Siraya K. ฮอร์โมนสำคัญ อย่างไรในวัยทอง....

Siraya K.

ฮอร์�โมนสำคั�ญฮอร์�โมนสำคั�ญอย่�งไร์ในวั�ย่ทองอย่�งไร์ในวั�ย่ทอง

Clinical Practice Guideline

Evidence-Based Medicine

Strength of Recommendation

Level of Evidence

ABCDI

IIIIII

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 Federationhttp://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

HRT – BenefitsSymptomatic

VasomotorMoodVaginal AtrophyInsomnia

Preventative:OsteoporosisCoronary Heart DzAlzheimer’sGenitourinary HealthColon CancerAtrophic VaginitisGeneral Sense of Well

BeingSexual Functioning

HRT – RISKBreast CaDeep Vein Thrombosis

(DVT)Pulmonary Emboli (PE)Endometrial CaGallbladder Dz

-> 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

PrinciplesPrinciples

Climacteric 2007;10:181–94

- 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

PrinciplesPrinciples

Climacteric 2007;10:181–94

- 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

PrinciplesPrinciples

Climacteric 2007;10:181–94

Guideline & Recommendation

Contraindication

Indication

Indication

OneOneOneOne TwoTwoTwoTwo ThreeThreeThreeThree

Moderate to severe symptoms of vulvar and vaginal atrophy

Moderate to severe symptoms of vulvar and vaginal atrophy

Prevention of postmenopaus

al osteoporosis

Prevention of postmenopaus

al osteoporosis

Moderate to severe vasomotor symptoms associated with menopause

Moderate to severe vasomotor symptoms associated with menopause

LOE 1, Grade A

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

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

Indication

OneOneOneOne TwoTwoTwoTwo ThreeThreeThreeThree

Moderate to severe symptoms of vulvar and vaginal atrophy

Moderate to severe symptoms of vulvar and vaginal atrophy

Prevention of postmenopaus

al osteoporosis

Prevention of postmenopaus

al osteoporosis

Moderate to severe vasomotor symptoms associated with menopause

Moderate to severe vasomotor symptoms associated with menopause

LOE 1, Grade A

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.

Systematic Review for Vaginal AtrophyThe 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.

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 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

Indication

OneOneOneOne TwoTwoTwoTwo ThreeThreeThreeThree

Moderate to severe symptoms of vulvar and vaginal atrophy

Moderate to severe symptoms of vulvar and vaginal atrophy

Prevention of postmenopaus

al osteoporosis

Prevention of postmenopaus

al osteoporosis

Moderate to severe vasomotor symptoms associated with menopause

Moderate to severe vasomotor symptoms associated with menopause

LOE 1, Grade A

Farquhar C, et al . Long term hormone therapy for perimenopausal

and postmenopausal women. Cochrane Database of Systematic Reviews 2009, Issue 2

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?

Additional indication

Mood disorders (depression)Sexual dysfunctionCognitive disruption

CommentNeed to exclude other causes

AACE & IMS

IMS, NAM & APMFSleep disturbances associated with vasomotor symptom

HRT can be effective in relieving dyspareunia.LubricationBlood flowSensation in vaginal tissueHRT is not the sole treatment for diminished sexual function.

Sexual function

NAMS 2010

Guideline & Recommendation

Contraindication

Indication

Contraindication

1) Current, past, or suspected breast cancer

2) Known or suspected estrogen-sensitive malignant conditions

3) Undiagnosed genital bleeding

4) Untreated EH5) 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 EH5) 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

2010 The North American Menopause Society

Mammogram & Breast Cancer Screening

Systematic Review & Meta-analysis

Reduction of Death from Mammogram

Ann Intern Med. 2002;137:347-360.

Breast Cancer Mortality & Screening Mammogram

Cancer Epidemiol Biomarkers Prev 2006;15(1):45–51

Screened Women Unscreened Women

Mortality Mortality

Mortality Mortality

Estrogen + Progestin , RR per 5 years of useRandomized Controlled trials

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 HTProgestogens with antimineralocorticoid activity preferred

Routes Estrogen treatmentRoutes Estrogen treatment

TOPICAL VAGINAL

ORAL TRANSDERMAL INJECTABLE

Estrogen

Progestogen

Cyclic sequential regimen

Continued estrogen everyday

Estradiol gel 1 mg/dayEstradiol oral 1 mg/day

Progestogen in last 14 days of cycle

MPA 5 mg/dayDydrogesterone 10 mg/day

- 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

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

แนวทางการให้� ฮอร�โมน