 and 2 after 1 and 2 years treatment, compare to before treatment years treatment, compare to before treatment

3000 island --44 Densitometer DXA 23+21PEROSI ------ 16 Branches

Osteopenia cases ranged from 30% - Osteopenia cases ranged from 30% - 40%40%Osteoporosis cases is between 5% - Osteoporosis cases is between 5% - 25% (male) and 25% - 55% (female)25% (male) and 25% - 55% (female)Number of hip fractures that are treated Number of hip fractures that are treated by doctor is between 10% - 90%by doctor is between 10% - 90%Number of vertebral fractures that are Number of vertebral fractures that are treated by doctor is between 20% - 70%treated by doctor is between 20% - 70%

Population in Indonesia is Population in Indonesia is around 222,051,300 people. around 222,051,300 people. Seventeen million of them Seventeen million of them are womenare women over 50 years over 50 years olds.olds. In year 2020, the In year 2020, the population will reach population will reach 261,005,000 and in the year 261,005,000 and in the year 2050, the population is 2050, the population is 273,219,200273,219,200

MORE OSTEOPOROSIS STUDIESPRIMARY OSTEOPOROSIS

SECONDARY OSTEOPOROSISFRACTURE OSTEOPOROSIS

ETCSHOULD BE DONE

IN INDONESIA

Ichramsjah A.RachmanIchramsjah A.Rachman

President The Indonesia Menopause SocietyPresident The Indonesia Menopause Society

President The Indonesian Osteoporosis SocietyPresident The Indonesian Osteoporosis Society

THANK YOUTHANK YOU