Management of menopause in women with BC involves lifestyle modification, psychological support/intervention, pharmacological therapies, prevention/treatment of the long term consequences of menopause and education. The excellent guidelines regarding management of menopausal symptoms in women with breast cancer written by Hickey and co-authors  (Hickey, Saunders et al. 2008) include a number of key points that should be addressed in the evaluation of women with BC and menopausal symptoms (see Table: Points to consider in evaluation of the menopausal woman).

Table: Points to consider in evaluation of the menopausal woman

What is the likely cause of the menopausal symptoms?

Establish the frequency and severity of menopausal symptoms and their impact on quality of life (questionnaires may be useful)

Assess lifestyle and environmental factors that may be triggering/exacerbate the hot flushes

Establish what the patient wishes and expects from intervention

Provide information regarding menopause and treatments

Data derived from (Hickey, Saunders et al. 2008) 

9.1 Management of vasomotor symptoms

Lifestyle measures, pharmacologic therapies, complementary therapies (including herbal, phytoestrogens, and bioidentical hormones) and mind-body therapies have been proposed for the treatment of vasomotor symptoms and are discussed below. Changing or ceasing adjuvant endocrine therapy may also need to be considered where symptoms persist. Use of tibolone/HRT may be considered in special circumstances where symptoms are resistant to treatment with significant impact on quality of life.

9.1.1 Lifestyle measures

Lifestyle measures considered to be useful in managing menopausal symptoms (by either reducing number/severity or improving tolerability) are described in Table: Lifestyle measures useful in management of vasomotor symptoms.
 

Table: Lifestyle measures useful in management of vasomotor symptoms

Cessation of smoking

At least 30 minutes of regular exercise daily

Maintenance of ideal weight

Dress in layers. Wear natural fibres

Use of cold packs

Avoid hot environmental temperatures

Identify (hot flush diary) and avoid potential hot flush triggers such as spicy foods, alcohol, stress, caffeine, hot external environment

Minimize stress and anxiety

Data derived from (Hickey, Saunders et al. 2008)

Downloadable patient resource

Australasian Menopause Society: NonHormonal Treatments for Menopausal Symptoms

9.1.2 Hormone replacement therapy and tibolone

The term “hormone replacement therapy” (HRT) as discussed here refers to the use of exogenous oestrogen, either alone (ET) or in combination with a progestogen (EPT) where a woman has an intact uterus to prevent endometrial hyperplasia/carcinoma. HRT is the most effective therapy for vasomotor symptoms; however, the use of HRT in women with BC is generally contraindicated due to the potential increased risk of BC recurrence (Holmberg and Anderson 2004). In certain circumstances of advanced cancer where quality of life is the main concern, use of HRT could be considered where other vasomotor symptom treatments have failed and after discussion of the risks/benefits with the woman concerned.

Tibolone, a synthetic steroid whose metabolites have estrogenic, progestogenic and androgenic properties, is an alternative to conventional HRT. Tibolone has positive effects on vasomotor and urogenital symptoms, sexual function, bone density and fracture risk. However, tibolone therapy in women with previous breast cancer is associated with an increase in recurrence compared with placebo particularly in women treated with aromatase inhibitors (Kenemans, Bundred et al. 2009). Tibolone is therefore not recommended for women with breast cancer unless advanced cancer where quality of life related to symptom control is the main aim of therapy or other treatment measures are ineffective and the woman has been counselled regarding potential benefits/risks including BC recurrence.

9.1.3 Non-hormonal pharmacologic therapies

“Non-hormonal” therapies refer to a variety of pharmacologic agents which do not have hormonal/ oestrogenic activity. A variety of selective serotonin reuptake inhibitors/serotonin noradrenalin reuptake inhibitors, gabapentin and clonidine have been evaluated in regard to treatment of vasomotor symptoms, primarily in women with breast cancer. A meta-analysis of non-hormonal therapies indicated that paroxetine, venlafaxine, gabapentin and clonidine were effective in reducing vasomotor symptoms (see Table: Non-hormonal therapies for vasomotor symptoms) with more recent evidence supporting the use of dulexetine and citalopram. However, most of these studies were of short duration ( 

