Appendix 3: Recommendation Grading Forms

Duijts 2012

Breast cancer

CBT

II

moderate

the Netherlands

Mann 2012

Breast cancer

CBT

II

moderate

UK

Velez Toral 2014

Menopause

CBT

I

moderate

UK

1. Evidence base

B

one level I study with a moderate risk of bias, two level II studies with a moderate risk of bias

2. Consistency

C

some inconsistency reflecting genuine uncertainty around clinical question

3. Clinical impact

D

slight or restricted

4. Generalisability

B

population/s studied in the body of evidence are similar to the target population for the guideline: some studies were in women treated for breast cancer and some studies were in a general menopausal population

5. Applicability

A

directly applicable to Australian healthcare context: all studies were conducted in Australia or developed countries with similar levels of health service delivery

Purpose-designed cognitive behavioural therapy can be considered for the management of moderate to severe vasomotor symptoms in women with a history of breast cancer.

GRADE OF RECOMMENDATION

C

Carson 2009

Breast cancer

Yoga

II

moderate

USA

Cramer 2015

Breast cancer

Yoga

II

moderate

Germany

Daley 2014

Menopause

Yoga

I

low

USA

Woods 2014

Menopause

Yoga

I

moderate

India

Newton 2014

Menopause

Yoga

II

low

USA

1. Evidence base

A

one level I study and one level II study with a low risk of bias, one level I and two level II studies with a moderate risk of bias

2. Consistency

D

evidence is inconsistent

3. Clinical impact

D

slight or restricted

4. Generalisability

B

population/s studied in the body of evidence are similar to the target population for the guideline

5. Applicability

B

applicable to Australian healthcare context with few caveats

Yoga can be considered for the management of vasomotor symptoms and sleep disturbance in women with a history of breast cancer noting there is inconsistent evidence regarding its effectiveness.

Practice Point A:

There is evidence that exercise has no effect on vasomotor symptoms in a general population, although there are other benefits of physical activity for women with a history of breast cancer.

GRADE OF RECOMMENDATION

D

Bokmand 2013

Breast cancer

acupuncture

II

low

Denmark

Deng 2007

Breast cancer

acupuncture

II

moderate

USA

Hervik 2009

Breast cancer

acupuncture

II

low

Norway

Liljegren 2012

Breast cancer

acupuncture

II

moderate

Sweden

Walker 2010

Breast cancer

acupuncture

II

high

USA

Dodin 2013

Menopause

acupuncture

I

low

Denmark, Korea, Norway, Sweden, USA

Ee 2016

Menopause

acupuncture

II

low

Australia

Frisk 2008/Frisk 2012

Breast cancer

electro-acupuncture

II

high

Sweden

Mao 2015

Breast cancer

electro-acupuncture

II

moderate

USA

Nedstrand 2005/Nedstrand 2006

Breast cancer

electro-acupuncture

II

high

Sweden

1. Evidence base

A

one level I study with a low risk of bias, two level II studies with a low risk of bias, three level II studies with a moderate risk of bias, three level II studies with a high risk of bias

2. Consistency

D

evidence is inconsistent

3. Clinical impact

C

moderate

4. Generalisability

B

population/s studied in the body of evidence are similar to the target population for the guideline: some studies were in women treated for breast cancer and some studies were in a general menopausal population

5. Applicability

A

directly applicable to Australian healthcare context: all studies were conducted in Australia or developed countries with similar levels of health service delivery

Acupuncture and electro-acupuncture can be considered for the management of moderate to severe vasomotor symptoms in women with a history of breast cancer noting there is inconsistent evidence regarding their effectiveness.

GRADE OF RECOMMENDATION

D

Elkins 2008

Breast cancer

hypnotherapy

II

moderate

USA

1. Evidence base

C

one level II study with a moderate risk of bias

2. Consistency

N/A

one study only

3. Clinical impact

D

slight or restricted

4. Generalisability

A

population/s studied in body of evidence are the same as the target population for the guideline: all studies were in women treated for breast cancer

5. Applicability

A

directly applicable to Australian healthcare context: all studies were conducted in Australia or developed countries with similar levels of health service delivery

Purpose-designed hypnotherapy can be considered for the management of moderate to severe vasomotor symptoms in women with a history of breast cancer.

