Intervention Protocol

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Bioidentical hormones for women with hot flushes

  1. Ana Marcia IS Gaudard1,
  2. Edina MK da Silva2,
  3. Sulani Silva de Souza3,
  4. Maria R Torloni4,
  5. Cristiane R Macedo4,*

Editorial Group: Cochrane Menstrual Disorders and Subfertility Group

Published Online: 28 FEB 2013

Assessed as up-to-date: 26 SEP 2012

DOI: 10.1002/14651858.CD010407


How to Cite

Gaudard AMIS, da Silva EMK, Silva de Souza S, Torloni MR, Macedo CR. Bioidentical hormones for women with hot flushes (Protocol). Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD010407. DOI: 10.1002/14651858.CD010407.

Author Information

  1. 1

    School of Sciences of Health/FEPECS, Management of educational evaluation, Brasília, Brazil

  2. 2

    Universidade Federal de São Paulo, Emergency Medicine and Evidence Based Medicine, São Paulo, São Paulo, Brazil

  3. 3

    School of Sciences of Health, Management of educational evaluation, Brasília, Brazil

  4. 4

    Centro de Estudos de Medicina Baseada em Evidências e Avaliação Tecnológica em Saúde, Brazilian Cochrane Centre, São Paulo, São Paulo, Brazil

*Cristiane R Macedo, Brazilian Cochrane Centre, Centro de Estudos de Medicina Baseada em Evidências e Avaliação Tecnológica em Saúde, Rua Borges Lagoa 564 cj 63, São Paulo, São Paulo, 04038-000, Brazil. crisrufa@uol.com.br.

Publication History

  1. Publication Status: New
  2. Published Online: 28 FEB 2013

SEARCH

 

Background

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support
 

Description of the condition

According to the criteria proposed by the Stages of Reproductive Aging Workshop (STRAW), the late menopausal transition (stage 1) is marked by the occurrence of times when menstrual periods are absent (amenorrhoea) for periods lasting 60 days or more. The late menopausal transition is characterized by increased variability in menstrual cycle length, extreme fluctuations in hormonal levels, and increased prevalence of anovulation. Follicle stimulating hormone (FSH) levels are sometimes elevated into the menopausal range (over 25 IU/L) and sometimes they are within the range of the earlier reproductive years, especially in association with high estradiol levels. This stage is estimated to last an average of one to three years. Symptoms, most notably vasomotor symptoms (hot flushes), are likely to occur during this stage (Harlow 2012) which usually occurs between 40 to 65 years of age and corresponds to the period when a woman passes from the reproductive stage of life through the premenopausal transition and menopause to the postmenopausal years (Speroff 2011; Sturdee 2011). The hormone change associated with the menopausal transition can lead to a wide variety of symptoms that may negatively affect a woman's quality of life. The most common symptoms include hot flushes (flashes), night sweats, emotional lability, poor concentration, and sleep disturbances. These symptoms can range from mild to severe (Speroff 2011).

