![](media/image1.png){width="5.96875in" height="0.41944444444444445in"}

Top of Form

## Complete Summary

#### GUIDELINE TITLE

Hormone replacement therapy.

#### BIBLIOGRAPHIC SOURCE(S)

Singapore Ministry of Health, Singapore Academy of Medicine, Chapter of
Obstetricians and Gynaecologists. Hormone replacement therapy.
Singapore: Singapore Ministry of Health; 2004 Apr. 30 p. \[51
references\]

#### GUIDELINE STATUS

This is the current release of the guideline.

### COMPLETE SUMMARY CONTENT

 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 CONTRAINDICATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

-   Symptoms of menopause, including vasomotor symptoms, vaginal
    dryness, and urinary symptoms

-   Premature menopause

**Note**: Conditions for which hormone replacement therapy is NOT
indicated are also discussed. These include osteoporosis, heart disease,
dementia, and colorectal cancer.

#### GUIDELINE CATEGORY

Evaluation\
Management\
Prevention\
Treatment

#### CLINICAL SPECIALTY

Family Practice\
Geriatrics\
Obstetrics and Gynecology

#### INTENDED USERS

Advanced Practice Nurses\
Allied Health Personnel\
Pharmacists\
Physicians

#### GUIDELINE OBJECTIVE(S)

-   To address the following issues:

    -   Indications for the use of hormone replacement therapy in the
        healthy postmenopausal woman

    -   Safety issues in the use of hormone replacement therapy

    -   Principles of treatment, dosing, and optimal duration of therapy

    -   Treatment of premature menopause

    -   Answers to frequently asked questions about hormone replacement
        therapy

-   To discuss the implications of the Women´s Health Initiative study
    (WHI), a large randomized controlled trial, on the role of hormone
    replacement therapy in stroke, cardiovascular disease, and various
    cancers

#### TARGET POPULATION

Women in Singapore with premature menopause or symptoms of menopause

#### INTERVENTIONS AND PRACTICES CONSIDERED

Hormone replacement therapy, including indications for use, dosage,
duration, and route of medications:

1.  Estrogens, oral: conjugated equine estrogen (Premarin); estradiol
    (Estrofem); estradiol valerate (Progynova)

2.  Estrogens, transdermal: estradiol patch (Estraderm); estrogel;
    estradiol hemihydrate (Estreva gel)

3.  Progestogens: medroxyprogesterone acetate (Provera); dydrogesterone
    (Duphaston); norethisterone (Micronor); intrauterine L-norgestrel
    system (Mirena); micronised progesterone (Utrogestan)

4.  Cyclical combined therapies: estradiol valerate and norgestrel
    (Progyluton); estradiol valerate and cyproterone acetate (Climens);
    conjugated equine estrogen and norgestrel (Prempak-C); conjugated
    equine estrogen and medroxyprogesterone acetate (Premelle cycle 5);
    estradiol and dydrogesterone (Femoston); estradiol and
    norethisterone acetate (Trisequens)

5.  Continuous combined therapies: conjugated equine estrogen and
    medroxyprogesterone acetate (Premelle 5 or Premelle 2.5); estradiol
    and norethisterone acetate (Kliogest or Activelle).

6.  Local therapy: estradiol pessary (Vagifem); conjugated equine
    estrogen cream (Premarin cream); colpotrophine 1% cream;
    colpotrophine pessary 10%; estradiol ring (Estring)

#### MAJOR OUTCOMES CONSIDERED

-   Relief of menopausal symptoms

-   Long-term risks of prolonged estrogen deficiency

-   Adverse effects of hormone replacement therapy, both short-term and
    long-term

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

Not stated

#### NUMBER OF SOURCE DOCUMENTS

Not stated

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Weighting According to a Rating Scheme (Scheme Given)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