GRADE OF RECOMMENDATION

D

Hernandez Munoz 2003

Breast cancer

black cohosh

II

high

Venezuela

Jacobson 2001

Breast cancer

black cohosh

II

low

USA

Pockaj 2006

Breast cancer

black cohosh

II

moderate

USA

Leach and Moore 2012

Menopause

black cohosh

I

low

Switzerland, USA

1. Evidence base

A

one level I study with a low risk of bias, one level II study with a low risk of bias, one level II study with a moderate risk of bias, one level II study with a high risk of bias

2. Consistency

A

all studies consistent

3. Clinical impact

N/A

none

4. Generalisability

B

population/s studied in the body of evidence are similar to the target population for the guideline: some studies were in women treated for breast cancer and some studies were in a general menopausal population

5. Applicability

B

applicable to Australian healthcare context with few caveats: most studies were conducted in Australia or developed countries with similar levels of health service delivery

Black cohosh is not recommended for the management of vasomotor symptoms in women with a history of breast cancer due to evidence that it is not effective.

GRADE OF RECOMMENDATION

B

Jacobs 2005

Breast cancer

homeopathy

II

high

USA

Thompson 2005

Breast cancer

homeopathy

II

low

UK

1. Evidence base

B

one level II study with a low risk of bias, one level II study with a high risk of bias

2. Consistency

A

all studies consistent

3. Clinical impact

N/A

none

4. Generalisability

A

population/s studied in body of evidence are the same as the target population for the guideline: all studies were in women treated for breast cancer

5. Applicability

A

directly applicable to Australian healthcare context: all studies were conducted in Australia or developed countries with similar levels of health service delivery

Homeopathy is not recommended for the management of vasomotor symptoms in women with a history of breast cancer due to evidence that it is not effective.

GRADE OF RECOMMENDATION

B

Carpenter 2002

Breast cancer

magnetic therapy

II

moderate

USA

1. Evidence base

C

one level II study with a moderate risk of bias

2. Consistency

N/A

One study only

3. Clinical impact

N/A

none

4. Generalisability

A

population/s studied in body of evidence are the same as the target population for the guideline: all studies were in women treated for breast cancer

5. Applicability

A

directly applicable to Australian healthcare context: all studies were conducted in Australia or developed countries with similar levels of health service delivery

Magnetic therapy is not recommended for the management of vasomotor symptoms in women with a history of breast cancer due to evidence that it is not effective.

GRADE OF RECOMMENDATION

C

Cohen 2014

Menopause

omega-3 supplementation

II

low

USA

1. Evidence base

B

one level II study with a low risk of bias

2. Consistency

N/A

One study only

3. Clinical impact

N/A

none

4. Generalisability

C

population/s studied in body of evidence differ to target population for guideline but it is clinically sensible to apply this evidence to target population: all studies were in a general menopausal population

5. Applicability

A

directly applicable to Australian healthcare context: all studies were conducted in Australia or developed countries with similar levels of health service delivery

Omega-3 supplementation is not recommended for the management of vasomotor symptoms in women with a history of breast cancer due to evidence that it is not effective.

GRADE OF RECOMMENDATION

C

MacGregor 2005

Breast cancer

isoflavones

II

low

UK

Nikander 2003

Breast cancer

isoflavones

II

moderate

Finland

Van Patten 2002

Breast cancer

soy isoflavones

II

high

Canada

Thomas 2014

Menopause

soy and other isoflavones

I

moderate

Brazil, Canada, Ecuador, Iran, Italy, Japan, Korea, Taiwan, UK, USA

1. Evidence base

B

one level I study with a moderate risk of bias, one level II study with a low risk of bias, one level II study with a moderate risk of bias and one level II study with a high risk of bias

2. Consistency

C

some inconsistency reflecting genuine uncertainty around clinical question

3. Clinical impact

D

slight or restricted

4. Generalisability

B

 Population/s studied in body of evidence differ to target population and hard to judge whether it is sensible to generalise to target population

5. Applicability

B

applicable to Australian healthcare context with few caveats: most studies were conducted in Australia or developed countries with similar levels of health service delivery

Phytoestrogens are not recommended for the management of vasomotor symptoms as the efficacy and long-term safety in women with a history of breast cancer has not been established.