The major benefits of hormone therapy (HT) include the relief of vasomotor symptoms (hot flushes), improvement of genitourinary atrophy (symptoms including vaginal dryness, itching, bleeding, dyspareunia, dysuria, urinary urgency, and recurrent urinary tract infections) and prevention of osteoporosis (Warren 2004; Sturdee 2011). Vasomotor symptoms (hot flushes) affect up to 75% to 80% of perimenopausal women, of whom 10% to 15% experience symptoms with sufficient severity to interfere with daily living activities as well as sleep (Hunter 1992a; Barbo 1998; Woods 2005). In most women, these symptoms persist for a year or two after the menopause, but in some they may continue for 10 or more years. The hot flush is described as a sudden onset of reddening of the skin over the head, neck and chest accompanied by a feeling of warmth, often associated with spontaneous sweating, palpitations, and anxiety, resulting from a vasomotor response caused by decreased estrogen levels (Nelson 2006). This aura is followed by measurable increased heat over the entire body surface. The duration of these episodes varies from a few seconds to several minutes and rarely they can last up to one hour. Flushes are more frequent and severe at night or during times of stress (Kronnenberg 1992). The physiology of hot flushes is still not yet completely understood, but they apparently originate in the hypothalamus and are brought about by a decline in estrogens. However, not all hot flushes are due to estrogen deficiency. The correlation between the onset of flushes and estrogen reduction is clinically supported by the effectiveness of estrogen therapy and absence of flushes in permanent hypoestrogen states, such as gonadal dysgenesis (Wilkin 1981; Freedman 2001; Freedman 2006). Among the many theories to explain why hot flashes occur, one of the most accepted (Tartaryn 1981) hypothesizes that hot flashes are thermoregulatory events that aim to keep the body´s temperature within a narrow thermoneutral zone. The brain has a thermoregulating centre, or thermostat, that constantly checks the body´s core temperature to ensure that it is within a specific range. Small increases in body temperature above a certain upper threshold trigger the brain to induce disseminated peripheral cutaneous vasodilation and sweating to dissipate heat and to lower the body´s temperature again. In many menopausal women, for reasons related to estrogen fluctuation not yet completely understood, this upper threshold of the brain´s thermostat is lowered thus leading to the brain to trigger heat dissipating mechanisms several times during the day and night, causing the repeated episodes of hot flushes that are typically reported by women in this period of their lives. The relationship between the luteinising hormone (LH) surge and the brain´s lowering of the sweating threshold is not yet completely clear (Cagnacci 2002).

 

Description of the intervention

The treatment of choice for moderate to severe vasomotor symptoms (hot flushes) is hormone therapy (Speroff 2011; NAMS 2012). For healthy women with annoying episodes of hot flushes, especially for those under 60 years of age and within the first 10 years after menopause, hormone therapy (HT) is still a reasonable choice. Physicians are advised to use the smallest effective dose for the shortest duration possible (Shifren 2010). Various preparations of HT can be prescribed for women in menopausal transition, including bioidentical hormone therapy (BHT). According to the Endocrine Society, BHTs are “compounds that have exactly the same chemical and molecular structure as hormones that are produced by the human body”. Currently, FDA-approved products containing bioidentical estrogen and progesterone are available (ES 2006). Bioidentical estrogen derived from plant sources (17 beta-estradiol) is available in pills, patches, sprays, creams, gels, and vaginal tablets. Progesterone bioidentical to that found in humans is currently available in certain FDA-approved preparations (such as oral micronized progesterone in oil or vaginal progesterone gel) (Shifren 2007; Sturdee 2011). The European Medicines Agency Pre-authorisation Evaluation of Medicines for Human Use (EMEA 2005) recommends estrogen alone or a combination of estrogen plus progestogen for the treatment of estrogen deficiency symptoms in postmenopausal women.

 

How the intervention might work

Many women seek both complementary and alternative therapies for their menopausal symptoms (Ni H 1999). The most likely scenario is that they will use both conventional and non-conventional therapies either simultaneously or sequentially. According to several studies, perimenopausal and menopausal women perceive complementary therapies as being safer and more effective because they are more 'natural' (Kaufert 1998; Seidl 1998; Adams 2001). The primary findings of the Estrogen plus Progestin trial of the Women's Health Initiative (WHI) suggested an overall increase in the risk of coronary heart disease (CHD) (hazard ratio 1.29) among women randomly assigned to combined hormone therapy as compared with those assigned to placebo. According to results of the WHI trial, women on estrogen-progestagen combinations had more abnormal mammograms that needed further assessment than did controls (9% to 4% versus 5% to 4%, respectively) (Flora 2003). Results from the WHI trial indicate that the combined postmenopausal hormones conjugated equine estrogens (CEE) 0.625 mg/d plus medroxyprogesterone acetate (MPA) 2.5 mg/d should not be initiated or continued for the primary prevention of CHD. In addition, the substantial risks for cardiovascular disease and breast cancer must be weighed against the benefit of fracture reduction in selecting from the available agents to prevent osteoporosis. The WHI findings changed the perceptions of women, and as a consequence many stopped HT and some opted for alternative therapies for the treatment of symptoms associated with the menopause (Hersh 2003). Some health professionals prescribe HT containing bioidentical hormones as a more natural, effective, and safer form of treatment than conventional HT. Consequently, many women are regarding these bioidentical hormonal combinations as a safer alternative compared to conventional HT (Drisko 2002; NAMS 2012).