Table: Non-hormonal therapies for vasomotor symptoms

Preparation	Dose	Reduction in hot flushes	Common side effects
Gabapentin	300-900mg/day in divided doses	Up to 66%	Dizziness , drowsiness
Venlafaxine XR	37.5-75mg/day	Up to 66%	Dry mouth, GIT upset, sexual dysfunction
Paroxetine	10-20mg/day	Up to 60%
Desvenlafaxine	100mg/day	60%
Citalopram	10-20mg/day	50%
Clonidine	0.1mg/day	26-40%	Dry mouth

Data derived from (Nelson, Vesco et al. 2006; Loprinzi, Sloan et al. 2009; Barton, LaVasseur et al. 2010)  (Bordeleau, Pritchard et al. 2010)

9.1.4 Complementary and Alternative therapies

Considerable interest has been expressed by women regarding the use of complementary/ alternative therapies; approximately 60% community living women aged 45-55 years reported using them in a South Australian study. This may relate in part to availability without prescription and also the misconception that these compounds are “natural” and therefore safe. However, these remedies exhibit medicinal properties and there is increasing recognition of adverse effects including interaction with conventional pharmaceuticals. An explanation for the observed effect of many of these therapies is the placebo response of up to 58% seen in RCTs for vasomotor symptoms (MacLennan 2009).

9.1.4.1 Phytoestrogens

Phytoestrogens are plant-derived oestrogen-like compounds which exhibit both oestrogenic and anti-oestrogenic properties. Genistein and daidzein, found in soybean, possess the greatest estrogenic activity. Despite observational studies indicating potential benefits of phytoestrogens in regard to cardiovascular risk factors, bone density and menopausal symptoms, meta-analyses of interventional studies show no benefit compared with placebo (Nedrow, Miller et al. 2006). There is conflicting evidence regarding phytoestrogen intake and reduced risk of breast cancer. The safety of phyto-oestrogens in this patient population is unknown (Boekhout, Beijnen et al. 2006; Roberts 2010).

9.1.4.2 Herbal therapies

Specific herbs purported to be efficacious for menopausal symptoms include ginseng, passion flower, St. John’s wort, valerian, balm, black cohosh, chaste tree and ginkgo; but, meta-analyses indicate no benefit compared with placebo (Nedrow, Miller et al. 2006; Geller, Shulman et al. 2009). The long term safety of these therapies is unknown with concern regarding liver toxicity associated with black cohosh (Boekhout, Beijnen et al. 2006; Roberts 2010). 

9.1.4.3 Alternative Therapies

There is a lack of high quality, consistent evidence in support of alternative therapies including homeopathy, reflexology and body manipulation in the management of menopausal symptoms (Boekhout, Beijnen et al. 2006; Nedrow, Miller et al. 2006). Mind body interventions including yoga, hypnosis, cognitive behavioural therapy, paced respiration, relaxation therapy and acupuncture show promise; however, the applicability of these studies are limited by methodological problems including small sample sizes, non-randomised design and lack of placebo/control groups (Nedrow, Miller et al. 2006; Avis 2008; Innesa, Selfea et al. 2010). More research is needed.

9.1.4.4 “Bio-identical” hormone therapy

“Bio-identical” hormone therapy is the use of preparations (usually creams or troches) containing various amounts/combinations of oestrogen, progesterone, testosterone, dehydroepiandrosterone, and other hormones prepared by compounding pharmacists.  They are often prescribed on the basis of salivary hormone testing results which can be inaccurate and are unsubstantiated. A common misconception is that they are safer than conventional HRT (MacLennan 2009); however, there is no credible scientific evidence regarding efficacy and safety. There is no data regarding safety in women with BC and the inclusion of different types of oestrogen in these preparations raises concern regarding BC recurrence. They are not TGA approved and the major menopause and endocrine societies do not support their use. 