GRADE OF RECOMMENDATION

d

Mann 2012

Breast cancer

CBT

II

moderate

UK

Matthews 2014

Breast cancer

CBT

II

low

USA

1. Evidence base

B

one II study with a low risk of bias, one level II study with a moderate risk of bias

2. Consistency

C

some inconsistency reflecting genuine uncertainty around clinical question

3. Clinical impact

C

moderate

4. Generalisability

A

population/s studied in body of evidence are the same as the target population for the guideline: all studies were in women treated for breast cancer

5. Applicability

A

directly applicable to Australian healthcare context: all studies were conducted in Australia or developed countries with similar levels of health service delivery

Purpose-designed cognitive behavioural therapy can be considered for the management of sleep disturbance in women with a history of breast cancer.

GRADE OF RECOMMENDATION

C

Woods 2014

Menopause

relaxation therapy

I

moderate

USA

1. Evidence base

B

One level I study with a moderate risk of bias

2. Consistency

N/A

one study only

3. Clinical impact

C

moderate

4. Generalisability

C

population/s studied in body of evidence differ to target population for guideline but it is clinically sensible to apply this evidence to target population: all studies were in a general menopausal population

5. Applicability

A

directly applicable to Australian healthcare context: all studies were conducted in Australia or developed countries with similar levels of health service delivery

Relaxation therapy can be considered for the management of sleep disturbance in women with a history of breast cancer.

GRADE OF RECOMMENDATION

C

Elkins 2008

Breast cancer

hypnotherapy

II

moderate

USA

1. Evidence base

C

one level II study with a moderate risk of bias

2. Consistency

N/A

one study only

3. Clinical impact

C

moderate

4. Generalisability

A

population/s studied in body of evidence are the same as the target population for the guideline: all studies were in women treated for breast cancer

5. Applicability

A

directly applicable to Australian healthcare context: all studies were conducted in Australia or developed countries with similar levels of health service delivery

Purpose-designed hypnotherapy can be considered for the management of sleep disturbance in women with a history of breast cancer.

GRADE OF RECOMMENDATION

C

Bokmand 2013

Breast cancer

acupuncture

II

low

Denmark

1. Evidence base

B

one level II study with a low risk of bias

2. Consistency

N/A

one study only

3. Clinical impact

C

moderate

4. Generalisability

A

population/s studied in body of evidence are the same as the target population for the guideline: all studies were in women treated for breast cancer

5. Applicability

A

directly applicable to Australian healthcare context: all studies were conducted in Australia or developed countries with similar levels of health service delivery

Acupuncture can be considered for the management of sleep disturbance in women with a history of breast cancer.

GRADE OF RECOMMENDATION

C

Biglia 2009

Breast cancer

Vitamin E

800 IU/d

II

moderate

Italy

1. Evidence base

C

one level II study with a moderate risk of bias

2. Consistency

N/A

one study only

3. Clinical impact

N/A

none

4. Generalisability

A

population/s studied in body of evidence are the same as the target population for the guideline: all studies were in women treated for breast cancer

5. Applicability

A

directly applicable to Australian healthcare context: all studies were conducted in Australia or developed countries with similar levels of health service delivery

Vitamin E is not recommended for the management of sleep disturbance in women with a history of breast cancer due to evidence that it is not effective.