 

Why it is important to do this review

Diminished sleep quality, irritability, difficulty concentrating, and subsequently reduced quality of life (QOL) are potential consequences of the vasomotor symptoms typical of the menopausal transition (NAMS 2012). The most common HTs include estrogens alone and estrogens combined with progestogens, and these options have benefits and risks. The use of BHT has escalated in recent years. It is necessary to look at the best available evidence on the effectiveness and safety of BHT. This review aims to assess the effectiveness and safety of the specific subgroup of bioidentical estrogen and progesterone formulations for the relief of vasomotor symptoms (NAMS 2012).

 

Objectives

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support

To determine the effectiveness and safety of bioidentical hormones in the relief of vasomotor symptoms in menopausal transition women compared to placebo, estrogen, or combined estrogen plus progestogen.

 

Methods

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support
 

Criteria for considering studies for this review

 

Types of studies

Randomised controlled trials (RCTs) comparing BHT for the relief of vasomotor symptoms with placebo or with non-bioidentical hormones..

 

Types of participants

Women in the menopausal transition (spontaneous or surgical menopause) with vasomotor symptoms.

 

Types of interventions

Prescription of bioidentical compared with prescription of not bioidentical hormones. Bioidentical hormones are compounds with a molecular chemical structure identical to hormones produced by the ovary. We will include 17-beta estradiol, alone or in combination with progesterone, used in any dose or route of administration in the first group. In the comparison group we will include women receiving equine products, estradiol valerate, micronized estradiol, estropipate (piperazine estrone sulfate), ethinyl estradiol alone or in combination with various progestogens (medroxyprogesterone acetate, norethindrone, norethindrone acetate, drospirenone, dienogest) administered in cyclic or continuous regimens. Other drugs used for the relief of vasomotor symptoms will not be included in this review.

 

Types of outcome measures

 

Primary outcomes

  • Frequency or intensity of vasomotor menopausal symptoms measured by any validated scale

 

Secondary outcomes

  • Incidence and severity of adverse effects
  • Quality of life evaluated with any validated instruments used for quality of life measures, such as the Menopause-Specific Quality of Life (Hilditch 1996), Women's Health Questionnaire (Hunter 1992b), or other generic measures

 

 

Search methods for identification of studies

 

Electronic searches

The following sources will be searched: Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE (1966 to date), EMBASE (1974 to date), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) (1982 to date) in consultation with the Menstrual Disorders and Subfertility Group (MDSG) Trials Search Co-ordinator.

Ongoing trials will be searched for on the following websites:

  • metaRegister of Controlled Trials (www.controlled-trials.com);
  • US National Institutes of Health ongoing trials register (www.clinicaltrials.gov);
  • World Health Organization International Clinical Trials Registry Platform (www.who.int/trialsearch);
  • EU Clinical Trials Register (https://www.clinicaltrialsregister.eu/).

The search terms will include: Keywords CONTAINS "Hot flushes" or " Hot flashes " or "vasomotor symptoms " or "HRT" or "Hormone Therapy" or "Hormone Substitution" or "estrogen" or "oestrogen" or "estradiol" or oestradiol" or "progestogen" or "progestagen" or "progestin" or "progesterone" or "norgestrel" or "norethisterone" or "desogestrel" or Title CONTAINS "Hot flushes" or " Hot flashes " or "vasomotor symptoms "or "HRT" or "Hormone Therapy" or "Hormone Substitution" or "estrogen" or "oestrogen" or "estradiol" or oestradiol" or "progestogen" or "progestagen" or "progestin" or "progesterone" or "norgestrel" or "norethisterone" or "desogestrel".

hot flush, vasomotor symptoms, hormone therapy, equine products, valerate estradiol, estradiol hemihydrate, progestogens, bioidentical hormones, 17-beta estradiol and progesterone

There will be no language restriction and translations will be sought where necessary.

 

Searching other resources

The reference lists of the included studies will be screened for additional potentially relevant studies. Specialists in the field will be contacted for any possible unpublished data.

