Dehydroepiandrosterone for menopausal women

  • Protocol
  • Intervention

Authors


Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

To assess the effectiveness and safety of administering DHEA to women with menopausal symptoms.

Background

Description of the condition

The menopause is said to have occurred once there is permanent cessation of menstruation. Prior to the final menstruation there is usually a gradual reduction in the frequency of menstrual periods, known as the perimenopause. Postmenopause is defined as the period of time following on from 12 months after a woman has experienced her last menstruation. During perimenopause there is a fluctuation in estrogen levels due to decreasing ovarian follicular response (Hoffman 2012; Rosen 2011; Speroff 2005). Most women become menopausal between 45 and 55 years of age, however there are also women who reach menopause at an earlier age for various reasons (for example premature ovarian insufficiency or bilateral oophorectomy). Menopausal women can develop a range of symptoms including vaginal dryness and dyspareunia secondary to vaginal atrophy, vasomotor symptoms such as hot flushes and night sweats, diminished general wellbeing and diminished sexual function (Genazzani 2002; Speroff 2005). Hormone replacement therapy (HRT) (estrogen alone or in combination with a progestin) is currently indicated for the treatment of menopausal symptoms. However, HRT has been associated with a significant increase in the risk of various conditions including breast cancer, coronary events, venous thromboembolism and stroke (Cameron 2005; Majoribanks 2012; Rossouw 2002; State-of-the-Science-Panel 2005; Taylor 2011).

Description of the intervention

Dehydroepiandrosterone (DHEA) is one of the main precursor sex steroids. DHEA is synthesized from cholesterol in the zona reticularis of the adrenal gland. It is converted to estrogens and testosterone by steroidogenic enzymes expressed in peripheral tissues such as the skeleton, breasts and ovary (Figure 1). DHEA peaks at the age of 25 years and then slowly declines to approximately 30% of initial levels at postmenopause (Genazzani 2002; Rosen 2011; Speroff 2005). In the United States of America (US) DHEA can be purchased without prescription, but in most countries it is only available by prescription. DHEA may be administered orally, intravaginally or by alternative routes of administration (for example transdermal patches).

Figure 1.

Biosynthesis of DHEA and estrogens.

As DHEA and eventually estrogen can be synthesized from cholesterol, levels of circulating estrogen and DHEA may differ in overweight women (body mass index (BMI) > 25) compared to women with a normal weight (BMI 18 to 25) or underweight women (BMI < 18) (Buster 2000; Miller 2002). Therefore, administered DHEA may have differing effects on women who are over or underweight compared to those with a normal BMI.

How the intervention might work

Due to a fluctuation and eventual decrease in estrogen levels, women can develop various perimenopausal and postmenopausal symptoms. While the body is adjusting to these hormonal changes women may experience symptoms such as hot flushes and night sweats. Low estrogen levels can cause vaginal dryness, which may lead to diminished sexual function (Hoffman 2012; Speroff 2005). All of these symptoms may cause a decrease in the general wellbeing of peri- and postmenopausal women. It is suggested that testosterone increases sexual desire and sexual function (Davis 2008; Pluchino 2013). As DHEA is one of the main precursors of androgens, which in turn are converted to testosterone and estrogens (Figure 1) (Simpson 2003; Vanson 1996), it is possible that the administration of DHEA may increase estrogen and testosterone levels in peri- and postmenopausal women to alleviate their symptoms and improve general wellbeing (Buster 2000; Davis 2008; Mayo 2002; Pluchino 2013; Raven 2007).

The effects of DHEA on menopausal women may differ from HRT because of the additional androgenic effect of DHEA (Dobs 2002; Labrie 2005). In postmenopausal women DHEA has been hypothesized to increase the incidence of breast cancer and caution is advised. However, there have been limited studies on this subject and the results of these studies are inconsistent (Morris 2001; Schwartz 2006; Shilkaitis 2005; Stoll 1999). No other serious adverse effects of DHEA have been described in the published literature. Doses of 50 mg and above have shown androgenic side effects (for example acne and increased hair growth) (Panjari 2010, Kroboth 1999).