Downloadable patient resource

 Bioidentical Hormones 103.09 Kb

9.2 Management of Urogenital symptoms

Vaginal oestrogen is the most effective therapy for isolated urogenital symptoms. Use of vaginal oestrogens has been considered to be associated with minimal systemic absorption. However, elevated serum oestrogen levels above pre-treatment levels have been observed with different vaginal oestrogen preparations and their use in women taking aromatase inhibitors as part of breast cancer therapy is controversial. Non-hormonal therapy for urogenital atrophy consists of vaginal moisturisers, used chronically to improve symptoms, and lubricants, used prior to sexual intercourse. Use of a vaginal moisturiser decreases vaginal pH, improves vaginal elasticity and reverses vaginal atrophy, although, to a lesser extent than vaginal oestrogen cream. Vaginal lubricants, such as KY Jelly, are not moisturizers and may increase vaginal dryness. Effective lifestyle measures for management of urogenital symptoms are shown in Table: Lifestyle management of urogenital symptoms. Published guidelines suggest use of lifestyle measures as initial therapy with introduction of vaginal moisturizers and lubricants as required. If no improvement after several weeks then consideration should be given to changing to an alternative anti-oestrogen therapy and/ or a trial of a vaginal oestriol (not oestradiol) preparation (Hickey, Saunders et al. 2008; Trinkhaus, Chin et al. 2008; Suckling, Kennedy et al. 2010).
 

Table: Lifestyle management of urogenital symptoms

Cessation of smoking

Regular sexual activity

Avoid scented soaps, lotions, panty liners

Downloadable patient resources

 Irritation of the Vulva 93.13 Kb

Australasian Menopause Society: Vaginal atrophy after breast cancer

9.3 Management of sexual dysfunction

Management of sexual dysfunction includes:

• Identification that there is a problem as women are often reluctant to disclose sexual dysfunction (see section 7.2: Diagnosis of early/premature menopause)
• Treatment of urogenital symptoms (see section 9.2: Management of urogenital symptoms)
• Consideration of ceasing/changing medication which can negatively impact on sexual function, such as antidepressants or aromatase inhibitors
• Assessment and treatment of any underlying depression/psychological disorder
• Counselling

There is a lack of data regarding the efficacy and long term safety of testosterone therapy (see section 6.4.3: Female Androgen Insufficiency) and the role of sildenafil or bupropion.

Downloadable patient resource

 Libido 117.38 Kb

9.4 Management of sleep disturbance

Management of sleep disorders involves treatment of vasomotor symptoms and behavioural therapies including sleep hygiene, relaxation, and sleep scheduling. Cognitive behavioural therapy, mindfulness and yoga also show promise in regard to the management of sleep disorders in women with breast cancer (Bower 2008).

Downloadable patient resource

 Sleep 167.53 Kb

9.5 Management of depression and mood disorders

It is necessary to distinguish depressive or anxiety disorders from depressive/anxiety symptoms which commonly occur in women with BC (particularly in the first year following diagnosis) and may require formal psychological/psychiatric evaluation. Positive effects on depressive symptoms in women with breast cancer have been observed with educational and nutritional interventions, cognitive behavioral therapy and supportive-expressive group therapy. The type of intervention required may vary depending on the stage of the cancer journey with treatments that focus on providing information about BC/BC therapy and managing disease-related stress may be particularly helpful for newly diagnosed patients, whereas interventions that emphasize support and emotional expression may be more useful for women with advanced-stage disease (Bower 2008). Pharmacotherapy should also be considered for the treatment of major depression in breast cancer patients. Antidepressants have been shown to improve depressive symptoms in breast cancer patients with improvement in mood also reported by women using antidepressant therapy for management of vasomotor symptoms.

Downloadable patient resources

 Early Menopause Wellbeing  196.17 Kb

 Emotional Health at Midlife 163.39 Kb

9.6 Management of long term consequences of menopause

9.6.1 Cardiovascular disease

Monitoring and treating modifiable risk factors is recommended according to national guidelines. This includes cessation of smoking, regular exercise, normal weight maintenance, monitoring of fasting lipid and glucose levels.