 

Data collection and analysis

 

Selection of studies

Two authors (AMISG, SSS) will independently screen the trials identified by the literature search. After merging the search results and removing duplicate records the authors will examine titles and abstracts to select the relevant reports. They will then retrieve and examine the full texts of selected studies for compliance with eligibility criteria. The reason for exclusion of individual trials will be documented. A third author (EMKS, CRM) will be consulted in case any disagreements arise (at this or at any other stage as listed below). We will not include data from trials under scrutiny until a consensus is reached.

 

Data extraction and management

Two authors (AMISG, SSS) will extract data independently using an extraction form designed and pilot-tested by the authors. Where studies have multiple publications, the main trial report will be used as the reference and additional details supplemented from secondary papers. Disagreements will be resolved by consensus or by discussion with the third author. We will contact the authors from all studies with incomplete information on outcomes of interest or additional missing details.

 

Assessment of risk of bias in included studies

The included studies will be assessed for risk of bias using the 'criteria for judging risk of bias' outlined in the Cochrane Collaboration's tool for assessing risk of bias (Higgins 2011). The analysis will include the following: sequence generation; allocation concealment; blinding of participants, providers and outcome assessors; incomplete outcome data; selective outcome reporting; and other potential sources of bias. Quality assessment will be performed by two independent authors. Disagreements will be resolved by consensus or discussion with a third author. All judgments will be fully described and justified.

 

Measures of treatment effect

We will express dichotomous data as odds ratio (OR) or risk ratio (RR) with 95% confidence interval (CI). For continuous data, mean differences and 95% CIs between treatment groups will be calculated if studies report exactly the same outcomes. If similar outcomes are reported on different scales, the standardised mean difference and 95% CI will be calculated. In the event that study authors do not make the necessary information available, any data from primary studies which are not parametric (for example effects reported as medians, quartiles, etc) or without sufficient statistical information (for example standard deviations, number of patients, etc) will be inserted into an 'Additional table'.

 

Unit of analysis issues

The unit of analysis will be the individual participants (unit to be randomised for interventions to be compared), that is the number of observations in the analysis should match the number of individuals randomised.

 

Dealing with missing data

In cases of missing outcomes, or any uncertainty regarding the data, we will contact the authors asking for the missing data or clarification. In the case of no response, irrespective of the type of data, dropout rates will be reported in the 'Characteristics of included studies' table and intention-to-treat analysis will be used (Higgins 2011). We will impute only the missing data of primary outcome (vasomotor symptoms) with replacement values. For dichotomous outcomes the missing data will be assumed as treatment failures and for continuous outcome we will impute the mean observed. We will perform sensitivity analyses by excluding the participants with missing data to assess the strength of the results.

 

Assessment of heterogeneity

Inconsistency among the pooled estimates will be qualified using the I2 = ((Q - df)/Q) x 100% statistic, where Q is the Chi2 statistic and df represents the degree of freedom. This illustrates the percentage of the variability in effect estimates resulting from heterogeneity rather than sampling error (Higgins 2011).

The thresholds for the interpretation of I2 will be as follows:

  • 0% to 25%, low heterogeneity;
  • 25% to 75%, moderate;
  • more than 75%, substantial heterogeneity (Higgins 2003).

 

Assessment of reporting biases

The authors will aim to minimize the potential impact by detecting and correcting publication bias and other reporting biases, by ensuring a comprehensive search for eligible studies, and by being alert for duplication of data.
If 10 or more studies are included in an analysis, a funnel plot will be used to investigate the possibility of small study effects (a tendency for the intervention to have a bigger impact in smaller studies).

 

Data synthesis

If no substantial heterogeneity is identified, pooled estimates of the treatment effect will be computed for each outcome under a fixed-effect model. If substantial heterogeneity is identified, a random-effects model analysis will be performed.

 

Subgroup analysis and investigation of heterogeneity

If substantial heterogeneity is found, and there are sufficient data, the possible causes will be investigated by using subgroup analyses. Where data are available, we will conduct the following subgroup analyses. 1. Type of menopause: natural; induced; not specified. 2. Participants' baseline status: women with hot flushes; women with other associated symptoms.