GRADE OF RECOMMENDATION

C

Thomas 2014

Menopause

soy and other isoflavones

I

moderate

Italy

1. Evidence base

B

One level I study with a moderate risk of bias

2. Consistency

N/A

one study only

3. Clinical impact

N/A

none

4. Generalisability

C

population/s studied in body of evidence differ to target population for guideline but it is clinically sensible to apply this evidence to target population: all studies were in a general menopausal population

5. Applicability

A

directly applicable to Australian healthcare context: all studies were conducted in Australia or developed countries with similar levels of health service delivery

Isoflavones are not recommended for the management of sleep disturbance in women with a history of breast cancer due to evidence that they are not effective.

GRADE OF RECOMMENDATION

C

Lee 2011

Breast cancer

non-hormonal vaginal gel

II

low

South Korea

1. Evidence base

B

one level II study with a low risk of bias

2. Consistency

N/A

one study only

3. Clinical impact

C

moderate

4. Generalisability

A

population/s studied in body of evidence are the same as the target population for the guideline: all studies were in women treated for breast cancer

5. Applicability

A

directly applicable to Australian healthcare context: all studies were conducted in Australia or developed countries with similar levels of health service delivery

Non-hormonal vaginal gels can be considered for the treatment of vulvovaginal symptoms in women with a history of breast cancer.

Practice Point B:

Non-hormonal vaginal moisturisers can be considered for the treatment of vulvovaginal symptoms in women with a history of breast cancer.

Practice point C:

Water-based or silicone-based vaginal lubricants can be used to enhance the comfort and ease of sexual intercourse.

GRADE OF RECOMMENDATION

C

Duijts 2012

Breast cancer

CBT

II

moderate

The Netherlands

1. Evidence base

C

one level II study with a moderate risk of bias

2. Consistency

N/A

one study only

3. Clinical impact

C

moderate

4. Generalisability

A

population/s studied in body of evidence are the same as the target population for the guideline: all studies were in women treated for breast cancer

5. Applicability

A

directly applicable to Australian healthcare context: all studies were conducted in Australia or developed countries with similar levels of health service delivery

Purpose-designed cognitive behavioural therapy can be considered for improving sexual function in women with a history of breast cancer.

GRADE OF RECOMMENDATION

C

Boekhout 2011

Breast cancer

venlafaxine

75mg/d (slow release)

II

low

the Netherlands

Bordeleau 2010

Breast cancer

venlafaxine

37.5-75mg/d

II

moderate

Canada

Buijs 2009

Breast cancer

venlafaxine

75mg/d

II

moderate

the Netherlands

Carpenter 2007

Breast cancer

venlafaxine

37.5mg/d

II

moderate

USA

Loibl 2007

Breast cancer

venlafaxine

75mg/d

II

moderate

Germany

Walker 2010

Breast cancer

venlafaxine

37.5-75mg/d

II

moderate

USA

Joffe 2014

Menopause

venlafaxine

37.5-75mg/d

II

low

USA

1. Evidence base

B

two level II studies with a low risk of bias, five level II studies with a moderate risk of bias

2. Consistency

A

all studies consistent

3. Clinical impact

B

substantial

4. Generalisability

A

evidence directly generalisable to target population

5. Applicability

A

directly applicable to Australian healthcare context

Venlafaxine (37.5 - 75 mg/day) can be considered for the management of moderate to severe vasomotor symptoms in women with a history of breast cancer.

GRADE OF RECOMMENDATION

A

Stearns 2005

Breast cancer

paroxetine

10-20 mg/d

II

low

USA

1. Evidence base

B

one level II study with a low risk of bias

2. Consistency

N/A

one study only

3. Clinical impact

B

substantial

4. Generalisability

A

population/s studied in body of evidence are the same as the target population for the guideline: all studies were in women treated for breast cancer

5. Applicability

B

evidence applicable to Australian healthcare context with few caveats

Other factors(Indicate here any other factors that you took into account when assessing the evidence base (for example,  issues that might cause the group to downgrade or upgrade  the recommendation)

Paroxetine (10 - 20 mg/day) can be considered for the management of moderate to severe vasomotor symptoms in women with a history of breast cancer who are not receiving tamoxifen.

This recommendation is not generalisable to other SSRIs as there is insufficient evidence in women with a history of breast cancer that they have comparable effects on vasomotor symptoms.

