2006 : TERAPIA ORMONALE SOSTITUTIVA DELLA MENOPAUSA CURRENT CONSENSUS GUIDELINES AND PRACTICE RECOMMENDATIONS Andrea R. Genazzani, MD, PhD, FRCOG President.

2006 : TERAPIA ORMONALE SOSTITUTIVA

DELLA MENOPAUSA

CURRENT CONSENSUS GUIDELINES AND

PRACTICE RECOMMENDATIONS

Andrea R. Genazzani, MD, PhD, FRCOG

President of the International Society of Gynecological EndocrinologyDirector of the Department of Obstetrics and Gynecology

University of Pisa

Research Support, Grants and Occasional Honoraria: Bracco, Eli Lilly&Company, Igea, Lunar Corporation, MS&D, Novartis, Novo Nordisk, Organon, Pfizer, P&G, Schering, Solvay, Wyeth.

An About-Face On Hormone Therapy

New Study Shows HRT May Actually

Improve Heart Health in Some Women:

Timing Is Key

By Tara Parker-Pope, The Wall Street Journal Jan 24, 2006

Guideline and Consensus Recommendations Practice in areas of controversy can be difficult

HRT has been controversial since 1998

HRT Evidence Base is progressively evolving

Authoritative recommendations provide guidance and a degree of security for practice in these circumstances

Recommendations

Government bodies

International organisations

Consensus Groups

Guideline and Consensus Recommendations Practice in areas of controversy can be difficult

HRT has been controversial since 1998

HRT Evidence Base is progressively evolving

Authoritative recommendations provide guidance and a degree of security for practice in these circumstances

Recommendations

Government bodies

International organisations

Consensus Groups

Guideline and Consensus Recommendations Practice in areas of controversy can be difficult

HRT has been controversial since 1998

HRT Evidence Base is progressively evolving

Authoritative recommendations provide guidance and a degree of security for practice in these circumstances

Recommendations

Government bodies

International organisations

Consensus Groups

Guideline and Consensus Recommendations

Government Guidance is minimal EMEA statement

International Societies

International Menopause Society (IMS)

European Menopause and Andropause Society (EMAS)

North American Menopause Society (NAMS)

Consensus Group Recommendations

International Consensus Group

Rome 2003

Lucerne 2004

Guideline and Consensus Recommendations

Government Guidance is minimal EMEA statement

International Societies

International Menopause Society (IMS)

European Menopause and Andropause Society (EMAS)

North American Menopause Society (NAMS)

Consensus Group Recommendations

International Consensus Group

Rome 2003

Lucerne 2004

Guideline and Consensus Recommendations

Government Guidance is minimal EMEA statement

International Societies

International Menopause Society (IMS)

European Menopause and Andropause Society (EMAS)

North American Menopause Society (NAMS)

Consensus Group Recommendations

International Consensus Group

Rome 2003

Lucerne 2004

EMEA Guidance - Dec 2003

HRT no longer first choice for preventing osteoporosis

these EMEA recommendations are unjustified by: Physiology Epidemiology Pharmachology Evidence Based Medicine

Statement from The International Menopause Society

The International Menopause Society (IMS) is profoundly concerned that the European Medicines Evaluation Agency (EMEA) has ignored important information in its decision to recommend that the risk/benefit balance of hormone replacement therapy (HRT) does not justify its use as first-line therapy for the indication for prevention of osteoporosis in women.In early postmenopausal women, there is no evidence that alternative treatments are as beneficial……Because of the age of the population studied in the WHI, safety concerns cannot be extrapolated to early postmenopausal women…………...Therefore, the IMS considers that the EMEA recommendations are unjustified and potentially harmful for the health of postmenopausal women.

http://www.imsociety.org/pages/news.html

EMEA – MHRA Guidance - Dec 2003

HRT provides effective relief of climacteric (vasomotor) symptoms typically occurring around the menopause

The risk:benefit of HRT is favourable for treatment of vasomotor symptoms

The risk:benefit balance of HRT is not favourable as first-line treatment for the prevention of osteoporosis or osteoporotic fractures in women…

- with risk factors

or

- established osteoporosis

EMEA – MHRA Guidance - Dec 2003

HRT provides effective relief of climacteric (vasomotor) symptoms typically occurring around the menopause

The risk:benefit of HRT is favourable for treatment of vasomotor symptoms

The risk:benefit balance of HRT is not favourable as first-line treatment for the prevention of osteoporosis or osteoporotic fractures in women…