 

Sensitivity analysis

We will conduct sensitivity analyses for the primary outcomes to determine whether the conclusions are robust to arbitrary decisions made during the review process regarding the eligibility for end 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. studies with outlying results had been excluded.

At first it is planned to perform sensitivity analyses on results to look at the possible contribution of differences in quality of studies depending on randomisation, blinding, and losses.

Heterogeneity between the results of different studies will be examined by inspecting the scatter in the data points on the graphs and the overlap in their CIs and, more formally, by checking the results of the Chi2 tests and by using the I2 statistic.

 

Overall quality of the body of evidence: Summary of Findings Table

A Summary of Findings Table will be generated using GRADEPRO software (GRADE PRO 2011). This table will evaluate the overall quality of the body of evidence for main review outcomes, using GRADE criteria (study limitations (i.e. risk of bias), consistency of effect, imprecision, indirectness and publication bias). Judgements about evidence quality (high, moderate or low) will be justified, documented, and incorporated into reporting of results for each outcome.

 

Acknowledgements

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support

We would like to thank the Cochrane Menstrual Disorders and Subfertility Editorial Team, mainly Ms. Helen Nagels for their thoughtful comments and suggestions and Trials Search Coordinator Marian Showell. We also want to acknowledge Evilásio Rodrigues Cortes for the valuable technical help with the RevMan program.

 

Appendices

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support
 

Appendix 1. Search Strategies

Database: Menstrual Disorders and Subfertility Specialised Register

Search Strategy:
--------------------------------------------------------------------------------

Keywords CONTAINS "menopausal"or "menopausal symptoms" or "*Menopause" or"perimenopausal"or"climacteric "or"vasomotor"or"hot flashes"or"hot flushes"or"night sweats"or"night time awakenings" or "sleep disturbances" or "hot flash" or "hot flush" or Title CONTAINS "menopausal"or "menopausal symptoms" or "*Menopause"or"perimenopausal"or"climacteric "or"vasomotor"or"hot flashes"or"hot flushes"or"night sweats"or"night time awakenings" or"sleep disturbances " or "hot flash" or "hot flush"

 AND

 Keywords CONTAINS "17-beta estradiol"or"17-beta estradiol - 3 beta - glucoside"or"17beta-estradiol + norethisterone acetate" or Title CONTAINS  "17-beta estradiol"or"17-beta estradiol - 3 beta - glucoside"or"17beta-estradiol + norethisterone acetate"

Database: EBM Reviews - Cochrane Central Register of Controlled Trials <December 2012>
Search Strategy:
--------------------------------------------------------------------------------

1 exp menopause/ or exp perimenopause/ or exp postmenopause/
2 climacter$.tw.
3 (postmenopaus$ or menopaus$).tw.
4 perimenopaus$.tw.
5 Climacteric/
6 exp Hot Flashes/
7 Hot Flash$.tw.
8 Hot Flush$.tw.
9 vasomotor.tw.
10 night$ sweat$.tw.
11 or/1-10
12 bioidentical.tw.
13 (natural adj5 hormon$).tw.
14 17 beta estradiol.tw.
15 17 beta oestradiol.tw.
16 estradiol-17beta.tw.
17 estradiol 17beta.tw.
18 estradiol 17 beta.tw.
19 17 beta-oestradiol.tw.
20 BHRT.tw.
21 bio-identical.tw.
22 or/12-21
23 11 and 22