Note: Paroxetine interacts with tamoxifen and reduces the serum concentration of tamoxifen and metabolites.

GRADE OF RECOMMENDATION

B

Shams 2014

Menopause

escitalopram

10-20 mg/d

I

low

USA

1. Evidence base

A

one level I study with a low risk of bias

2. Consistency

A

all studies consistent

3. Clinical impact

B

substantial

4. Generalisability

C

population/s studied in body of evidence differ to target population for guideline but it is clinically sensible to apply this evidence to target population: all studies were in a general menopausal population

5. Applicability

A

directly applicable to Australian healthcare context: all studies were conducted in Australia or developed countries with similar levels of health service delivery

Escitalopram (10–20 mg/d) can be considered for the management of moderate to severe vasomotor symptoms in women with a history of breast cancer, based on evidence from a general population of menopausal women.

Note: Escitalopram may reduce the efficacy of tamoxifen by slowing metabolism to the active form. There is little evidence for clinical concern resulting from their concomitant use.

GRADE OF RECOMMENDATION

B

Sun 2013

Menopause

desvenlafaxine

100-150 mg/day

I

low

not reported

Berhan 2014

Menopause

desvenlafaxine

≥100 mg/d

I

moderate

Europe, North America, South Africa

1. Evidence base

A

one level I study with a low risk of bias, one level I study with a moderate risk of bias

2. Consistency

B

most studies consistent and inconsistency may be explained

3. Clinical impact

B

substantial

4. Generalisability

C

population/s studied in body of evidence differ to target population for guideline but it is clinically sensible to apply this evidence to target population: all studies were in a general menopausal population

5. Applicability

B

evidence applicable to Australian healthcare context with few caveats

Desvenlafaxine (100–150 mg/d) can be considered for the management of moderate to severe vasomotor symptoms in women with a history of breast cancer, based on evidence from a general population of menopausal women.

Note: Desvenlafaxine may alter the serum concentration of tamoxifen and metabolites. There is little evidence for clinical concern resulting from their concomitant use.

GRADE OF RECOMMENDATION

B

Boekhout 2011

Breast cancer

venlafaxine

75mg/d (slow release)

II

low

the Netherlands

Bordeleau 2010

Breast cancer

venlafaxine

37.5-75mg/d

II

moderate

Canada

Buijs 2009

Breast cancer

venlafaxine

75mg/d

II

moderate

the Netherlands

Loprinzi 2002

Breast cancer

fluoxetine 20 mg/d

II

low

USA

Nunez 2013

Breast cancer

bupropion 300 mg/d

II

moderate

Brazil

Stearns 2005

Breast cancer

paroxetine

10-20 mg/d

II

low

USA

Shams 2014

Menopause

escitalopram

10-20 mg/d

I

low

USA

Practice Point D:

The doses of antidepressants used for the management of vasomotor symptoms are not generally associated with increases in adverse sexual symptoms.

Boekhout 2011

Breast cancer

clonidine

0.1mg/d

II

low

the Netherlands

Buijs 2009

Breast cancer

clonidine

0.1mg/d

II

moderate

the Netherlands

Loibl 2007

Breast cancer

clonidine

0.15mg/d

II

moderate

Germany

1. Evidence base

B

one level II study with a low risk of bias, two level II studies with a moderate risk of bias

2. Consistency

B

most studies consistent and inconsistency may be explained

3. Clinical impact

B

substantial

4. Generalisability

A

population/s studied in body of evidence are the same as the target population for the guideline: all studies were in women treated for breast cancer

5. Applicability

A

directly applicable to Australian healthcare context

Clonidine (0.10 - 0.15 mg/day) can be considered for the management of moderate to severe vasomotor symptoms in women with a history of breast cancer.

