Summary of Evidence - Methodology

A Cancer Australia systematic review on the management of menopausal symptoms in women with a history of breast cancer was undertaken based on evidence published between January 2001 and November 2015. A systematic literature search was conducted in PubMed, Medline, EMBASE, PsychINFO, CINAHL and the Cochrane Library. A search of key menopause organisations, guidelines organisations, clinical trial websites and conference websites was also conducted.

This systematic review focused on evidence for the management of menopausal symptoms in the specific subgroup of women with a history of breast cancer. The systematic review did not include studies on the management of vasomotor symptoms in men who have a history of breast cancer. Outcome measures of interest were improvement or reduction of menopausal symptoms including vasomotor symptoms (hot flushes and/or night sweats); sleep disturbances; vulvovaginal symptoms including vaginal dryness, dyspareunia and sexual function; as well as psychological wellbeing, global quality of life, breast cancer recurrence and adverse events.

A total of 4157 citations were identified for review. Following application of the exclusion criteria, first to titles and abstracts, and then to full articles, and excluding studies with ≤ 10 participants in any one treatment arm, a total of 45 studies (41 RCTs, 1 sub-study and 3 updates) were identified as eligible. These citations addressed the primary research question: What is the effectiveness of interventions for the management of menopausal symptoms in women who have received treatment for breast cancer?

Following review of the evidence, it was revealed that a number of interventions of interest had no RCT evidence available specifically in the population of women who had received treatment for breast cancer. Interventions considered to be of interest were the antidepressants escitalopram and desvenlafaxine, the male hormone testosterone, and the menopausal hormone therapies vaginal oestrogen and compounded hormones (often referred to as ‘bioidentical’ hormones). Thus, an additional systematic review was undertaken to identify evidence for these interventions in the general female menopausal population, with available evidence from January 2001 to November 2015.

A systematic literature search was conducted in PubMed, Medline, EMBASE, PsychINFO and the Cochrane Library to identify relevant systematic reviews. A total of 589 citations were identified for review. Following application of the exclusion criteria, first to titles and abstracts, and then to full articles, a total of six relevant systematic reviews were identified: two for testosterone and one each for the other interventions. These citations addressed a secondary research question:  What is the effectiveness of escitalopram, desvenlafaxine, testosterone, vaginal oestrogen and compounded hormones (‘bioidentical hormones’) for the management of menopausal symptoms in the general female menopausal population?

After careful consideration, it was recognised that clinical trial evidence from a general female menopausal population was generalisable to a breast cancer population.  Consequently the Supplementary Evidence Review included studies of women experiencing menopausal symptoms in the general population treated with the same interventions considered in the primary Systematic Review with the addition of the interventions with no available evidence in the breast cancer population (escitalopram, desvenlafaxine, testosterone, vaginal oestrogen, and compounded hormones). The Supplementary Evidence Review supplements the evidence found in the Primary Systematic Review from the breast cancer population. Both of these reviews support and inform the development of this clinical practice guideline.

Evidence Summaries were drafted based on the body of evidence identified for this guideline and these have been used to grade each recommendation. Of note, in both the Primary Systematic Review and Supplementary Evidence Review the studies on depression, anxiety, mood, global quality of life and mental health were of poor quality and the evidence was poorly reported. Consequently, for these symptoms no Evidence Summaries were developed in view of the poor quality of the studies: these symptoms were reported as secondary outcomes and the dosages of psychotropic medications used were below that needed to treat mental health conditions. Therefore for this guideline no recommendations have been made for the symptoms of depression, anxiety, mood, global quality of life and mental health.