Different effects of DHEA have been described using different routes of administration (Casson 1996). Intravaginal administration of DHEA has been reported to have a better effect on alleviating the symptoms of vaginal atrophy and improving sexual function than oral administration of DHEA (Goel 2011).

Why it is important to do this review

Treatment with DHEA is controversial as there is uncertainty about its effectiveness and safety (Buster 2000; Panjari 2010; Raven 2007). Inconsistent findings have been published on the effects of DHEA in menopausal women and much of the data from clinical trials are limited by small sample sizes and short duration of treatment (Cameron 2005; Panjari 2010). This review should clearly outline the evidence for DHEA in the treatment of menopausal symptoms and evaluate its effectiveness and safety by combining the results of randomised controlled trials.

Objectives

To assess the effectiveness and safety of administering DHEA to women with menopausal symptoms.

Methods

Criteria for considering studies for this review

Types of studies

Published and unpublished randomised controlled trials (RCTs) will be eligible for inclusion. We will exclude non-randomised studies (for example studies with evidence of inadequate sequence generation such as alternate days, patient numbers) as they are associated with a high risk of bias.

Types of participants

Menopausal women: women who are going through the menopausal transition or women who are postmenopausal.

Perimenopause: the period of menopausal transition leading to a natural menopause, which ends 12 months after the final menstrual period. A specific staging can be found in the Stages of Reproductive Aging Workshop (STRAW) + 10 criteria (Harlow 2013).

Postmenopause: after one year with absence of menses and follicle stimulating hormone (FSH) levels > 40 IU/L, also women following surgical menopause (removal of both ovaries) will be included.

Types of interventions

Trials comparing any dose and form of DHEA by any route of administration versus any other active intervention, placebo or no treatment will be eligible for inclusion. Treatment duration should be no less than one week.

Types of outcome measures

Primary outcomes
Effectiveness

General wellbeing or quality of life (as defined by different scoring scales for example the Psychological General Well-Being Index (PGWB), The Medical Outcomes Study 36-item short form survey (SF-36), Life Satisfaction Index-Z (LSI-Z), Satisfaction with Life Scale (SWLS), Health Status Questionnaire (HSQ), Quality of Life scale (QoL), Beck Depression Inventory (BDI), Hamilton Depression Scale (HDRS)).

Any adverse effects

Adverse effects will be described as they have been reported in the studies (for example risk of breast cancer, cardiovascular risk, androgenic side effects).

Secondary outcomes

Menopausal symptoms (e.g. vaginal dryness, hot flushes, night sweats defined by different scoring scales including the Menopause Rating Scale (MRS) (Heinemann 2004), Kupperman Index (KI), Greene Climacteric Scale (GCS)).

Sexual function (defined by different scoring scales e.g. the Female Sexual Function Index (FSFI), Brief Index of Sexual Functioning for Women (BISF-W), Changes in Sexual Functioning Questionnaire (CSFQ), Derogatis Interview for Sexual Functioning (DISF/DISF-SR), Golombok-Rust Inventory of Sexual Satisfaction (GRISS)).

Search methods for identification of studies

We will search for all published and unpublished RCTs investigating the effects of DHEA in menopausal women, without language restriction and in consultation with the Menstrual Disorders and Subfertility Group (MDSG) Trials Search Co-ordinator. We will use ENDNOTE for the bibliographic management of references found in the search output.

Electronic searches

(1) We will search the following electronic databases, trial registers and websites from inception to the present:
Menstrual Disorders and Subfertility Group (MDSG) Specialised Register of controlled trials (Appendix 1), the Cochrane Central Register of Controlled Trials (CENTRAL) (Appendix 2), MEDLINE (Appendix 3) , EMBASE (Appendix 4), PsycINFO (Appendix 5) and CINAHL (Appendix 6). The MEDLINE search will be combined with the Cochrane highly sensitive search strategy for identifying randomised trials which appears in the Cochrane Handbook for Systematic Reviews of Interventions (Version 5.0.2, chapter 6, 6.4.11). The EMBASE, PsycINFO and CINAHL searches are combined with trial filters developed by the Scottish Intercollegiate Guidelines Network (SIGN) (www.sign.ac.uk/methodology/filters.html#random).