Database: Ovid MEDLINE(R) <1946 to to January Week 2 2013>
Search Strategy:
--------------------------------------------------------------------------------
1 exp menopause/ or exp perimenopause/ or exp postmenopause/
2 climacter$.tw.
3 (postmenopaus$ or menopaus$).tw.
4 perimenopaus$.tw.
5 Climacteric/
6 exp Hot Flashes/
7 Hot Flash$.tw.
8 Hot Flush$.tw.
9 vasomotor.tw.
10 night$ sweat$.tw.
11 or/1-10
12 bioidentical.tw.
13 (natural adj5 hormon$).tw.
14 17 beta estradiol.tw.
15 17 beta oestradiol.tw.
16 estradiol-17beta.tw.
17 estradiol 17beta.tw.
18 estradiol 17 beta.tw.
19 17 beta-oestradiol.tw.
20 BHRT.tw.
21 bio-identical.tw.
22 or/12-21
23 11 and 22
24 randomized controlled trial.pt.
25 controlled clinical trial.pt.
26 randomized.ab.
27 randomised.ab.
28 placebo.tw.
29 clinical trials as topic.sh.
30 randomly.ab.
31 trial.ti.
32 (crossover or cross-over or cross over).tw.
33 or/24-32
34 exp animals/ not humans.sh.
35 33 not 34
36 23 and 35

Database: Embase <1980 to 2013 Week 02>
Search Strategy:
--------------------------------------------------------------------------------
1 exp menopause/ or exp "menopause and climacterium"/
2 exp climacterium/
3 exp postmenopause/
4 climacter$.tw.
5 (postmenopaus$ or menopaus$).tw.
6 perimenopaus$.tw.
7 exp climacterium/
8 exp hot flush/
9 hot flush$.tw.
10 Hot Flash$.tw.
11 vasomotor.tw.
12 night$ sweat$.tw.
13 or/1-12
14 bioidentical.tw.
15 (natural adj5 hormon$).tw.
16 17 beta estradiol.tw.
17 17 beta oestradiol.tw.
18 estradiol-17beta.tw.
19 estradiol 17beta.tw.
20 estradiol 17 beta.tw.
21 17 beta-oestradiol.tw.
22 BHRT.tw.
23 bio-identical.tw.
24 or/14-23
25 13 and 24
26 Clinical Trial/
27 Randomized Controlled Trial/
28 exp randomization/
29 Single Blind Procedure/
30 Double Blind Procedure/
31 Crossover Procedure/
32 Placebo/
33 Randomi?ed controlled trial$.tw.
34 Rct.tw.
35 random allocation.tw.
36 randomly allocated.tw.
37 allocated randomly.tw.
38 (allocated adj2 random).tw.
39 Single blind$.tw.
40 Double blind$.tw.
41 ((treble or triple) adj blind$).tw.
42 placebo$.tw.
43 prospective study/
44 or/26-43
45 case study/
46 case report.tw.
47 abstract report/ or letter/
48 or/45-47
49 44 not 48
50 25 and 49

Database: PsycINFO <1806 to January Week 2 2013>
Search Strategy:
--------------------------------------------------------------------------------
1 exp menopause/
2 climacter$.tw.
3 (postmenopaus$ or menopaus$).tw.
4 perimenopaus$.tw.
5 Hot Flash$.tw.
6 Hot Flush$.tw.
7 vasomotor.tw.
8 night$ sweat$.tw.
9 or/1-8
10 bioidentical.tw.
11 (natural adj5 hormon$).tw.
12 17 beta estradiol.tw.
13 17 beta oestradiol.tw.
14 estradiol-17beta.tw.
15 estradiol 17beta.tw.
16 estradiol 17 beta.tw.
17 17 beta-oestradiol.tw.
18 BHRT.tw.
19 bio-identical.tw.
20 or/10-19
21 random.tw.
22 control.tw.
23 double-blind.tw.
24 clinical trials/
25 placebo/
26 exp Treatment/
27 or/21-26
28 9 and 20 and 27

Database: LILACS <1982 to 2013>
Search Strategy:
--------------------------------------------------------------------------------

((MH:G08.686.157.500) OR (MH:G08.686.785.880.249.500) OR (TW:Menopause) OR (TW:Menopausia) OR (TW:Menopausa) OR (TW:Mudança de Vida Feminina) OR (TW:Cambio de Vida Femenina) OR (TW:Female Change of Life) OR (MH:G08.686.157.500.562) OR (MH:G08.686.785.880.249.500.562) OR (TW:Perimenopause) OR (TW:Perimenopausia) OR (TW:Perimenopausa) OR (MH:G08.686.157.500.625) OR (MH:G08.686.785.880.249.500.625) OR (TW:Postmenopause) OR (TW:Posmenopausia) OR (TW:Pós-menopausa) OR (TW:climacter$) OR (TW:climater$) OR (MH:G08.686.157) OR (MH:G08.686.785.880.249) OR (TW:Climacteric) OR (TW:Change of Life) OR (MH:C23.888.475) OR (TW:Hot Flash$) OR (TW:Hot Flush$) OR (TW:Sofoco$) OR (TW:Fogacho$) OR (TW:vasomotor) OR (TW:night$ sweat$) OR (TW:suor$ noturno$))