Downloadable patient resources

 Heart Disease 156.38 Kb

 Healthy Eating for You 116.18 Kb

 Physical Activity 98.89 Kb

9.6.2 Osteoporosis

As with cardiovascular disease, monitoring and treating modifiable risk factors is recommended. Bone mineral density assessments should be performed in women with premature/early menopause, women commencing aromatase inhibitor therapy, women aged >70 years or where other significant risk factors for osteoporosis exist (see Bone Health for Life website). Women should maintain adequate calcium intake with use of supplements if dietary intake inadequate to achieve the 1000mg recommended calcium dose for postmenopausal woman. Vitamin D levels should be monitored and supplements used to achieve Vitamin D levels in the normal range. If bone mineral density is reduced then specialist referral should be considered for further management with anti-resorptive agents. Current guidelines vary as to the threshold T score at which bisphosphonate therapy should be introduced in BC women treated with aromatase inhibitors and there is a lack of data regarding the use of other agents in women with BC.

Downloadable patient resources

 Bone Health - Preventing Osteoporosis 114.00 Kb

 Vitamin D 95.53 Kb

9.7 Education

Education/information with reference to the woman’s understanding of and attitude towards  menopausal issues, cultural beliefs, expectations and concerns regarding the potential therapies available is essential. Many women with BC are not provided with menopause information or consider the information inadequate, particularly regarding infertility in younger women and also long term complications (Duffy, Allen et al. 2005; Thewes, Meiser et al. 2005). Women’s information needs differ according to their age and stage of their cancer journey with infertility related information preferred by younger women at BC diagnosis whereas menopause related information is required with chemotherapy (Thewes, Meiser et al. 2005). Effective dissemination of information seems to protect against depression and anxiety (Burgess, Cornelius et al. 2005), and may help to promote compliance with therapy. Information may be the only intervention women desire or need for management of menopause (Hickey, Saunders et al. 2008). A list of internet based menopause and other relevant resources are provided in section 11.

Downloadable patient resources

 Early and Premature Menopause 98.33 Kb

 Menopause 113.91 Kb

Australasian Menopause Society: Early Menopause due to Chemotherapy
 

Key Points : Menopause Management Lifestyle modification may assist menopausal symptom control, psychological symptomatology and cardiovascular and osteoporosis risk reduction. HRT is the most effective method for relieving hot flushes, urogenital symptoms, andsleeplessness ; however , use of HRT in women with BC is usually contra-indicated. Vaginal oestrogen is effective for isolated urogenital symptoms and is associated with minimal systemic absorption although concurrent use with aromatase inhibitors is controversial. Gabapentin, desvenlafaxine, venlafaxine, paroxetine, citalopram and clonidine are non-hormonal alternatives for relieving vasomotor symptoms. Current scientific evidence does not support the use of complementary/alternative therapies in the management of menopausal symptoms.

 

Selected References:

Boekhout, A. H., J. H. Beijnen, et al. (2006). "Symptoms and Treatment in Cancer Therapy-Induced Early Menopause." Oncologist 11(6): 641-654.

Geller SE, Shulman LP et al., Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomised controlled trial. Menopause (2009) 16:1-11.

Hickey M, Saunders C et al., Practical clinical guidelines for assessing and managing menopausal symptoms after breast cancer. Annals of Oncology (2008) 19:1669-1680.

Innesa, K. E., T. K. Selfea, et al. (2010). "Mind-body therapies for menopausal symptoms: A systematic review

Loprinzi, C. L., J. Sloan, et al. (2009). "Newer Antidepressants and Gabapentin for Hot Flashes: An Individual Patient Pooled Analysis." Journal of Clinical Oncology 27(17): 2831-2837.

Nelson HD, Vesco KK et al., Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA (2006) 295: 2057-2071.

Roberts, H. (2010). "Safety of herbal medicinal products in women with breast cancer. Maturitas 66: 363-369.

Santen RJ, Allred DC et al., Post menopausal hormone therapy: An Endocrine Society Scientific Statement. J Clin Endocrinol Metab (2010) 95, Suppl 1:S1-S66.

Trinkaus M, Chin S, et al. (2008). "Should Urogenital Atrophy in Breast Cancer Survivors Be Treated with Topical Estrogens?." The Oncologist 13: 222-231.

10. When to Refer and Where to Refer To

Content updated May 16, 2011