(2) Other electronic sources of trials will include (Appendix 7):
• trial registers for ongoing and registered trials
o www.clinicaltrials.gov (a service of the US National Institutes of Health),
o www.who.int/trialsearch/Default.aspx (World Health Organization International Clinical Trials Registry Platform search portal);
• DARE (Database of Abstracts of Reviews of Effects) in The Cochrane Library at http://onlinelibrary.wiley.com/o/cochrane/cochrane_cldare_articles_fs.html (for reference lists from relevant non-Cochrane reviews);
• the Web of Knowledge at http://wokinfo.com/ (another source of trials and conference abstracts);
• OpenGrey at www.opengrey.eu/ for unpublished literature from Europe;
• LILACS database at http://regional.bvsalud.org/php/index.php?lang=en (for trials from the Portuguese and Spanish speaking world);
• PubMed and Google (for recent trials not yet indexed in MEDLINE).

Searching other resources

3. We will handsearch reference lists of articles retrieved by the search and contact experts in the field to obtain additional data. We will also handsearch relevant journals and conference abstracts that are not covered in the MDSG Specialised Register, in liaison with the Trials Search Co-ordinator.

Data collection and analysis

Selection of studies

Only RCTs studying the effectiveness and safety of DHEA administration for menopausal women will be included. Data from crossover trials will be included and analysed using the generic inverserse variance method. The authors will independently scan the titles and abstracts of the articles retrieved by the search. Full texts of potentially eligible studies will be retrieved and examined independently by the authors. The full text articles will be selected according to the inclusion criteria. In the case of doubts or disagreement between the two authors, a third author will be consulted to gain consensus on whether to include the trial or not. The selection process will be documented with a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart.

Data extraction and management

The data obtained will be extracted by two review authors. In the case of a disagreement between the two authors, a third author will be consulted to achieve consensus. Data will be extracted by using a data extraction form designed and pilot tested by the authors. If studies are reported in multiple publications, the data will be extracted from the different publications and will be combined into a single data extraction form so no data will go missing. The following characteristics of included studies will be included in the extraction form: methods, participants, interventions and outcomes.

Assessment of risk of bias in included studies

To assess the risk of bias in the included studies the Cochrane Collaboration's recommended tool is a domain based evaluation. We will use this tool to assess the following domains and divide the assessments into high, unclear or low risk of bias.

Selection bias (random sequence generation, allocation concealment).
Performance bias (blinding of participants and personnel).
Detection bias (blinding of outcome assessment).
Attrition bias (incomplete outcome data).
Reporting bias (selective reporting).
Other bias (other sources of bias).

Disagreements will be resolved by discussion or by a third review author. We will describe all judgements fully and present the conclusions in the risk of bias table, which will be incorporated into the interpretation of review findings by means of sensitivity analyses (see below). We will take care to search for within-trial selective reporting, such as trials failing to report obvious outcomes, or reporting them in insufficient detail to allow inclusion. We will seek published protocols and compare the outcomes between the protocol and the final published study.

Measures of treatment effect

For dichotomous data we will use the numbers of events in the control and intervention groups of each study to calculate the Mantel-Haenszel odds ratios (ORs). For continuous data, if all studies report the same outcomes we will calculate mean differences (MDs) between treatment groups. If similar outcomes are reported on different scales, we will calculate the standardised mean difference (SMD). We will treat ordinal data as continuous data or it may be possible to categorise the findings as dichotomous data. We will calculate 95% confidence intervals (CIs) for all outcomes. Where data for calculation of ORs or MDs are not available we will use the most detailed numeric data available that may facilitate similar analyses of included studies.