- with risk factors

or

- established osteoporosis

Climacteric 2004; 7: 333-7

IMS Position Statement

Section 1

Critique of WHI and other recent studies

Section 2

Summary recommendations for practice

Climacteric 2004; 7: 333-7

EMAS Position Statement

Section 1

Critique of WHI and other recent studies

Section 2

Recommendations for practice with evidence gradings

Maturitas 2005; 51: 8-14

North American Menopause Society Position Statement

Menopause 2004. 11; 589-600

NAMS Position Statement

Recommendations from Expert Panel Consensus Group – telephone & electronic communication

Discussion of measures of risk and the nature of different types of study

Recommendations for practice

areas of consensus

areas where insufficient or conflicting evidence precludes consensus

the need for future research

Menopause 2004. 11; 589-600

International Consensus Group Rome 2003, Lucerne 2004

Climacteric 2004 7: 210-216

International Consensus Group Rome 2003, Lucerne 2004

International Expert Group

Extended Consensus Meetings

Burger H (AUS)

Archer DF (USA) Barlow D (UK) Birkhäuser M (CH)Calaf-Alsina J (E) Gambacciani M (I) Genazzani A (I)Hadji P (GER) Iversen OE (N) Kuhl H (GER)Lobo RA (USA) Maudelonde T (F) Neves e Castro M (P)Notelovitz M (USA) Palacios S (E) Paszkowski T (PL)Peer E (IL) Pines A (IL) Samsioe G (SWE)Stevenson J (UK) Skouby S (DK) Sturdee D (UK)de Villiers T (RSA) Whitehead M (UK) Ylikorkala O (FIN)

Climacteric 2004 7: 210-216

International Consensus Group Rome 2003, Lucerne 2004

International Expert Group

Extended Consensus Meetings

Draft Practical Recommendations drafted at meeting by group leaders

Henry Burger & David Archer

Comments received from Group in discussion at meeting and by subsequent electronic communication

Final Recommendations published

Climacteric 2004 7: 210-216

Indications

HRT should only be prescribed when it is clearly indicated

Vasomotor symptoms (there is no effective alternative)

Urogenital atrophy (Topical low-dose products are the treatment choice if only local symptoms present

Fracture risk reduction (HRT may be an initial option in woman at significantly increased fracture risk)

Indications

HRT should only be prescribed when it is clearly indicated

Vasomotor symptoms (there is no effective alternative)

Urogenital atrophy (Topical low-dose products are the treatment choice if only local symptoms present

Fracture risk reduction (HRT may be an initial option in woman at significantly increased fracture risk)

Indications

HRT should only be prescribed when it is clearly indicated

Vasomotor symptoms (there is no effective alternative)

Central reason for use of HRT

All guidelines endorse this use (including EMEA advice)

Evidence base secure

No equivalently effective alternative

Indications

HRT should only be prescribed when it is clearly indicated

Vasomotor symptoms (there is no effective alternative)

Urogenital atrophy (Topical low-dose products are the treatment choice if only local symptoms present

Fracture risk reduction (HRT may be an initial option in woman at significantly increased fracture risk)

Indications

HRT should only be prescribed when it is clearly indicated

Vasomotor symptoms (there is no effective alternative)

Urogenital atrophy (Topical low-dose products are the treatment choice if only local symptoms present

Important indication for estrogen use

All guidelines endorse this

Local E-only suggested by NAMS & EMAS

Likely to be long term indication (EMAS)

Indications

HRT should only be prescribed when it is clearly indicated

Vasomotor symptoms (there is no effective alternative)

Urogenital atrophy (Topical low-dose products are the treatment choice if only local symptoms present

Fracture risk reduction (HRT may be an initial option in woman at significantly increased fracture risk)

Evidence agreed by all guidelines

Duration of use needs to be long-term for effective action

no complete consensus from guidelines

IndicationsHRT should only be prescribed when it is clearly indicated

Fracture risk reduction (HRT may be an initial option in woman at significantly increased fracture risk)

Evidence agreed by all guidelines

Duration of use needs to be long-term for effective action

no complete consensus from guidelines

EMEA – not first-line therapy

IMS – Clear endorsement – long term therapy but individualise

EMAS – Best option in younger and symptomatic women

Alternatives more suitable in older women

NAMS – Definite evidence for effect – weigh risks:benefits against alternatives

Indications

HRT should only be prescribed when it is clearly indicated

Vasomotor symptoms (there is no effective alternative)

Urogenital atrophy (Topical low-dose products are the treatment choice if only local symptoms present

Fracture risk reduction (HRT may be an initial option in woman at significantly increased fracture risk)

Initiation of treatment

Sequential (SC) HRT:

Preferably progestogen-dominant

Bleed free continuous combined (CC) HRT can be recommended later

Switch from SC to CC HRT should meet the following criteria:

Patient is likely to be postmenopausal (age >50 years)

Patient should have had regular withdrawal bleeding and no irregular bleeding while taking SC HRT