**Levels of Evidence**

**Level Ia**: Evidence obtained from meta-analysis of randomised
controlled trials

**Level Ib**: Evidence obtained from at least one randomised controlled
trial

**Level IIa**: Evidence obtained from at least one well-designed
controlled study without randomisation

**Level IIb**: Evidence obtained from at least one other type of
well-designed quasi-experimental study

**Level III**: Evidence obtained from well-designed nonexperimental
descriptive studies, such as comparative studies, correlation studies,
and case studies

**Level IV**: Evidence obtained from expert committee reports or
opinions and/or clinical experiences of respected authorities

#### METHODS USED TO ANALYZE THE EVIDENCE

Review of Published Meta-Analyses\
Systematic Review

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

Not stated

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

These guidelines were developed by a workgroup made up of specialists in
the field of obstetrics and gynaecology with a special interest in
hormone replacement therapy and care of menopausal woman, as well as a
family practitioner. An exhaustive search into the medical literature as
well as guidelines from various colleges around the world formed the
basis of these guidelines and recommendations.

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

**Grades of Recommendations**

**Grade A** (evidence levels Ia, Ib): Requires at least one randomised
controlled trial as part of the body of literature of overall good
quality and consistency addressing the specific recommendation.

**Grade B** (evidence levels IIa, IIb, III): Requires availability of
well conducted clinical studies but no randomised clinical trials on the
topic of recommendation.

**Grade C** (evidence level IV): Requires evidence obtained from expert
committee reports or opinions and/or clinical experiences of respected
authorities. Indicates absence of directly applicable clinical studies
of good quality.

**GPP** (good practice points): Recommended best practice based on the
clinical experience of the guideline development group.

#### COST ANALYSIS

A formal cost analysis was not performed and published cost analyses
were not reviewed.

#### METHOD OF GUIDELINE VALIDATION

Not stated

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

Not applicable

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

The recommendations that follow are those from the guideline´s executive
summary; detailed recommendations can be found in the original guideline
document. Each recommendation is rated based on the level of the
evidence and the grades of recommendation. Definitions of the grades of
the recommendations (A, B, C, Good Practice Points \[GPP\]) and level of
the evidence (Level I--Level IV) are presented at the end of the Major
Recommendations field.

**A** -- Hormone replacement therapy (HRT) is recommended for the
short-term control of vasomotor symptoms, vaginal dryness, and urinary
symptoms in menopause. **(Grade A, Level Ib)**

**C** - Combination HRT should not be used to reduce the risk of
osteoporosis and subsequent fractures if it is the only indication for
starting hormone replacement therapy. Alternatives such as
bisphosphonates (Black et al., 1996) and raloxifene (Ettingeter et al.,
1999) should instead be considered. **(Grade C, Level IV)**

**A** - HRT should not be used for primary or secondary prevention of
heart disease. **(Grade A, Level Ib)**

**C** - Prevention of colorectal cancer should not be the reason for
long-term hormone replacement therapy. **(Grade C, Level IV)**

**A** - HRT is not recommended for the prevention of Alzheimer´s disease
or dementia. **(Grade A, Level Ib)**

**A** - The use of unopposed HRT in a woman with an intact uterus has
been shown to increase the risk of endometrial cancer by several fold
(Chlebowski et al., 2003; Shields et al., 1999). Therefore combined
hormone replacement therapy should be used in patients with intact
uteri. **(Grade A, Level Ia)**

**C** - HRT is the cornerstone in the management of patients with
premature menopause. It is effective in the relief of menopausal
symptoms and protects against the long-term risks associated with
prolonged estrogen deficiency (\"Risks and benefits of estrogen,\" 2002;
Davis, 1996; Willhite & O´Connell, 2001; Cardozo et al, 1998). **(Grade
C, Level IV)**

**Grades of Recommendations**

**Grade A** (evidence levels Ia, Ib): Requires at least one randomised
controlled trial as part of the body of literature of overall good
quality and consistency addressing the specific recommendation.

**Grade B** (evidence levels IIa, IIb, III): Requires availability of
well conducted clinical studies but no randomised clinical trials on the
topic of recommendation.