Unit of analysis issues

The primary analysis will be per woman randomised. Data that do not allow valid analysis will be briefly summarized in an additional table and will not be included in the meta-analysis. Statistical advice will be sought regarding the analysis of crossover trials to facilitate the appropriate inclusion of crossover data in the meta-analysis.

Dealing with missing data

If relevant data are missing from an included study the original investigators of the trial will be contacted to request the missing data from them. If the original investigator can not be contacted or does not reply, we will determine whether to include or exclude the trial or only include the data that are fully available. If variance data for the primary outcome are missing (for example SD) then these will be imputed from the range where possible.

Assessment of heterogeneity

We will consider whether the clinical and methodological characteristics of the included studies are sufficiently similar for meta-analysis to provide a clinically meaningful summary. Statistical heterogeneity will be assessed by measuring the I² statistic. We will assume that there is substantial heterogeneity when I² is calculated to be greater than 50% (Higgins 2003; Higgins 2011).

Assessment of reporting biases

In view of the difficulty of detecting and correcting for publication bias and other reporting biases, the authors will aim to minimise their potential impact by ensuring a comprehensive search for eligible studies and by being alert to duplication of data. If there are 10 or more studies in an analysis, we will use a funnel plot to explore the possibility of small study effects (a tendency for estimates of the intervention effect to be more beneficial in smaller studies).

Data synthesis

Where sufficient data are available, data will be combined for the primary outcomes by using a fixed-effect model. The following comparisons will be made:

1. DHEA versus control (placebo or no intervention);
2. oral versus other routes of administration (e.g. intravaginal DHEA, transdermal patches);
3. DHEA versus hormone therapy (estrogen and progesterone in combination and separately, androgen therapy);
4. DHEA versus any other medical treatment (e.g. antidepressants or clonidine);
5. DHEA versus any other non-medical treatment (e.g. non-medical therapies such as acupuncture or complementary therapies).

Subgroup analysis and investigation of heterogeneity

Where sufficient data are available, we will conduct subgroup analyses for the primary outcomes to determine the separate evidence within the following subgroups:
1. BMI (< 18 kg/m2, 18 to 25 kg/m2, > 25 kg/m2);
2. menopausal status (peri- or postmenopausal);
3. duration of the intervention (≤ 6 weeks, > 6 to 26 weeks, > 26 weeks);
4. younger female (< 40 years, after bilateral oophorectomy or premature ovarian insufficiency);
5. hyposexual desire disorder or low libido;
5. inflammatory disease (e.g. systemic lupus erythematosus (SLE), Sjögren);
6. breast cancer.

If we detect substantial heterogeneity we will explore possible explanations in sensitivity analyses. We will take any statistical heterogeneity into account when interpreting the results, especially if there is any variation in the direction of effect.

Sensitivity analysis

We will conduct sensitivity analyses ;for the primary outcomes to determine whether the conclusions are robust to arbitrary decisions made regarding the eligibility and analysis. These analyses will include consideration of whether the review conclusions would have differed if:

1. eligibility was restricted to studies without high risk of bias;
2. a random-effects model had been adopted;
3. alternative imputation strategies had been implemented;
4. the summary effect measure was relative risk rather than odds ratio.

Overall quality of the body of evidence: summary of findings table

We will prepare a summary of findings table using GRADEPRO or Guideline Development Tool software. This table will evaluate the overall quality of the body of evidence for the primary review outcomes (general wellbeing or quality of life and adverse effects) using the GRADE criteria (study limitations (that is risk of bias), consistency of effect, imprecision, indirectness and publication bias). Judgements about the quality of evidence (high, moderate or low) will be justified, documented and incorporated into the reporting of results for each outcome.

Acknowledgements

We would like to thank the Cochrane Menstrual Disorders and Subfertility Group, in particular Marian Showell (Trials Search Co-ordinator) for support writing and running the search and Helen Nagels (Managing Editor) for answering questions.