GRADE OF RECOMMENDATION

B

Pandya 2005

Breast cancer

gabapentin

900 mg/d

II

moderate

USA

Bordeleau 2010

Breast cancer

gabapentin

300-900 mg/d

II

moderate

Canada

Ahimahalle 2012

Breast cancer

gabapentin

300 mg/d

II

high

Iran

Biglia 2009

Breast cancer

gabapentin

900 mg/d

II

moderate

Italy

Mao 2015

Breast cancer

gabapentin

300-900 mg/d

II

moderate

USA

1. Evidence base

C

Four level II studies with a moderate risk of bias, one level II study with a high risk of bias

2. Consistency

C

some inconsistency reflecting genuine uncertainty around clinical question

3. Clinical impact

B

Substantial

4. Generalisability

A

population/s studied in body of evidence are the same as the target population for the guideline: all studies were in women treated for breast cancer

5. Applicability

B

Evidence applicable to Australian healthcare context with few caveats

Other factors  (Indicate here any other factors that you took into account when assessing the evidence base (for example,  issues that might cause the group to downgrade or upgrade  the recommendation)

Gabapentin (300 - 900 mg/day) can be considered for the management of moderate to severe vasomotor symptoms in women with a history of breast cancer.

GRADE OF RECOMMENDATION

C

Nunez 2013

Breast cancer

bupropion 300 mg/d

II

moderate

Brazil

1. Evidence base

C

one level II study with a moderate risk of bias

2. Consistency

N/A

one study only

3. Clinical impact

D

slight or restricted

4. Generalisability

A

population/s studied in body of evidence are the same as the target population for the guideline: all studies were in women treated for breast cancer

5. Applicability

B

applicable to Australian healthcare context with few caveats

Bupropion is not recommended for the management of menopausal symptoms in women with a history of breast cancer due to evidence that it is not effective.

GRADE OF RECOMMENDATION

C

Sun 2013

Menopause

desvenlafaxine

100-150mg/d

I

low

USA

1. Evidence base

A

one level I study with a low risk of bias

2. Consistency

A

all studies consistent

3. Clinical impact

B

substantial

4. Generalisability

C

population/s studied in body of evidence different to target population for guideline, but it is clinically sensible to apply this evidence to target population: all studies were in a general menopausal population

5. Applicability

A

directly applicable to Australian healthcare context: all studies were conducted in Australia or developed countries with similar levels of health service delivery

Desvenlafaxine (100 - 150 mg/d) can be considered for the management of sleep disturbance in women with a history of breast cancer, based on evidence from a general population of menopausal women.

Note: Desvenlafaxine may alter the serum concentration of tamoxifen and metabolites. There is little evidence for clinical concern resulting from their concomitant use.

GRADE OF RECOMMENDATION

B

Stearns 2005

Breast cancer

paroxetine

10-20 mg/d

II

low

USA

1. Evidence base

B (paroxetine)

one level II study with a low risk of bias

2. Consistency

N/A

One study only

3. Clinical impact

C

moderate

4. Generalisability

A

population/s studied in body of evidence are the same as the target population for the guideline: all studies were in women treated for breast cancer

5. Applicability

A

directly applicable to Australian healthcare context: all studies were conducted in Australia or developed countries with similar levels of health service delivery

Paroxetine (10 - 20 mg/day) can be considered for the management of sleep disturbance in women with a history of breast cancer who are not receiving tamoxifen.

This recommendation is not generalisable to other SSRIs as there is insufficient evidence that they have comparable effects on sleep disturbance.

Note: Paroxetine interacts with tamoxifen and reduces the serum concentration of tamoxifen and metabolites.

GRADE OF RECOMMENDATION

C

Joffe 2010

Breast cancer

zolpidem

10 mg/d

II

moderate

USA

1. Evidence base

C

one level II study with a moderate risk of bias

2. Consistency

N/A

one study only

3. Clinical impact

C

moderate

4. Generalisability

A

population/s studied in body of evidence are the same as the target population for the guideline: all studies were in women treated for breast cancer

5. Applicability

A

directly applicable to Australian healthcare context: all studies were conducted in Australia or developed countries with similar levels of health service delivery

The addition of zolpidem (10 mg/d) to an SSRI or SNRI can be considered for the management of sleep disturbance for women with a history of breast cancer.