Patient had no bleeding on SC HRT

Early initiation is important – it enables both relief of menopausal symptoms and protects against the consequences of oestrogen deficiency

Combined preparation should be used in women with intact uterus

Initiation of treatment

All guidelines support early initiation

early relief of symptoms

possible early effects on systemic aspects

NAMS emphasises moderate/severe symptoms as indication

Early initiation is important – it enables both relief of menopausal symptoms and protects against the consequences of oestrogen deficiency

Combined preparation should be used in women with intact uterus

Initiation of treatment

Sequential (SC) HRT:

Preferably progestogen-dominant

Bleed free continuous combined (CC) HRT can be recommended later

Switch from SC to CC HRT should meet the following criteria:

Patient is likely to be postmenopausal (age >50 years)

Patient should have had regular withdrawal bleeding and no irregular bleeding while taking SC HRT

Patient had no bleeding on SC HRT

Early initiation is important – it enables both relief of menopausal symptoms and protects against the consequences of oestrogen deficiency

Combined preparation should be used in women with intact uterus

Initiation of treatment

Sequential (SC) HRT:

Preferably progestogen-dominant

Bleed free continuous combined (CC) HRT can be recommended later

Switch from SC to CC HRT should meet the following criteria:

Patient is likely to be postmenopausal (age >50 years)

Patient should have had regular withdrawal bleeding and no irregular bleeding while taking SC HRT

Patient had no bleeding on SC HRT

Early initiation is important – it enables both relief of menopausal symptoms and protects against the consequences of oestrogen deficiency

Combined preparation should be used in women with intact uterus

Initiation of treatment

Sequential (SC) HRT:

Preferably progestogen-dominant

Bleed free continuous combined (CC) HRT can be recommended later

All guidelines accept that (CC) HRT will be main approach

All recognise that continuous progestogen effect

needs further research

Early initiation is important – it enables both relief of menopausal symptoms and protects against the consequences of oestrogen deficiency

Combined preparation should be used in women with intact uterus

Initiation of treatment

Sequential (SC) HRT:

Preferably progestogen-dominant

Bleed free continuous combined (CC) HRT can be recommended later

Switch from SC to CC HRT should meet the following criteria:

Patient is likely to be postmenopausal (age >50 years)

Patient should have had regular withdrawal bleeding and no irregular bleeding while taking SC HRT

Patient had no bleeding on SC HRT

Early initiation is important – it enables both relief of menopausal symptoms and protects against the consequences of oestrogen deficiency

Combined preparation should be used in women with intact uterus

Dose recommendation

Lowest effective dose should be used

Recommended starting doses include:

0.5 – 1mg 17β-oestradiol (oral)

0.3 – 0.45mg conjugated equine oestrogens (oral)

25 – 37.5µg transdermal (patch) oestradiol

0.5mg oestradiol gel

150µg intranasal oestradiol

Dose recommendation

Lowest effective dose should be used

Recommended starting doses include:

0.5 – 1mg 17β-oestradiol (oral)

0.3 – 0.45mg conjugated equine oestrogens (oral)

25 – 37.5µg transdermal (patch) oestradiol

0.5mg oestradiol gel

150µg intranasal oestradiol

Monitoring treatment

Pre-treatment assessment History Menopausal symptoms Menstrual history Personal and/or family history of Osteoporotic fracture VTE Breast cancer CVD

Physical examination incl. weight and blood pressure

Additional assessments may include/require Vaginal ultrasound and/or endometrial biopsy Mammography (frequency according to local guidelines) Bone mineral density based on local guidelines

Patients should be re-evaluated annually

Monitoring treatment

Pre-treatment assessment History Menopausal symptoms Menstrual history Personal and/or family history of Osteoporotic fracture VTE Breast cancer CVD

Physical examination incl. weight and blood pressure

Additional assessments may include/require Vaginal ultrasound and/or endometrial biopsy Mammography (frequency according to local guidelines) Bone mineral density based on local guidelines

Patients should be re-evaluated annually

Monitoring treatment

Pre-treatment assessment History Menopausal symptoms Menstrual history Personal and/or family history of Osteoporotic fracture VTE Breast cancer CVD

Physical examination incl. weight and blood pressure

Additional assessments may include/require Vaginal ultrasound and/or endometrial biopsy Mammography (frequency according to local guidelines) Bone mineral density based on local guidelines