Appendices

Appendix 1. Menstrual Disorders and Subfertility Group search strategy (PROCITE platform)

From inception to present
Menstrual Disorders and Subfertility (MDSG) database search.

Keywords CONTAINS "menopausal"or"*Menopause"or"perimenopause"or"perimenopausal"or "Postmenopausal"or "postmenopause"or"climacteric "or "vasomotor"or"hot flashes"or "hot flushes"or"vaginal atrophy"or "vaginal dryness" or "night sweats"or "night sweats-outcome"or"night time awakenings"or "nocturnal diaphoresis"or"sexual function"or"sexual fuctioning"or "Sexual functioning"or "sexual satisfaction" or Title CONTAINS "menopausal"or"*Menopause"or"perimenopause"or"perimenopausal"or "Postmenopausal"or "postmenopause"or"climacteric "or "vasomotor"or"hot flashes"or "hot flushes"or"vaginal atrophy"or "vaginal dryness" or "night sweats"or "night sweats-outcome"or"night time awakenings"or "nocturnal diaphoresis"or"sexual function"or"sexual fuctioning"or "Sexual functioning"or "sexual satisfaction"

AND

Keywords CONTAINS "DHEA"or "DHEAS" or"dehydroepiandrosterone"or "androstenedione" or "Prasterone" or Title CONTAINS "DHEA"or "DHEAS" or"dehydroepiandrosterone"or "androstenedione" or "Prasterone"

Appendix 2. CENTRAL search strategy (Ovid platform)

From inception to present
Database: EBM Reviews - Cochrane Central Register of Controlled Trials
Search Strategy:

1 (climacteric or menopaus$).tw.
2 (postmenopaus$ or perimenopaus$).tw.
3 vasomotor.tw.
4 exp Menopause, Premature/ or exp Menopause/
5 exp Climacteric/
6 exp Perimenopause/
7 exp Postmenopause/
8 exp Hot Flashes/
9 (hot flash$ or hot flush$).tw.
10 night sweat$.tw.
11 Nocturnal diaphoresis.tw.
12 vagina$ dry$.tw.
13 sexual function$.tw.
14 sexual satisfaction.tw.
15 vagina$ atrophy.tw.
16 or/1-15
17 exp Dehydroepiandrosterone Sulfate/ or exp Dehydroepiandrosterone/
18 Dehydroepiandrosterone.tw.
19 DHEA$.tw.
20 androstenedione.tw.
21 Prasterone.tw.
22 dehydroisoandrosterone.tw.
23 dha sulfate.tw.
24 androstenolone.tw.
25 or/17-24
26 16 and 25

Appendix 3. MEDLINE search strategy (Ovid platform)

From inception to present
Database: Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R) <1946 to Present>
Search Strategy:

1 (climacteric or menopaus$).tw.
2 (postmenopaus$ or perimenopaus$).tw.
3 vasomotor.tw.
4 exp Menopause, Premature/ or exp Menopause/
5 exp Climacteric/
6 exp Perimenopause/
7 exp Postmenopause/
8 exp Hot Flashes/
9 (hot flash$ or hot flush$).tw.
10 night sweat$.tw.
11 Nocturnal diaphoresis.tw.
12 vagina$ dry$.tw.
13 sexual function$.tw.
14 sexual satisfaction.tw.
15 vagina$ atrophy.tw.
16 or/1-15
17 exp Dehydroepiandrosterone Sulfate/ or exp Dehydroepiandrosterone/
18 Dehydroepiandrosterone.tw.
19 DHEA$.tw.
20 androstenedione.tw.
21 Prasterone.tw.
22 dehydroisoandrosterone.tw.
23 dha sulfate.tw.
24 androstenolone.tw.
25 or/17-24
26 16 and 25
27 randomized controlled trial.pt.
28 controlled clinical trial.pt.
29 randomized.ab.
30 randomised.ab.
31 placebo.tw.
32 clinical trials as topic.sh.
33 randomly.ab.
34 trial.ti.
35 (crossover or cross-over or cross over).tw.
36 or/27-35
37 exp animals/ not humans.sh.
38 36 not 37
39 26 and 38