GRADE OF RECOMMENDATION

C

Biglia 2009

Breast cancer

gabapentin

900 mg/d

II

moderate

Italy

Bordeleau 2010

Breast cancer

gabapentin

900 mg/d

II

moderate

Canada

Pandya 2005

Breast cancer

gabapentin

300–900 mg/d

II

moderate

USA

1. Evidence base

C

three level II studies with a moderate risk of bias

2. Consistency

C

Some inconsistency reflecting genuine uncertainty around clinical question

3. Clinical impact

C

Moderate

4. Generalisability

A

population/s studied in body of evidence are the same as the target population for the guideline: all studies were in women treated for breast cancer

5. Applicability

A

directly applicable to Australian healthcare context: all studies were conducted in Australia or developed countries with similar levels of health service delivery

Gabapentin (300– 900mg/d) can be considered for the management of sleep disturbance in women with a history of breast cancer.

Practice point E:

Gabapentin doses of up to 1200 mg/day can be considered for the alleviation of sleep disturbance in women with a history of breast cancer.

GRADE OF RECOMMENDATION

C

Goetsch 2015

Breast cancer

topical lidocaine

II

moderate

USA

1. Evidence base

C

one level II study with a moderate risk of bias

2. Consistency

N/A

one study only

3. Clinical impact

C

moderate

4. Generalisability

A

population/s studied in body of evidence are the same as the target population for the guideline: all studies were in women treated for breast cancer

5. Applicability

A

directly applicable to Australian healthcare context: all studies were conducted in Australia or developed countries with similar levels of health service delivery

Topical lidocaine treatments to the vulvovaginal area can be considered for women with a history of breast cancer experiencing dyspareunia.

Note: The treatment used in the included study was a 4% lidocaine solution applied to the vulvar vestibule for three minutes, followed by application of a silicone lubricant.

GRADE OF RECOMMENDATION

C

Cui 2013

Menopause

ospemifene

60 mg/d

I

low

USA

1. Evidence base

A

one level I study with a low risk of bias

2. Consistency

B

most studies consistent and inconsistency may be explained

3. Clinical impact

C

moderate

4. Generalisability

D

Population/s studied in body of evidence differ to target population and hard to judge whether it is sensible to generalise to target population

5. Applicability

A

directly applicable to Australian healthcare context: all studies were conducted in Australia or developed countries with similar levels of health service delivery

Ospemifene is not recommended for the management of vulvovaginal symptoms as the efficacy and long-term safety in women with a history of breast cancer has not been established.

GRADE OF RECOMMENDATION

C

Frisk 2008/2012 (HABITS)

Breast cancer

MHT

II

high

Sweden

Von Schoultz 2005; Fahlen 2011

Breast cancer

MHT

II

high

Sweden

Marsden 2001

Breast cancer

MHT

II

high

UK

Holmberg 2004

Breast cancer

MHT

II

high

Sweden

Corbelli 2014

Menopause

oestradiol

< 0.05 mg/d

I

low

Italy, USA

Derzko 2016

Menopause

MHT

I

moderate

North America,  Europe

MacLennan 2004

Menopause

MHT

I

low

Europe, Russia, USA

Nastri 2013

Menopause

MHT

I

low

multinational

Joffe 2014

Menopause

oestradiol

0.5mg/d

II

low

USA

Reed 2014

Menopause

oestradiol

0.5mg/d

II

low

USA

1. Evidence base

A

three level I studies with a low risk of bias, one level I study with a moderate risk of bias, one level II study with a low risk of bias and four level II studies with a high risk of bias.

2. Consistency

B

most studies consistent and inconsistency may be explained

3. Clinical impact

B

substantial

4. Generalisability

B

population/s studied in the body of evidence are similar to the target population for the guideline

5. Applicability

B

applicable to Australian healthcare context with few caveats

Systemic menopause hormone therapy (oestrogen-only or combined oestrogen and progestogen) should generally be avoided in women with a history of breast cancer because it may increase the risk of new or recurrent breast cancer.

