ฮอร์โมนสำคัญอย่างไรในวัยทอง

1. ฮอร์โมนสำคัญอย่างไรในวัยทองฮอร์โมนสำคัญอย่างไรในวัยทอง Siraya K.

3. Clinical Practice Guideline

4. Evidence-Based Medicine Strength of Recommendation A B C D I Level of Evidence I II III

5. 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 Menopause (2006) The Endocine Society. The Journal of Clinical Endocrinology & Metabolism, July 2010, Vol 95, Suppl 1. No 07

6. Symptomatic Vasomotor Mood Vaginal Atrophy Insomnia HRT – Benefits • 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

7. -> 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

8. - 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

9. - 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

10. Guideline & Recommendation Indication Contraindication

11. 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

12. Systematic review & Meta-analysis

13. HRT VS placeboHot 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

14. 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

15. 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

16. Systematic review & meta-analysis

17. 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.

18. Systematic Review 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. 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

19. Systematic Review 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. 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).

20. Urinary Disorders Cody JD et al. Cochrane Database of Systematic Reviews 2009, Issue 4. 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

21. Urinary Disorders Perrotta C et al. Cochrane Database of Systematic Reviews 2008, Issue 2. Art Urinary tract infection - Oral estrogens did not reduce UTI - Vaginal estrogens versus placebo reduced the number of women with UTIs

22. 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

23. Systematic review & Meta-analysis

24. Farquhar C, et al . Long term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database of Systematic Reviews 2009, Issue 2

25. When to use HRT for osteoporotic prevention?

26. When to use HRT for osteoporotic prevention? 2010 The North American Menopause Society 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.

27. Additional indication AACE & IMS IMS, NAM & APMF Sleep disturbances associated with vasomotor symptom Mood disorders (depression) Sexual dysfunction Cognitive disruption Comment Need to exclude other causes

28. 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.

29. Guideline & Recommendation Indication Contraindication

30. Contraindication • Current, past, or suspected breast cancer • Known or suspected estrogen-sensitive malignant conditions • Undiagnosed genital bleeding • Untreated EH • Known hypersensitivity to the active substances of HT Active liver disease Previous idiopathic or current venous thromboembolism Active or recent arterial thromboembolic disease Untreated hypertension Porphyriacutaneatarda

31. 2010 The North American Menopause Society

32. Mammogram & Breast Cancer Screening

33. Systematic Review & Meta-analysisReduction of Death from Mammogram Ann Intern Med. 2002;137:347-360.

34. Breast Cancer Mortality & Screening Mammogram Mortality  Mortality  Mortality  Mortality  Screened Women Unscreened Women Cancer Epidemiol Biomarkers Prev 2006;15(1):45–51

35. Hrt in breast cancer

36. Randomized Controlled trials Observational trials Estrogen + Progestin , RR per 5 years of use

37. 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

38. Routes Estrogen treatment ORAL TRANSDERMAL INJECTABLE TOPICAL VAGINAL

39. Estrogen Progestogen

40. 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

41. 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)

42. 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

43. Femoston conti. • - Solvay Pharmaceuticals • - Containing • 5 mg dydrogesterone • 1 mg estradiol

44. แนวทางการให้ ฮอร์โมน

45. Thank you for your attention