Appendix 4. EMBASE search strategy (Ovid platform)

From inception to present
Database: Embase
Search Strategy:

1 exp menopause/ or exp early menopause/ or exp menopause related disorder/ or exp "menopause and climacterium"/
2 exp climacterium/
3 exp postmenopause bleeding/ or exp postmenopause/ or exp postmenopause osteoporosis/
4 exp hot flush/
5 (climacteric or menopaus$).tw.
6 (postmenopaus$ or perimenopaus$).tw.
7 vasomotor.tw.
8 (hot flash$ or hot flush$).tw.
9 night sweat$.tw.
10 Nocturnal diaphoresis.tw.
11 vagina$ dry$.tw.
12 sexual function$.tw.
13 sexual satisfaction.tw.
14 or/1-13
15 exp prasterone/
16 Dehydroepiandrosterone.tw.
17 DHEA$.tw.
18 androstenedione.tw.
19 Prasterone.tw.
20 dehydroisoandrosterone.tw.
21 dha sulfate.tw.
22 androstenolone.tw.
23 or/15-22
24 14 and 23
25 Clinical Trial/
26 Randomized Controlled Trial/
27 exp randomization/
28 Single Blind Procedure/
29 Double Blind Procedure/
30 Crossover Procedure/
31 Placebo/
32 Randomi?ed controlled trial$.tw.
33 Rct.tw.
34 random allocation.tw.
35 randomly allocated.tw.
36 allocated randomly.tw.
37 (allocated adj2 random).tw.
38 Single blind$.tw.
39 Double blind$.tw.
40 ((treble or triple) adj blind$).tw.
41 placebo$.tw.
42 prospective study/
43 or/25-42
44 case study/
45 case report.tw.
46 abstract report/ or letter/
47 or/44-46
48 43 not 47
49 24 and 48

Appendix 5. PsycINFO search strategy (Ovid platform)

From inception to present
Database: PsycINFO
Search Strategy:

1 exp Menopause/
2 (climacteric or menopaus$).tw.
3 (postmenopaus$ or perimenopaus$).tw.
4 vasomotor.tw.
5 (hot flash$ or hot flush$).tw.
6 night sweat$.tw.
7 Nocturnal diaphoresis.tw.
8 vagina$ dry$.tw.
9 sexual function$.tw.
10 sexual satisfaction.tw.
11 vagina$ atroph$.tw.
12 or/1-11
13 Dehydroepiandrosterone.tw.
14 DHEA$.tw.
15 androstenedione.tw.
16 Prasterone.tw.
17 dehydroisoandrosterone.tw.
18 dha sulfate.tw.
19 androstenolone.tw.
20 or/13-19
21 12 and 20
22 random.tw.
23 control.tw.
24 double-blind.tw.
25 clinical trials/
26 placebo/
27 exp Treatment/
28 or/22-27
29 21 and 28

Appendix 6. CINAHL search strategy (EBSCO platform)