Menopause Hormone Therapy may be considered in exceptional cases for women with a history of breast cancer with severe, intractable vasomotor symptoms. In these cases the potential risks and benefits should be discussed with the treatment team, and treatment should only proceed with the informed consent of the woman and at the lowest effective dose for that woman.

GRADE OF RECOMMENDATION

B

Kenemans 2009/Sismondi 2011 (LIBERATE)

Breast cancer

Tibolone

II

Low

Multinational

Formoso 2012

Menopause

Tibolone

I

Low

Multinational

1. Evidence base

A

one level I study with a low risk of bias and one level II study with a low risk of bias

2. Consistency

B

most studies consistent and inconsistency may be explained

3. Clinical impact

B

substantial

4. Generalisability

B

population/s studied in the body of evidence are similar to the target population for the guideline

5. Applicability

B

applicable to Australian healthcare context with few caveats

Tibolone should be avoided in women with a history of breast cancer because it increases the risk of new and recurrent breast cancer.

Tibolone may be considered in exceptional cases for women with a history of breast cancer with severe, intractable vasomotor symptoms. In these cases the potential risks and benefits should be discussed with the treatment team, and treatment should only proceed with the informed consent of the woman and at the lowest effective dose for that woman.

GRADE OF RECOMMENDATION

B

Whelan 2013

Menopause

Compounded progesterone cream

I

moderate

Australia, UK, USA

1. Evidence base

B

One level I study with a moderate risk of bias

2. Consistency

D

evidence is inconsistent

3. Clinical impact

C

moderate

4. Generalisability

D

Population/s studied in body of evidence differ to target population and hard to judge whether it is sensible to generalise to target population

5. Applicability

A

directly applicable to Australian healthcare context

Compounded hormones (‘bioidentical’ hormones) are not recommended for the management of menopausal symptoms in women with a history of breast cancer because the evidence of their effect is inconsistent and their safety after breast cancer is not known.

Note: Compounded hormones are systemically absorbed and may contain high levels of sex steroids which may increase the risk of new or recurrent breast cancer.

GRADE OF RECOMMENDATION

C

Rahn 2014

Menopause

vaginal oestrogen

I

low

Europe, Israel, UK, USA

Suckling 2006

Menopause

vaginal oestrogen

I

low

Australia, Europe, North America, Thailand

1. Evidence base

A

two level I studies with a low risk of bias

2. Consistency

B

most studies consistent and inconsistency may be explained

3. Clinical impact

C

moderate

4. Generalisability

C

population/s studied in body of evidence differ to target population for guideline but it is clinically sensible to apply this evidence to target population: all studies were in a general menopausal population

5. Applicability

B

directly applicable to Australian healthcare context: all studies were conducted in Australia or developed countries with similar levels of health service delivery

Vaginal oestrogens can be considered for the management of persistent vulvovaginal symptoms in women with a history of breast cancer who are non-responsive to non-hormonal vaginal gels or lubricants. A discussion of the potential risks and benefits between the woman and her treating team is recommended.

Note: Vaginal oestrogen may be systemically absorbed. For women taking Aromatase Inhibitors this may results in measurable increases in circulating oestrogens. The clinical significance of systemic absorption is uncertain.

GRADE OF RECOMMENDATION

C

Elraiyah 2014

Menopause

testosterone

I

low

multinational

Somboonporn 2005

Menopause

testosterone

I

low

multinational

1. Evidence base

B

two level I studies with a low risk of bias; no evidence of safety or efficacy in a breast cancer population

2. Consistency

B

most studies consistent and inconsistency may be explained

3. Clinical impact

C

moderate

4. Generalisability

D

Population/s studied in body of evidence differ to target population and hard to judge whether it is sensible to generalise to target population

5. Applicability

B

applicable to Australian healthcare context with few caveats: most studies were conducted in Australia or developed countries with similar levels of health service delivery

Exogenous testosterone is not recommended as a treatment to improve sexual function as the efficacy and long-term safety in women with a history of breast cancer has not been established.

GRADE OF RECOMMENDATION

C