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1 여성갱년기환자에서여성호르몬의새로운접근법 / 박샛별 여성갱년기환자에서여성호르몬의새로운접근법 박샛별 아주의대가정의학과 Contents General Consideration Clinical Symptoms Evaluation Treatment Summary General consideration 연령별인구자료 여성인구분포의변화 x 5, 1% 1, 3, 2, 1, 5% 가임기후가임기가임기전 여성남성폐경여성총인구 % 통계청

213 대한임상건강증진학회추계합동학술대회 평균수명 Symptom of menopause 9 8 7 Age, year early intermediate late 5 5 55 6 65 7+ 6 5 나이 3 2 1 Hot flushes Sweating Vaginal atrophy Insomnia Dyspareunia Osteoporosis Menstrual

2 213 대한임상건강증진학회추계합동학술대회 평균수명 Symptom of menopause Age, year early intermediate late 나이 Hot flushes Sweating Vaginal atrophy Insomnia Dyspareunia Osteoporosis Menstrual Skin atrophy Atherosclerosis irregularity Incontinence CHD Psychological CVD symptom Alzheimer s Dis 년도 Reduce QOL 여 전체 골다공증 (Osteoporosis) 성별, 연령에따른심혈관질환의발생율 Percent of population , 77,8 75, 68,5 56,5 52,9 36,2 36,6 22,9 17,6 11,2 6, Men Women Age s HRT Benefits Risks Vasomotor symptoms Breast Cancer Urogenital Symptoms & VTE Sexual function Stroke Osteoporosis Endometrial cancer Colon Cancer Uncertainties Cardiovascular disease Alzheimer s disease Ovarian cancer Quality of life WHI,WHI,WHI? 5.2 years of combined hormone (EP) therapy 7 years of estrogen only hormone therapy British Menopause Society Consensus Statement (MacLennan et al., Climacteric 2) 12

여성갱년기환자에서여성호르몬의새로운접근법 / 박샛별 Absolute Risk 5 3 2 1 Number of Events

-3 CHD Stroke VTE Breast Cancer Writing Group for the Women's Health

JAMA 27;297:165 177. Total Death Global Index How long?

Making (October 2 2, 27) Mechanism of hot flushes Thermoregulation

3 여성갱년기환자에서여성호르몬의새로운접근법 / 박샛별 Absolute Risk Number of Events per 1, Women per Year (E only) Clinical Symptoms CHD Stroke VTE Breast Cancer Writing Group for the Women's Health Initiative Investigators. JAMA 2;291: Rossouw, et al. JAMA 27;297: Total Death Global Index How long? 열성홍조 The 29th Annual Meeting of the Society for Medical Decision Making (October 2 2, 27) Mechanism of hot flushes Thermoregulation Abnormality of thermoregulation Changes of neurotransmitters Peripheral vascular response 13

4 213 대한임상건강증진학회추계합동학술대회 Ajou FM Functional associations of the paraventricular nucleus(pvn) and the endocrine and autonomic systems Atrophic Vaginitis Psychological Symptoms Psychological symptoms Depressive mood Anxiety Sleep disturbance Memory impairment Temper Mood swing Lonely Headache 1

여성갱년기환자에서여성호르몬의새로운접근법 / 박샛별 Menopausal Arthralgia: Fact or fiction Evaluation Cartilage growth factor (TGF β) IGF-1, IL, TNF Pain pathway 여성갱년기평가검사 Menopause Rating Scale (MRS) 점수 = /, 5 7, 8 15, 16

(mammography), 유방초음파검사 2 3 5 6 7 심장불편감 ( 갑자기가슴두근거림, 맥박이건너뜀, 박동이빨라짐, 가슴이조여드는느낌 ) 수면문제 ( 잠들기어려움, 수면을지속하기어려움, 잠에서이르게깸 ) 우울한기분 ( 기분이쳐짐, 슬픔, 쉽게눈물이남, 의욕없음, 감정이수시로변함 ) 과민성 ( 신경이날카로워지는느낌, 내성적긴장감, 공격적으로되는느낌 )