From inception to present
CINAHL search strategy

# Query
S37S22 AND S36
S36S23 OR S24 or S25 or S26 OR S27 OR S28 OR S29 OR S30 OR S31 OR S32 OR S33 OR S34 OR S35
S35TX allocat* random*
S34(MH "Quantitative Studies")
S33(MH "Placebos")
S32TX placebo*
S31TX random* allocat*
S30(MH "Random Assignment")
S29TX randomi* control* trial*
S28TX ( (singl* n1 blind*) or (singl* n1 mask*) ) or TX ( (doubl* n1 blind*) or (doubl* n1 mask*) ) or TX ( (tripl* n1 blind*) or (tripl* n1 mask*) ) or TX ( (trebl* n1 blind*) or (trebl* n1 mask*) )
S27TX ( (trebl* n1 blind*) or (trebl* n1 mask*) )
S26TX ( (trebl* n1 blind*) or (trebl* n1 mask*) )
S25TX clinic* n1 trial*
S24PT Clinical trial
S23(MH "Clinical Trials+")
S22S15 AND S21
S21S16 OR S17 OR S18 OR S19 OR S20
S20TX androstenedione
S19TX Prasterone
S18TX DHEA
S17TX Dehydroepiandrosterone
S16(MM "Dehydroepiandrosterone")
S15S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14
S14TX Nocturnal diaphoresis
S13TX sexual satisfaction
S12TX sexual function*
S11TX vagina* atrophy
S10TX vagina* dry*
S9TX night sweat*
S8TX hot flush*
S7TX hot flash*
S6TX Climacteri*
S5(MH "Climacteric+") OR (MH "Hot Flashes")
S4TX perimenopaus*
S3TX postmenopaus*
S2TX Menopaus*
S1(MH "Menopause+") OR (MM "Menopause, Premature") OR (MM "Perimenopause") OR (MM "Postmenopause")

Appendix 7. Search strategies for other databases

From inception to present

The search strategy for trials registers

ClinicalTrials.gov; http://www.clinicaltrials.gov and ICTRP (The World Health Organisation International Trials Registry Platform search portal) http://www.who.int/trialsearch/Default.aspx

'DHEA' AND 'Menopause'

'DHEA' AND 'postmenopause'

'Dehydroepiandrosterone' AND 'Menopause'

'Dehydroepiandrosterone' AND 'Postmenopause'

The search strategy for DARE (Database of Abstracts of Reviews of Effects)

The Cochrane Library at http://onlinelibrary.wiley.com/o/cochrane/cochrane_cldare_articles_fs.html (for reference lists from relevant non-Cochrane reviews)

'DHEA' AND 'Menopause'

DHEA' AND 'postmenopause'

'Dehydroepiandrosterone' AND 'Menopause'

'Dehydroepiandrosterone' AND 'Postmenopause'

The search strategy for the Web of Knowledge

http://wokinfo.com/

'DHEA' AND 'Menopaus*'

'DHEA' AND 'postmenopaus*'

'Dehydroepiandrosterone' AND 'Menopaus*'

'Dehydroepiandrosterone' AND 'Postmenopaus*'

The search strategy for the OpenGrey

http://www.opengrey.eu/

'DHEA' AND 'Menopause'

DHEA' AND 'postmenopause'

'Dehydroepiandrosterone' AND 'Menopause'

'Dehydroepiandrosterone' AND 'Postmenopause'

The search strategy for LILACS

http://regional.bvsalud.org/php/index.php?lang=en

'DHEA' AND 'Menopaus*'

'DHEA' AND 'postmenopaus*'

'Dehydroepiandrosterone' AND 'Menopaus*'

'Dehydroepiandrosterone' AND 'Postmenopaus*'

(limit to LILACS)

The search strategy for PubMed and Google (for recent trials not yet indexed in MEDLINE)

PubMed; http://www.ncbi.nlm.nih.gov/pubmed

'DHEA' AND 'Menopause'

DHEA' AND 'postmenopause'

'Dehydroepiandrosterone' AND 'Menopause'

'Dehydroepiandrosterone' AND 'Postmenopause'

Google Scholar; http://scholar.google.co.nz/

'DHEA' AND 'Menopause'

DHEA' AND 'postmenopause'

'Dehydroepiandrosterone' AND 'Menopause'

'Dehydroepiandrosterone' AND 'Postmenopause'

Contributions of authors

CS - drafted protocol
AC - read and adjusted, approved draft
CF - provided expert advice on background, read and adjusted draft
SA - read and adjusted, approved draft

Declarations of interest

None

Sources of support

Internal sources

  • None, Not specified.

External sources

  • Groninger Universiteitsfonds, Netherlands.

    Internship Funding

  • RIjksuniversiteit Groningen, Netherlands.

    Marco Polo Funding/Internship funding

Ancillary