Transcript Cochrane Database of Systematic Reviews 2009, Issue 4.
ฮอร ์โมนส ำคัญ อย่ำงไรในวัยทอง
Siraya K.
Clinical Practice Guideline
Evidence-Based Medicine
Strength of Recommendation A B C D I Level of Evidence I II III
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
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
Principles -> 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
Climacteric
2007;10:181 –94
Principles - 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
Climacteric
2007;10:181 –94
Principles - 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
Climacteric
2007;10:181 –94
Guideline & Recommendation
Indication Contraindication
Indication
One Two Three Moderate to severe vasomotor symptoms associated with menopause Moderate to severe symptoms of vulvar and vaginal atrophy Prevention of postmenopausal osteoporosis LOE 1, Grade A
SYSTEMATIC REVIEW & META-ANALYSIS
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
HRT VS placebo Hot flush severity
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
Indication
One Two Three Moderate to severe vasomotor symptoms associated with menopause Moderate to severe symptoms of vulvar and vaginal atrophy Prevention of postmenopausal osteoporosis LOE 1, Grade A
SYSTEMATIC REVIEW & META-ANALYSIS
Rings Pessaries Tablets Creams
equally effective for vaginal atrophy
Suckling JA, Kennedy R, Lethaby A, Roberts H. Local oestrogen for vaginal atrophy in postmenopausal women.
Cochrane Database of Systematic Reviews 2006 , Issue 4.
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.
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.
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.
Urinary Disorders
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
Indication
One Two Three Moderate to severe vasomotor symptoms associated with menopause Moderate to severe symptoms of vulvar and vaginal atrophy Prevention of postmenopausal osteoporosis LOE 1, Grade A
SYSTEMATIC REVIEW & META-ANALYSIS
Farquhar C, et al . Long term hormone therapy for perimenopausal and postmenopausal women.
Cochrane Database of Systematic Reviews 2009 , Issue 2
WHEN TO USE HRT FOR OSTEOPOROTIC PREVENTION?
When to use HRT for osteoporotic prevention?
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
Additional indication
AACE & IMS Mood disorders (depression) Sexual dysfunction Cognitive disruption Comment Need to exclude other causes IMS, NAM & APMF Sleep disturbances associated with vasomotor symptom
Sexual function
NAMS 2010 HRT can be effective in relieving dyspareunia.
Lubrication Blood flow Sensation in vaginal tissue HRT is not the sole treatment for diminished sexual function.
Guideline & Recommendation
Indication Contraindication
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 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
History taking & PE • Assessment of risk factors for stroke, CHD, VTE, osteoporosis, Breast cancer Mammogram • • Should be performed according to national guidelines and age preferably within the 12 months before initiation of therapy Bone mineral density measurement • May be considered on a case-by-case basis.
Other • • Lipid profile Blood sugar 2010 The North American Menopause Society
Mammogram & Breast Cancer Screening
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.
Breast Cancer Mortality & Screening Mammogram Mortality Mortality Mortality Mortality
Screened Women Unscreened Women Cancer Epidemiol Biomarkers Prev 2006;15(1):45 – 51
HRT IN BREAST CANCER
Randomized Controlled trials
Estrogen + Progestin , RR per 5 years of use
Observational trials
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
Routes Estrogen treatment
ORAL TRANSDERMAL INJECTABLE TOPICAL VAGINAL
Estrogen Progestogen
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
Cycloprogynova - 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)
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
Femoston conti.
- Solvay Pharmaceuticals - Containing 5 mg dydrogesterone 1 mg estradiol
แนวทางการให ้ ฮอร์โมน
พร่อง ฮอร์โมน E มีข ้อบ่งชี้ ในการได ้ ฮอร์โมน No Contraindication Contraindication ไม่มีข ้อ บ่งชี้ Advise มีมดลูก ไม่มีมดลูก E+P E