5 여성갱년기환자에서여성호르몬의새로운접근법 / 박샛별 Menopausal Arthralgia: Fact or fiction Evaluation Cartilage growth factor (TGF β) IGF-1, IL, TNF Pain pathway 여성갱년기평가검사 Menopause Rating Scale (MRS) 점수 = /, 5 7, 8 15, 16 안면홍조, 발한 1 ( 갑작스럽게땀이나는경헙 ) 매우 없음 약간 보통 심함 심함 여성호르몬검사 : E2 2 pg/ml, FSH IU/L 고지혈증검사, 심혈관계예측지표 (hs-crp) 심전도 체지방, 근육량측정 골밀도검사 ( 척추, 대퇴골 : DEXA), 골표지자검사, 25(OH)D 척추 X-ray ( 단순촬영 ) 유방암검사 (mammography), 유방초음파검사 심장불편감 ( 갑자기가슴두근거림, 맥박이건너뜀, 박동이빨라짐, 가슴이조여드는느낌 ) 수면문제 ( 잠들기어려움, 수면을지속하기어려움, 잠에서이르게깸 ) 우울한기분 ( 기분이쳐짐, 슬픔, 쉽게눈물이남, 의욕없음, 감정이수시로변함 ) 과민성 ( 신경이날카로워지는느낌, 내성적긴장감, 공격적으로되는느낌 ) 불안감 ( 내적인초조감, 공황상태가되는느낌 ) 신체및정신적피로 ( 일상생활수행능력의전반적인감소, 기억력감퇴, 집중력감소, 건망증 ) 복부초음파검사 ( 담석확인 ) 8 성적인문제 ( 성적욕구의변화, 성행위의변화, 성적만족감의변화 ) 기타기본적인혈액, 소변검사 ( 간기능, 당뇨, 빈혈등 ) 9 배뇨문제 ( 배뇨어려움, 소변이자주마려움, 요실금 ) 갑상선기능검사 필요시자궁내막검사, 난소암검사, 유즙분비호르몬등 1 11 질건조감 ( 질부위의건조감또는화끈한느낌, 성교시불편감 ) 관절및근육불편감 ( 관절통증, 류마티스와유사한증상 ) 호르몬요법 (Hormone Therapy) Treatment 생동일성호르몬 - 체내에서분비되는호르몬과분자적, 화학적구조가동일 비생동일성호르몬 천연호르몬 (natural hormone) 합성호르몬 (synthetic hormone) 15

213 대한임상건강증진학회추계합동학술대회 Indication of HT Moderate Vasomotor Sx Vaginal atrophy -> topical estrogen Not used for Primary prevention cardiovascular ds Consider other drug for osteoporosis Lowest

6 213 대한임상건강증진학회추계합동학술대회 Indication of HT Moderate Vasomotor Sx Vaginal atrophy -> topical estrogen Not used for Primary prevention cardiovascular ds Consider other drug for osteoporosis Lowest possible dose shortest possible time CIx of HT Pregnancy Abnormal vaginal bleeding Breast cancer Estrogen dependent tumor Active DVT Pulmonary embolism Acute MI Cerebral infarction Liver disease Hypersensitivity to drug BLEEDING REGIMEN Strategies of HRT POST MENOPAUSAL INTACT UTERUS NON BLEEDING REGIMEN ABSENT UTERUS UNOPPOSED ESTROGENS CYCLICAL E & P TIBOLONE CONTINOUS E & P EPT: Continuous vs Cyclic Estrogen Estrogen Cliane Livial ( 리브론 ) Indivina estradiol hemihydrate 2 mg, norethisterone acetate 1 mg tibolone estradiol valerate 1/2 mg, medroxyprogesterone acetate 2.5/5 mg Progestin Progestin Climen estradiol valerate 2 mg, cyproterone acetate 1 mg Divina estradiol valerate 2 mg, medroxyprogesterone acetate 1 mg Estrogen Estrogen Progestin mens Progestin 16

7 여성갱년기환자에서여성호르몬의새로운접근법 / 박샛별 Low Dose HT 저용량 표준용량의 ½ 초저용량 표준용량의 ¼ Cliovelle Angeliq estradiol hemihydrate 1.3 mg, norethisterone acetate.5 mg estradiol hemihydrate 1.33 mg, drospirerone 2 mg CEE.3mg/.15mg 17ß-Estradiol.5mg/.25mg Transdermal estradiol 25mcg/1mcg Prestwood study] -.25 mg 17β-estradiol w/ Cal 13 mg + Vit D 1 IU for 3 yr - BMD & Hot flushes effective, breast ca risk (-) ET Premina Preda Progynova Climara patch conjugated equine estrogens.3/.625 mg etradiol hemihydrate 1.3 mg/ 2.7 mg estradiol valerate 1 mg/ 2 mg estradiol hemihydrate 3.9 mg/12.5 cm 2, weekly Alternatives of HT progestin/ low dose oral contraceptives (IA) nonhormonal prescription therapy (IB) natural health products: limited evidence (IB) Vaginal bleeding after 12 months of amenorrhea should be investigated (IA). Topical Apply & OC Esgen vag cream Estreva gel Estrodose gel estropipate estradiol hemihydrate mg/g.5mg/puff ⅹ3, daily estradiol hemihydrate.62 mg/g Yaz(yasmin) Triquilar Evra patch ethinyl estradiol.2 mg, drospirerone 3 mg ethinyl estradiol.3 mg/. mg/.3 mg, levonorgestrel.5 mg/.75 mg/.125 mg ethinyl estradiol.6 mg, norelgestromin 6 mg, weekly, for 3 wk 천연호르몬제제 17