**Grade C** (evidence level IV): Requires evidence obtained from expert
committee reports or opinions and/or clinical experiences of respected
authorities. Indicates absence of directly applicable clinical studies
of good quality.

**GPP** (good practice points): Recommended best practice based on the
clinical experience of the guideline development group.

**Levels of Evidence**

**Level Ia**: Evidence obtained from meta-analysis of randomised
controlled trials

**Level Ib**: Evidence obtained from at least one randomised controlled
trial

**Level IIa**: Evidence obtained from at least one well-designed
controlled study without randomisation

**Level IIb**: Evidence obtained from at least one other type of
well-designed quasi-experimental study

**Level III**: Evidence obtained from well-designed nonexperimental
descriptive studies, such as comparative studies, correlation studies
and case studies

**Level IV**: Evidence obtained from expert committee reports or
opinions and/or clinical experiences of respected authorities

#### CLINICAL ALGORITHM(S)

None provided

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### REFERENCES SUPPORTING THE RECOMMENDATIONS

[References open in a new
window](http://www.guideline.gov/summary/select_ref.aspx?doc_id=5294)

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The type of supporting evidence is identified and graded for each
recommendation (see \"Major Recommendations\")

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

-   Short-term hormone replacement therapy (HRT) helps control
    menopausal vasomotor symptoms, urinary symptoms, and symptoms of
    vaginal dryness.

-   HRT is the cornerstone in the management of patients with premature
    menopause. It is effective in the relief of significant menopausal
    symptoms and protects against the long-term risks associated with
    prolonged estrogen deficiency.

-   In the Women´s Health Initiative (WHI) study, a large randomized
    controlled trial, combination HRT was associated with reduced risk
    of endometrial cancer, hip fractures, and colorectal cancers.
    Estrogen alone appears to marginally decrease risk of hip fracture
    in postmenopausal women with hysterectomies.

#### POTENTIAL HARMS

-   Combination hormone replacement therapy (HRT) is associated with
    significant risk of deep vein thrombosis and pulmonary embolism.

-   Combination HRT is associated with a small increase of ischaemic
    stroke in healthy postmenopausal women. Results with estrogen alone
    replacement indicated that the increased risk of stroke is similar
    to that found in the trial of estrogen plus progestin when it was
    stopped after 5.2 years of follow up.

-   Combination HRT, and unopposed estrogen replacement therapy are
    associated with a small but significant risk of breast cancer.
    Estrogen only therapy did not show an increased risk in
    hysterectomized women.

-   Combination HRT is associated with a doubled rate of dementia
    including Alzheimer´s disease.

-   There is evidence that mammographic changes associated with hormone
    usage may hinder and delay the diagnosis of breast cancer.

-   Other HRT side effects are breast tenderness, irregular vaginal
    bleeding, and headaches.

### CONTRAINDICATIONS

#### CONTRAINDICATIONS

The use of unopposed hormone replacement therapy (HRT) in a woman with
an intact uterus has been shown to increase the risk of endometrial
cancer by several fold. Therefore combined HRT should be used in
patients with intact uteri.

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

-   These guidelines are not intended to serve as a standard of medical
    care. Standards of medical care are determined on the basis of all
    clinical data available for an individual case and are subject to
    change as scientific knowledge advances and patterns of care evolve.

-   The contents of this publication are guidelines to clinical
    practice, based on the best available evidence at the time of
    development. Adherence to these guidelines may not ensure a
    successful outcome in every case, nor should they be construed as
    including all proper methods of care or excluding other acceptable
    methods of care. Each physician is ultimately responsible for the
    management of his/her unique patient in the light of the clinical
    data presented by the patient and the diagnostic and treatment
    options available.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

The guidelines propose the following audit parameter:

Percentage of women with intact uteri on hormone replacement therapy
receiving estrogen-only therapy. (The use of unopposed hormone
replacement therapy in a woman with an intact uterus has been shown to
increase the risk of endometrial cancer by several fold. Therefore
combined hormone replacement therapy should be used in patients with
intact uteri.)

