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Siraya K. ฮอร์โมนสำคัญ อย่างไรในวัยทอง
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Clinical Practice Guideline
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Evidence-Based Medicine Strength of Recommendation Level of Evidence ABCDIABCDI I II III
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Guideline & Recommendations International Menopause Society (Climacteric) http://www.imsociety.org/index.php (2007) North American Menopause Society (Menopause) http://www.menopause.org/ (2010) Asia Pacific Menopause Federation http://www.apmf.net/ (2008) American Association of Clinical Endocrinologists Medical Guideline for Clinical Practice for the Diagnosis and the Treatment of Menopaus e (2006) The Endocine Society. The Journal of Clinical Endocrinology & Metabolism, July 2010, Vol 95, Suppl 1. No 07
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HRT – Benefits Symptomatic Vasomotor Mood Vaginal Atrophy Insomnia Preventative: Osteoporosis Coronary Heart Dz Alzheimer’s Genitourinary Health Colon Cancer Atrophic Vaginitis General Sense of Well Being Sexual Functioning HRT – RISK Breast Ca Deep Vein Thrombosis (DVT) Pulmonary Emboli (PE) Endometrial Ca Gallbladder Dz
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-> Overall strategy - lifestyle recommendations: diet, exercise, smoking and alcohol - Hormone therapy -> HT must be individualized (symptoms and need for prevention) -> The risks and benefits of HT differ - Age of menopause woman - hormonal products and routes of administration Principles Climacteric 2007;10:181–94
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- Spontaneous or iatrogenic menopause before the age of 45 and particularly before 40 are at higher risk for cardiovascular disease and osteoporosis -> benefit from hormone replacement (should be given at least until the normal age of menopause - Counseling should convey the benefits and risks Principles Climacteric 2007;10:181–94
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- Dosage should be titrated to the lowest effective dose - Progestogen should be added to systemic estrogen for all women with a uterus to prevent endometrial hyperplasia and cancer Principles Climacteric 2007;10:181–94
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Guideline & Recommendation Contraindication Indication
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OneOneTwoTwoThreeThree Moderate to severe symptoms of vulvar and vaginal atrophy Prevention of postmenopausal osteoporosis Moderate to severe vasomotor symptoms associated with menopause LOE 1, Grade A
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HRT VS placebo Hot flushes frequency/week Study HRT Placebo Mean Difference Weight Mean difference N Mean (SD) N Mean (SD) 95% CI 95% CI Less with HRT Less with placebo Cochrane Database of Systematic Reviews 2004, Issue 4. Art
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Study HRT Placebo Mean Difference Weight Mean difference N Mean (SD) N Mean (SD) 95% CI 95% CI Less with HRT Less with placebo HRT VS placebo Hot flush severity Cochrane Database of Systematic Reviews 2004, Issue 4. Art
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IndicationOneOneTwoTwoThreeThree Moderate to severe symptoms of vulvar and vaginal atrophy Prevention of postmenopausal osteoporosis Moderate to severe vasomotor symptoms associated with menopause LOE 1, Grade A
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equally effective for vaginal atrophy Creams Pessaries Rings Tablets Suckling JA, Kennedy R, Lethaby A, Roberts H. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database of Systematic Reviews 2006, Issue 4.
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Systematic Review for Vaginal Atrophy The CEE cream is associated with significant adverse effects when compared to E2 tablets (OR 0.18, 95% CI 0.07 to 0.50) Uterine bleeding Breast pain Perineal pain Suckling JA, Kennedy R, Lethaby A, Roberts H. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database of Systematic Reviews 2006, Issue 4.
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Systematic Review for Vaginal Atrophy Significant endometrial overstimulation with the CEE cream group when compared to the ring (OR 0.29, 95% CI 0.11 to 0.78) 2% incidence of simple hyperplasia in the ring group when compared to the CEE cream 4% incidence of hyperplasia in the CEE cream group when compared to the tablet (E2). Suckling JA, Kennedy R, Lethaby A, Roberts H. Local oestrogen for vaginal atrophy in postmenopausal women. Cochrane Database of Systematic Reviews 2006, Issue 4.
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Urinary Disorders Urinary incontinence Systemic estrogen + progestin worsen incontinence RR 1.32, 95% CI 1.17 -1.48 Local estrogens use improve incontinence RR 0.74, 95%CI 0.64-0.86 Cody JD et al. Cochrane Database of Systematic Reviews 2009, Issue 4.