8 213 대한임상건강증진학회추계합동학술대회 Phytoestrogen: 5mg/day Klimaktoplan: 1 2T po bid/tid Remifemin: 1T po bid Feramin Q: 1 2T po bid 생동일성호르몬 Bioidentical Hormone 콩 (soy) 이나멕시코산야생얌 (Mexican yam) 등의식물에서추출 디오스게닌 (diosgenin) 이라는화합물로부터합성됨 : 스테로이드와구조적으로유사 > 프로게스트론으로전환 > 안드로겐과에스트로겐의전구체역할 체내비결합호르몬의균형을맞춤 SSRI & 기타제제 18

여성갱년기환자에서여성호르몬의새로운접근법 / 박샛별 SSRI & SNRI 적응증 ] 6 대이상의여성에서지속적이고심한홍조 유방암의병력 열성홍조와심리적인증상을함께호소 금기 ]

Clonidine - Fluoxetine -Vitamin E - Venlafaxine * Vit E (8IU) & behavioral interventions: -5%, no

MAO 억제로 Dopamine, Serotonin, Norepinephrine 등신경전달물질의대사활성화 3.

8 MRS-psychological * * HPE 7.8 7.6 6.3 placebo 8 6 2 MRS-somatic * * 7.9 7. 6.6 5.

9 여성갱년기환자에서여성호르몬의새로운접근법 / 박샛별 SSRI & SNRI 적응증 ] 6 대이상의여성에서지속적이고심한홍조 유방암의병력 열성홍조와심리적인증상을함께호소 금기 ] tamoxifen 을복용하고있는유방암환자 중간활성물질인 endoxifen 으로전환되는것을방해 NOIROMIN s Triple action - Placebo - Soy - Clonidine - Fluoxetine -Vitamin E - Venlafaxine * Vit E (8IU) & behavioral interventions: -5%, no toxicity 1. 신경말단에서 Dopamine, Serotonin, Norepinephrine 재흡수차단 농도증가 2. MAO 억제로 Dopamine, Serotonin, Norepinephrine 등신경전달물질의대사활성화 3. 면역조직계를자극하여 Interleukin-6 방출억제 스트레스호르몬 (cortisol) 분비저하 HPE baseline after Ginkgo Extract MRS-psychological * * HPE placebo MRS-somatic * * HPE placebo MRS-urogenital * * HPE placebo *; P<.5 by paired samples t-test MRS-total * * HPE 13.6 placebo ; P<.5 by ANCOVA (adjusting age and BMI)

213 대한임상건강증진학회추계합동학술대회 Lymphatic circulation: Entelon 15 mg bid Minerals Mg: for metabolic SD Zn: for

effective treatment for menopausal symptoms but is only one option combination therapy For most women under 6

10 213 대한임상건강증진학회추계합동학술대회 Lymphatic circulation: Entelon 15 mg bid Minerals Mg: for metabolic SD Zn: for hormonal secretion Gabapentin DHEAS ANS disorder NAd Ach 교감신경흥분제 부교감신경흥분제 Ephedrine Phenylephrine 사용하지않음 교감신경차단제 부교감신경차단제 B 차단제 ex) Kerlone.5T QD Atropine 진경제 Anxiolytics Vitamines : VA, VB1/6/12, VC, VE Hormones Summary HT remains the most effective treatment for menopausal symptoms but is only one option combination therapy For most women under 6 the Risk/benefit ratio for HT is beneficial Vulnerable groups such as POF need particular attention Our role as experts is to provide upto date information, advice and guidance regular observation & f/up 11

Treatment and Role of Hormaonal Replaement Therapy

Treatment and Role of Hormaonal Replaement Therapy Treatment and Role of Hormone Replacement Therapy Chung-Ang University Hospital Chee Jeong Kim 7.2 5.3 6.4 5.6 7.3 5.5 1 1 2 3 4 10 11 7 34 49 122 123 1.0 - - 10. 2001 1998 1998 Improvement of postmenopausal