Patients should be re-evaluated annually

Duration of treatment

Based on the indication for treatment

Dose and type should be re-evaluated annually

Need for continuation can be determined by temporarily discontinuing therapy

Prevention or treatment of osteoporosis

Only long-term therapy is effective

Urogenital atrophy

Long-term therapy, usually topical, may be required

Duration of treatment

Based on the indication for treatment

Dose and type should be re-evaluated annually

Need for continuation can be determined by temporarily discontinuing therapy

Prevention or treatment of osteoporosis

Only long-term therapy is effective

Urogenital atrophy

Long-term therapy, usually topical, may be required

Duration of treatment

Based on the indication for treatment

Dose and type should be re-evaluated annually

Need for continuation can be determined by temporarily discontinuing therapy

Guidelines not entirely consistent

NAMS – extended treatment OK if…

benefit > risk but ? try to stop at intervals

no consensus on stopping – therefore individualise

no consensus on tapering

IMS – No new reason for mandatory limit

No reason to stop when symptom-free on treatment

Duration of treatment

Based on the indication for treatment

Dose and type should be re-evaluated annually

Need for continuation can be determined by temporarily discontinuing therapy

Prevention or treatment of osteoporosis

Only long-term therapy is effective

Urogenital atrophy

Long-term therapy, usually topical, may be required

Duration of treatment

Based on the indication for treatment

Dose and type should be re-evaluated annually

Need for continuation can be determined by temporarily discontinuing therapy

Prevention or treatment of osteoporosis

Only long-term therapy is effective

Agreed by all guidelines but differences on effect of this on approach

adopted

IMS – strongest view supporting use beyond early PM years

Duration of treatment

Based on the indication for treatment

Dose and type should be re-evaluated annually

Need for continuation can be determined by temporarily discontinuing therapy

Prevention or treatment of osteoporosis

Only long-term therapy is effective

Urogenital atrophy

Long-term therapy, usually topical, may be required

Duration of treatment

Based on the indication for treatment

Dose and type should be re-evaluated annually

Need for continuation can be determined by temporarily discontinuing therapy

Prevention or treatment of osteoporosis

Only long-term therapy is effective

Urogenital atrophy

Long-term therapy, usually topical, may be required

Good consensus across the guidelines in support of

local E-only therapy in extended use

Conclusions

Conclusions

The international groups demonstrate a good consensus on the use of HRT today

The central role of HRT in symptom relief is unchallenged

The detailed management approach is remarkably similar across the guidelines but all stress the need for individualisation

The longer-term benefits and risks remain controversial and influence longer-term management approaches even where effectiveness is clear – fracture prevention

All criticise a “too simplistic” interpretation of WHI

All agree that more evidence is needed concerning different…...

forms of estrogen and progestogen

routes of administration

levels of hormone dose

Conclusions

The international groups demonstrate a good consensus on the use of HRT today

The central role of HRT in symptom relief is unchallenged

The detailed management approach is remarkably similar across the guidelines but all stress the need for individualisation

The longer-term benefits and risks remain controversial and influence longer-term management approaches even where effectiveness is clear – fracture prevention

All criticise a “too simplistic” interpretation of WHI

All agree that more evidence is needed concerning different…...

forms of estrogen and progestogen

routes of administration

levels of hormone dose

Conclusions

The international groups demonstrate a good consensus on the use of HRT today

The central role of HRT in symptom relief is unchallenged

The detailed management approach is remarkably similar across the guidelines but all stress the need for individualisation

The longer-term benefits and risks remain controversial and influence longer-term management approaches even where effectiveness is clear – fracture prevention

All criticise a “too simplistic” interpretation of WHI

All agree that more evidence is needed concerning different…...

forms of estrogen and progestogen

routes of administration

levels of hormone dose

Conclusions

The international groups demonstrate a good consensus on the use of HRT today

The central role of HRT in symptom relief is unchallenged

The detailed management approach is remarkably similar across the guidelines but all stress the need for individualisation

The longer-term benefits and risks remain controversial and influence longer-term management approaches even where effectiveness is clear – fracture prevention

All criticise a “too simplistic” interpretation of WHI

All agree that more evidence is needed concerning different…...

forms of estrogen and progestogen

routes of administration

levels of hormone dose

Conclusions

The international groups demonstrate a good consensus on the use of HRT today

The central role of HRT in symptom relief is unchallenged

The detailed management approach is remarkably similar across the guidelines but all stress the need for individualisation

The longer-term benefits and risks remain controversial and influence longer-term management approaches even where effectiveness is clear – fracture prevention

All criticise a “too simplistic” interpretation of WHI

All agree that more evidence is needed concerning different…...

forms of estrogen and progestogen

routes of administration

levels of hormone dose

Conclusions

The international groups demonstrate a good consensus on the use of HRT today

The central role of HRT in symptom relief is unchallenged

The detailed management approach is remarkably similar across the guidelines but all stress the need for individualisation

The longer-term benefits and risks remain controversial and influence longer-term management approaches even where effectiveness is clear – fracture prevention

All criticise a “too simplistic” interpretation of WHI

All agree that more evidence is needed concerning different…...

forms of estrogen and progestogen

routes of administration

levels of hormone dose