AND

((TW: bioidentical) OR (TW:bioidentico) OR (TW:terapia hormonal com bioidenticos) OR (TW:hormonios bioidenticos) OR (TW:estrogenio bioidentico) OR (TW:hormonio natural) OR (TW:17 beta estradiol) OR (TW:17 beta oestradiol) OR(TW:estradiol-17beta) OR (TW:estradiol 17beta) OR (TW:estradiol 17 beta) OR (TW:17 beta-oestradiol) OR (TW:BHRT) OR (TW:bio-identical))

 

Contributions of authors

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support

Drafting the protocol: Ana Marcia IS Gaudard, Edina MK da Silva, and Sulani Silva de Souza

Development of search strategy: Ana Marcia IS Gaudard, Cristiane R Macedo

Search for trials: Ana Marcia IS Gaudard, Cristiane R Macedo

Selection of which trials to include: Ana Marcia IS Gaudard, Edina MK da Silva, Sulani Silva de Souza, Maria R Torloni, and Cristiane R Macedo

Extraction of data from trials: Ana Marcia IS Gaudard, Edina MK da Silva, Sulani Silva de Souza, Maria R Torloni, and Cristiane R Macedo

Assessment of risk of bias in included studies: Ana Marcia IS Gaudard, Edina MK da Silva, Sulani Silva de Souza, and Cristiane R Macedo

Entry of data into RevMan: Ana Marcia IS Gaudard

 

Declarations of interest

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support

None known

 

Sources of support

  1. Top of page
  2. Background
  3. Objectives
  4. Methods
  5. Acknowledgements
  6. Appendices
  7. Contributions of authors
  8. Declarations of interest
  9. Sources of support
 

Internal sources

  • New Source of support, Brazil.
    Brazilian Cochrane Center will conduct the searches in LILACS

 

External sources

  • None, Not specified.

References

Additional references

  1. Top of page
  2. Abstract
  3. Background
  4. Objectives
  5. Methods
  6. Acknowledgements
  7. Appendices
  8. Contributions of authors
  9. Declarations of interest
  10. Sources of support
  11. Additional references
Adams 2001
Barbo 1998
  • Barbo DM. Menopause. Texbook of women's health. Philadelphia: Lippincolt-Raven, 1998.
Cagnacci 2002
Drisko 2002
  • Drisko JA. Natural isomolecular hormone replacement: an evidence-based medicine approach. International Journal of Pharmaceutical Compounding 2000;4:414-20.
EMEA 2005
  • European Medicines Agency. Guideline on clinical investigation of medicinal products for hormone replacement therapy of oestrogen deficiency symptoms in postmenopausal women. http://www.ema.europa.eu/ema/ Accessed September 2012.
ES 2006
  • Endocrine Society. Bioidentical hormones: position statement. http://www.endo-society.org/advocacy/policy/upload/BH_position_Statement_final_10_25_06_w_Header.pdf Accessed May 20, 2012.
Flora 2003
  • Flora E Van Leeuwe, Matti A Rookusn. Breast cancer and hormone-replacement therapy: the Million Women Study. Lancet 2003;362(9392):1330.
Freedman 2001
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  • GRADE Working Group. GRADE Profile Software. GRADE Working Group, 2011.
Harlow 2012
  • Harlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW, et al. STRAW + 10 Collaborative Group. Executive summary of the Stages of Reproductive Aging Workshop D10: addressing the unfinished agenda of staging reproductive aging. Journal of Clinical Endocrinology and Metabolism April 2012;97(4):1159-68.
Hersh 2003
Higgins 2003
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