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Getting Better\
Staying Healthy

#### IOM DOMAIN

Effectiveness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Singapore Ministry of Health, Singapore Academy of Medicine, Chapter of
Obstetricians and Gynaecologists. Hormone replacement therapy.
Singapore: Singapore Ministry of Health; 2004 Apr. 30 p. \[51
references\]

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

2004 Apr

#### GUIDELINE DEVELOPER(S)

Chapter of Obstetricians and Gynaecologists, Academy of Medicine
(Singapore) - Medical Specialty Society\
Singapore Ministry of Health - National Government Agency \[Non-U.S.\]

#### SOURCE(S) OF FUNDING

Singapore Ministry of Health (MOH)

#### GUIDELINE COMMITTEE

Workgroup on Hormone Replacement Therapy

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

*Workgroup Members*: Dr Yu Su Ling, Head & Senior Consultant, Dept of
Obstetrics and Gynaecology, Singapore General Hospital (Chairman); Dr
Lee Puay Hoon, Julinda, Associate Consultant, Dept of Obstetrics and
Gynaecology, Singapore General Hospital; Dr Lisa Chin Yue Kim, Chin Y K
Clinic for Women and Menopause Centre, Gleneagles Medical Centre; Dr
Phyllis Liauw, TLC Gynaecology Practice, Thomson Medical Centre; Dr
Sandy Lek, Joo Chiat Clinic for Women; Dr Ling Yee Kiang, Geylang
Polyclinic; Dr Yeoh Swee Choo, The Obstetrics & Gynaecology Practice,
Mount Elizabeth Medical Centre; Dr Khong Chit Chong, Head and Senior
Consultant, Menopause Unit, KK Women & Children´s Hospital; Dr Oei Pau
Ling, My Gynae Women´s Clinic, Gleneagles Medical Centre; Dr Loh Foo
Hoe, Women´s Specialist Associates, Mount Elizabeth Medical Centre

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

Not stated

#### GUIDELINE STATUS

This is the current release of the guideline.

#### GUIDELINE AVAILABILITY

Electronic copies: Available in Portable Document Format (PDF) from the
[Singapore Ministry of Health Web
site](http://www.hpp.moh.gov.sg/HPP/1130910778681.html).

Print copies: Available from the Singapore Ministry of Health, College
of Medicine Building, Mezzanine Floor 16 College Rd, Singapore 169854.

#### AVAILABILITY OF COMPANION DOCUMENTS

None available

#### PATIENT RESOURCES

None available

#### NGC STATUS

This NGC summary was completed by ECRI on July 28, 2004.

#### COPYRIGHT STATEMENT

This NGC summary is based on the original guideline, which is subject to
the guideline developer\'s copyright restrictions. Please contact the
Ministry of Health, Singapore by e-mail at <MOH_INFO@MOH.GOV.SG>.

### DISCLAIMER

#### NGC DISCLAIMER

The National Guideline Clearinghouse™ (NGC) does not develop, produce,
approve, or endorse the guidelines represented on this site.

All guidelines summarized by NGC and hosted on our site are produced
under the auspices of medical specialty societies, relevant professional
associations, public or private organizations, other government
agencies, health care organizations or plans, and similar entities.

Guidelines represented on the NGC Web site are submitted by guideline
developers, and are screened solely to determine that they meet the NGC
Inclusion Criteria which may be found at
<http://www.guideline.gov/about/inclusion.aspx> .

NGC, AHRQ, and its contractor ECRI Institute make no warranties
concerning the content or clinical efficacy or effectiveness of the
clinical practice guidelines and related materials represented on this
site. Moreover, the views and opinions of developers or authors of
guidelines represented on this site do not necessarily state or reflect
those of NGC, AHRQ, or its contractor ECRI Institute, and inclusion or
hosting of guidelines in NGC may not be used for advertising or
commercial endorsement purposes.

Readers with questions regarding guideline content are directed to
contact the guideline developer.

Bottom of Form

© 1998-2008 National Guideline Clearinghouse

Date Modified: 11/3/2008