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Urinary tract infection - Oral estrogens did not reduce UTI - Vaginal estrogens versus placebo reduced the number of women with UTIs Perrotta C et al. Cochrane Database of Systematic Reviews 2008, Issue 2. Art Urinary Disorders
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IndicationOneOneTwoTwoThreeThree Moderate to severe symptoms of vulvar and vaginal atrophy Prevention of postmenopausal osteoporosis Moderate to severe vasomotor symptoms associated with menopause LOE 1, Grade A
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Farquhar C, et al. Long term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database of Systematic Reviews 2009, Issue 2
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Established reduction in bone mass, regardless of menopause symptoms when alternate therapies are not appropriate or cause side effects when the benefits of extended use are expected to exceed the risks. 2010 The North American Menopause Society When to use HRT for osteoporotic prevention?
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Additional indication Mood disorders (depression) Sexual dysfunction Cognitive disruption Comment Need to exclude other causes AACE & IMS IMS, NAM & APMF Sleep disturbances associated with vasomotor symptom
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HRT can be effective in relieving dyspareunia. Lubrication Blood flow Sensation in vaginal tissue HRT is not the sole treatment for diminished sexual function. Sexual function NAMS 2010
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Guideline & Recommendation Contraindication Indication
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Contraindication 1)Current, past, or suspected breast cancer 2)Known or suspected estrogen-sensitive malignant conditions 3)Undiagnosed genital bleeding 4)Untreated EH 5)Known hypersensitivity to the active substances of HT 1)Current, past, or suspected breast cancer 2)Known or suspected estrogen-sensitive malignant conditions 3)Undiagnosed genital bleeding 4)Untreated EH 5)Known hypersensitivity to the active substances of HT 6) Active liver disease 7)Previous idiopathic or current venous thromboembolism 7) Active or recent arterial thromboembolic disease 8)Untreated hypertension 9)Porphyria cutanea tarda 6) Active liver disease 7)Previous idiopathic or current venous thromboembolism 7) Active or recent arterial thromboembolic disease 8)Untreated hypertension 9)Porphyria cutanea tarda
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Assessment of risk factors for stroke, CHD, VTE, osteoporosis, Breast cancer History taking & PE Should be performed according to national guidelines and age preferably within the 12 months before initiation of therapy Mammogram May be considered on a case-by-case basis. Bone mineral density measurement Lipid profile Blood sugar Other 2010 The North American Menopause Society
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Mammogram & Breast Cancer Screening
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Systematic Review & Meta-analysis Reduction of Death from Mammogram Women > 50 RR 0.84 (95% CI, 0.77, 0.91) NNT 1224 (95% CI, 665, 2564) Women 40-50 yrs RR 0.85 (95% CI, 0.73, 0.99) NNT 1792 (95%CI, 764, 10 540) Ann Intern Med. 2002;137:347-360.
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Breast Cancer Mortality & Screening Mammogram Cancer Epidemiol Biomarkers Prev 2006;15(1):45–51 Screened Women Unscreened Women Mortality Mortality
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Estrogen + Progestin, RR per 5 years of use Randomized Controlled trials Observational trials
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Tips Endometrial & breast cancer remain contraindications Ovarian cancer, cervical cancer, are not contraindication HT is not a contraindication. Women at different levels of CV risk with either optimal BP or with HT Progestogens with antimineralocorticoid activity preferred
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Routes Estrogen treatment TOPICALVAGINAL ORAL TRANSDERMALINJECTABLE
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Estrogen Progestogen
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Cyclic sequential regimen Continued estrogen everyday Estradiol gel 1 mg/day Estradiol oral 1 mg/day Progestogen in last 14 days of cycle MPA 5 mg/day Dydrogesterone 10 mg/day
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- Schering, Germany. - Pills N=21 calendaristic packing. Composition: - Estradiol Valerate 2 mg (11 white Pills) - Estradiol Valerate 2 mg and Norgestrel 0.5 mg (10 light-brown Pills) Cycloprogynova
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Continuous combined regimen E+P everyday Estrogen Estradiol gel 1 mg/day Estradiol oral 1 mg/day Progestogen MPA 1.5 or 2.5 mg/day Dydrogesterone 5 mg/day Levonorgestrel IUD
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Femoston conti. - Solvay Pharmaceuticals - Containing 5 mg dydrogesterone 1 mg estradiol
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แนวทางการให้ ฮอร์โมน มีภาวะ พร่อง ฮอร์โมน E มีข้อบ่งชี้ ในการได้ ฮอร์โมน No Contraindication มีมดลูกE+Pไม่มีมดลูกEContraindication ไม่มีข้อ บ่งชี้ Advise
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